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Amyloid Imaging And Safety Study Of ACC-001 In Subjects With Early Alzheimer's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01227564
Recruitment Status : Completed
First Posted : October 25, 2010
Results First Posted : February 25, 2016
Last Update Posted : February 25, 2016
Sponsor:
Collaborator:
JANSSEN Alzheimer Immunotherapy Research & Development, LLC
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Alzheimer's Disease
Interventions Biological: ACC-001 3 μg/ QS-21 50 μg
Biological: ACC-001 10 μg/ QS-21 50 μg
Other: Placebo- Phosphate buffered saline (PBS)
Enrollment 63
Recruitment Details Twenty study centers in the United States of America participated. One of these did not enroll any participants.
Pre-assignment Details Participants, who were found eligible, were randomized to 1 of 3 groups in a 1:1:1 ratio between ACC-001 3 μg+QS-21, or ACC-001 10 μg+QS-21, or placebo (which was administrated as phosphate buffered saline [PBS]). The study randomization was stratified based on apolipoprotein E (Apo E) genotype (E4 carrier or non-carrier).
Arm/Group Title ACC 3 μg+QS-21 ACC 10 μg+QS-21 Placebo
Hide Arm/Group Description Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months. Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months. Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Period Title: Overall Study
Started 22 20 21
Treated 22 20 21
Completed Treatment 21 [1] 18 [2] 17 [3]
Completed 18 [4] 18 [4] 15 [4]
Not Completed 4 2 6
Reason Not Completed
No Longer Willing to Participate             4             2             5
Participant moved to another town             0             0             1
[1]
1 participant discontinued treatment due to an adverse event (AE).
[2]
2 participants discontinued treatment due to no longer willing to participate in study.
[3]
1 participant stopped treatment due to lack of efficacy, 3 due to no longer willing to participate.
[4]
Completed study
Arm/Group Title ACC 3 μg+QS-21 ACC 10 μg+QS-21 Placebo Total
Hide Arm/Group Description Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months. Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months. Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months. Total of all reporting groups
Overall Number of Baseline Participants 22 20 21 63
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 22 participants 20 participants 21 participants 63 participants
66.8  (7.31) 68.5  (7.02) 69.6  (6.82) 68.3  (7.04)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 20 participants 21 participants 63 participants
Female
11
  50.0%
13
  65.0%
9
  42.9%
33
  52.4%
Male
11
  50.0%
7
  35.0%
12
  57.1%
30
  47.6%
MMSE Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score
Number Analyzed 22 participants 20 participants 21 participants 63 participants
27.3  (1.64) 27.7  (1.63) 28.0  (1.47) 27.6  (1.58)
[1]
Measure Description: The MMSE is a brief, structured examination of cognitive function consisting of the 11 item: Orientation-What, Orientation-Where, Registration-Objects, Attention and Calculation, Recall, Language-Naming, Language-Repetition, Language-Comprehension, Language-Reading, Language-Writing, and Language- Drawing. MMSE total score was the sum of the 11 item scores and it ranges from 0 to 30 with higher score indicating greater cognitive functioning. If any individual item is missing, then the MMSE total score is set to missing.
1.Primary Outcome
Title Change From Baseline in Brain Fibrillar Beta-Amyloid Protein (Aβ) at Week 104 as Measured by Standard Uptake Value Ratios (SUVRs) Over the Composite Regions of Interest (ROIs)
Hide Description Fibrillar brain Aβ was measured by retention of florbetapir F18 as measured by positron emission tomography (PET) scans. A positive change indicating an improvement from baseline.
Time Frame 104 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) population included all randomized participants who had at least one dose of investigational product.
Arm/Group Title ACC 3 μg+QS-21 ACC 10 μg+QS-21 Overall ACC + QS21 Placebo
Hide Arm/Group Description:
Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Overall Number of Participants Analyzed 22 20 42 21
Least Squares Mean (95% Confidence Interval)
Unit of Measure: ratio
Week 52 (N: 22, 19, 41, 20)
0.009
(-0.042 to 0.060)
0.017
(-0.039 to 0.073)
0.013
(-0.025 to 0.051)
0.011
(-0.043 to 0.065)
Week 78 (N: 21, 18, 39, 16)
-0.011
(-0.084 to 0.062)
-0.022
(-0.101 to 0.057)
-0.017
(-0.071 to 0.038)
-0.014
(-0.096 to 0.068)
Week 104 (N: 14, 15, 29, 13)
-0.018
(-0.097 to 0.061)
-0.018
(-0.098 to 0.062)
-0.018
(-0.075 to 0.038)
0.032
(-0.052 to 0.115)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed-effect model repeated measures was used, with the baseline measure of average SUVRs over ROIs and Apo E4 Status (Carrier or Non-carrier) as covariates, time, treatment, and treatment*time as fixed effects. Estimates of the adjusted mean differences (test-reference) and corresponding 95% confidence intervals were obtained from the model. ACC 3 µg+QS-21 50 µg was the test treatment and placebo was the reference treatment. Statistical analysis presented above for Week 52.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9538
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.002
Confidence Interval (2-Sided) 95%
-0.075 to 0.071
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed-effect model repeated measures was used, with the baseline measure of average SUVRs over ROIs and Apo E4 Status (Carrier or Non-carrier) as covariates, time, treatment, and treatment*time as fixed effects. Estimates of the adjusted mean differences (test-reference) and corresponding 95% confidence intervals were obtained from the model. ACC 10 µg+QS-21 50 µg was the test treatment and placebo was the reference treatment. Statistical analysis presented above for Week 52.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8787
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.006
Confidence Interval (2-Sided) 95%
-0.070 to 0.081
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed-effect model repeated measures was used, with the baseline measure of average SUVRs over ROIs and Apo E4 Status (Carrier or Non-carrier) as covariates, time, treatment, and treatment*time as fixed effects. Estimates of the adjusted mean differences (test-reference) and corresponding 95% confidence intervals were obtained from the model. ACC 3 µg or ACC 10 µg + QS-21 50 µg was the test treatment and placebo was the reference treatment. Statistical analysis presented above for Week 52.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9544
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.002
Confidence Interval (2-Sided) 95%
-0.062 to 0.066
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed-effect model repeated measures was used, with the baseline measure of average SUVRs over ROIs and Apo E4 Status (Carrier or Non-carrier) as covariates, time, treatment, and treatment*time as fixed effects. Estimates of the adjusted mean differences (test-reference) and corresponding 95% confidence intervals were obtained from the model. ACC 3 µg+QS-21 50 µg was the test treatment and placebo was the reference treatment. Statistical analysis presented above for Week 78.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9550
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.003
Confidence Interval (2-Sided) 95%
-0.106 to 0.112
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed-effect model repeated measures was used, with the baseline measure of average SUVRs over ROIs and Apo E4 Status (Carrier or Non-carrier) as covariates, time, treatment, and treatment*time as fixed effects. Estimates of the adjusted mean differences (test-reference) and corresponding 95% confidence intervals were obtained from the model. ACC 10 µg+QS-21 50 µg was the test treatment and placebo was the reference treatment. Statistical analysis presented above for Week 78.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8874
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.008
Confidence Interval (2-Sided) 95%
-0.121 to 0.105
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed-effect model repeated measures was used, with the baseline measure of average SUVRs over ROIs and Apo E4 Status (Carrier or Non-carrier) as covariates, time, treatment, and treatment*time as fixed effects. Estimates of the adjusted mean differences (test-reference) and corresponding 95% confidence intervals were obtained from the model. ACC 3 µg or ACC 10 µg + QS-21 50 µg was the test treatment and placebo was the reference treatment. Statistical analysis presented above for Week 78.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9595
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.002
Confidence Interval (2-Sided) 95%
-0.099 to 0.095
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed-effect model repeated measures was used, with the baseline measure of average SUVRs over ROIs and Apo E4 Status (Carrier or Non-carrier) as covariates, time, treatment, and treatment*time as fixed effects. Estimates of the adjusted mean differences (test-reference) and corresponding 95% confidence intervals were obtained from the model. ACC 3 µg+QS-21 50 µg was the test treatment and placebo was the reference treatment. Statistical analysis presented above for Week 104.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3826
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.050
Confidence Interval (2-Sided) 95%
-0.164 to 0.064
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed-effect model repeated measures was used, with the baseline measure of average SUVRs over ROIs and Apo E4 Status (Carrier or Non-carrier) as covariates, time, treatment, and treatment*time as fixed effects. Estimates of the adjusted mean differences (test-reference) and corresponding 95% confidence intervals were obtained from the model. ACC 10 µg+QS-21 50 µg was the test treatment and placebo was the reference treatment. Statistical analysis presented above for Week 104.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3912
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.049
Confidence Interval (2-Sided) 95%
-0.164 to 0.065
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed-effect model repeated measures was used, with the baseline measure of average SUVRs over ROIs and Apo E4 Status (Carrier or Non-carrier) as covariates, time, treatment, and treatment*time as fixed effects. Estimates of the adjusted mean differences (test-reference) and corresponding 95% confidence intervals were obtained from the model. ACC 3 µg or ACC 10 µg + QS-21 50 µg was the test treatment and placebo was the reference treatment. Statistical analysis presented above for Week 104.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3221
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -0.050
Confidence Interval (2-Sided) 95%
-0.149 to 0.050
Estimation Comments [Not Specified]
2.Other Pre-specified Outcome
Title Change From Baseline in Cerebrospinal Fluid (CSF) Aβ x-40
Hide Description For the majority of the participants, the lumbar puncture for the first CSF sample was collected up to 3 days prior to injection of investigational product. For the participants who had a CSF being already drawn at week 80, no CSF sample was drawn at week 104, nor at the Early termination (ET) visit. For those participants who early terminated the study before week 80, CSF was drawn at ET visit.
Time Frame Week 80 or Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population included all randomized participants who had at least one dose of investigational product.
Arm/Group Title ACC 3 μg+QS-21 ACC 10 μg+QS-21 Overall ACC + QS21 Placebo
Hide Arm/Group Description:
Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Overall Number of Participants Analyzed 22 18 40 17
Least Squares Mean (95% Confidence Interval)
Unit of Measure: μg/ml
192.93
(-652.96 to 1038.82)
726.74
(-252.11 to 1705.58)
459.83
(-178.24 to 1097.91)
144.76
(-816.20 to 1105.71)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments Analysis of Covariance (ANCOVA) was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9384
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 48.18
Confidence Interval (2-Sided) 95%
-1197.07 to 1293.42
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3945
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 581.98
Confidence Interval (2-Sided) 95%
-778.17 to 1942.13
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5773
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 315.08
Confidence Interval (2-Sided) 95%
-812.15 to 1442.30
Estimation Comments [Not Specified]
3.Other Pre-specified Outcome
Title Change From Baseline in CSF Aβ x-42
Hide Description For the majority of the participants, the lumbar puncture for the first CSF sample was collected up to 3 days prior to injection of investigational product. For the participants who had a CSF being already drawn at week 80, no CSF sample was drawn at week 104, nor at ET visit. For those participants who early terminated the study before week 80, CSF was drawn at ET visit.
Time Frame Week 80 or Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population included all randomized participants who had at least one dose of investigational product.
Arm/Group Title ACC 3 μg+QS-21 ACC 10 μg+QS-21 Overall ACC + QS21 Placebo
Hide Arm/Group Description:
Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Overall Number of Participants Analyzed 22 18 40 17
Least Squares Mean (95% Confidence Interval)
Unit of Measure: μg/ml
15.29
(-43.14 to 73.71)
75.55
(11.89 to 139.21)
45.42
(1.56 to 89.28)
-8.87
(-75.24 to 57.50)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5818
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 24.16
Confidence Interval (2-Sided) 95%
-63.31 to 111.62
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0648
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 84.42
Confidence Interval (2-Sided) 95%
-5.37 to 174.21
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1672
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 54.29
Confidence Interval (2-Sided) 95%
-23.47 to 132.05
Estimation Comments [Not Specified]
4.Other Pre-specified Outcome
Title Change From Baseline in CSF p-Tau
Hide Description For the majority of the participants, the lumbar puncture for the first CSF sample was collected up to 3 days prior to injection of investigational product. For the participants who had a CSF being already drawn at week 80, no CSF sample was drawn at week 104, nor at ET visit. For those participants who early terminated the study before week 80, CSF was drawn at ET visit.
Time Frame Week 80 or Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population included all randomized participants who had at least one dose of investigational product.
Arm/Group Title ACC 3 μg+QS-21 ACC 10 μg+QS-21 Overall ACC + QS21 Placebo
Hide Arm/Group Description:
Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Overall Number of Participants Analyzed 22 18 40 17
Least Squares Mean (95% Confidence Interval)
Unit of Measure: μg/ml
-2.32
(-6.80 to 2.15)
-3.47
(-8.43 to 1.49)
-2.90
(-6.14 to 0.35)
1.03
(-3.89 to 5.96)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3106
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.36
Confidence Interval (2-Sided) 95%
-9.94 to 3.22
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1876
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.51
Confidence Interval (2-Sided) 95%
-11.28 to 2.27
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1742
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.93
Confidence Interval (2-Sided) 95%
-9.66 to 1.79
Estimation Comments [Not Specified]
5.Other Pre-specified Outcome
Title Change From Baseline in CSF Total Tau
Hide Description For the majority of the participants, the lumbar puncture for the first CSF sample was collected up to 3 days prior to injection of investigational product. For the participants who had a CSF being already drawn at week 80, no CSF sample was drawn at week 104, nor at ET visit. For those participants who early terminated the study before week 80, CSF was drawn at ET visit.
Time Frame Week 80 or Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population included all randomized participants who had at least one dose of investigational product.
Arm/Group Title ACC 3 μg+QS-21 ACC 10 μg+QS-21 Overall ACC + QS21 Placebo
Hide Arm/Group Description:
Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Overall Number of Participants Analyzed 22 18 40 17
Least Squares Mean (95% Confidence Interval)
Unit of Measure: μg/ml
25.56
(-24.38 to 75.50)
-27.48
(-83.48 to 28.49)
-0.96
(-37.23 to 35.31)
55.92
(0.97 to 110.86)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4089
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -30.36
Confidence Interval (2-Sided) 95%
-103.52 to 42.81
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0327
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -83.40
Confidence Interval (2-Sided) 95%
-159.69 to -7.11
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0801
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -56.88
Confidence Interval (2-Sided) 95%
-120.82 to 7.06
Estimation Comments [Not Specified]
6.Other Pre-specified Outcome
Title Change From Baseline in Plasma Aβ x-40
Hide Description Site personnel collecting the samples for plasma Aβ (x-40) concentrations and the results were blinded to the participant treatment group assignment.
Time Frame 104 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population included all randomized participants who had at least one dose of investigational product.
Arm/Group Title ACC 3 μg+QS-21 ACC 10 μg+QS-21 Overall ACC + QS21 Placebo
Hide Arm/Group Description:
Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Overall Number of Participants Analyzed 22 20 42 21
Least Squares Mean (95% Confidence Interval)
Unit of Measure: pg/mL
Week 12 (N: 22, 19, 41, 20)
30.42
(-9.80 to 70.63)
61.70
(18.55 to 104.85)
46.06
(16.49 to 75.63)
10.64
(-31.24 to 52.52)
Week 26 (N: 22, 18, 40, 19)
150.51
(45.32 to 255.70)
276.86
(162.50 to 391.66)
213.68
(135.80 to 291.57)
51.22
(-61.16 to 163.60)
Week 52 (N: 22, 18, 40, 19)
252.87
(166.03 to 339.72)
313.34
(218.29 to 408.38)
283.11
(218.68 to 347.53)
138.74
(45.73 to 231.75)
Week 78 (N: 22, 17, 39, 17)
225.15
(105.18 to 345.11)
344.13
(210.80 to 477.45)
284.64
(194.93 to 374.35)
117.31
(-13.47 to 248.08)
Week 104 (N: 18, 17, 35, 13)
216.51
(111.67 to 321.35)
279.00
(164.37 to 393.63)
247.76
(170.03 to 325.48)
74.60
(-42.18 to 191.37)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 12.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4892
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 19.78
Confidence Interval (2-Sided) 95%
-37.15 to 76.71
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 12.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0915
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 51.06
Confidence Interval (2-Sided) 95%
-8.51 to 110.63
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 12.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1638
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 35.42
Confidence Interval (2-Sided) 95%
-14.88 to 85.72
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2006
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 99.29
Confidence Interval (2-Sided) 95%
-54.28 to 252.86
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0067
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 225.63
Confidence Interval (2-Sided) 95%
65.18 to 386.09
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0204
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 162.46
Confidence Interval (2-Sided) 95%
26.05 to 298.87
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0766
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 114.13
Confidence Interval (2-Sided) 95%
-12.63 to 240.89
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0181
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 226.82
Confidence Interval (2-Sided) 95%
40.23 to 413.41
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0387
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 167.33
Confidence Interval (2-Sided) 95%
9.03 to 325.63
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2277
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 107.84
Confidence Interval (2-Sided) 95%
-69.29 to 284.97
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0181
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 226.82
Confidence Interval (2-Sided) 95%
40.23 to 413.41
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0387
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 167.33
Confidence Interval (2-Sided) 95%
9.03 to 325.63
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0747
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 141.92
Confidence Interval (2-Sided) 95%
-14.62 to 298.45
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0151
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 204.40
Confidence Interval (2-Sided) 95%
41.02 to 367.79
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0161
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 173.16
Confidence Interval (2-Sided) 95%
33.25 to 313.07
Estimation Comments [Not Specified]
7.Other Pre-specified Outcome
Title Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI)
Hide Description BBSI measures whole brain atrophy from registered MRI scan pairs, by subtracting the area under the intensity profile across a boundary in the repeat scans from the initial scan (baseline).
Time Frame 104 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population included all randomized participants who had at least one dose of investigational product.
Arm/Group Title ACC 3 μg+QS-21 ACC 10 μg+QS-21 Overall ACC + QS21 Placebo
Hide Arm/Group Description:
Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Overall Number of Participants Analyzed 22 20 42 21
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mL
Week 10 (N: 22, 20, 42, 20)
-4.100
(-6.850 to -1.351)
-0.952
(-3.840 to 1.935)
-2.526
(-4.544 to -0.509)
-1.449
(-4.316 to 1.419)
Week 24 (N: 22, 20, 42, 21)
-6.080
(-8.781 to -3.379)
-2.357
(-5.193 to 0.480)
-4.218
(-6.201 to -2.236)
-5.906
(-8.683 to -3.128)
Week 50 (N: 22, 19, 41, 18)
-12.329
(-15.812 to -8.846)
-5.926
(-9.640 to -2.213)
-9.128
(-11.692 to -6.564)
-10.684
(-14.435 to -6.933)
Week 76 (N: 21, 17, 38, 15)
-16.579
(-21.361 to -11.797)
-10.802
(-16.022 to -5.582)
-13.690
(-17.242 to -10.138)
-16.196
(-21.573 to -10.818)
Week 104 (N: 18, 16, 34, 14)
-20.982
(-26.683 to -15.101)
-12.662
(-19.008 to -6.316)
-16.822
(-21.128 to -12.486)
-18.772
(-25.335 to -12.209)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1807
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.652
Confidence Interval (2-Sided) 95%
-6.570 to 1.267
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8051
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.497
Confidence Interval (2-Sided) 95%
-3.515 to 4.508
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5331
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.078
Confidence Interval (2-Sided) 95%
-4.519 to 2.364
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9274
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.174
Confidence Interval (2-Sided) 95%
-3.990 to 3.641
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0743
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.549
Confidence Interval (2-Sided) 95%
-0.360 to 7.458
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3163
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.687
Confidence Interval (2-Sided) 95%
-1.656 to 5.031
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5190
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.645
Confidence Interval (2-Sided) 95%
-6.721 to 3.430
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0740
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.758
Confidence Interval (2-Sided) 95%
-0.476 to 9.991
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4909
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 5.394
Confidence Interval (2-Sided) 95%
-2.937 to 6.049
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9151
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.383
Confidence Interval (2-Sided) 95%
-7.549 to 6.783
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1533
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.394
Confidence Interval (2-Sided) 95%
-2.069 to 12.857
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4371
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.506
Confidence Interval (2-Sided) 95%
-3.904 to 8.915
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6167
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.210
Confidence Interval (2-Sided) 95%
-10.999 to 6.579
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1844
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 6.110
Confidence Interval (2-Sided) 95%
-2.993 to 15.212
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6205
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.950
Confidence Interval (2-Sided) 95%
-5.888 to 9.878
Estimation Comments [Not Specified]
8.Other Pre-specified Outcome
Title Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI)
Hide Description VBSI measures ventricular volume change from registered MRI scan pairs, by subtracting the area under the intensity profile across a boundary in the repeat scans.
Time Frame 104 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population included all randomized participants who had at least one dose of investigational product.
Arm/Group Title ACC 3 μg+QS-21 ACC 10 μg+QS-21 Overall ACC + QS21 Placebo
Hide Arm/Group Description:
Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Overall Number of Participants Analyzed 22 20 42 21
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mL
Week 10 (N: 22, 20, 42, 20)
0.913
(0.500 to 1.327)
0.643
(0.209 to 1.076)
0.778
(0.474 to 1.082)
0.496
(0.056 to 0.935)
Week 24 (N: 22, 20, 42, 21)
1.540
(1.066 to 2.014)
1.229
(0.732 to 1.726)
1.385
(1.038 to 1.731)
1.533
(1.039 to 2.027)
Week 50 (N: 22, 19, 41, 18)
3.023
(2.194 to 3.853)
2.242
(1.364 to 3.120)
2.632
(2.027 to 3.238)
3.038
(2.160 to 3.915)
Week 76 (N: 22, 17, 39, 16)
4.729
(3.322 to 6.136)
3.445
(1.923 to 4.967)
4.087
(3.050 to 5.124)
4.474
(2.940 to 6.008)
Week 104 (N: 18, 16, 34, 14)
6.422
(4.586 to 8.257)
4.970
(2.999 to 6.941)
5.696
(4.348 to 7.043)
5.770
(3.770 to 7.769)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1695
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.418
Confidence Interval (2-Sided) 95%
-0.183 to 1.018
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6331
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.147
Confidence Interval (2-Sided) 95%
-0.465 to 0.759
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2907
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.282
Confidence Interval (2-Sided) 95%
-0.247 to 0.812
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9846
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.007
Confidence Interval (2-Sided) 95%
-0.675 to 0.688
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3845
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.304
Confidence Interval (2-Sided) 95%
-1.000 to 0.392
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6204
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.149
Confidence Interval (2-Sided) 95%
-0.748 to 0.450
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9810
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.014
Confidence Interval (2-Sided) 95%
-1.221 to 1.192
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2034
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.796
Confidence Interval (2-Sided) 95%
-2.034 to 0.443
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4491
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -0.405
Confidence Interval (2-Sided) 95%
-1.469 to 0.659
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8074
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.255
Confidence Interval (2-Sided) 95%
-1.827 to 2.337
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3444
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.029
Confidence Interval (2-Sided) 95%
-3.189 to 1.131
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6772
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.387
Confidence Interval (2-Sided) 95%
-2.239 to 1.464
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6325
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.652
Confidence Interval (2-Sided) 95%
-2.063 to 3.367
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5706
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.800
Confidence Interval (2-Sided) 95%
-3.606 to 2.007
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9513
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.074
Confidence Interval (2-Sided) 95%
-2.485 to 2.337
Estimation Comments [Not Specified]
9.Other Pre-specified Outcome
Title Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total
Hide Description Left HBSI and Right HBSI respectively measure the left hippocampal atrophy and the right hippocampal atrophy from registered MRI scan pairs, by subtracting the corresponding area under the intensity profile across a boundary in the repeat scans. HBSI (Total) is defined as the summation of the left HBSI and the right HBSI.
Time Frame 104 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population included all randomized participants who had at least one dose of investigational product.
Arm/Group Title ACC 3 μg+QS-21 ACC 10 μg+QS-21 Overall ACC + QS21 Placebo
Hide Arm/Group Description:
Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Overall Number of Participants Analyzed 22 20 42 21
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mL
Week 10 (N: 22, 20, 42, 20)
-0.056
(-0.097 to -0.015)
-0.016
(-0.059 to 0.027)
-0.036
(-0.066 to -0.006)
-0.041
(-0.084 to 0.002)
Week 24 (N: 22, 20, 42, 21)
-0.124
(-0.167 to -0.081)
-0.065
(-0.110 to -0.020)
-0.094
(-0.126 to -0.063)
-0.099
(-0.143 to -0.055)
Week 50 (N: 22, 19, 41, 18)
-0.251
(-0.316 to -0.187)
-0.159
(-0.228 to -0.090)
-0.205
(-0.252 to -0.158)
-0.226
(-0.295 to -0.157)
Week 76 (N: 22, 17, 39, 16)
-0.357
(-0.460 to -0.253)
-0.255
(-0.368 to -0.142)
-0.306
(-0.383 to -0.229)
-0.334
(-0.448 to -0.219)
Week 104 (N: 18, 16, 34, 14)
-0.468
(-0.601 to -0.335)
-0.329
(-0.472 to -0.185)
-0.398
(-0.496 to -0.301)
-0.471
(-0.620 to -0.323)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6054
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.015
Confidence Interval (2-Sided) 95%
-0.074 to 0.043
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4087
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.025
Confidence Interval (2-Sided) 95%
-0.035 to 0.084
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8518
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.005
Confidence Interval (2-Sided) 95%
-0.046 to 0.056
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4216
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.025
Confidence Interval (2-Sided) 95%
-0.085 to 0.036
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2730
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.034
Confidence Interval (2-Sided) 95%
-0.028 to 0.097
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8549
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.005
Confidence Interval (2-Sided) 95%
-0.048 to 0.058
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5847
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.026
Confidence Interval (2-Sided) 95%
-0.120 to 0.068
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1740
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.067
Confidence Interval (2-Sided) 95%
-0.030 to 0.163
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6255
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.020
Confidence Interval (2-Sided) 95%
-0.063 to 0.103
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7658
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.023
Confidence Interval (2-Sided) 95%
-0.177 to 0.131
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3309
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.079
Confidence Interval (2-Sided) 95%
-0.082 to 0.240
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6872
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.028
Confidence Interval (2-Sided) 95%
-0.110 to 0.166
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9752
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.003
Confidence Interval (2-Sided) 95%
-0.196 to 0.202
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1715
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.143
Confidence Interval (2-Sided) 95%
-0.064 to 0.349
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4145
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.073
Confidence Interval (2-Sided) 95%
-0.105 to 0.250
Estimation Comments [Not Specified]
10.Other Pre-specified Outcome
Title Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left
Hide Description Left HBSI measures the left hippocampal atrophy from registered MRI scan pairs, by subtracting the corresponding area under the intensity profile across a boundary in the repeat scans.
Time Frame 104 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population included all randomized participants who had at least one dose of investigational product.
Arm/Group Title ACC 3 μg+QS-21 ACC 10 μg+QS-21 Overall ACC + QS21 Placebo
Hide Arm/Group Description:
Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Overall Number of Participants Analyzed 22 20 42 21
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mL
Week 10 (N: 22, 20, 42, 20)
-0.029
(-0.051 to -0.007)
-0.010
(-0.034 to 0.014)
-0.020
(-0.036 to -0.003)
-0.019
(-0.042 to 0.005)
Week 24 (N: 22, 20, 42, 21)
-0.057
(-0.081 to -0.034)
-0.037
(-0.062 to -0.012)
-0.047
(-0.064 to -0.030)
-0.040
(-0.064 to -0.015)
Week 50 (N: 22, 19, 41, 18)
-0.119
(-0.152 to -0.086)
-0.080
(-0.115 to -0.045)
-0.099
(-0.124 to -0.075)
-0.107
(-0.142 to -0.072)
Week 76 (N: 22, 17, 39, 16)
-0.163
(-0.213 to -0.114)
-0.117
(-0.171 to -0.064)
-0.140
(-0.177 to -0.104)
-0.157
(-0.211 to -0.102)
Week 104 (N: 18, 16, 34, 14)
-0.222
(-0.288 to -0.155)
-0.158
(-0.230 to -0.086)
-0.190
(-0.239 to -0.140)
-0.230
(-0.305 to -0.155)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5134
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.011
Confidence Interval (2-Sided) 95%
-0.043 to 0.022
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6083
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.008
Confidence Interval (2-Sided) 95%
-0.024 to 0.041
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9401
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.001
Confidence Interval (2-Sided) 95%
-0.029 to 0.027
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2950
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.018
Confidence Interval (2-Sided) 95%
-0.051 to 0.016
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8817
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.003
Confidence Interval (2-Sided) 95%
-0.031 to 0.037
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6072
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.008
Confidence Interval (2-Sided) 95%
-0.037 to 0.022
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6259
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.012
Confidence Interval (2-Sided) 95%
-0.060 to 0.036
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2807
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.027
Confidence Interval (2-Sided) 95%
-0.023 to 0.076
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7224
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.008
Confidence Interval (2-Sided) 95%
-0.035 to 0.050
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8532
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.007
Confidence Interval (2-Sided) 95%
-0.080 to 0.067
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3116
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.039
Confidence Interval (2-Sided) 95%
-0.038 to 0.116
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6246
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.016
Confidence Interval (2-Sided) 95%
-0.049 to 0.082
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8697
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.008
Confidence Interval (2-Sided) 95%
-0.092 to 0.108
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1707
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.072
Confidence Interval (2-Sided) 95%
-0.032 to 0.176
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3732
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.040
Confidence Interval (2-Sided) 95%
-0.049 to 0.129
Estimation Comments [Not Specified]
11.Other Pre-specified Outcome
Title Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right
Hide Description Right HBSI measures the right hippocampal atrophy from registered MRI scan pairs, by subtracting the corresponding area under the intensity profile across a boundary in the repeat scans.
Time Frame 104 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population included all randomized participants who had at least one dose of investigational product.
Arm/Group Title ACC 3 μg+QS-21 ACC 10 μg+QS-21 Overall ACC + QS21 Placebo
Hide Arm/Group Description:
Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Overall Number of Participants Analyzed 22 20 42 21
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mL
Week 10 (N: 22, 20, 42, 20)
-0.027
(-0.051 to -0.004)
-0.005
(-0.030 to 0.020)
-0.016
(-0.033 to 0.001)
-0.021
(-0.046 to 0.003)
Week 24 (N: 22, 20, 42, 21)
-0.067
(-0.091 to -0.044)
-0.027
(-0.052 to -0.002)
-0.047
(-0.064 to -0.030)
-0.059
(-0.084 to -0.035)
Week 50 (N: 22, 19, 41, 18)
-0.133
(-0.168 to -0.098)
-0.078
(-0.116 to -0.041)
-0.106
(-0.132 to -0.080)
-0.119
(-0.157 to -0.081)
Week 76 (N: 22, 17, 39, 16)
-0.194
(-0.252 to -0.135)
-0.136
(-0.199 to -0.072)
-0.165
(-0.208 to -0.121)
-0.177
(-0.242 to -0.113)
Week 104 (N: 18, 16, 34, 14)
-0.247
(-0.318 to -0.175)
-0.170
(-0.247 to -0.093)
-0.208
(-0.261 to -0.156)
-0.240
(-0.320 to -0.161)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7259
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.006
Confidence Interval (2-Sided) 95%
-0.040 to 0.028
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3517
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.016
Confidence Interval (2-Sided) 95%
-0.018 to 0.051
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7311
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.005
Confidence Interval (2-Sided) 95%
-0.024 to 0.035
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6446
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.008
Confidence Interval (2-Sided) 95%
-0.041 to 0.026
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0640
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.032
Confidence Interval (2-Sided) 95%
-0.002 to 0.066
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4057
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.012
Confidence Interval (2-Sided) 95%
-0.017 to 0.041
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5742
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.015
Confidence Interval (2-Sided) 95%
-0.066 to 0.037
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1336
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.040
Confidence Interval (2-Sided) 95%
-0.013 to 0.093
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5734
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.013
Confidence Interval (2-Sided) 95%
-0.033 to 0.058
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7067
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.016
Confidence Interval (2-Sided) 95%
-0.104 to 0.071
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3600
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.042
Confidence Interval (2-Sided) 95%
-0.049 to 0.132
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7454
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.013
Confidence Interval (2-Sided) 95%
-0.065 to 0.090
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection ACC 3 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9037
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.006
Confidence Interval (2-Sided) 95%
-0.113 to 0.100
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection ACC 10 μg+QS-21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2082
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.070
Confidence Interval (2-Sided) 95%
-0.040 to 0.181
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Overall ACC + QS21, Placebo
Comments A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5044
Comments Analysis was two-sided and performed at the 0.05 significance level. No multiplicity adjustments due to multiple endpoints or multiple assessments were applied. Nominal p-values were reported in the analysis.
Method Mixed-Effects Model Repeated Measures
Comments Kenward-Roger was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.032
Confidence Interval (2-Sided) 95%
-0.063 to 0.127
Estimation Comments [Not Specified]
12.Other Pre-specified Outcome
Title Change From Baseline in Neuropsychological Test Battery (NTB)
Hide Description The NTB evaluated cognitive domains that are known to be affected early in the course of Alzheimer's disease (AD). The cognitive tests included in the NTB were: Rey Auditory Verbal Learning Test – Immediate recall, Detection, Identification, Go-No-Go Task, One Back Task, Controlled Oral Word Association Test, Category Fluency Test, and Rey Auditory Verbal Learning Test – delayed recall and recognition. For each of the eight NTB components, an individual z-score was derived based on the primary raw score of each test. Based on the individual z-scores, a composite z-score was derived using the formula: (z1-z2-z3-z4+z5+z6+z7+z8)/8. Positive change indicating an improvement from baseline.
Time Frame 104 weeks