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

Age-Related Maculopathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01577381
• Other study ID #: B1181003
• Secondary ID: 2012-000823-42
• Status: Terminated
• Phase: Phase 2
• First received: April 11, 2012
• Last updated: February 16, 2016
• Start date: August 2012
• Est. completion date: October 2013

Study information

• Verified date: February 2016
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: October 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years to 90 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Age-Related Maculopathy
• Geographic Atrophy
• Macular Degeneration

Intervention

Biological:
• RN6G
Intravenous, 11 doses, 30 minute infusion, dose ranging from 2.5 mg/kg up to a maximum of 15 mg/kg
• Placebo
Intravenous, 11 doses, 30 minute infusion

Locations

Country	Name	City	State
United States	Florida Eye Clinic	Altamonte Springs	Florida
United States	Maitland Avenue Urgent Care (Physical and Neurologic Exams Only)	Altamonte Springs	Florida
United States	Mid Florida Imaging (MRI Only)	Altamonte Springs	Florida
United States	Methodist Hospital of Southern California	Arcadia	California
United States	Retina Institute of California	Arcadia	California
United States	Innovative Infusion	Arlington	Texas
United States	Kevin E. Conner	Arlington	Texas
United States	Radiology Associates of North Texas	Arlington	Texas
United States	Radiology Associates of North Texas	Arlington	Texas
United States	Texas Retina Associates	Arlington	Texas
United States	Brian B. Berger, MD, PA	Austin	Texas
United States	Retina Research Center	Austin	Texas
United States	River Ranch Radiology	Austin	Texas
United States	Sleep Medicine Consultants	Austin	Texas
United States	Proliance Surgeons, Inc. PS DBA Vitreo Retinal Associates	Bellevue	Washington
United States	Sound Prescriptions LLC	Bellevue	Washington
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	King's Pharmacy	Brooklyn	New York
United States	Specialty Compounding	Cedar park	Texas
United States	Cincinnati Eye Institute	Cincinnati	Ohio
United States	Hawthorne Pharmacy	Columbia	South Carolina
United States	InMed (MRI Facility)	Columbia	South Carolina
United States	Zwager - Pesiri Radiology Group - MRI Exam Facility Only	East Setauket	New York
United States	Advanced Radiology Services	Edinburg	Texas
United States	Edinburg Family Pharmacy	Edinburg	Texas
United States	Center for Retina and Macular Disease	Lakeland	Florida
United States	Sabates Eye Center Research Division	Leawood	Kansas
United States	Advanced Neurological Care, PC - Neurology Exam Facility Only	Lynbrook	New York
United States	Ophthalmic Consultants of Long Island	Lynbrook	New York
United States	Pro Scan Imaging	Mason	Ohio
United States	McAllen Advanced Medical Imaging	McAllen	Texas
United States	McAllen Surgical Specialty Center	McAllen	Texas
United States	Tommy Yee MD	McAllen	Texas
United States	Valley Retina Institute,P.A.	McAllen	Texas
United States	Zwager - Pesiri Radiology Group - MRI Exam Facility Only	Merrick	New York
United States	Medeye Associates	Miami	Florida
United States	Open MRI & CT of South Miami	Miami	Florida
United States	O'Brien Pharmacy (Drug Shipment Only)	Mission	Kansas
United States	Northern California Retina Vitreous Associates	Mountain View	California
United States	Valley Radiology Medical Associates, Inc.	Mountain View	California
United States	Centennial Medical Center (MRI Only)	Nashville	Tennessee
United States	Tennessee Retina, P.C	Nashville	Tennessee
United States	Lenox Hill Radiology (MRI Only)	New York	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	Diagnostic Imaging (MRI Only)	Overland Park	Kansas
United States	Retina Care Specialists, LLP	Palm Beach Gardens	Florida
United States	Fairmount Pharmacy	Pasadena	California
United States	Associated Retina Consultants, Ltd.	Phoenix	Arizona
United States	Premier Research Group Limited	Phoenix	Arizona
United States	Scottsdale Medical Imaging	Phoenix	Arizona
United States	Zwager - Pesiri Radiology Group - MRI Exam Facility Only	Plainview	New York
United States	Apothecary By Design	Portland	Maine
United States	Charles Cathcart M.D.	Portland	Maine
United States	Maine Eye Center	Portland	Maine
United States	Cardiology Consultants of Long Island, PC- Physical Exam Facility Only	Rockville Centre	New York
United States	Radiological Associates of Sacramento Medical Group, Inc. (MRI Imaging Only)	Roseville	California
United States	Retinal Consultants Medical Group, Inc.	Sacramento	California
United States	Leiter's Compounding Pharmacy	San Jose	California
United States	Cardiology Specialist of Orange County (ECG Evaluation Only)	Santa Ana	California
United States	Kenneth L. Nudleman M.D. (Neurology Exam Only)	Santa Ana	California
United States	Open Advantage MRI (Brain MRI Only)	Santa Ana	California
United States	Orange County Retina Medical Group	Santa Ana	California
United States	Quest Diagnostics Patient Service Center (Blood Draw Lab only)	Santa Ana	California
United States	Orthopedic Physician Assoc. - MRI	Seattle	Washington
United States	Proliance Surgeons, Inc. PS DBA Vitreo Retinal Associates	Seattle	Washington
United States	Intermed Diagnostic Imaging	South Portland	Maine
United States	Advanced Open MRI	Toms River	New Jersey
United States	Retina Vitreous Center	Toms River	New Jersey
United States	Shore Neurology, PA	Toms River	New Jersey
United States	Radiology Limited	Tucson	Arizona
United States	Reeds Compounding Pharmacy	Tucson	Arizona
United States	Retina Associates	Tucson	Arizona
United States	Advanced Neurological Care, PC - Neurology Exam Facility Only	Valley Stream	New York
United States	Weslaco Advanced Imaging	Weslaco	Texas
United States	Jay Markowitz, MD and Associates (Physical Exams Only)	West Columbia	South Carolina
United States	Palmetto Retina Center	West Columbia	South Carolina
United States	South Carolina Neurological Clinic (Neurological Exams Only)	West Columbia	South Carolina
United States	Associates in Ophthalmology, Ltd.	West Mifflin	Pennsylvania
United States	Premiere Research Institute At Palm Beach Neurology (MRI, Physical Exam, and Neurological Exam Only)	West Palm Beach	Florida
United States	UPMC West Mifflin (MRI Only)	WestMifflin	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	Maximum Observed Plasma Concentration (Cmax)		Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449	No
Secondary	Minimum Observed Plasma Trough Concentration (Cmin)		Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449	No
Secondary	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	No
Secondary	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	No
Secondary	Accumulation Ratio (Rac) for AUCt		Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

External Links

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