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

Phase 2

Terminated

Conditions: Age-Related Maculopathy

Registration Number: NCT01577381

Lead Sponsor: Pfizer

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 10

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Mean Reduction (in Study Eye) in Rate of Growth of Geographic Atrophy (GA) at Day 309	Baseline and 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).
Mean Reduction (in Study Eye) in Rate of Growth of GA at Day 449 (End of Study)	Baseline and Day 449	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).

Secondary Outcome Measures

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

Trial Locations

Locations (78): Scottsdale Medical Imaging
🇺🇸
Phoenix, Arizona, United States
Associated Retina Consultants, Ltd.
🇺🇸
Phoenix, Arizona, United States
Premier Research Group Limited
🇺🇸
Phoenix, Arizona, United States
Radiology Limited
🇺🇸
Tucson, Arizona, United States
Retina Associates
🇺🇸
Tucson, Arizona, United States
Reeds Compounding Pharmacy
🇺🇸
Tucson, Arizona, United States
Methodist Hospital of Southern California
🇺🇸
Arcadia, California, United States
Retina Institute of California
🇺🇸
Arcadia, California, United States
Mink Radiologic Imaging
🇺🇸
Beverly Hills, California, United States
Retina Vitreous Associates Medical Group
🇺🇸
Beverly Hills, California, United States
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Scottsdale Medical Imaging
🇺🇸Phoenix, Arizona, United States