Efficacy, Safety And Tolerability Study Of RN6G In Subjects With Geographic Atrophy Secondary to Age-related Macular Degeneration

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy, safety and tolerability of multiple doses of RN6G in subjects with Geographic Atrophy Secondary to Age-related Macular Degeneration.

Detailed Description
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The trial was terminated early on April 12, 2013 due to an organizational decision, which was not based on safety or efficacy concerns. Subjects who were already enrolled into the study were followed.

Official Title
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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

Conditions
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Age-Related Maculopathy

Intervention / Treatment
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* Biological: RN6G
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women between the ages of 60 and 90 years. Diagnosis of a geographic atrophy (GA) secondary to dry Age-Related Macular Degeneration. Best Corrected Visual Acuity (BCVA) of 20/80 or better in the study eye Exclusion Criteria: Evidence of ocular disease other than geographic atrophy (GA) secondary to dry Age-Related Macular Degeneration in the study eye. History or diagnosis of exudative (wet) Age-Related Macular Degeneration, with subretinal or choroidal neovascular lesions in the study eye. Presence of disease or condition that might compromise the cardiovascular, hematological, renal, hepatic, pulmonary, endocrine, central nervous, immune, or gastrointestinal system

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-04382923<br> | Biological: RN6G<br>* Intravenous, 11 doses, 30 minute infusion, dose ranging from 2.5 mg/kg up to a maximum of 15 mg/kg<br>|
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* Intravenous, 11 doses, 30 minute infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Reduction (in Study Eye) in Rate of Growth of Geographic Atrophy (GA) at Day 309 | 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). | Baseline and Day 309 | 
| Mean Reduction (in Study Eye) in Rate of Growth of GA at Day 449 (End of Study) | 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). | Baseline and Day 449 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Best Corrected Visual Acuity (BCVA) at 9, 12, 15 Months and End of Study | 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). | Baseline, Month 9, Month 12, Month 15, and End of Study | 
| Percentage Change From Baseline in BCVA Correct Number of Letters at 9, 12, 15 Months and End of Study | 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). | Baseline, Month 9, Month 12, Month 15, and End of Study | 
| Percentage Change From Baseline in BCVA Correct Number of Lines at Months 9, 12, 15 Months and End of Study | 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). | Baseline, Month 9, Month 12, Month 15, and End of Study | 
| Mean Low Luminance Best Corrected Visual Acuity (LL-BCVA) at 9, 12, 15 Months and End of Study | LL-BCVA is the measure of visual acuity under low light conditions. | Baseline, Month 9, Month 12, Month 15, and End of Study | 
| Percentage Change From Baseline in LL-BCVA Correct Number of Letters at 9, 12, 15 Months and End of Study | LL-BCVA is the measure of visual acuity under low light conditions. | Baseline, Month 9, Month 12, Month 15, and End of Study | 
| Percentage Change From Baseline in LL-BCVA Correct Number of Lines at 9, 12, 15 Months and End of Study | LL-BCVA is the measure of visual acuity under low light conditions. | Baseline, Month 9, Month 12, Month 15, and End of Study | 
| Change From Baseline in Contrast Sensitivity at 9, 12, 15 Months and End of Study | 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. | Baseline, Month 9, Month 12, Month 15, and End of Study | 
| Percentage Change From Baseline in Contrast Sensitivity at 9, 12, 15 Months and End of Study | 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. | Baseline, Month 9, Month 12, Month 15, and End of Study | 
| Change From Baseline in Reading Speed at 9, 12, 15 Months and End of Study | 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. | Baseline, Month 9, Month 12, Month 15, and End of Study | 
| Change From Placebo in Reading Speed at 9, 12, 15 Months and End of Study | 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. | Baseline, Month 9, Month 12, Month 15, and End of Study | 
| Percentage Change From Baseline in Reading Speed at 9, 12, 15 Months and End of Study | 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. | Baseline, Month 9, Month 12, Month 15, and End of Study | 
| Change From Baseline in Reading Acuity at 9, 12, 15 Months and End of Study | Reading Acuity was measured using the Radner reading charts and expressed in terms of logRAD (logrithmic Reading Acuity Determination). | Baseline, Month 9, Month 12, Month 15, and End of Study | 
| Change From Placebo in Reading Acuity at 9, 12, 15 Months and End of Study | Reading Acuity was measured using the Radner reading charts and expressed in terms of logRAD. | Baseline, Month 9, Month 12, Month 15, and End of Study | 
| Percentage Change From Baseline in Reading Acuity at 9, 12, 15 Months and End of Study | Reading Acuity was measured using the Radner reading charts and expressed in terms of logRAD. | Baseline, Month 9, Month 12, Month 15, and End of Study | 
| Change From Baseline in Critical Print Size Reading at 9, 12, 15 Months and End of Study | The critical print size is the smallest print size at which participants can read with their maximum reading speed. | Baseline, Month 9, Month 12, Month 15, and End of Study | 
| Change From Placebo in Critical Print Size Reading at 9, 12, 15 Months and End of Study | The critical print size is the smallest print size at which participants can read with their maximum reading speed. | Baseline, Month 9, Month 12, Month 15, and End of Study | 
| Number of Participants With Treatment-Emergent Laboratory Abnormalities | 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. | Day 85 and Day 169 | 
| Number of Participants With Abnormal Change From Baseline in Vital Signs | Vital sign assessments include: supine systolic and diastolic blood pressure, pulse rate and body temperature. | Screening, Days 28, 57, 85, 113, 141, and 169 | 
| Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings | 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. | Days 28, 57, 85, 113 and 169 | 
| Number of Participants With Positive Anti-Drug Antibody (ADA) | The number of participants with positive ADA was to be summarized for each treatment arm. | Day 57 and Day 169 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) According to Seriousness | 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. | Days 28, 57, 85, 113, 141 and 169 | 
| Number of Participants With Treatment-Related TEAEs | 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. | Days 28, 57, 85, 113, 141 and 169 | 
| Maximum Observed Plasma Concentration (Cmax) |  | Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449 | 
| Minimum Observed Plasma Trough Concentration (Cmin) |  | Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449 | 
| Area Under the Concentration-Time Curve From Time Zero Until Last Sampling Time (AUCt) |  | Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449 | 
| Clearance at Steady State (CLss) | Steady state total body clearance equals infusion rate (zero order) divided by steady state plasma concentration of study drug (R0/Css) | Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449 | 
| Accumulation Ratio (Rac) for AUCt |  | Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449 | 
| Plasma Population PK Parameters | Population PK parameters were to be evaluated for Cmax, AUCt, Cmin, CLss, and Rac for AUCt between the first and last (11th) doses. | Days 1, 28, 57, 85, 169, 253, 281, 309, 337 and 449 | 
| Change From Baseline in Total Amyloid Beta (A-Beta) 1-x Plasma Concentration at End of Study (Day 449) | Concentration of total amino acid peptide, known as A-Beta 1-x, in plasma. | Baseline, Day 449 | 
| Change From Baseline in Amyloid Beta (A-Beta) 1-40 Plasma Concentration at End of Study (Day 449) | Concentration of amino acid peptide, known as A-Beta 1-40, in plasma. | Baseline, Day 449 | 
| Change From Baseline in Amyloid Beta (A-Beta) 1-42 Plasma Concentration at End of Study (Day 449) | Concentration of amino acid peptide, known as A-Beta 1-42, in plasma. | Baseline, Day 449 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 2, Advanced Dry Age-Related Macular Degeneration, Geographic Atrophy, RN6G