Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of CAD106 and CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease (GS1)

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: NCT02565511
Recruitment Status : Terminated
First Posted : October 1, 2015
Results First Posted : July 8, 2021
Last Update Posted : July 8, 2021
Sponsor:
Collaborators:
Banner Alzheimer's Institute
National Institute on Aging (NIA)
Amgen
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Alzheimers Disease
Interventions Biological: CAD106 Immunotherapy
Other: Placebo to CAD106
Drug: CNP520
Other: Placebo to CNP520
Other: Alum
Enrollment 480
Recruitment Details  
Pre-assignment Details 713 participants were screened
Arm/Group Title Cohort I (CI) CAD106 Cohort I (CI) CAD106 Placebo Cohort II (CII) CNP520 Cohort II (CII) CNP520 Placebo
Hide Arm/Group Description CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter CNP520 (50 mg) capsules taken once daily orally Placebo to CNP520 capsules taken once daily orally
Period Title: Overall Study
Started 42 23 251 164
3 Patients Were Mis-randomized 0 0 2 1
Completed 0 0 0 0
Not Completed 42 23 251 164
Reason Not Completed
Study terminated by Sponsor             35             22             235             156
Withdrawal by Subject             3             0             12             5
Adverse Event             0             0             1             1
Lost to Follow-up             4             1             0             1
Physician Decision             0             0             0             1
Protocol deviation             0             0             3             0
Arm/Group Title Cohort I (CI) CAD106 Cohort I (CI) CAD106 Placebo Cohort II (CII) CNP520 Cohort II (CII) CNP520 Placebo Total
Hide Arm/Group Description CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter CNP520 (50 mg) capsules taken once daily orally Placebo to CNP520 capsules taken once daily orally Total of all reporting groups
Overall Number of Baseline Participants 42 23 249 163 477
Hide Baseline Analysis Population Description
Three participants were included in the Participant Flow in Cohort II but not included in Baseline Characteristics because they were mis-randomized.
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
<=64 years Number Analyzed 42 participants 23 participants 249 participants 163 participants 477 participants
20 9 77 52 158
65-69 years Number Analyzed 42 participants 23 participants 249 participants 163 participants 477 participants
18 7 116 65 206
>70 years Number Analyzed 42 participants 23 participants 249 participants 163 participants 477 participants
4 7 56 46 113
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 42 participants 23 participants 249 participants 163 participants 477 participants
Female
27
  64.3%
17
  73.9%
129
  51.8%
102
  62.6%
275
  57.7%
Male
15
  35.7%
6
  26.1%
120
  48.2%
61
  37.4%
202
  42.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Caucasian Number Analyzed 42 participants 23 participants 249 participants 163 participants 477 participants
41 22 241 162 466
Black Number Analyzed 42 participants 23 participants 249 participants 163 participants 477 participants
1 1 1 0 3
Asian Number Analyzed 42 participants 23 participants 249 participants 163 participants 477 participants
0 0 4 0 4
Pacific Islander Number Analyzed 42 participants 23 participants 249 participants 163 participants 477 participants
0 0 1 0 1
Other Number Analyzed 42 participants 23 participants 249 participants 163 participants 477 participants
0 0 1 0 1
Unknown Number Analyzed 42 participants 23 participants 249 participants 163 participants 477 participants
0 0 1 1 2
Cohort I API Preclinical Composite Cognitive Battery (APCC)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 42 participants 23 participants 0 participants 0 participants 65 participants
78.0  (5.53) 79.0  (6.76) 78.3  (5.96)
[1]
Measure Description: APCC (API Preclinical Compo site Cognitive Battery) is a composite score derived from RBANS (Repeatable Battery for Assessment of Neurological Status), MMSE (Mini-Mental State Examination) and the Raven's Progressive Matrices; scores are 0-100 and higher scores indicate better cognitive performance.
[2]
Measure Analysis Population Description: Numbers in row represent participants in either Cohort I or Cohort II
Cohort I Repeatable Battery for Assessment of Neurological Status (RBANS)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 42 participants 23 participants 0 participants 0 participants 65 participants
104.4  (12.03) 108.7  (12.83) 106.0  (12.39)
[1]
Measure Description: RBANS is a tool to detect/characterize neurocognitive dementia changes in 5 neurocognitive domains; scores are 40-160 and higher scores indicate better cognitive functioning.
[2]
Measure Analysis Population Description: Numbers in row represent participants in either Cohort I or Cohort II
Cohort I Clinical Dementia Rating Sum of Boxes (CDR-SOB)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 42 participants 23 participants 0 participants 0 participants 65 participants
0.10  (0.276) 0.04  (0.209) 0.08  (0.254)
[1]
Measure Description: Clinical Dementia Rating Sum of Boxes (CDR-SOB) measures cognition and functioning in 6 domains; scores are : 0-18 and higher scores indicate greater disease severity
[2]
Measure Analysis Population Description: Numbers in row represent participants in either Cohort I or Cohort II
Cohort II API Preclinical Composite Cognitive Battery (APCC)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 0 participants 0 participants 249 participants 163 participants 412 participants
29.0  (1.17) 28.9  (1.33) 29.0  (1.23)
[1]
Measure Description: Assessment of Neurological Status), MMSE(Mini-Mental State Examination) and the Raven's Progressive Matrices; scores are 0-100 and higher scores indicate better cognitive APCC(API Preclinical Composite Cognitive Battery) is a composite score derived from RBANS(Repeatable Battery for performance
[2]
Measure Analysis Population Description: Numbers in row represent participants in either Cohort I or Cohort II
Cohort II Repeatable Battery for Assessment of Neurological Status (RBANS)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 0 participants 0 participants 249 participants 163 participants 412 participants
102.6  (12.22) 103.2  (12.03) 102.9  (12.13)
[1]
Measure Description: RBANS is a tool to detect/characterize neurocognitive dementia changes in 5 neurocognitive domains; scores are 40-160 and higher scores indicate better cognitive functioning
[2]
Measure Analysis Population Description: Numbers in row represent participants in either Cohort I or Cohort II
Cohort II Clinical Dementia Rating Sum of Boxes (CDR-SOB)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 0 participants 0 participants 249 participants 163 participants 412 participants
0.16  (0.15) 0.15  (0.417) 0.16  (0.409)
[1]
Measure Description: Clinical Dementia Rating Sum of Boxes (CDR-SOB) measures cognition and functioning in 6 domains; scores are : 0-18 and higher scores indicate greater disease severity
[2]
Measure Analysis Population Description: Numbers in row represent participants in either Cohort I or Cohort II
1.Primary Outcome
Title Time to Event (Diagnosis of Mild Cognitive Impairment or Dementia, Due to Alzheimer's Disease (AD))
Hide Description Event was defined as the first confirmed diagnosis of MCI due to Alzheimer's disease (AD) or dementia due to AD (whichever occurred first) after adjudication by the progression adjudication committee (PAC) as triggered either by an investigator diagnosis or an increase in the Clinical Dementia Rating (CDR) global score. An event had to be confirmed by the PAC at two consecutive visits. In case no confirmed event was observed for a participant, the observation was censored, and the censoring date was defined as the last date where the diagnostic classification was assessed. The Study was terminated and only confirmed events collected up to the data cut-off point were counted. Due to the early termination of the study only a small number of events were observed and time-to-event could not be analyzed. Kaplan-Meyer (KM) estimates were provided to estimate probability that a subject would have an event prior to the specified visit.
Time Frame Baseline to end of exposure for a maximum of 1455 days for CI and 907 days for CII
Hide Outcome Measure Data
Hide Analysis Population Description
n=number of participants at risk to experience an event at the time-point
Arm/Group Title Cohort I (CI) CAD106 Cohort I (CI) CAD106 Placebo Cohort II (CII) CNP520 Cohort II (CII) CNP520 Placebo
Hide Arm/Group Description:
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
CNP520 (50 mg) capsules taken once daily orally
Placebo to CNP520 capsules taken once daily orally
Overall Number of Participants Analyzed 41 22 193 126
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
Week 26 Number Analyzed 41 participants 22 participants 193 participants 126 participants
1.00
(1.00 to 1.00)
1.00
(1.00 to 1.00)
0.98
(0.95 to 0.99)
0.98
(0.94 to 0.99)
Week 52 Number Analyzed 40 participants 22 participants 95 participants 63 participants
1.00
(1.00 to 1.00)
1.00
(1.00 to 1.00)
0.93
(0.88 to 0.96)
0.95
(0.90 to 0.98)
Week 78 Number Analyzed 37 participants 21 participants 18 participants 9 participants
0.97
(0.83 to 1.00)
1.00
(1.00 to 1.00)
0.88
(0.79 to 0.93)
0.85
(0.63 to 0.94)
Week 104 Number Analyzed 22 participants 15 participants 5 participants 2 participants
0.97
(0.83 to 1.00)
1.00
(1.00 to 1.00)
0.88
(0.79 to 0.93)
0.85
(0.63 to 0.94)
2.Primary Outcome
Title Change in the Alzheimer's Prevention Initiative Composite Cognitive (APCC) Test Score
Hide Description APCC is a composite score derived from the specific scores from the Repeatable Battery for the Assessment of Neurological Status (RBANS), Mini-Mental State Examination (MMSE) and the Raven's Progressive Matrices. The APCC score is a weighted score with ranges from from 0 to 100 where higher scores correspond to better cognitive performance.
Time Frame CI = Baseline to Weeks 26, 52,78 104 and Baseline to last assessment; CII = Baseline to Weeks 26, 52, 78, 104 and Baseline to Last on-treatment and Baseline to Last off-treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Arm/Group Title Cohort I (CI) CAD106 Cohort I (CI) CAD106 Placebo Cohort II (CII) CNP520 Cohort II (CII) CNP520 Placebo
Hide Arm/Group Description:
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
CNP520 (50 mg) capsules taken once daily orally
Placebo to CNP520 capsules taken once daily orally
Overall Number of Participants Analyzed 41 23 179 125
Mean (Standard Deviation)
Unit of Measure: Total scores
Week 26 Number Analyzed 41 participants 23 participants 154 participants 105 participants
-1.1  (4.10) -2.0  (3.90) -3.3  (4.54) -1.0  (4.65)
Week 52 Number Analyzed 41 participants 22 participants 64 participants 36 participants
0.9  (4.24) 1.4  (3.36) 0.3  (4.27) 2.2  (6.11)
Week 78 Number Analyzed 27 participants 18 participants 7 participants 8 participants
0.2  (4.15) -0.7  (5.48) -4.1  (4.14) 2.4  (4.23)
Week 104 Number Analyzed 17 participants 9 participants 3 participants 0 participants
-1.4  (4.67) 0.3  (4.00) -6.7  (3.95)
CI-Last post BL assessment Number Analyzed 41 participants 23 participants 0 participants 0 participants
0.0  (4.62) 0.1  (3.87)
CII - Last on treatment Number Analyzed 0 participants 0 participants 179 participants 125 participants
-1.7  (4.81) 0.1  (4.58)
CII-Last off treatment Number Analyzed 0 participants 0 participants 166 participants 90 participants
-0.1  (4.72) 0.2  (4.56)
3.Secondary Outcome
Title Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Score
Hide Description The CDR was obtained through semi-structured interviews of participants and informants, and cognitive functioning was rated on a 5-point scale of functioning in six domains: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. The CDR global score ranged from zero to three, while the CDR-SOB was the sum of the ratings from the six domains, ranging from 0 to 18 with a minimum increment of 0.5. Higher scores indicated greater disease severity.
Time Frame CI = Baseline to Weeks 26, 52,78 104 and Baseline to last assessment; CII = Baseline to Weeks 26, 52, 78, 104 and Baseline to Last on-treatment and Baseline to Last off-treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Arm/Group Title Cohort I (CI) CAD106 Cohort I (CI) CAD106 Placebo Cohort II (CII) CNP520 Cohort II (CII) CNP520 Placebo
Hide Arm/Group Description:
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
CNP520 (50 mg) capsules taken once daily orally
Placebo to CNP520 capsules taken once daily orally
Overall Number of Participants Analyzed 41 23 174 122
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Week 26 Number Analyzed 41 participants 23 participants 153 participants 105 participants
-0.04  (0.234) 0.00  (0.000) 0.04  (0.361) 0.00  (0.336)
Week 52 Number Analyzed 41 participants 23 participants 64 participants 36 participants
-0.01  (0.237) 0.02  (0.104) -0.02  (0.281) -0.08  (0.541)
Week 78 Number Analyzed 27 participants 18 participants 7 participants 7 participants
-0.04  (0.237) 0.03  (0.118) 0.14  (0.802) -0.14  (0.244)
Week 104 Number Analyzed 17 participants 9 participants 3 participants 0 participants
0.15  (0.460) 0.06  (0.167) -0.17  (0.764)
CI Last post baseline assessment Number Analyzed 41 participants 23 participants 0 participants 0 participants
0.04  (0.343) 0.00  (0.302)
CII Last on-treatment Number Analyzed 0 participants 0 participants 174 participants 122 participants
0.06  (0.505) 0.03  (0.410)
CII Last off-treatment Number Analyzed 0 participants 0 participants 156 participants 90 participants
0.05  (0.464) -0.01  (0.519)
4.Secondary Outcome
Title Change in the Total Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Hide Description Repeatable Battery for the Assessment of Neurological Status (RBANS) is a clinical tool designed to detect and characterize the earliest neurocognitive changes associated with dementia. The RBANS generates age-adjusted index scores for five neurocognitive domains: Immediate Memory, Visuospatial/Constructional, Language, Attention and Delayed Memory, which are used to calculate a Total Scale Index score. Index scores and total score range from 40 to 160 and a higher score indicates better cognitive functioning.
Time Frame CI = Baseline to Weeks 26, 52,78 104 and Baseline to last assessment; CII = Baseline to Weeks 26, 52, 78, 104 and Baseline to Last on-treatment and Baseline to Last off-treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Arm/Group Title Cohort I (CI) CAD106 Cohort I (CI) CAD106 Placebo Cohort II (CII) CNP520 Cohort II (CII) CNP520 Placebo
Hide Arm/Group Description:
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
CNP520 (50 mg) capsules taken once daily orally
Placebo to CNP520 capsules taken once daily orally
Overall Number of Participants Analyzed 41 23 209 141
Mean (Standard Deviation)
Unit of Measure: scores
Total Week 26 Number Analyzed 41 participants 23 participants 154 participants 105 participants
-5.1  (7.25) -3.0  (7.51) -4.1  (8.58) -2.6  (7.83)
Total Week 52 Number Analyzed 41 participants 22 participants 64 participants 37 participants
-1.2  (7.82) 4.5  (7.10) -0.1  (7.91) 1.4  (8.06)
Total Week 78 Number Analyzed 27 participants 18 participants 7 participants 8 participants
-2.1  (7.69) -4.0  (7.82) -12.1  (7.40) -4.8  (5.99)
Total Week 104 Number Analyzed 17 participants 9 participants 3 participants 0 participants
-1.4  (6.74) -3.0  (8.34) -7.7  (15.57)
Total CI Last post baseline assessment Number Analyzed 41 participants 23 participants 0 participants 0 participants
-1.0  (9.27) 0.4  (7.20)
Total CII Last on-treatment Number Analyzed 0 participants 0 participants 209 participants 141 participants
-2.7  (8.65) -0.2  (9.22)
Total CII Last off-treatment Number Analyzed 0 participants 0 participants 169 participants 93 participants
-1.5  (9.20) -0.6  (8.83)
5.Secondary Outcome
Title Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Hide Description Repeatable Battery for the Assessment of Neurological Status (RBANS) is a clinical tool designed to detect and characterize the earliest neurocognitive changes associated with dementia. The RBANS generates age-adjusted index scores for five neurocognitive domains: Immediate Memory, Visuospatial/Constructional, Language, Attention and Delayed Memory, which are used to calculate a Total Scale Index score. Index scores and total score range from 40 to 160 and a higher score indicates better cognitive functioning.
Time Frame CI = Baseline to Weeks 26, 52 and Baseline to last assessment; CII = Baseline to Weeks 26, 52 and Baseline to Last on-treatment and Baseline to Last off-treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Arm/Group Title Cohort I (CI) CAD106 Cohort I (CI) CAD106 Placebo Cohort II (CII) CNP520 Cohort II (CII) CNP520 Placebo
Hide Arm/Group Description:
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
CNP520 (50 mg) capsules taken once daily orally
Placebo to CNP520 capsules taken once daily orally
Overall Number of Participants Analyzed 41 23 209 141
Mean (Standard Deviation)
Unit of Measure: scores
Immediate memory - Week 26 Number Analyzed 41 participants 23 participants 154 participants 105 participants
-8.6  (10.68) -3.8  (11.16) -7.4  (13.11) -3.7  (12.15)
Immediate memory - Week 52 Number Analyzed 41 participants 22 participants 64 participants 37 participants
1.3  (10.81) 4.8  (8.68) 0.6  (13.55) 5.1  (11.73)
CI Immediate memory - Last post baseline assessment Number Analyzed 41 participants 23 participants 0 participants 0 participants
-1.1  (13.11) 1.1  (14.52)
CII Immediate memory - Last on-treatment Number Analyzed 0 participants 0 participants 209 participants 141 participants
-3.7  (14.43) 0.6  (13.54)
CII Immediate memory - Last off-treatment Number Analyzed 0 participants 0 participants 169 participants 93 participants
-3.2  (13.76) -2.0  (11.90)
Visuospatial Week 26 Number Analyzed 41 participants 23 participants 154 participants 105 participants
-6.5  (15.21) 0.7  (12.39) -3.5  (14.98) -2.4  (13.00)
Visuospatial Week 52 Number Analyzed 41 participants 22 participants 64 participants 37 participants
-6.5  (14.59) 3.0  (15.09) -1.4  (14.29) -4.8  (12.60)
CI Visuospatial Last post baseline assessment Number Analyzed 41 participants 23 participants 0 participants 0 participants
-4.7  (13.91) 1.9  (12.72)
CII Visuospatial Last on-treatment n= Number Analyzed 0 participants 0 participants 209 participants 141 participants
-3.5  (14.59) -2.6  (14.92)
CII Visuospatial Last off-treatment Number Analyzed 0 participants 0 participants 169 participants 93 participants
-1.2  (15.13) -0.8  (15.18)
Language Week 26 Number Analyzed 41 participants 23 participants 154 participants 105 participants
-1.4  (12.91) -2.8  (11.42) -0.1  (12.05) -1.5  (11.87)
Language Week 52 Number Analyzed 41 participants 22 participants 64 participants 37 participants
2.6  (10.29) 2.0  (11.51) -0.3  (12.88) 0.8  (9.72)
CI Language Last post baseline assessment Number Analyzed 41 participants 23 participants 0 participants 0 participants
1.9  (13.00) -4.5  (12.86)
CII Language Last on-treatment Number Analyzed 0 participants 0 participants 209 participants 141 participants
-0.1  (12.07) -0.1  (11.93)
CII Language Last off-treatment Number Analyzed 0 participants 0 participants 169 participants 93 participants
-1.0  (13.19) -1.8  (11.25)
Attention Week 26 Number Analyzed 41 participants 23 participants 154 participants 105 participants
1.8  (9.40) -0.6  (14.19) -0.7  (10.42) -0.6  (11.67)
Attention Week 52 Number Analyzed 41 participants 22 participants 64 participants 37 participants
0.9  (10.80) -0.5  (13.09) -0.2  (10.02) 2.7  (10.77)
CI Attention Last post baseline assessment Number Analyzed 41 participants 23 participants 0 participants 0 participants
2.0  (12.91) 2.0  (10.25)
CII Attention Last on-treatment Number Analyzed 0 participants 0 participants 209 participants 141 participants
0.1  (10.80) 0.8  (11.20)
CII-Attention Last off-treatment Number Analyzed 0 participants 0 participants 169 participants 93 participants
1.0  (1.64) 1.2  (11.07)
Delayed memory - Week 26 Number Analyzed 41 participants 23 participants 154 participants 105 participants
-3.8  (7.83) -2.7  (7.64) -3.8  (11.20) -2.6  (8.85)
Delayed memory - Week 52 Number Analyzed 41 participants 22 participants 64 participants 37 participants
-2.0  (8.01) 3.2  (6.23) 2.3  (9.09) 0.6  (11.73)
CI Delayed memory - Last post baseline assessment Number Analyzed 41 participants 23 participants 0 participants 0 participants
-1.0  (10.20) 1.3  (8.44)
CII Delayed memory - Last on-treatment Number Analyzed 0 participants 0 participants 209 participants 141 participants
-2.5  (10.61) 0.4  (10.28)
CII Delayed memory - Last off-treatment Number Analyzed 0 participants 0 participants 169 participants 93 participants
-1.1  (10.75) 1.1  (11.28)
6.Secondary Outcome
Title Change in the Everyday Cognition Scale (ECog-Subject) Total Scores
Hide Description Everyday Cognition Scale (ECog) measures cognitively-relevant everyday abilities comprised of 39 items covering 6 cognitively-relevant domains: Everyday Memory, Everyday Language, Everyday Visuospatial Abilities, Everyday Planning, Everyday Organization, and Everyday Divided Attention. The questionnaire is a self-reported measure completed by both participant and study partner (informant). The total score for the 39 items ranges from 39 to 195, with greater scores indicating worse daily function.
Time Frame CI = Baseline to Weeks 26, 52 and Baseline to last assessment; CII = Baseline to Weeks 26, 52 and Baseline to Last on-treatment and Baseline to Last off-treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Arm/Group Title Cohort I (CI) CAD106 Cohort I (CI) CAD106 Placebo Cohort II (CII) CNP520 Cohort II (CII) CNP520 Placebo
Hide Arm/Group Description:
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
CNP520 (50 mg) capsules taken once daily orally
Placebo to CNP520 capsules taken once daily orally
Overall Number of Participants Analyzed 40 22 178 119
Mean (Standard Deviation)
Unit of Measure: Total scores
Week 26 Number Analyzed 40 participants 22 participants 151 participants 103 participants
-1.0  (2.94) 2.3  (4.80) 1.8  (6.03) 0.6  (6.45)
Week 52 Number Analyzed 40 participants 21 participants 63 participants 37 participants
0.6  (5.23) 0.4  (2.99) 2.7  (6.16) 0.2  (5.01)
CI Last post baseline assessment Number Analyzed 40 participants 22 participants 0 participants 0 participants
0.6  (5.02) 1.6  (4.07)
CII Last on-treatment Number Analyzed 0 participants 0 participants 178 participants 119 participants
2.6  (7.81) 0.9  (6.48)
CII Last off-treatment Number Analyzed 0 participants 0 participants 162 participants 86 participants
1.6  (6.77) 0.8  (6.13)
7.Secondary Outcome
Title Change in the Everyday Cognition Scale (ECog-Informant) Total Scores
Hide Description Everyday Cognition Scale (ECog) measures cognitively-relevant everyday abilities comprised of 39 items covering 6 cognitively-relevant domains: Everyday Memory, Everyday Language, Everyday Visuospatial Abilities, Everyday Planning, Everyday Organization, and Everyday Divided Attention. The questionnaire is a self-reported measure completed by both participant and study partner (informant). The total score for the 39 items ranges from 39 to 195, with greater scores indicating worse daily function. Cohort I=C I and Cohort II=C II.
Time Frame CI = Baseline to Weeks 26, 52 and Baseline to last assessment; CII = Baseline to Weeks 26, 52 and Baseline to Last on-treatment and Baseline to Last off-treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Arm/Group Title Cohort I (CI) CAD106 Cohort I (CI) CAD106 Placebo Cohort II (CII) CNP520 Cohort II (CII) CNP520 Placebo
Hide Arm/Group Description:
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
CNP520 (50 mg) capsules taken once daily orally
Placebo to CNP520 capsules taken once daily orally
Overall Number of Participants Analyzed 37 23 160 113
Mean (Standard Deviation)
Unit of Measure: Total scores
Week 26 Number Analyzed 37 participants 23 participants 142 participants 95 participants
-0.4  (4.21) -1.0  (4.87) 0.1  (6.84) -0.7  (8.69)
Week 52 Number Analyzed 37 participants 22 participants 57 participants 29 participants
-0.2  (3.15) -0.3  (5.12) 1.4  (5.18) -0.2  (9.59)
CI Last post baseline assessment Number Analyzed 37 participants 23 participants 0 participants 0 participants
-1.1  (4.23) -1.0  (4.88)
CII Last on-treatment Number Analyzed 0 participants 0 participants 160 participants 113 participants
1.3  (8.76) 0.1  (9.12)
CII Last off-treatment Number Analyzed 0 participants 0 participants 143 participants 77 participants
1.4  (8.49) -0.5  (10.10)
8.Secondary Outcome
Title Number of Participants With Newly Occurring Safety MRI Abnormalities (ARIA-E, ARIA-H,White Matter Disease and Any Other MRI Abnormalities)
Hide Description Safety MRI included sequences necessary for ascertainment of possible ARIA-E (Amyloid Related Imaging Abnormality-Edema), ARIA-H (Amyloid Related Imaging Abnormality- Hemorrhage, including superficial siderosis and microhemorrhages), assessment of recent infarcts and white matter integrity examination (White matter disease worsening since baseline) and a general assessment of brain abnormalities. Assessment of cerebral amyloid angiopathy (CAA) is included in the overall safety MRI findings results.
Time Frame Baseline to end of exposure for a maximum of 1455 days for CI and 907 days for CII
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set - only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Arm/Group Title Cohort I (CI) CAD106 Cohort I (CI) CAD106 Placebo Cohort II (CII) CNP520 Cohort II (CII) CNP520 Placebo
Hide Arm/Group Description:
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
CNP520 (50 mg) capsules taken once daily orally
Placebo to CNP520 capsules taken once daily orally
Overall Number of Participants Analyzed 42 23 249 163
Measure Type: Count of Participants
Unit of Measure: Participants
Questionable presence of ARIA-E
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.6%
Presence of ARIA-E
1
   2.4%
0
   0.0%
0
   0.0%
2
   1.2%
ARIA-E - If present, the worst Severity=moderate
1
   2.4%
0
   0.0%
0
   0.0%
2
   1.2%
Presence of ARIA-H - >4 microhemorrhages (new hemosiderin deposits < 10 mm)
2
   4.8%
0
   0.0%
6
   2.4%
2
   1.2%
White matter disease worsening: 1-3 increase
0
   0.0%
2
   8.7%
6
   2.4%
1
   0.6%
White matter disease worsening: 4 - 8 increase
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White matter disease worsening > 8 increase
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Any other MRI abnormalities
2
   4.8%
1
   4.3%
0
   0.0%
0
   0.0%
9.Secondary Outcome
Title Annualized Percent Change on Volume of Brain Regions
Hide Description Annualized % change from baseline in volume of specific brain regions of interest (ROIs): whole brain (WB), hippocampus (Hip), and lateral ventricles (LV). Annualized percentage change was calculated as (percentage per participant / time interval (in days)) x 365.25. Time interval (in days) was derived as date of current MRI assessment on study drug - date of baseline MRI assessment + 1.
Time Frame CI = Baseline to Weeks 26, 52 and Baseline to last assessment; CII = Baseline to Weeks 26, 52 and Baseline to Last on-treatment and Baseline to Last off-treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set - only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Arm/Group Title Cohort I (CI) CAD106 Cohort I (CI) CAD106 Placebo Cohort II (CII) CNP520 Cohort II (CII) CNP520 Placebo
Hide Arm/Group Description:
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
CNP520 (50 mg) capsules taken once daily orally
Placebo to CNP520 capsules taken once daily orally
Overall Number of Participants Analyzed 42 23 201 135
Mean (Standard Deviation)
Unit of Measure: Percentage of volume change
WB Week 26 Number Analyzed 35 participants 23 participants 145 participants 104 participants
-0.7570  (1.33114) -0.6044  (1.29608) -0.9318  (1.06843) -0.4616  (1.00537)
WB Week 52 Number Analyzed 37 participants 22 participants 63 participants 40 participants
-0.5144  (0.66578) -0.3395  (0.75810) -0.6590  (0.64838) -0.4227  (0.58778)
WB CI Last post baseline assessment Number Analyzed 40 participants 23 participants 0 participants 0 participants
-0.4645  (0.57503) -0.5321  (0.46526)
WB CII Last on-treatment Number Analyzed 0 participants 0 participants 148 participants 108 participants
-0.8268  (0.94889) -0.5181  (0.92086)
WB CII Last off-treatment Number Analyzed 0 participants 0 participants 36 participants 23 participants
-0.6748  (0.62542) -0.3317  (0.62616)
Hip Week 26 Number Analyzed 35 participants 23 participants 145 participants 104 participants
-1.3262  (2.35453) -0.9245  (2.81731) -1.6603  (2.65529) -0.8817  (2.06227)
Hip Week 52 Number Analyzed 37 participants 22 participants 63 participants 40 participants
-1.0376  (1.44310) -0.7780  (1.81604) -1.2438  (1.79988) -0.9567  (1.42941)
Hip CI Last post baseline assessment Number Analyzed 40 participants 23 participants 0 participants 0 participants
-1.0801  (1.38061) -1.0477  (1.33603)
Hip CII Last on-treatment Number Analyzed 0 participants 0 participants 148 participants 108 participants
-1.4790  (2.36526) -0.9984  (1.85655)
Hip CII Last off-treatment Number Analyzed 0 participants 0 participants 36 participants 23 participants
-1.9375  (2.03593) -1.0498  (1.66596)
LV Week 26 Number Analyzed 35 participants 23 participants 145 participants 104 participants
4.1848  (5.77286) 2.5581  (7.54667) 4.5176  (5.59748) 3.9735  (4.23237)
LV Week 52 Number Analyzed 37 participants 22 participants 63 participants 40 participants
4.2060  (3.92877) 2.8232  (5.04358) 3.3854  (3.71214) 2.9059  (3.18734)
LV CI Last post baseline assessment Number Analyzed 40 participants 23 participants 0 participants 0 participants
4.0543  (3.75310) 3.5427  (3.53772)
LV CII Last on-treatment Number Analyzed 0 participants 0 participants 148 participants 108 participants
4.3588  (5.07839) 4.0308  (3.64102)
LV CII Last off-treatment Number Analyzed 0 participants 0 participants 36 participants 23 participants
3.9617  (2.61831) 2.6052  (3.54903)
10.Secondary Outcome
Title Change in Cerebrospinal Fluid (CSF) Levels of Amyloid Beta 40 (Aβ40)
Hide Description Alzheimer's Disease-related biomarkers analyzed in cerebrospinal fluid (CSF): Amyloid Beta 40 (Aβ40)
Time Frame Baseline to last assessment
Hide Outcome Measure Data
Hide Analysis Population Description
No lumbar punctures for CSF collection were performed due to early termination of trial
Arm/Group Title Cohort I (CI) CAD106 Cohort I (CI) CAD106 Placebo Cohort II (CII) CNP520 Cohort II (CII) CNP520 Placebo
Hide Arm/Group Description:
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
CNP520 (50 mg) capsules taken once daily orally
Placebo to CNP520 capsules taken once daily orally
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
11.Secondary Outcome
Title Change in Cerebrospinal Fluid (CSF) Levels of Amyloid Beta 42 (Aβ42)
Hide Description Alzheimer's Disease-related biomarkers analyzed in cerebrospinal fluid (CSF): Amyloid Beta 42 (Aβ42)
Time Frame Baseline to last assessment
Hide Outcome Measure Data
Hide Analysis Population Description
No lumbar punctures for CSF collection were performed due to early termination of trial
Arm/Group Title Cohort I (CI) CAD106 Cohort I (CI) CAD106 Placebo Cohort II (CII) CNP520 Cohort II (CII) CNP520 Placebo
Hide Arm/Group Description:
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
CNP520 (50 mg) capsules taken once daily orally
Placebo to CNP520 capsules taken once daily orally
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
12.Secondary Outcome
Title Change in Cerebrospinal Fluid (CSF) Levels of Total Tau and Phosphorylated Tau
Hide Description Alzheimer's Disease-related biomarkers analyzed in cerebrospinal fluid (CSF): total tau protein and phosphorylated tau protein levels
Time Frame Baseline to last assessment
Hide Outcome Measure Data
Hide Analysis Population Description
No lumbar punctures for CSF collection were performed due to early termination of trial
Arm/Group Title Cohort I (CI) CAD106 Cohort I (CI) CAD106 Placebo Cohort II (CII) CNP520 Cohort II (CII) CNP520 Placebo
Hide Arm/Group Description:
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
CNP520 (50 mg) capsules taken once daily orally
Placebo to CNP520 capsules taken once daily orally
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
13.Secondary Outcome
Title Change in Neurofibrillary Tangle Burden as Measured by Standardized Uptake Ratio (SUVR) of PET Scans With Tau Radiotracer (Where Available)
Hide Description To demonstrate the effects of CNP520 vs placebo on tau pathology in the brain
Time Frame Baseline to last assessment
Hide Outcome Measure Data
Hide Analysis Population Description
No post baseline data collected
Arm/Group Title Cohort I (CI) CAD106 Cohort I (CI) CAD106 Placebo Cohort II (CII) CNP520 Cohort II (CII) CNP520 Placebo
Hide Arm/Group Description:
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
CNP520 (50 mg) capsules taken once daily orally
Placebo to CNP520 capsules taken once daily orally
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
14.Secondary Outcome
Title Cohort I : Annualized Change in Amyloid Deposition as Measured by Centiloids of Positron Emission Tomography (PET) Scan With Amyloid Radiotracer
Hide Description To demonstrate the effects of CAD106 vs placebo on Alzheimer's Disease-related biomarkers
Time Frame Baseline up to approximately Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
Only available for Cohort I. For Cohort II, no post-baseline (year 2) amyloid PET scans could be obtained due to the early trial termination
Arm/Group Title Cohort I (CI) CAD106 Cohort I (CI) CAD106 Placebo
Hide Arm/Group Description:
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
Overall Number of Participants Analyzed 42 23
Mean (Standard Deviation)
Unit of Measure: Centiloids
-0.911  (5.6596) 8.367  (6.6805)
15.Secondary Outcome
Title Change in Serum Neurofilaments
Hide Description Alzheimer's Disease-related biomarkers analyzed in blood serum: light chain neurofilaments (NfL)
Time Frame Baseline to Week 26 and week 52, CI baseline to last assessment. CII baseline to last on-treatment and to last off-treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants with a value at both Baseline and that visit are included. CI last post-baseline assessment. CII Last on-treatment is the last assessment before or at last day on study drug + 31 days.
Arm/Group Title Cohort I (CI) CAD106 Cohort I (CI) CAD106 Placebo Cohort II (CII) CNP520 Cohort II (CII) CNP520 Placebo
Hide Arm/Group Description:
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
CNP520 (50 mg) capsules taken once daily orally
Placebo to CNP520 capsules taken once daily orally
Overall Number of Participants Analyzed 20 10 72 53
Mean (Standard Deviation)
Unit of Measure: pg/mL
Week 26 Number Analyzed 20 participants 10 participants 72 participants 53 participants
1.44  (3.165) -3.89  (13.058) 0.644  (3.4879) 0.362  (6.7547)
Week 52 Number Analyzed 8 participants 6 participants 8 participants 9 participants
2.63  (5.716) -6.09  (16.542) 1.921  (4.0515) -4.852  (14.2270)
C I Last post baseline assessment Number Analyzed 20 participants 10 participants 0 participants 0 participants
1.77  (4.643) -3.31  (12.858)
C II Last on-treatment Number Analyzed 0 participants 0 participants 72 participants 51 participants
0.647  (3.5357) 0.280  (6.8289)
C II Last off-treatment Number Analyzed 0 participants 0 participants 2 participants 2 participants
-0.004  (3.7102) -2.145  (2.6799)
16.Secondary Outcome
Title Number of Suicidal Ideation or Behavior Events
Hide Description Prospective suicidality assessment was performed with the use of Columbia-Suicide Severity Rating Scale (C-SSRS), a questionnaire using a detailed branched logic algorithm evaluating participant's suicidality ideation and behavior. Answer "yes" on item 4 or 5 of the Suicidal Ideation section or "yes" on any item of the Suicidal Behavior section was considered positive.
Time Frame Baseline to end of exposure for a maximum of 1455 days for CI and 907 days for CII
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set which includes only participants with events
Arm/Group Title Cohort I (CI) CAD106 Cohort I (CI) CAD106 Placebo Cohort II (CII) CNP520 Cohort II (CII) CNP520 Placebo
Hide Arm/Group Description:
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
CNP520 (50 mg) capsules taken once daily orally
Placebo to CNP520 capsules taken once daily orally
Overall Number of Participants Analyzed 42 23 249 163
Measure Type: Number
Unit of Measure: events
Any suicidal ideation 2 1 12 4
Any suicidal behavior 0 0 1 1
17.Secondary Outcome
Title Cohort I : Change in Cognition as Measured by APCC and CDR-SOB Scores and Antibody Response
Hide Description [Not Specified]
Time Frame Month 6 to Month 60
Hide Outcome Measure Data
Hide Analysis Population Description
No analysis performed due to early termination, no month 60 data
Arm/Group Title Cohort I (CI) CAD106 Cohort I (CI) CAD106 Placebo Cohort II (CII) CNP520 Cohort II (CII) CNP520 Placebo
Hide Arm/Group Description:
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
CNP520 (50 mg) capsules taken once daily orally
Placebo to CNP520 capsules taken once daily orally
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
18.Secondary Outcome
Title Cohort I: Peak Concentration (Cmax) of CAD106 Induced Abeta-specific Antibody Titers
Hide Description

Cmax is the maximum Titer Concentration of any post-baseline 'on treatment' visit. A visit is considered as 'on treatment' if visit date is within {last injection + 180 days}.

- Geometric mean and CI's are back-transformed from the estimates for Log mean and CI's.

Time Frame Week 9, 13, 15, 26 and quarterly thereafter (trough values)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Cohort I (CI) CAD106
Hide Arm/Group Description:
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
Overall Number of Participants Analyzed 41
Geometric Mean (95% Confidence Interval)
Unit of Measure: Days x titer levels rel. to ref. serum
128.76
(99.05 to 167.37)
19.Secondary Outcome
Title Cohort I: Area Under the Concentration Curve (AUC) of CAD106 Induced Abeta-specific Antibody Titers
Hide Description AUC is calculated based on 'on treatment' visit only.(missing values for peak visits were linearly interpolated for calculation; missing values for trough visits were imputed by average of non-missing trough values.).
Time Frame Week 9, 13, 15, 26 and quarterly thereafter (trough values)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Cohort I (CI) CAD106
Hide Arm/Group Description:
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
Overall Number of Participants Analyzed 42
Geometric Mean (95% Confidence Interval)
Unit of Measure: Days x titer levels rel. to ref. serum
34999.89
(22992.17 to 53278.68)
Time Frame Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort I @CAD106 Cohort I @Placebo Cohort II (CNP520 50) Cohort II Placebo
Hide Arm/Group Description Cohort I @CAD106 Cohort I @Placebo CNP520 (50 mg) capsules taken once daily orally Cohort II @Placebo
All-Cause Mortality
Cohort I @CAD106 Cohort I @Placebo Cohort II (CNP520 50) Cohort II Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/42 (0.00%)   0/23 (0.00%)   0/249 (0.00%)   0/163 (0.00%) 
Hide Serious Adverse Events
Cohort I @CAD106 Cohort I @Placebo Cohort II (CNP520 50) Cohort II Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/42 (9.52%)   3/23 (13.04%)   8/249 (3.21%)   7/163 (4.29%) 
Cardiac disorders         
Atrial flutter  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Cardiac failure congestive  1  0/42 (0.00%)  0/23 (0.00%)  0/249 (0.00%)  1/163 (0.61%) 
Coronary artery disease  1  0/42 (0.00%)  0/23 (0.00%)  1/249 (0.40%)  0/163 (0.00%) 
Stress cardiomyopathy  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Gastrointestinal disorders         
Hiatus hernia  1  0/42 (0.00%)  0/23 (0.00%)  1/249 (0.40%)  0/163 (0.00%) 
Nausea  1  1/42 (2.38%)  0/23 (0.00%)  0/249 (0.00%)  0/163 (0.00%) 
General disorders         
Asthenia  1  1/42 (2.38%)  0/23 (0.00%)  0/249 (0.00%)  0/163 (0.00%) 
Feeling jittery  1  1/42 (2.38%)  0/23 (0.00%)  0/249 (0.00%)  0/163 (0.00%) 
Non-cardiac chest pain  1  1/42 (2.38%)  0/23 (0.00%)  0/249 (0.00%)  0/163 (0.00%) 
Infections and infestations         
Abscess limb  1  0/42 (0.00%)  0/23 (0.00%)  1/249 (0.40%)  0/163 (0.00%) 
Cellulitis  1  0/42 (0.00%)  0/23 (0.00%)  0/249 (0.00%)  1/163 (0.61%) 
Injury, poisoning and procedural complications         
Animal bite  1  1/42 (2.38%)  0/23 (0.00%)  0/249 (0.00%)  0/163 (0.00%) 
Fall  1  0/42 (0.00%)  0/23 (0.00%)  0/249 (0.00%)  1/163 (0.61%) 
Femoral neck fracture  1  0/42 (0.00%)  0/23 (0.00%)  1/249 (0.40%)  0/163 (0.00%) 
Fibula fracture  1  0/42 (0.00%)  0/23 (0.00%)  1/249 (0.40%)  0/163 (0.00%) 
Rib fracture  1  0/42 (0.00%)  0/23 (0.00%)  0/249 (0.00%)  1/163 (0.61%) 
Metabolism and nutrition disorders         
Hyponatraemia  1  0/42 (0.00%)  0/23 (0.00%)  1/249 (0.40%)  0/163 (0.00%) 
Musculoskeletal and connective tissue disorders         
Osteoarthritis  1  0/42 (0.00%)  0/23 (0.00%)  0/249 (0.00%)  1/163 (0.61%) 
Rotator cuff syndrome  1  0/42 (0.00%)  0/23 (0.00%)  1/249 (0.40%)  0/163 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Malignant melanoma in situ  1  1/42 (2.38%)  0/23 (0.00%)  0/249 (0.00%)  0/163 (0.00%) 
Nervous system disorders         
Cerebellar haemorrhage  1  0/42 (0.00%)  0/23 (0.00%)  0/249 (0.00%)  1/163 (0.61%) 
Cerebrovascular accident  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  1/163 (0.61%) 
Subarachnoid haemorrhage  1  0/42 (0.00%)  0/23 (0.00%)  0/249 (0.00%)  1/163 (0.61%) 
Syncope  1  1/42 (2.38%)  0/23 (0.00%)  0/249 (0.00%)  1/163 (0.61%) 
Transient ischaemic attack  1  0/42 (0.00%)  0/23 (0.00%)  1/249 (0.40%)  0/163 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Pneumothorax  1  0/42 (0.00%)  0/23 (0.00%)  0/249 (0.00%)  1/163 (0.61%) 
Pulmonary mass  1  0/42 (0.00%)  0/23 (0.00%)  0/249 (0.00%)  1/163 (0.61%) 
Skin and subcutaneous tissue disorders         
Hyperhidrosis  1  1/42 (2.38%)  0/23 (0.00%)  0/249 (0.00%)  0/163 (0.00%) 
1
Term from vocabulary, MedDRA (23.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2.5%
Cohort I @CAD106 Cohort I @Placebo Cohort II (CNP520 50) Cohort II Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   36/42 (85.71%)   21/23 (91.30%)   106/249 (42.57%)   76/163 (46.63%) 
Cardiac disorders         
Atrial fibrillation  1  0/42 (0.00%)  2/23 (8.70%)  1/249 (0.40%)  0/163 (0.00%) 
Atrial flutter  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Palpitations  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  1/163 (0.61%) 
Congenital, familial and genetic disorders         
Type V hyperlipidaemia  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Ear and labyrinth disorders         
Deafness bilateral  1  2/42 (4.76%)  0/23 (0.00%)  0/249 (0.00%)  0/163 (0.00%) 
Tinnitus  1  2/42 (4.76%)  0/23 (0.00%)  3/249 (1.20%)  0/163 (0.00%) 
Endocrine disorders         
Hypothyroidism  1  2/42 (4.76%)  0/23 (0.00%)  0/249 (0.00%)  0/163 (0.00%) 
Thyroid mass  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Eye disorders         
Glaucoma  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Vitreous detachment  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  1/163 (0.61%) 
Gastrointestinal disorders         
Abdominal pain upper  1  0/42 (0.00%)  2/23 (8.70%)  0/249 (0.00%)  1/163 (0.61%) 
Constipation  1  3/42 (7.14%)  0/23 (0.00%)  7/249 (2.81%)  2/163 (1.23%) 
Diarrhoea  1  3/42 (7.14%)  1/23 (4.35%)  6/249 (2.41%)  3/163 (1.84%) 
Eosinophilic oesophagitis  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Nausea  1  2/42 (4.76%)  0/23 (0.00%)  5/249 (2.01%)  4/163 (2.45%) 
Pancreatic cyst  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Salivary gland disorder  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
General disorders         
Chills  1  2/42 (4.76%)  0/23 (0.00%)  0/249 (0.00%)  0/163 (0.00%) 
Fatigue  1  11/42 (26.19%)  1/23 (4.35%)  3/249 (1.20%)  1/163 (0.61%) 
Influenza like illness  1  5/42 (11.90%)  0/23 (0.00%)  0/249 (0.00%)  0/163 (0.00%) 
Injection site erythema  1  1/42 (2.38%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Injection site pain  1  10/42 (23.81%)  0/23 (0.00%)  0/249 (0.00%)  0/163 (0.00%) 
Injection site pruritus  1  2/42 (4.76%)  0/23 (0.00%)  0/249 (0.00%)  0/163 (0.00%) 
Injection site reaction  1  4/42 (9.52%)  0/23 (0.00%)  0/249 (0.00%)  0/163 (0.00%) 
Malaise  1  3/42 (7.14%)  1/23 (4.35%)  1/249 (0.40%)  0/163 (0.00%) 
Non-cardiac chest pain  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  1/163 (0.61%) 
Oedema peripheral  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Pyrexia  1  7/42 (16.67%)  1/23 (4.35%)  4/249 (1.61%)  0/163 (0.00%) 
Immune system disorders         
Seasonal allergy  1  2/42 (4.76%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Infections and infestations         
Acute sinusitis  1  0/42 (0.00%)  2/23 (8.70%)  1/249 (0.40%)  0/163 (0.00%) 
Bronchitis  1  2/42 (4.76%)  1/23 (4.35%)  1/249 (0.40%)  8/163 (4.91%) 
Cellulitis  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  1/163 (0.61%) 
Conjunctivitis bacterial  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Dacryocanaliculitis  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Gastroenteritis  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  1/163 (0.61%) 
Gastroenteritis viral  1  0/42 (0.00%)  1/23 (4.35%)  1/249 (0.40%)  1/163 (0.61%) 
Influenza  1  1/42 (2.38%)  2/23 (8.70%)  3/249 (1.20%)  0/163 (0.00%) 
Nasopharyngitis  1  4/42 (9.52%)  2/23 (8.70%)  10/249 (4.02%)  2/163 (1.23%) 
Pharyngitis  1  1/42 (2.38%)  1/23 (4.35%)  1/249 (0.40%)  0/163 (0.00%) 
Respiratory tract infection  1  2/42 (4.76%)  0/23 (0.00%)  0/249 (0.00%)  1/163 (0.61%) 
Sinusitis  1  3/42 (7.14%)  1/23 (4.35%)  5/249 (2.01%)  8/163 (4.91%) 
Upper respiratory tract infection  1  7/42 (16.67%)  3/23 (13.04%)  11/249 (4.42%)  11/163 (6.75%) 
Urinary tract infection  1  0/42 (0.00%)  2/23 (8.70%)  5/249 (2.01%)  4/163 (2.45%) 
Injury, poisoning and procedural complications         
Arthropod bite  1  0/42 (0.00%)  1/23 (4.35%)  2/249 (0.80%)  4/163 (2.45%) 
Contusion  1  3/42 (7.14%)  0/23 (0.00%)  1/249 (0.40%)  3/163 (1.84%) 
Fall  1  4/42 (9.52%)  1/23 (4.35%)  8/249 (3.21%)  4/163 (2.45%) 
Injection related reaction  1  2/42 (4.76%)  0/23 (0.00%)  0/249 (0.00%)  0/163 (0.00%) 
Mallet finger  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Meniscus injury  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Pelvic fracture  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Skin abrasion  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Investigations         
C-reactive protein increased  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Lumbar puncture  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Urine albumin/creatinine ratio increased  1  0/42 (0.00%)  0/23 (0.00%)  9/249 (3.61%)  2/163 (1.23%) 
Weight decreased  1  0/42 (0.00%)  0/23 (0.00%)  7/249 (2.81%)  1/163 (0.61%) 
Weight increased  1  2/42 (4.76%)  0/23 (0.00%)  0/249 (0.00%)  1/163 (0.61%) 
Metabolism and nutrition disorders         
Hyperlipidaemia  1  2/42 (4.76%)  0/23 (0.00%)  0/249 (0.00%)  0/163 (0.00%) 
Vitamin B12 deficiency  1  1/42 (2.38%)  2/23 (8.70%)  4/249 (1.61%)  0/163 (0.00%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  4/42 (9.52%)  1/23 (4.35%)  6/249 (2.41%)  7/163 (4.29%) 
Back pain  1  4/42 (9.52%)  0/23 (0.00%)  7/249 (2.81%)  6/163 (3.68%) 
Exostosis  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  1/163 (0.61%) 
Flank pain  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Foot deformity  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Muscle spasms  1  2/42 (4.76%)  0/23 (0.00%)  5/249 (2.01%)  1/163 (0.61%) 
Musculoskeletal pain  1  2/42 (4.76%)  0/23 (0.00%)  1/249 (0.40%)  3/163 (1.84%) 
Musculoskeletal stiffness  1  2/42 (4.76%)  0/23 (0.00%)  1/249 (0.40%)  0/163 (0.00%) 
Myalgia  1  3/42 (7.14%)  3/23 (13.04%)  3/249 (1.20%)  0/163 (0.00%) 
Osteoarthritis  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  1/163 (0.61%) 
Pain in extremity  1  4/42 (9.52%)  2/23 (8.70%)  6/249 (2.41%)  5/163 (3.07%) 
Rotator cuff syndrome  1  2/42 (4.76%)  1/23 (4.35%)  0/249 (0.00%)  1/163 (0.61%) 
Tendonitis  1  0/42 (0.00%)  1/23 (4.35%)  1/249 (0.40%)  1/163 (0.61%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Basal cell carcinoma  1  2/42 (4.76%)  0/23 (0.00%)  0/249 (0.00%)  2/163 (1.23%) 
Benign neoplasm of thyroid gland  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Haemangioma of liver  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Melanocytic naevus  1  1/42 (2.38%)  1/23 (4.35%)  0/249 (0.00%)  1/163 (0.61%) 
Uterine leiomyoma  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Nervous system disorders         
Ageusia  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Carpal tunnel syndrome  1  1/42 (2.38%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Cerebral cyst  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Cervical radiculopathy  1  0/42 (0.00%)  1/23 (4.35%)  1/249 (0.40%)  1/163 (0.61%) 
Dizziness  1  0/42 (0.00%)  0/23 (0.00%)  7/249 (2.81%)  1/163 (0.61%) 
Headache  1  7/42 (16.67%)  0/23 (0.00%)  6/249 (2.41%)  9/163 (5.52%) 
Lethargy  1  2/42 (4.76%)  0/23 (0.00%)  2/249 (0.80%)  0/163 (0.00%) 
Paraesthesia  1  1/42 (2.38%)  1/23 (4.35%)  2/249 (0.80%)  0/163 (0.00%) 
Presyncope  1  0/42 (0.00%)  1/23 (4.35%)  1/249 (0.40%)  0/163 (0.00%) 
Radiculopathy  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Psychiatric disorders         
Abnormal dreams  1  2/42 (4.76%)  1/23 (4.35%)  19/249 (7.63%)  5/163 (3.07%) 
Anxiety  1  0/42 (0.00%)  0/23 (0.00%)  11/249 (4.42%)  0/163 (0.00%) 
Insomnia  1  2/42 (4.76%)  1/23 (4.35%)  4/249 (1.61%)  9/163 (5.52%) 
Irritability  1  1/42 (2.38%)  1/23 (4.35%)  2/249 (0.80%)  0/163 (0.00%) 
Renal and urinary disorders         
Cystitis haemorrhagic  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Dysuria  1  1/42 (2.38%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Hypercalciuria  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  3/42 (7.14%)  0/23 (0.00%)  5/249 (2.01%)  2/163 (1.23%) 
Oropharyngeal pain  1  0/42 (0.00%)  1/23 (4.35%)  4/249 (1.61%)  0/163 (0.00%) 
Throat irritation  1  1/42 (2.38%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Skin and subcutaneous tissue disorders         
Dermatitis contact  1  2/42 (4.76%)  0/23 (0.00%)  1/249 (0.40%)  2/163 (1.23%) 
Nail disorder  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Pruritus  1  0/42 (0.00%)  0/23 (0.00%)  10/249 (4.02%)  5/163 (3.07%) 
Urticaria  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
Vascular disorders         
Essential hypertension  1  0/42 (0.00%)  1/23 (4.35%)  0/249 (0.00%)  0/163 (0.00%) 
1
Term from vocabulary, MedDRA (23.0)
Indicates events were collected by systematic assessment
The study was terminated due to unexpected changes in cognitive function, brain volume loss, and body weight loss. Cohort II (CNP520) treatment was stopped and evaluated through an off-treatment follow-up period. After the decision to terminate Cohort II of the study (CNP520), treatment with CAD106 (Cohort I) was also terminated
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: + 1 862 778 8300
EMail: Novartis.email@Novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02565511    
Other Study ID Numbers: CAPI015A2201J
2015-002715-15 ( EudraCT Number )
1UF1AG046150-01 ( U.S. NIH Grant/Contract )
First Submitted: September 28, 2015
First Posted: October 1, 2015
Results First Submitted: April 29, 2021
Results First Posted: July 8, 2021
Last Update Posted: July 8, 2021