Clinical Trial Results:
A PHASE 2 MULTI-CENTER, RANDOMIZED, DOUBLE-MASKED, PLACEBO CONTROLLED, MULTI-DOSE STUDY TO INVESTIGATE THE EFFICACY, SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF RN6G (PF 04382923) IN SUBJECTS WITH GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION
Summary
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EudraCT number |
2012-000823-42 |
Trial protocol |
DE GB IT |
Global end of trial date |
10 Oct 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Jun 2016
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First version publication date |
12 Jul 2015
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
B1181003
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01577381 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
US IND Number : 102691 | ||
Sponsors
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Sponsor organisation name |
Pfizer Inc.
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Sponsor organisation address |
235 E 42nd Street, New York, United States, 10017
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Public contact |
Clinical Trials.gov Call Center, Pfizer Inc, +1 8007181021, ClinicalTrials.govCallCenter@pfizer.com
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Scientific contact |
Clinical Trials.gov Call Center, Pfizer Inc, +1 8007181021, ClinicalTrials.govCallCenter@pfizer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 Sep 2014
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
10 Oct 2013
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To determine the efficacy of RN6G (PF-04382923) in subjects with geographic atrophy in the study eye.
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Protection of trial subjects |
This study used an External Data Monitoring Committee (E-DMC). The E-DMC (consisted of physicians, ophthalmologists, safety specialists and statisticians) was responsible for ongoing safety monitoring of subjects in the study and may review efficacy in the context of risk-benefit assessment.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
11 Jun 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 10
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Worldwide total number of subjects |
10
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
2
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From 65 to 84 years |
8
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
The study was conducted in the United States of America (USA). Eligible subjects were men and women (of non-childbearing potential) between the ages of 60 and 90 years with a diagnosis of a well-demarcated area of geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD). | ||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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PF-04382923 2.5 mg/kg | ||||||||||||||||||||||||||||||
Arm description |
PF-04382923 (RN6G) at 2.5 milligrams per kilogram (mg/kg) was administered as an intravenous (IV) infusion over 30 minutes every 28 days for 11 doses. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
PF-04382923
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Investigational medicinal product code |
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Other name |
RN6G
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Pharmaceutical forms |
Injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
IV infusion over at least 30 minutes every 28 days for 11 doses.
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Arm title
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PF-04382923 7.5 mg/kg | ||||||||||||||||||||||||||||||
Arm description |
PF-04382923 at 7.5 mg/kg was administered as an IV infusion over 30 minutes every 28 days for 11 doses. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
PF-04382923
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Investigational medicinal product code |
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Other name |
RN6G
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Pharmaceutical forms |
Injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
IV infusion over at least 30 minutes every 28 days for 11 doses.
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Arm title
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PF-04382923 15.0 mg/kg | ||||||||||||||||||||||||||||||
Arm description |
PF-04382923 at 15.0 mg/kg was administered as an IV infusion over 30 minutes every 28 days for 11 doses. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
PF-04382923
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Investigational medicinal product code |
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Other name |
RN6G
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Pharmaceutical forms |
Injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
IV infusion over at least 30 minutes every 28 days for 11 doses.
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Arm title
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Placebo | ||||||||||||||||||||||||||||||
Arm description |
Placebo was administered as an IV infusion over at least 30 minutes every 28 days for 11 doses. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
IV infusion over at least 30 minutes every 28 days for 11 doses.
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Baseline characteristics reporting groups
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Reporting group title |
PF-04382923 2.5 mg/kg
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Reporting group description |
PF-04382923 (RN6G) at 2.5 milligrams per kilogram (mg/kg) was administered as an intravenous (IV) infusion over 30 minutes every 28 days for 11 doses. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
PF-04382923 7.5 mg/kg
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Reporting group description |
PF-04382923 at 7.5 mg/kg was administered as an IV infusion over 30 minutes every 28 days for 11 doses. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
PF-04382923 15.0 mg/kg
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Reporting group description |
PF-04382923 at 15.0 mg/kg was administered as an IV infusion over 30 minutes every 28 days for 11 doses. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Placebo was administered as an IV infusion over at least 30 minutes every 28 days for 11 doses. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
PF-04382923 2.5 mg/kg
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Reporting group description |
PF-04382923 (RN6G) at 2.5 milligrams per kilogram (mg/kg) was administered as an intravenous (IV) infusion over 30 minutes every 28 days for 11 doses. | ||
Reporting group title |
PF-04382923 7.5 mg/kg
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Reporting group description |
PF-04382923 at 7.5 mg/kg was administered as an IV infusion over 30 minutes every 28 days for 11 doses. | ||
Reporting group title |
PF-04382923 15.0 mg/kg
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Reporting group description |
PF-04382923 at 15.0 mg/kg was administered as an IV infusion over 30 minutes every 28 days for 11 doses. | ||
Reporting group title |
Placebo
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Reporting group description |
Placebo was administered as an IV infusion over at least 30 minutes every 28 days for 11 doses. |
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End point title |
Mean Reduction (in Study Eye) in Rate of Geographic Atrophy (GA) at Day 309 [1] | ||||||||||||||||||||
End point description |
GA is the advanced form of dry age-related macular degeneration (AMD). The reduction in GA area of the study eye was based on Fundus Autofluorescence (FAF) at 30 days post last dose administration (Day 309).
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End point type |
Primary
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End point timeframe |
Baseline and Day 309
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Analysis of GA reduction was not performed due to early study termination. |
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Notes [2] - Analysis of GA reduction was not performed due to early study termination. [3] - Analysis of GA reduction was not performed due to early study termination. [4] - Analysis of GA reduction was not performed due to early study termination. [5] - Analysis of GA reduction was not performed due to early study termination. |
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No statistical analyses for this end point |
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End point title |
Mean Reduction (in Study Eye) in Rate of Growth of GA at Day 449 (End of Study) [6] | ||||||||||||||||||||
End point description |
GA is the advanced form of dry AMD. The reduction in GA area in the study eye was based on FAF at end of study (Day 449).
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End point type |
Primary
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End point timeframe |
Baseline and Day 449
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Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Analysis of GA reduction was not performed due to early study termination. |
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Notes [7] - Analysis of GA reduction was not performed due to early study termination. [8] - Analysis of GA reduction was not performed due to early study termination. [9] - Analysis of GA reduction was not performed due to early study termination. [10] - Analysis of GA reduction was not performed due to early study termination. |
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No statistical analyses for this end point |
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End point title |
Mean Best Corrected Visual Acuity (BCVA) at 9, 12, 15 Months and End of Study | ||||||||||||||||||||
End point description |
BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity).
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End point type |
Secondary
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End point timeframe |
Baseline, Month 9, Month 12, Month 15, and End of Study
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Notes [11] - Analysis of BCVA was not performed due to early study termination. [12] - Analysis of BCVA was not performed due to early study termination. [13] - Analysis of BCVA was not performed due to early study termination. [14] - Analysis of BCVA was not performed due to early study termination. |
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No statistical analyses for this end point |
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End point title |
Percentage Change From Baseline in BCVA Correct Number of Letters at 9, 12, 15 Months and End of Study | ||||||||||||||||||||
End point description |
BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity).
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End point type |
Secondary
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End point timeframe |
Baseline, Month 9, Month 12, Month 15, and End of Study
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Notes [15] - Analysis of BCVA was not performed due to early study termination. [16] - Analysis of BCVA was not performed due to early study termination. [17] - Analysis of BCVA was not performed due to early study termination. [18] - Analysis of BCVA was not performed due to early study termination. |
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No statistical analyses for this end point |
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End point title |
Percentage Change From Baseline in BCVA Correct Number of Lines at Months 9, 12, 15 Months and End of Study | ||||||||||||||||||||
End point description |
BCVA is measured using an eye chart and is reported as the number of lines read correctly in the study eye. The lower the number of lines read correctly on the eye chart, the worse the vision (or visual acuity).
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End point type |
Secondary
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End point timeframe |
Baseline, Month 9, Month 12, Month 15, and End of Study
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Notes [19] - Analysis of BCVA was not performed due to early study termination. [20] - Analysis of BCVA was not performed due to early study termination. [21] - Analysis of BCVA was not performed due to early study termination. [22] - Analysis of BCVA was not performed due to early study termination. |
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No statistical analyses for this end point |
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End point title |
Mean Low Luminance Best Corrected Visual Acuity (LL-BCVA) at 9, 12, 15 Months and End of Study | ||||||||||||||||||||
End point description |
LL-BCVA is the measure of visual acuity under low light conditions.
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End point type |
Secondary
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End point timeframe |
Baseline, Month 9, Month 12, Month 15, and End of Study
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Notes [23] - Analysis of LL-BCVA was not performed due to early study termination. [24] - Analysis of LL-BCVA was not performed due to early study termination. [25] - Analysis of LL-BCVA was not performed due to early study termination. [26] - Analysis of LL-BCVA was not performed due to early study termination. |
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No statistical analyses for this end point |
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End point title |
Percentage Change From Baseline in LL-BCVA Correct Number of Letters at 9, 12, 15 Months and End of Study | ||||||||||||||||||||
End point description |
LL-BCVA is the measure of visual acuity under low light conditions.
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End point type |
Secondary
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End point timeframe |
Baseline, Month 9, Month 12, Month 15, and End of Study
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Notes [27] - Analysis of LL-BCVA was not performed due to early study termination. [28] - Analysis of LL-BCVA was not performed due to early study termination. [29] - Analysis of LL-BCVA was not performed due to early study termination. [30] - Analysis of LL-BCVA was not performed due to early study termination. |
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No statistical analyses for this end point |
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End point title |
Percentage Change From Baseline in LL-BCVA Correct Number of Lines at 9, 12, 15 Months and End of Study | ||||||||||||||||||||
End point description |
LL-BCVA is the measure of visual acuity under low light conditions.
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End point type |
Secondary
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End point timeframe |
Baseline, Month 9, Month 12, Month 15, and End of Study
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Notes [31] - Analysis of LL-BCVA was not performed due to early study termination. [32] - Analysis of LL-BCVA was not performed due to early study termination. [33] - Analysis of LL-BCVA was not performed due to early study termination. [34] - Analysis of LL-BCVA was not performed due to early study termination. |
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Contrast Sensitivity at 9, 12, 15 Months and End of Study | ||||||||||||||||||||
End point description |
Contrast sensitivity was measured using the Pelli-Robson chart at 1 meter. Participants were tested for contrast sensitivity using +0.50 addition over the protocol refraction providing the best-corrected distance VA. Contrast sensitivity was recorded as the log of the faintest triplet for which 2 of the 3 letters were read correctly.
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End point type |
Secondary
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End point timeframe |
Baseline, Month 9, Month 12, Month 15, and End of Study
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Notes [35] - Analysis of contrast sensitivity was not performed due to early study termination. [36] - Analysis of contrast sensitivity was not performed due to early study termination. [37] - Analysis of contrast sensitivity was not performed due to early study termination. [38] - Analysis of contrast sensitivity was not performed due to early study termination. |
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No statistical analyses for this end point |
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End point title |
Percentage Change From Baseline in Contrast Sensitivity at 9, 12, 15 Months and End of Study | ||||||||||||||||||||
End point description |
Contrast sensitivity was measured using the Pelli-Robson chart at 1 meter. Subjects were tested for contrast sensitivity using +0.50 addition over the protocol refraction providing the best-corrected distance VA. Contrast sensitivity was recorded as the log of the faintest triplet for which 2 of the 3 letters were read correctly.
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End point type |
Secondary
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End point timeframe |
Baseline, Month 9, Month 12, Month 15, and End of Study
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Notes [39] - Analysis of contrast sensitivity was not performed due to early study termination. [40] - Analysis of contrast sensitivity was not performed due to early study termination. [41] - Analysis of contrast sensitivity was not performed due to early study termination. [42] - Analysis of contrast sensitivity was not performed due to early study termination. |
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Reading Speed at 9, 12, 15 Months and End of Study | ||||||||||||||||||||
End point description |
Reading speed in the study eye was assessed using modified Bailey-Lovie word charts. Participants read the chart for 2 minutes and the number of words read correctly per minute was totaled. An increase in the number of words read correctly indicated an improvement and a decrease in the number of words read correctly indicated a worsening.
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End point type |
Secondary
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End point timeframe |
Baseline, Month 9, Month 12, Month 15, and End of Study
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Notes [43] - Analysis of reading speed was not performed due to early study termination. [44] - Analysis of reading speed was not performed due to early study termination. [45] - Analysis of reading speed was not performed due to early study termination. [46] - Analysis of reading speed was not performed due to early study termination. |
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No statistical analyses for this end point |
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End point title |
Change From Placebo in Reading Speed at 9, 12, 15 Months and End of Study | ||||||||||||||||||||
End point description |
Reading speed in the study eye was assessed using modified Bailey-Lovie word charts. Participants read the chart for 2 minutes and the number of words read correctly per minute was totaled. An increase in the number of words read correctly indicated an improvement and a decrease in the number of words read correctly indicated a worsening.
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End point type |
Secondary
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End point timeframe |
Baseline, Month 9, Month 12, Month 15, and End of Study
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Notes [47] - Analysis of reading speed was not performed due to early study termination. [48] - Analysis of reading speed was not performed due to early study termination. [49] - Analysis of reading speed was not performed due to early study termination. [50] - Analysis of reading speed was not performed due to early study termination. |
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No statistical analyses for this end point |
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End point title |
Percentage Change From Baseline in Reading Speed at 9, 12, 15 Months and End of Study | ||||||||||||||||||||
End point description |
Reading speed in the study eye was assessed using modified Bailey-Lovie word charts. Participants read the chart for 2 minutes and the number of words read correctly per minute was totaled. An increase in the number of words read correctly indicated an improvement and a decrease in the number of words read correctly indicated a worsening.
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End point type |
Secondary
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End point timeframe |
Baseline, Month 9, Month 12, Month 15, and End of Study
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Notes [51] - Analysis of reading speed was not performed due to early study termination. [52] - Analysis of reading speed was not performed due to early study termination. [53] - Analysis of reading speed was not performed due to early study termination. [54] - Analysis of reading speed was not performed due to early study termination. |
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Reading Acuity at 9, 12, 15 Months and End of Study | ||||||||||||||||||||
End point description |
Reading Acuity was measured using the Radner reading charts and expressed in terms of logRAD (logarithmic Reading Acuity Determination).
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End point type |
Secondary
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End point timeframe |
Baseline, Month 9, Month 12, Month 15, and End of Study
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|
|||||||||||||||||||||
Notes [55] - Analysis of reading acuity was not performed due to early study termination. [56] - Analysis of reading acuity was not performed due to early study termination. [57] - Analysis of reading acuity was not performed due to early study termination. [58] - Analysis of reading acuity was not performed due to early study termination. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change From Placebo in Reading Acuity at 9, 12, 15 Months and End of Study | ||||||||||||||||||||
End point description |
Reading Acuity was measured using the Radner reading charts and expressed in terms of logRAD.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline, Month 9, Month 12, Month 15, and End of Study
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [59] - Analysis of reading acuity was not performed due to early study termination. [60] - Analysis of reading acuity was not performed due to early study termination. [61] - Analysis of reading acuity was not performed due to early study termination. [62] - Analysis of reading acuity was not performed due to early study termination. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage Change From Baseline in Reading Acuity at 9, 12, 15 Months and End of Study | ||||||||||||||||||||
End point description |
Reading Acuity was measured using the Radner reading charts and expressed in terms of logRAD.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline, Month 9, Month 12, Month 15, and End of Study
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [63] - Analysis of reading acuity was not performed due to early study termination. [64] - Analysis of reading acuity was not performed due to early study termination. [65] - Analysis of reading acuity was not performed due to early study termination. [66] - Analysis of reading acuity was not performed due to early study termination. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change From Baseline in Critical Print Size Reading at 9, 12, 15 Months and End of Study | ||||||||||||||||||||
End point description |
The critical print size is the smallest print size at which participants can read with their maximum reading speed.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline, Month 9, Month 12, Month 15, and End of Study
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [67] - Analysis of critical print size reading was not performed due to early study termination. [68] - Analysis of critical print size reading was not performed due to early study termination. [69] - Analysis of critical print size reading was not performed due to early study termination. [70] - Analysis of critical print size reading was not performed due to early study termination. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change From Placebo in Critical Print Size Reading at 9, 12, 15 Months and End of Study | ||||||||||||||||||||
End point description |
The critical print size is the smallest print size at which participants can read with their maximum reading speed.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline, Month 9, Month 12, Month 15, and End of Study
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [71] - Analysis of critical print size reading was not performed due to early study termination. [72] - Analysis of critical print size reading was not performed due to early study termination. [73] - Analysis of critical print size reading was not performed due to early study termination. [74] - Analysis of critical print size reading was not performed due to early study termination. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Number of Participants with Treatment-Emergent Laboratory Abnormalities | |||||||||||||||
End point description |
Laboratory assessments include: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein); coagulation assessments.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Day 85 and Day 169
|
|||||||||||||||
|
||||||||||||||||
Notes [75] - Analysis of laboratory abnormalities was not performed due to early study termination. [76] - Analysis of laboratory abnormalities was not performed due to early study termination. [77] - Analysis of laboratory abnormalities was not performed due to early study termination. [78] - Analysis of laboratory abnormalities was not performed due to early study termination. |
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Number of Participants with Abnormal Change From Baseline in Vital Signs | |||||||||||||||
End point description |
Vital sign assessments include: supine systolic and diastolic blood pressure, pulse rate and body temperature.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Screening, Days 28, 57, 85, 113, 141, and 169
|
|||||||||||||||
|
||||||||||||||||
Notes [79] - Analysis of vital signs was not performed due to early study termination. [80] - Analysis of vital signs was not performed due to early study termination. [81] - Analysis of vital signs was not performed due to early study termination. [82] - Analysis of vital signs was not performed due to early study termination. |
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Number of Participants with Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings | |||||||||||||||
End point description |
Clinically significant ECG findings include: corrected QT (QTc) > 450 msec, QTc >500 msec, change in QTc between 30 and 60 msec, change in QTc greater than or equal to 60 msec.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Days 28, 57, 85, 113 and 169
|
|||||||||||||||
|
||||||||||||||||
Notes [83] - Analysis of ECG parameters was not performed due to early study termination. [84] - Analysis of ECG parameters was not performed due to early study termination. [85] - Analysis of ECG parameters was not performed due to early study termination. [86] - Analysis of ECG parameters was not performed due to early study termination. |
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Number of Participants with Positive Anti-Drug Antibody (ADA) | |||||||||||||||
End point description |
The number of participants with positive ADA was to be summarized for each treatment arm.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Day 57 and Day 169
|
|||||||||||||||
|
||||||||||||||||
Notes [87] - Analysis of ADA was not performed due to early study termination. [88] - Analysis of ADA was not performed due to early study termination. [89] - Analysis of ADA was not performed due to early study termination. [90] - Analysis of ADA was not performed due to early study termination. |
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||
End point title |
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) According to Seriousness | |||||||||||||||||||||||||
End point description |
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Seriousness of an AE was assessed under the criteria of serious adverse event (SAE). 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.
|
|||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||
End point timeframe |
Days 28, 57, 85, 113, 141 and 169
|
|||||||||||||||||||||||||
|
||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Number of Participants with Treatment-Related TEAEs | |||||||||||||||
End point description |
An AE was an untoward medical occurrence in a participant who received study drug without regard to causal relationship. An investigator's relationship assessment is the determination of whether there exists a reasonable possibility that the investigational product caused or contributed to an AE.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Days 28, 57, 85, 113, 141 and 169
|
|||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Maximum Observed Plasma Concentration (Cmax) [91] | ||||||||||||||||
End point description |
|||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Days 1, 28, 57, 85, 169, 253, 281, 309, 337, and 449
|
||||||||||||||||
Notes [91] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: PK parameters were not planned for the placebo group. |
|||||||||||||||||
|
|||||||||||||||||
Notes [92] - Analysis of Cmax was not performed due to early study termination. [93] - Analysis of Cmax was not performed due to early study termination. [94] - Analysis of Cmax was not performed due to early study termination. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Minimum Observed Plasma Trough Concentration (Cmin) [95] | ||||||||||||||||
End point description |
|||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Days 1, 28, 57, 85, 169, 253, 281, 309, 337, and 449
|
||||||||||||||||
Notes [95] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: PK parameters were not planned for the placebo group. |
|||||||||||||||||
|
|||||||||||||||||
Notes [96] - Analysis of Cmin was not performed due to early study termination. [97] - Analysis of Cmin was not performed due to early study termination. [98] - Analysis of Cmin was not performed due to early study termination. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Area Under the Concentration-Time Curve From Time Zero Until Last Sampling Time (AUCt) [99] | ||||||||||||||||
End point description |
|||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Days 1, 28, 57, 85, 169, 253, 281, 309, 337, and 449
|
||||||||||||||||
Notes [99] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: PK parameters were not planned for the placebo group. |
|||||||||||||||||
|
|||||||||||||||||
Notes [100] - Analysis of AUCt was not performed due to early study termination. [101] - Analysis of AUCt was not performed due to early study termination. [102] - Analysis of AUCt was not performed due to early study termination. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Clearance at Steady State (CLss) [103] | ||||||||||||||||
End point description |
Steady state total body clearance equals infusion rate (zero order) divided by steady state plasma concentration of study drug (R0/Css).
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Days 1, 28, 57, 85, 169, 253, 281, 309, 337, and 449
|
||||||||||||||||
Notes [103] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: PK parameters were not planned for the placebo group. |
|||||||||||||||||
|
|||||||||||||||||
Notes [104] - Analysis of CLss was not performed due to early study termination. [105] - Analysis of CLss was not performed due to early study termination. [106] - Analysis of CLss was not performed due to early study termination. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Accumulation Ratio (Rac) for AUCt [107] | ||||||||||||||||
End point description |
|||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Days 1, 28, 57, 85, 169, 253, 281, 309, 337, and 449
|
||||||||||||||||
Notes [107] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: PK parameters were not planned for the placebo group. |
|||||||||||||||||
|
|||||||||||||||||
Notes [108] - Analysis of Rac for AUCt was not performed due to early study termination. [109] - Analysis of Rac for AUCt was not performed due to early study termination. [110] - Analysis of Rac for AUCt was not performed due to early study termination. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Plasma Population PK Parameters [111] | ||||||||||||||||
End point description |
Population PK parameters were to be evaluated for Cmax, AUCt, Cmin, CLss, and Rac for AUCt between the first and last (11th) doses.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Days 1, 28, 57, 85, 169, 253, 281, 309, 337 and 449
|
||||||||||||||||
Notes [111] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: PK parameters were not planned for the placebo group. |
|||||||||||||||||
|
|||||||||||||||||
Notes [112] - Analysis of population PK parameters was not performed due to early study termination. [113] - Analysis of population PK parameters was not performed due to early study termination. [114] - Analysis of population PK parameters was not performed due to early study termination. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change From Baseline in Total Amyloid Beta (A-Beta) 1-x Plasma Concentration at End of Study (Day 449) | ||||||||||||||||||||
End point description |
Concentration of total amino acid peptide, known as A-Beta 1-x, in plasma.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline, Day 449
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [115] - Analysis of A-Beta 1-x was not performed due to early study termination. [116] - Analysis of A-Beta 1-x was not performed due to early study termination. [117] - Analysis of A-Beta 1-x was not performed due to early study termination. [118] - Analysis of A-Beta 1-x was not performed due to early study termination. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change From Baseline in Amyloid Beta (A-Beta) 1-40 Plasma Concentration at End of Study (Day 449) | ||||||||||||||||||||
End point description |
Concentration of amino acid peptide, known as A-Beta 1-40, in plasma.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline, Day 449
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [119] - Analysis of A-Beta 1-40 was not performed due to early study termination. [120] - Analysis of A-Beta 1-40 was not performed due to early study termination. [121] - Analysis of A-Beta 1-40 was not performed due to early study termination. [122] - Analysis of A-Beta 1-40 was not performed due to early study termination. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change From Baseline in Amyloid Beta (A-Beta) 1-42 Plasma Concentration at End of Study (Day 449) | ||||||||||||||||||||
End point description |
Concentration of amino acid peptide, known as A-Beta 1-42, in plasma.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline, Day 449
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [123] - Analysis of A-Beta 1-42 was not performed due to early study termination. [124] - Analysis of A-Beta 1-42 was not performed due to early study termination. [125] - Analysis of A-Beta 1-42 was not performed due to early study termination. [126] - Analysis of A-Beta 1-42 was not performed due to early study termination. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Days 28, 57, 85, 113, 141, and 169 (or early termination)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
PF-04382923 2.5 mg/kg
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
PF-04382923 (RN6G) at 2.5 milligrams per kilogram (mg/kg) was administered as an intravenous (IV) infusion over 30 minutes every 28 days for 11 doses. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
PF-04382923 7.5 mg/kg
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
PF-04382923 at 7.5 mg/kg was administered as an IV infusion over 30 minutes every 28 days for 11 doses. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
PF-04382923 15.0 mg/kg
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
PF-04382923 at 15.0 mg/kg was administered as an IV infusion over 30 minutes every 28 days for 11 doses. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Placebo was administered as an IV infusion over at least 30 minutes every 28 days for 11 doses. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
The study was terminated early due to an organizational decision, which was not based on safety or efficacy concerns. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses |