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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
Interventions
Biological: Placebo
Biological: RN6G
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
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo-
PF-04382923RN6G-
Primary Outcome Measures
NameTimeMethod
Mean Reduction (in Study Eye) in Rate of Growth of Geographic Atrophy (GA) at Day 309Baseline 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
NameTimeMethod
Percentage Change From Baseline in BCVA Correct Number of Lines at Months 9, 12, 15 Months and End of StudyBaseline, 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 StudyBaseline, 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 StudyBaseline, 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 StudyBaseline, 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 StudyBaseline, 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) FindingsDays 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 TEAEsDays 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 StudyBaseline, 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 StudyBaseline, 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 StudyBaseline, 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 StudyBaseline, 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 StudyBaseline, 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 StudyBaseline, 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 StudyBaseline, 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 StudyBaseline, 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 AUCtDays 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 StudyBaseline, 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 SignsScreening, 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 SeriousnessDays 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 StudyBaseline, 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 StudyBaseline, 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 AbnormalitiesDay 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 ParametersDays 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)

Apothecary By Design

🇺🇸

Portland, Maine, United States

Cardiology Consultants of Long Island, PC- Physical Exam Facility Only

🇺🇸

Rockville Centre, New York, United States

South Carolina Neurological Clinic (Neurological Exams Only)

🇺🇸

West Columbia, South Carolina, United States

Charles Cathcart M.D.

🇺🇸

Portland, Maine, United States

Radiology Limited

🇺🇸

Tucson, Arizona, United States

Orthopedic Physician Assoc. - MRI

🇺🇸

Seattle, Washington, United States

Proliance Surgeons, Inc. PS DBA Vitreo Retinal Associates

🇺🇸

Seattle, Washington, United States

Open MRI & CT of South Miami

🇺🇸

Miami, Florida, United States

Diagnostic Imaging (MRI Only)

🇺🇸

Overland Park, Kansas, United States

O'Brien Pharmacy (Drug Shipment Only)

🇺🇸

Mission, Kansas, United States

Sabates Eye Center Research Division

🇺🇸

Leawood, Kansas, United States

Ophthalmic Consultants of Long Island

🇺🇸

Lynbrook, New York, United States

Scottsdale Medical Imaging

🇺🇸

Phoenix, Arizona, United States

Associated Retina Consultants, Ltd.

🇺🇸

Phoenix, Arizona, United States

Premier Research Group Limited

🇺🇸

Phoenix, Arizona, United States

Centennial Medical Center (MRI Only)

🇺🇸

Nashville, Tennessee, United States

Tennessee Retina, P.C

🇺🇸

Nashville, Tennessee, United States

Methodist Hospital of Southern California

🇺🇸

Arcadia, California, United States

Reeds Compounding Pharmacy

🇺🇸

Tucson, Arizona, United States

Northern California Retina Vitreous Associates

🇺🇸

Mountain View, California, United States

Mink Radiologic Imaging

🇺🇸

Beverly Hills, California, United States

Retina Vitreous Associates Medical Group

🇺🇸

Beverly Hills, California, United States

Retina-Vitreous Associates Medical Group

🇺🇸

Beverly Hills, California, United States

Retina Institute of California

🇺🇸

Arcadia, California, United States

Valley Radiology Medical Associates, Inc.

🇺🇸

Mountain View, California, United States

Fairmount Pharmacy

🇺🇸

Pasadena, California, United States

Retinal Consultants Medical Group, Inc.

🇺🇸

Sacramento, California, United States

Radiological Associates of Sacramento Medical Group, Inc. (MRI Imaging Only)

🇺🇸

Roseville, California, United States

Leiter's Compounding Pharmacy

🇺🇸

San Jose, California, United States

Florida Eye Clinic

🇺🇸

Altamonte Springs, Florida, United States

Mid Florida Imaging (MRI Only)

🇺🇸

Altamonte Springs, Florida, United States

Quest Diagnostics Patient Service Center (Blood Draw Lab only)

🇺🇸

Santa Ana, California, United States

Center for Retina and Macular Disease

🇺🇸

Lakeland, Florida, United States

Medeye Associates

🇺🇸

Miami, Florida, United States

Maitland Avenue Urgent Care (Physical and Neurologic Exams Only)

🇺🇸

Altamonte Springs, Florida, United States

Retina Care Specialists, LLP

🇺🇸

Palm Beach Gardens, Florida, United States

Intermed Diagnostic Imaging

🇺🇸

South Portland, Maine, United States

Advanced Open MRI

🇺🇸

Toms River, New Jersey, United States

Maine Eye Center

🇺🇸

Portland, Maine, United States

Retina Vitreous Center

🇺🇸

Toms River, New Jersey, United States

Shore Neurology, PA

🇺🇸

Toms River, New Jersey, United States

Advanced Neurological Care, PC - Neurology Exam Facility Only

🇺🇸

Valley Stream, New York, United States

Lenox Hill Radiology (MRI Only)

🇺🇸

New York, New York, United States

Zwager - Pesiri Radiology Group - MRI Exam Facility Only

🇺🇸

Plainview, New York, United States

Lenox Hill Radiology/Regency Medical Imaging (MRI Only)

🇺🇸

New York, New York, United States

Macula Care, Pllc

🇺🇸

New York, New York, United States

King's Pharmacy

🇺🇸

Brooklyn, New York, United States

Cincinnati Eye Institute

🇺🇸

Cincinnati, Ohio, United States

Pro Scan Imaging

🇺🇸

Mason, Ohio, United States

UPMC West Mifflin (MRI Only)

🇺🇸

WestMifflin, Pennsylvania, United States

Associates in Ophthalmology, Ltd.

🇺🇸

West Mifflin, Pennsylvania, United States

Hawthorne Pharmacy

🇺🇸

Columbia, South Carolina, United States

Palmetto Retina Center

🇺🇸

West Columbia, South Carolina, United States

InMed (MRI Facility)

🇺🇸

Columbia, South Carolina, United States

Jay Markowitz, MD and Associates (Physical Exams Only)

🇺🇸

West Columbia, South Carolina, United States

Radiology Associates of North Texas

🇺🇸

Arlington, Texas, United States

Innovative Infusion

🇺🇸

Arlington, Texas, United States

Kevin E. Conner

🇺🇸

Arlington, Texas, United States

River Ranch Radiology

🇺🇸

Austin, Texas, United States

Specialty Compounding

🇺🇸

Cedar park, Texas, United States

Brian B. Berger, MD, PA

🇺🇸

Austin, Texas, United States

Retina Research Center

🇺🇸

Austin, Texas, United States

Sleep Medicine Consultants

🇺🇸

Austin, Texas, United States

Advanced Radiology Services

🇺🇸

Edinburg, Texas, United States

Tommy Yee MD

🇺🇸

McAllen, Texas, United States

Edinburg Family Pharmacy

🇺🇸

Edinburg, Texas, United States

Valley Retina Institute,P.A.

🇺🇸

McAllen, Texas, United States

McAllen Advanced Medical Imaging

🇺🇸

McAllen, Texas, United States

McAllen Surgical Specialty Center

🇺🇸

McAllen, Texas, United States

Weslaco Advanced Imaging

🇺🇸

Weslaco, Texas, United States

Sound Prescriptions LLC

🇺🇸

Bellevue, Washington, United States

Premiere Research Institute At Palm Beach Neurology (MRI, Physical Exam, and Neurological Exam Only)

🇺🇸

West Palm Beach, Florida, United States

Cardiology Specialist of Orange County (ECG Evaluation Only)

🇺🇸

Santa Ana, California, United States

Open Advantage MRI (Brain MRI Only)

🇺🇸

Santa Ana, California, United States

Kenneth L. Nudleman M.D. (Neurology Exam Only)

🇺🇸

Santa Ana, California, United States

Orange County Retina Medical Group

🇺🇸

Santa Ana, California, United States

Texas Retina Associates

🇺🇸

Arlington, Texas, United States

Retina Associates

🇺🇸

Tucson, Arizona, United States

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