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

Phase 2TerminatedNCT01577381

Pfizer10 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Age-Related Maculopathy

Interventions

RN6GBIOLOGICAL

Intravenous, 11 doses, 30 minute infusion, dose ranging from 2.5 mg/kg up to a maximum of 15 mg/kg

PlaceboBIOLOGICAL

Intravenous, 11 doses, 30 minute infusion

Eligibility

Sex: ALLMin age: 60 YearsMax age: 90 Years

Medical Language ↔ Plain English

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

Locations (83)

Outcomes

Primary Outcomes

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).

Time frame: 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).

Time frame: Baseline and Day 449

Secondary Outcomes

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).

Time frame: 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

Time frame: 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).

Time frame: Baseline, Month 9, Month 12, Month 15, and End of Study

Data from ClinicalTrials.gov

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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

...and 73 more locations

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Days 28, 57, 85, 113, 141 and 169

Maximum Observed Plasma Concentration (Cmax)

Time frame: Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449

Minimum Observed Plasma Trough Concentration (Cmin)

Time frame: 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)

Time frame: 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)

Time frame: Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449

Accumulation Ratio (Rac) for AUCt

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline, Day 449