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Study Evaluating the Safety,Tolerability and Efficacy of PF-04360365 in Adults With Probable Cerebral Amyloid Angiopathy

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ClinicalTrials.gov Identifier: NCT01821118
Recruitment Status : Completed
First Posted : March 29, 2013
Results First Posted : November 3, 2016
Last Update Posted : May 10, 2017
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Cerebral Amyloid Angiopathy
Interventions Biological: Ponezumab
Other: placebo
Enrollment 36
Recruitment Details  
Pre-assignment Details  
Arm/Group Title PF-04360365 Placebo
Hide Arm/Group Description Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight. Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min.
Period Title: Overall Study
Started 24 12
Completed 24 11
Not Completed 0 1
Reason Not Completed
Death             0             1
Arm/Group Title PF-04360365 Placebo Total
Hide Arm/Group Description Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight. Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min. Total of all reporting groups
Overall Number of Baseline Participants 24 12 36
Hide Baseline Analysis Population Description
All participants assigned to study treatment were included in the baseline analysis population.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants 12 participants 36 participants
68.8  (6.8) 65.0  (5.7) 67.6  (6.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 12 participants 36 participants
Female
8
  33.3%
5
  41.7%
13
  36.1%
Male
16
  66.7%
7
  58.3%
23
  63.9%
1.Primary Outcome
Title Change From Baseline to Day 2 in Cerebrovascular Reactivity as Measured by the Slope (Amplitude Over Time to Peak) From Visual Task-evoked Functional Magnetic Resonance Imaging (fMRI)
Hide Description Blood Oxygen Level Dependant (BOLD) fMRI was performed at Screening (Baseline) and on Days 2 and 90. During each of these sessions, BOLD fMRI images were acquired in rapid succession as a flashing radial black and white checkerboard was presented alternately with a gray screen. This well established visual stimulus is known to produce a reliable increase in BOLD fMRI signal within the visual cortex region of the occipital lobe. The time course of the BOLD fMRI signal was used to assess the vascular reactivity. Imaging sites also acquired cerebral blood flow data using Arterial Spin Labeled (ASL) scans at Screening and on Days 2 and 90. A standard T1-weighted image was also acquired to aid image analysis. All efficacy scans were analyzed centrally. Geometric means are presented in the original scale and standard errors (SE) are presented in logarithmic (log e) scale.
Time Frame Baseline, Day 2
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) consisted of all participants who received at least 1 post-dose efficacy measurement. n=number of evaluable participants for the specified region of interest (ROI) at Day 2.
Arm/Group Title PF-04360365 Placebo
Hide Arm/Group Description:
Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight.
Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min.
Overall Number of Participants Analyzed 24 12
Geometric Mean (Standard Error)
Unit of Measure: percent/second
Region of interest (ROI) 1 (n=20, 11) 0.954  (0.085) 0.969  (0.073)
ROI2 (n=23, 11) 0.933  (0.050) 0.999  (0.055)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04360365, Placebo
Comments ROI1: Analysis of the change from baseline in log(slope) was carried out using a Bayesian linear model (ANCOVA). Treatment was a fixed effect within the model and the log(slope) at baseline was included as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.984
Confidence Interval (2-Sided) 90%
0.820 to 1.184
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.112
Estimation Comments SE of mean is presented in log e scale.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-04360365, Placebo
Comments ROI2: Analysis of the change from baseline in log(slope) was carried out using a Bayesian linear model (ANCOVA). Treatment was a fixed effect within the model and the log(slope) at baseline was included as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.934
Confidence Interval (2-Sided) 90%
0.825 to 1.056
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.075
Estimation Comments SE of mean is presented in log e scale.
2.Primary Outcome
Title Change From Baseline to Day 90 in Cerebrovascular Reactivity as Measured by the Slope (Amplitude Over Time to Peak) From Visual Task-evoked fMRI
Hide Description BOLD fMRI was performed at Screening (Baseline) and on Days 2 and 90. During each of these sessions, BOLD fMRI images were acquired in rapid succession as a flashing radial black and white checkerboard was presented alternately with a gray screen. This well established visual stimulus is known to produce a reliable increase in BOLD fMRI signal within the visual cortex region of the occipital lobe. The time course of the BOLD fMRI signal was used to assess the vascular reactivity. Imaging sites also acquired cerebral blood flow data using ASL scans at Screening and on Days 2 and 90. A standard T1-weighted image was also acquired to aid image analysis. All efficacy scans were analyzed centrally. Geometric means are presented in the original scale and SEs are presented in log e scale.
Time Frame Baseline, Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) consisted of all participants who received at least 1 post-dose efficacy measurement. n=number of evaluable participants for the specified ROI at Day 90.
Arm/Group Title PF-04360365 Placebo
Hide Arm/Group Description:
Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight.
Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min.
Overall Number of Participants Analyzed 24 12
Geometric Mean (Standard Error)
Unit of Measure: percent/second
ROI1 (n=20, 10) 0.817  (0.064) 0.958  (0.063)
ROI2 (n=23, 10) 0.857  (0.055) 0.950  (0.060)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04360365, Placebo
Comments ROI1: Analysis of the change from baseline in log(slope) was carried out using a Bayesian linear model (ANCOVA). Treatment was a fixed effect within the model and the log(slope) at baseline was included as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.852
Confidence Interval (2-Sided) 90%
0.735 to 0.989
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.091
Estimation Comments SE of mean is presented on log e scale.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-04360365, Placebo
Comments ROI2: Analysis of the change from baseline in log(slope) was carried out using a Bayesian linear model (ANCOVA). Treatment was a fixed effect within the model and the log(slope) at baseline was included as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.902
Confidence Interval (2-Sided) 90%
0.788 to 1.031
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.082
Estimation Comments SE of mean presented on log e scale.
3.Secondary Outcome
Title Change From Baseline to Day 2 and Day 90 in Cerebrovascular Reactivity as Measured by the Time to Peak From Visual Task-evoked fMRI
Hide Description BOLD fMRI was performed at Screening (Baseline) and on Days 2 and 90. During each of these sessions, BOLD fMRI images were acquired in rapid succession as a flashing radial black and white checkerboard was presented alternately with a gray screen. This well established visual stimulus is known to produce a reliable increase in BOLD fMRI signal within the visual cortex region of the occipital lobe. The time course of the BOLD fMRI signal was used to assess the vascular reactivity. Imaging sites also acquired cerebral blood flow data using ASL scans at Screening and on Days 2 and 90. A standard T1-weighted image was also acquired to aid image analysis. All efficacy scans were analyzed centrally. Geometric means are presented in the original scale and SEs are presented in log e scale.
Time Frame Baseline, Day 2, Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) consisted of all participants who received at least 1 post-dose efficacy measurement. n=number of evaluable participants for the specified ROI at the specified day.
Arm/Group Title PF-04360365 Placebo
Hide Arm/Group Description:
Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight.
Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min.
Overall Number of Participants Analyzed 24 12
Geometric Mean (Standard Error)
Unit of Measure: seconds
ROI1, Day 2 (n=20, 11) 1.012  (0.028) 1.007  (0.037)
ROI1, Day 90 (n=20, 10) 1.065  (0.020) 1.015  (0.030)
ROI2, Day 2 (n=23, 11) 1.008  (0.018) 1.010  (0.026)
ROI2, Day 90 (n=23, 10) 1.039  (0.018) 1.028  (0.026)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04360365, Placebo
Comments ROI1, Day 2: Analysis of the change from baseline in log(time to peak) was carried out using a Bayesian linear model (ANCOVA). Treatment was a fixed effect within the model and the log(time to peak) at baseline was included as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 1.005
Confidence Interval (2-Sided) 90%
0.933 to 1.086
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.046
Estimation Comments SE of mean presented on log e scale.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-04360365, Placebo
Comments ROI1, Day 90: Analysis of the change from baseline in log(time to peak) was carried out using a Bayesian linear model (ANCOVA). Treatment was a fixed effect within the model and the log(time to peak) at baseline was included as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 1.049
Confidence Interval (2-Sided) 90%
0.990 to 1.114
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.036
Estimation Comments SE of mean presented on log e scale.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-04360365, Placebo
Comments ROI2, Day 2: Analysis of the change from baseline in log(time to peak) was carried out using a Bayesian linear model (ANCOVA). Treatment was a fixed effect within the model and the log(time to peak) at baseline was included as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.998
Confidence Interval (2-Sided) 90%
0.947 to 1.052
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.032
Estimation Comments SE of mean presented on log e scale.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection PF-04360365, Placebo
Comments ROI2, Day 90: Analysis of the change from baseline in log(time to peak) was carried out using a Bayesian linear model (ANCOVA). Treatment was a fixed effect within the model and the log(time to peak) at baseline was included as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 1.010
Confidence Interval (2-Sided) 90%
0.960 to 1.063
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.031
Estimation Comments SE of mean presented on log e scale.
4.Secondary Outcome
Title Change From Baseline to Day 2 and Day 90 in Cerebrovascular Reactivity as Measured by the Amplitude From Visual Task-evoked fMRI
Hide Description BOLD fMRI was performed at Screening (Baseline) and on Days 2 and 90. During each of these sessions, BOLD fMRI images were acquired in rapid succession as a flashing radial black and white checkerboard was presented alternately with a gray screen. This well established visual stimulus is known to produce a reliable increase in BOLD fMRI signal within the visual cortex region of the occipital lobe. The time course of the BOLD fMRI signal was used to assess the vascular reactivity. Imaging sites also acquired cerebral blood flow data using ASL scans at Screening and on Days 2 and 90. A standard T1-weighted image was also acquired to aid image analysis. All efficacy scans were analyzed centrally. All values are presented in log e scale.
Time Frame Baseline, Day 2, Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) consisted of all participants who received at least 1 post-dose efficacy measurement. n=number of evaluable participants for the specified ROI at the specified day.
Arm/Group Title PF-04360365 Placebo
Hide Arm/Group Description:
Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight.
Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min.
Overall Number of Participants Analyzed 24 12
Least Squares Mean (90% Confidence Interval)
Unit of Measure: percent
ROI1, Day 2 (n=20, 11)
-0.0381
(-0.1655 to 0.0894)
-0.0983
(-0.2715 to 0.0750)
ROI1, Day 90 (n=20, 10)
-0.1389
(-0.2513 to -0.0264)
-0.053
(-0.2135 to 0.1075)
ROI2, Day 2 (n=23, 11)
-0.0714
(-0.1584 to 0.0156)
-0.0226
(-0.1484 to 0.1033)
ROI2, Day 90 (n=23, 10)
-0.1245
(-0.2236 to -0.0254)
-0.0357
(-0.1861 to 0.1146)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04360365, Placebo
Comments ROI1, Day 2: Analysis of the change from baseline in log(amplitude) was carried out using a linear model (ANCOVA). Treatment was a fixed effect within the model and the log(amplitude) at baseline was included as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Treatment Difference (log e)
Estimated Value 0.0602
Confidence Interval (2-Sided) 90%
-0.1576 to 0.2781
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1281
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-04360365, Placebo
Comments ROI1, Day 90: Analysis of the change from baseline in log(amplitude) was carried out using a linear model (ANCOVA). Treatment was a fixed effect within the model and the log(amplitude) at baseline was included as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Treatment Difference (log e)
Estimated Value -0.0859
Confidence Interval (2-Sided) 90%
-0.2843 to 0.1124
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1165
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-04360365, Placebo
Comments ROI2, Day 2: Analysis of the change from baseline in log(amplitude) was carried out using a linear model (ANCOVA). Treatment was a fixed effect within the model and the log(amplitude) at baseline was included as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Treatment Difference (log e)
Estimated Value -0.0488
Confidence Interval (2-Sided) 90%
-0.2018 to 0.1042
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0902
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection PF-04360365, Placebo
Comments ROI2, Day 90: Analysis of the change from baseline in log(amplitude) was carried out using a linear model (ANCOVA). Treatment was a fixed effect within the model and the log(amplitude) at baseline was included as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Treatment Difference (log e)
Estimated Value -0.0888
Confidence Interval (2-Sided) 90%
-0.2689 to 0.0914
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1061
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline to Day 2 and Day 90 in Cerebrovascular Reactivity as Measured by the Time to Return to Baseline From Visual Task-evoked fMRI
Hide Description BOLD fMRI was performed at Screening (Baseline) and on Days 2 and 90. During each of these sessions, BOLD fMRI images were acquired in rapid succession as a flashing radial black and white checkerboard was presented alternately with a gray screen. This well established visual stimulus is known to produce a reliable increase in BOLD fMRI signal within the visual cortex region of the occipital lobe. The time course of the BOLD fMRI signal was used to assess the vascular reactivity. Imaging sites also acquired cerebral blood flow data using ASL scans at Screening and on Days 2 and 90. A standard T1-weighted image was also acquired to aid image analysis. All efficacy scans were analyzed centrally. All values are presented in log e scale.
Time Frame Baseline, Day 2, Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) consisted of all participants who received at least 1 post-dose efficacy measurement. n=number of evaluable participants for the specified ROI at the specified day.
Arm/Group Title PF-04360365 Placebo
Hide Arm/Group Description:
Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight.
Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min.
Overall Number of Participants Analyzed 24 12
Least Squares Mean (90% Confidence Interval)
Unit of Measure: seconds
ROI1, Day 2 (n=20, 11)
0.0245
(-0.0155 to 0.0644)
-0.022
(-0.0759 to 0.0319)
ROI1, Day 90 (n=20, 10)
0.0558
(0.0182 to 0.0934)
-0.0179
(-0.0711 to 0.0354)
ROI2, Day 2 (n=23, 11)
0.0045
(-0.0280 to 0.0369)
-0.0174
(-0.0643 to 0.0295)
ROI2, Day 90 (n=23, 10)
0.0275
(-0.0040 to 0.0589)
0.0158
(-0.0322 to 0.0637)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04360365, Placebo
Comments ROI1, Day 2: Analysis of the change from baseline in log(time to return to baseline) was carried out using a linear model (ANCOVA). Treatment was a fixed effect within the model and the log(time to return to baseline) at baseline was included as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Treatment Difference (log e)
Estimated Value 0.0464
Confidence Interval (2-Sided) 90%
-0.0207 to 0.1136
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0395
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-04360365, Placebo
Comments ROI1, Day 90: Analysis of the change from baseline in log(time to return to baseline) was carried out using a linear model (ANCOVA). Treatment was a fixed effect within the model and the log(time to return to baseline) at baseline was included as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Treatment Difference (log e)
Estimated Value 0.0737
Confidence Interval (2-Sided) 90%
0.0084 to 0.1390
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0383
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-04360365, Placebo
Comments ROI2, Day 2: Analysis of the change from baseline in log(time to return to baseline) was carried out using a linear model (ANCOVA). Treatment was a fixed effect within the model and the log(time to return to baseline) at baseline was included as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Treatment Difference (log e)
Estimated Value 0.0219
Confidence Interval (2-Sided) 90%
-0.0352 to 0.0790
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0337
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection PF-04360365, Placebo
Comments ROI2, Day 90: Analysis of the change from baseline in log(time to return to baseline) was carried out using a linear model (ANCOVA). Treatment was a fixed effect within the model and the log(time to return to baseline) at baseline was included as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Treatment Difference (log e)
Estimated Value 0.0117
Confidence Interval (2-Sided) 90%
-0.0460 to 0.0694
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.034
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Concentration of Total Plasma Amyloid Beta (AB)
Hide Description Cerebral amyloid angiopathy (CAA) is caused by the progressive deposition of amyloid, predominantly AB40, within the walls of cerebral blood vessels with a predisposition for the vessels of the occipital lobe. As such, it is of interest to investigate the effect of PF-04360365 on AB concentrations. AB1-x and AB1-40 were investigated.
Time Frame Baseline, 8 hours post dose on Day 1, Day 2, Day 30, 90 and 240
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All 36 participants who received study treatment were included in this pharmacodynamic analysis. n=number of participants with measurable AB at the specified time point.
Arm/Group Title PF-04360365 Placebo
Hide Arm/Group Description:
Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight.
Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min.
Overall Number of Participants Analyzed 24 12
Mean (Standard Deviation)
Unit of Measure: picograms (pg)/milliliter (mL)
AB1-x, Day 1 (n=4, 3) 4374.0  (420.62) 5.3  (26.01)
AB1-x, Day 2 (n=4, 3) 13911.8  (3292.88) -37.7  (29.02)
AB1-x, Day 30 (n=4, 3) 94468.5  (11946.21) -48.3  (103.32)
AB1-x, Day 90 (n=4, 2) 111312.8  (24677.74) -62.0  (141.42)
AB1-x, Day 240 (n=4, 3) 30495.8  (10931.16) 13.0  (116.76)
AB1-40, Day 1 (n=23, 11) 4747.6  (1039.96) -8.4  (30.08)
AB1-40, Day 2 (n=23, 11) 12845.2  (2887.91) 0.5  (30.90)
AB1-40, Day 30 (n=23, 10) 68010.1  (17396.04) -5.0  (46.81)
AB1-40, Day 90 (n=23, 10) 87710.8  (18699.28) 0.7  (44.02)
AB1-40, Day 240 (n=23, 9) 20665.6  (7132.91) -6.2  (35.63)
7.Secondary Outcome
Title Number of Participants With Brain Structural Magnetic Resonance Imaging (sMRI) Abnormalities
Hide Description Brain sMRI abnormalities included cerebral edema and total infarcts (including cortical infarcts, white matter infarcts, and subcortical gray matter infarcts). "Total infarcts" is the total number of participants with at least 1 type of infarct.
Time Frame Baseline/Screening, Day 15, Day 45, Day 90,
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All 36 participants who received study treatment were analyzed for this endpoint.
Arm/Group Title PF-04360365 Placebo
Hide Arm/Group Description:
Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight.
Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min.
Overall Number of Participants Analyzed 24 12
Measure Type: Number
Unit of Measure: participants
Cerebral edema, Screening 0 1
Cerebral edema, Day 15 0 1
Cerebral edema, Day 45 0 1
Cerebral edema, Day 90 1 1
Total infarcts, Screening 5 3
Total infarcts, Day 15 5 3
Total infarcts, Day 45 5 3
Total infarcts, Day 90 5 3
Cortical infarcts, Screening 0 0
Cortical infarcts, Day 15 0 0
Cortical infarcts, Day 45 0 0
Cortical infarcts, Day 90 0 0
White matter infarcts, Screening 3 2
White matter infarcts, Day 15 3 2
White matter infarcts, Day 45 3 2
White matter infarcts, Day 90 3 2
Subcortical gray matter infarcts, Screening 3 1
Subcortical gray matter infarcts, Day 15 3 1
Subcortical gray matter infarcts, Day 45 3 1
Subcortical gray matter infarcts, Day 90 3 1
8.Secondary Outcome
Title Mean Montreal Cognitive Assessment (MoCA) Total Score Over Time
Hide Description The Montreal Cognitive Assessment (MoCA) was used as a safety outcome measure to assess any changes in cognition. The MoCA is a 1-page 30-point test administered in approximately 10 minutes. The MoCA assessed short term memory, visuospatial abilities, multiple aspects of executive functions, attention, concentration, working memory, and language, as well as orientation to time and place. The total scale ranges from 0 to 30, with lower numbers indicating lower cognition performance.
Time Frame Screening; Days 0, 1, 30, 60, 90, and 240
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All 36 participants who received study treatment were included in the analysis. On Day 240, the number of evaluable participants in the placebo group was 11 instead of 12.
Arm/Group Title PF-04360365 Placebo
Hide Arm/Group Description:
Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight.
Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min.
Overall Number of Participants Analyzed 24 12
Mean (Standard Deviation)
Unit of Measure: units on a scale
Screening 25.4  (4.24) 25.9  (1.73)
Day 0 25.5  (3.41) 25.9  (3.34)
Day 1 25.1  (3.10) 25.8  (2.73)
Day 30 27.0  (2.46) 26.8  (2.53)
Day 60 26.6  (3.12) 26.8  (3.33)
Day 90 26.0  (3.46) 26.7  (3.14)
Day 240 26.1  (3.43) 26.5  (2.73)
9.Secondary Outcome
Title Number of Participants With All Causality and Treatment-related Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to Adverse Events (AEs)
Hide Description An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs comprised both SAEs and non-SAEs. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse events (TEAEs) were defined as newly occurring AEs or those worsening after first dose.
Time Frame Baseline up to Day 240
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Hide Analysis Population Description
All 36 participants who received study drug were included in the AE summarization/analysis.
Arm/Group Title PF-04360365 Placebo
Hide Arm/Group Description:
Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight.
Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min.
Overall Number of Participants Analyzed 24 12
Measure Type: Number
Unit of Measure: participants
All causality TEAEs 16 8
Treatment-related TEAEs 2 2
All causality SAEs 2 2
Treatment-related SAEs 0 1
All causality severe TEAEs 2 2
Treatment-related severe TEAEs 0 1
Discontinued due to all causality TEAEs 0 0
10.Secondary Outcome
Title Number of Participants With Laboratory Abnormalities
Hide Description Number of participants with laboratory test abnormalities without regard to baseline abnormality. Laboratory test parameters included hematology, liver function (including Hy's Law Criteria), renal function, electrolytes, clinical chemistry, and urinalysis (dipstick and microscopy).
Time Frame Baseline up to Day 240
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All 36 participants who received study drug were included in the analysis.
Arm/Group Title PF-04360365 Placebo
Hide Arm/Group Description:
Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight.
Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min.
Overall Number of Participants Analyzed 24 12
Measure Type: Number
Unit of Measure: participants
14 10
11.Secondary Outcome
Title Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria
Hide Description Categorical summarization criteria in vital signs included: supine systolic blood pressure (SBP) of less than (<)90 millimeters of mercury (mm Hg) or more than (>) 160 mm Hg; supine diastolic blood pressure (DBP) <50 mm Hg or >100 mm Hg; supine pulse rate of <60 beats per minute (bpm) or >100 bpm; maximum changes (increase or decrease) from baseline in supine SBP of >=20 mm Hg; maximum increase from baseline in supine DBP of >=20 mm Hg; and maximum decrease from baseline in supine DBP of >=10 mm Hg.
Time Frame Baseline up to Day 240
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All 36 participants who received study drug were included in the analysis.
Arm/Group Title PF-04360365 Placebo
Hide Arm/Group Description:
Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight.
Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min.
Overall Number of Participants Analyzed 24 12
Measure Type: Number
Unit of Measure: participants
Supine SBP <90 mm Hg 1 0
Supine SBP >160 mm Hg 2 2
Supine DBP <50 mm Hg 1 0
Supine DBP >100 mm Hg 0 1
Supine pulse rate <60 bpm 16 7
Supine pulse rate >100 bpm 0 1
Increase from baseline in supine SBP >=20 mm Hg 6 4
Increase from baseline in supine DBP >=20 mm Hg 1 1
Decrease from baseline in supine SBP >=20 mm Hg 9 6
Decrease from baseline in supine DBP >=10 mm Hg 13 5
12.Secondary Outcome
Title Overall Number of Participants With Positive Responses to Questions on the Columbia Suicide Severity Rating Scale (C-SSRS)
Hide Description C-SSRS assessed whether participant responded "yes" to the following: completed suicide, suicide attempt, preparatory acts toward imminent suicidal behavior, suicidal ideation, self-injurious behavior with no suicidal intent.
Time Frame Baseline up to Day 240
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All 36 participants who received study drug were included in the analysis.
Arm/Group Title PF-04360365 Placebo
Hide Arm/Group Description:
Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight.
Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min.
Overall Number of Participants Analyzed 24 12
Measure Type: Number
Unit of Measure: participants
Completed suicide 0 0
Suicide attempt 0 0
Preparatory acts to imminent suicidal behaviour 0 0
Self-injurious behaviour, no suicidal intent 1 0
13.Secondary Outcome
Title Number of Participants With Significant Changes From Baseline in Physical Examination at Final Visit
Hide Description A complete physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, skeletal, and neurological systems.
Time Frame Baseline up to Final Visit (Day 240)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All 36 participants who received study drug were included in the analysis.
Arm/Group Title PF-04360365 Placebo
Hide Arm/Group Description:
Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight.
Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min.
Overall Number of Participants Analyzed 24 12
Measure Type: Number
Unit of Measure: participants
0 0
14.Secondary Outcome
Title Number of Participants With Significant Changes in Neurological Examination Results
Hide Description A complete/full neurological examination included assessment of the cranial nerves; muscle strength, tone, cortical drift, abnormal movements; deep tendon reflexes; sensory exam, coordination, gait and station.
Time Frame Baseline up till Day 240
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All 36 participants who received study drug were included in the analysis.
Arm/Group Title PF-04360365 Placebo
Hide Arm/Group Description:
Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight.
Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min.
Overall Number of Participants Analyzed 24 12
Measure Type: Number
Unit of Measure: participants
2 1
15.Secondary Outcome
Title Number of Participants With Anti-PF-04360365 Antibodies
Hide Description Blood samples were collected from participants who received active treatment to assess for presence/absence of anti-PF-04360365 antibodies.
Time Frame Day 1 up to Day 240
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All 24 participants who received PF-04360365 were included in this analysis.
Arm/Group Title PF-04360365
Hide Arm/Group Description:
Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight.
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: participants
0
Time Frame Adverse events (AEs) and serious AEs (SAEs) monitoring started from screening through and including 28 calendar days after the last administration of the investigational product.
Adverse Event Reporting Description All treated participants were analyzed for AEs. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and a nonserious event during the study.
 
Arm/Group Title PF-04360365 Placebo
Hide Arm/Group Description Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight. Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min.
All-Cause Mortality
PF-04360365 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
PF-04360365 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   2/24 (8.33%)   2/12 (16.67%) 
Injury, poisoning and procedural complications     
Subdural haematoma * 1  1/24 (4.17%)  0/12 (0.00%) 
Nervous system disorders     
Aphasia * 1  1/24 (4.17%)  0/12 (0.00%) 
Cerebral haemorrhage * 1  1/24 (4.17%)  0/12 (0.00%) 
Haemorrhage intracranial * 1  0/24 (0.00%)  1/12 (8.33%) 
Migraine with aura * 1  0/24 (0.00%)  1/12 (8.33%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA v18.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
PF-04360365 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   16/24 (66.67%)   8/12 (66.67%) 
Cardiac disorders     
Palpitations * 1  1/24 (4.17%)  0/12 (0.00%) 
Eye disorders     
Dry eye * 1  1/24 (4.17%)  0/12 (0.00%) 
Vitreous floaters * 1  1/24 (4.17%)  0/12 (0.00%) 
Gastrointestinal disorders     
Constipation * 1  1/24 (4.17%)  0/12 (0.00%) 
Diarrhoea * 1  1/24 (4.17%)  0/12 (0.00%) 
Paraesthesia oral * 1  0/24 (0.00%)  1/12 (8.33%) 
Toothache * 1  0/24 (0.00%)  1/12 (8.33%) 
Vomiting * 1  1/24 (4.17%)  0/12 (0.00%) 
General disorders     
Chest pain * 1  0/24 (0.00%)  1/12 (8.33%) 
Fatigue * 1  1/24 (4.17%)  0/12 (0.00%) 
Gait disturbance * 1  1/24 (4.17%)  0/12 (0.00%) 
Immune system disorders     
Hypersensitivity * 1  1/24 (4.17%)  0/12 (0.00%) 
Infections and infestations     
Fungal skin infection * 1  1/24 (4.17%)  0/12 (0.00%) 
Influenza * 1  1/24 (4.17%)  0/12 (0.00%) 
Nasopharyngitis * 1  1/24 (4.17%)  0/12 (0.00%) 
Sinusitis * 1  0/24 (0.00%)  1/12 (8.33%) 
Upper respiratory tract infection * 1  3/24 (12.50%)  0/12 (0.00%) 
Urinary tract infection * 1  0/24 (0.00%)  2/12 (16.67%) 
Injury, poisoning and procedural complications     
Fall * 1  2/24 (8.33%)  0/12 (0.00%) 
Jaw fracture * 1  1/24 (4.17%)  0/12 (0.00%) 
Road traffic accident * 1  1/24 (4.17%)  0/12 (0.00%) 
Investigations     
Haemoglobin decreased * 1  1/24 (4.17%)  0/12 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  2/24 (8.33%)  1/12 (8.33%) 
Neck pain * 1  1/24 (4.17%)  0/12 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Squamous cell carcinoma * 1  1/24 (4.17%)  0/12 (0.00%) 
Nervous system disorders     
Aphasia * 1  1/24 (4.17%)  1/12 (8.33%) 
Balance disorder * 1  1/24 (4.17%)  0/12 (0.00%) 
Cerebellar syndrome * 1  1/24 (4.17%)  0/12 (0.00%) 
Cerebrovascular accident * 1  1/24 (4.17%)  0/12 (0.00%) 
Coordination abnormal * 1  1/24 (4.17%)  0/12 (0.00%) 
Dizziness * 1  1/24 (4.17%)  0/12 (0.00%) 
Epilepsy * 1  0/24 (0.00%)  1/12 (8.33%) 
Headache * 1  3/24 (12.50%)  1/12 (8.33%) 
Hypoaesthesia * 1  1/24 (4.17%)  1/12 (8.33%) 
Migraine * 1  1/24 (4.17%)  0/12 (0.00%) 
Paraesthesia * 1  0/24 (0.00%)  1/12 (8.33%) 
Partial seizures * 1  0/24 (0.00%)  1/12 (8.33%) 
Presyncope * 1  1/24 (4.17%)  0/12 (0.00%) 
Superficial siderosis of central nervous system * 1  0/24 (0.00%)  1/12 (8.33%) 
Psychiatric disorders     
Depression * 1  0/24 (0.00%)  1/12 (8.33%) 
Emotional disorder * 1  1/24 (4.17%)  0/12 (0.00%) 
Reproductive system and breast disorders     
Testicular cyst * 1  1/24 (4.17%)  0/12 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal pain * 1  0/24 (0.00%)  1/12 (8.33%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  0/24 (0.00%)  1/12 (8.33%) 
Eczema * 1  1/24 (4.17%)  0/12 (0.00%) 
Pruritus * 1  1/24 (4.17%)  1/12 (8.33%) 
Rash * 1  0/24 (0.00%)  1/12 (8.33%) 
Rash macular * 1  1/24 (4.17%)  0/12 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA v18.1
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.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc
Phone: 18007181021
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01821118     History of Changes
Other Study ID Numbers: A9951024
2013-001557-27 ( EudraCT Number )
First Submitted: March 4, 2013
First Posted: March 29, 2013
Results First Submitted: September 14, 2016
Results First Posted: November 3, 2016
Last Update Posted: May 10, 2017