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

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

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.

Study Overview

• Status: Terminated
• Conditions: Age-Related Maculopathy
• Intervention / Treatment: Biological: RN6G; Biological: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85027
      • Premier Research Group Limited
    • Phoenix, Arizona, United States, 85020
      • Associated Retina Consultants, Ltd.
    • Phoenix, Arizona, United States, 85016
      • Scottsdale Medical Imaging
    • Tucson, Arizona, United States, 85710
      • Retina Associates
    • Tucson, Arizona, United States, 85710
      • Radiology Limited
    • Tucson, Arizona, United States, 85716
      • Reeds Compounding Pharmacy
  • California
    • Arcadia, California, United States, 91007
      • Retina Institute of California
    • Arcadia, California, United States, 91007
      • Methodist Hospital of Southern California
    • Beverly Hills, California, United States, 90211
      • Retina-Vitreous Associates Medical Group
    • Beverly Hills, California, United States, 90211
      • Retina Vitreous Associates Medical Group
    • Beverly Hills, California, United States, 90211
      • Mink Radiologic Imaging
    • Mountain View, California, United States, 94040
      • Northern California Retina Vitreous Associates
    • Mountain View, California, United States, 94040
      • Valley Radiology Medical Associates, Inc.
    • Pasadena, California, United States, 91105
      • Fairmount Pharmacy
    • Roseville, California, United States, 95661
      • Radiological Associates of Sacramento Medical Group, Inc. (MRI Imaging Only)
    • Sacramento, California, United States, 95841
      • Retinal Consultants Medical Group, Inc.
    • San Jose, California, United States, 95126
      • Leiter's Compounding Pharmacy
    • Santa Ana, California, United States, 92705
      • Orange County Retina Medical Group
    • Santa Ana, California, United States, 92705
      • Cardiology Specialist of Orange County (ECG Evaluation Only)
    • Santa Ana, California, United States, 92705
      • Kenneth L. Nudleman M.D. (Neurology Exam Only)
    • Santa Ana, California, United States, 92705
      • Open Advantage MRI (Brain MRI Only)
    • Santa Ana, California, United States, 92705
      • Quest Diagnostics Patient Service Center (Blood Draw Lab only)
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • Florida Eye Clinic
    • Altamonte Springs, Florida, United States, 32701
      • Maitland Avenue Urgent Care (Physical and Neurologic Exams Only)
    • Altamonte Springs, Florida, United States, 32714
      • Mid Florida Imaging (MRI Only)
    • Lakeland, Florida, United States, 33805
      • Center for Retina and Macular Disease
    • Miami, Florida, United States, 33143
      • MedEye Associates
    • Miami, Florida, United States, 33143
      • Open MRI & CT of South Miami
    • Palm Beach Gardens, Florida, United States, 33410
      • Retina Care Specialists, LLP
    • West Palm Beach, Florida, United States, 33407
      • Premiere Research Institute At Palm Beach Neurology (MRI, Physical Exam, and Neurological Exam Only)
  • Kansas
    • Leawood, Kansas, United States, 66211
      • Sabates Eye Center Research Division
    • Mission, Kansas, United States, 66205
      • O'Brien Pharmacy (Drug Shipment Only)
    • Overland Park, Kansas, United States, 66211
      • Diagnostic Imaging (MRI Only)
  • Maine
    • Portland, Maine, United States, 04101
      • Apothecary By Design
    • Portland, Maine, United States, 04101
      • Charles Cathcart M.D.
    • Portland, Maine, United States, 4102
      • Maine Eye Center
    • South Portland, Maine, United States, 04106
      • Intermed Diagnostic Imaging
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • Shore Neurology, PA
    • Toms River, New Jersey, United States, 08755
      • Retina Vitreous Center
    • Toms River, New Jersey, United States, 08755
      • Advanced Open MRI
  • New York
    • Brooklyn, New York, United States, 11238
      • King's Pharmacy
    • East Setauket, New York, United States, 11733
      • Zwager - Pesiri Radiology Group - MRI Exam Facility Only
    • Lynbrook, New York, United States, 11563
      • Ophthalmic Consultants of Long Island
    • Lynbrook, New York, United States, 11563
      • Advanced Neurological Care, PC - Neurology Exam Facility Only
    • Merrick, New York, United States, 11566
      • Zwager - Pesiri Radiology Group - MRI Exam Facility Only
    • New York, New York, United States, 10021
      • Lenox Hill Radiology/Regency Medical Imaging (MRI Only)
    • New York, New York, United States, 10021
      • Macula Care, Pllc
    • New York, New York, United States, 10075
      • Lenox Hill Radiology (MRI Only)
    • Plainview, New York, United States, 11803
      • Zwager - Pesiri Radiology Group - MRI Exam Facility Only
    • Rockville Centre, New York, United States, 11570
      • Cardiology Consultants of Long Island, PC- Physical Exam Facility Only
    • Valley Stream, New York, United States, 11570
      • Advanced Neurological Care, PC - Neurology Exam Facility Only
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Cincinnati Eye Institute
    • Mason, Ohio, United States, 45040
      • Pro Scan Imaging
  • Pennsylvania
    • West Mifflin, Pennsylvania, United States, 15122
      • Associates in Ophthalmology, Ltd.
    • WestMifflin, Pennsylvania, United States, 15122
      • UPMC West Mifflin (MRI Only)
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • Hawthorne Pharmacy
    • Columbia, South Carolina, United States, 29201
      • InMed (MRI Facility)
    • West Columbia, South Carolina, United States, 29169
      • Palmetto Retina Center
    • West Columbia, South Carolina, United States, 29169
      • Jay Markowitz, MD and Associates (Physical Exams Only)
    • West Columbia, South Carolina, United States, 29169
      • South Carolina Neurological Clinic (Neurological Exams Only)
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Centennial Medical Center (MRI Only)
    • Nashville, Tennessee, United States, 37203
      • Tennessee Retina, P.C
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Retina Associates
    • Arlington, Texas, United States, 76011
      • Radiology Associates of North Texas
    • Arlington, Texas, United States, 76012
      • Innovative Infusion
    • Arlington, Texas, United States, 76015
      • Kevin E. Conner
    • Arlington, Texas, United States, 76018
      • Radiology Associates of North Texas
    • Austin, Texas, United States, 78705
      • Retina Research Center
    • Austin, Texas, United States, 78705
      • Brian B. Berger, MD, PA
    • Austin, Texas, United States, 78731
      • Sleep Medicine Consultants
    • Austin, Texas, United States, 78705
      • River Ranch Radiology
    • Cedar park, Texas, United States, 78613
      • Specialty Compounding
    • Edinburg, Texas, United States, 78539
      • Advanced Radiology Services
    • Edinburg, Texas, United States, 78539
      • Edinburg Family Pharmacy
    • McAllen, Texas, United States, 78501
      • McAllen Advanced Medical Imaging
    • McAllen, Texas, United States, 78503
      • McAllen Surgical Specialty Center
    • McAllen, Texas, United States, 78503
      • Tommy Yee MD
    • McAllen, Texas, United States, 78503
      • Valley Retina Institute,P.A.
    • Weslaco, Texas, United States, 78596
      • Weslaco Advanced Imaging
  • Washington
    • Bellevue, Washington, United States, 98004
      • Proliance Surgeons, Inc. PS DBA Vitreo Retinal Associates
    • Bellevue, Washington, United States, 98004
      • Sound Prescriptions LLC
    • Seattle, Washington, United States, 98104
      • Orthopedic Physician Assoc. - MRI
    • Seattle, Washington, United States, 98104
      • Proliance Surgeons, Inc. PS DBA Vitreo Retinal Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: April 11, 2012
• First Submitted That Met QC Criteria: April 11, 2012
• First Posted (Estimate): April 13, 2012

Study Record Updates

• Last Update Posted (Estimate): March 16, 2016
• Last Update Submitted That Met QC Criteria: February 16, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Phase 2; Geographic Atrophy; Advanced Dry Age-Related Macular Degeneration; RN6G
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Pathological Conditions, Anatomical; Macular Degeneration; Geographic Atrophy; Atrophy
• Other Study ID Numbers: B1181003; 2012-000823-42 (EudraCT Number)