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

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01577381
First received: April 11, 2012
Last updated: February 16, 2016
Last verified: February 2016
  Purpose
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.

Condition Intervention Phase
Age-Related Maculopathy
Biological: RN6G
Biological: Placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Mean Reduction (in Study Eye) in Rate of Growth of Geographic Atrophy (GA) at Day 309 [ Time Frame: Baseline and Day 309 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline and Day 449 ] [ Designated as safety issue: No ]
    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:
  • Mean Best Corrected Visual Acuity (BCVA) at 9, 12, 15 Months and End of Study [ Time Frame: Baseline, Month 9, Month 12, Month 15, and End of Study ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Month 9, Month 12, Month 15, and End of Study ] [ Designated as safety issue: No ]
    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 Lines at Months 9, 12, 15 Months and End of Study [ Time Frame: Baseline, Month 9, Month 12, Month 15, and End of Study ] [ Designated as safety issue: No ]
    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).

  • Mean Low Luminance Best Corrected Visual Acuity (LL-BCVA) at 9, 12, 15 Months and End of Study [ Time Frame: Baseline, Month 9, Month 12, Month 15, and End of Study ] [ Designated as safety issue: No ]
    LL-BCVA is the measure of visual acuity under low light conditions.

  • Percentage Change From Baseline in LL-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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Month 9, Month 12, Month 15, and End of Study ] [ Designated as safety issue: No ]
    LL-BCVA is the measure of visual acuity under low light conditions.

  • Change From Baseline in Contrast Sensitivity at 9, 12, 15 Months and End of Study [ Time Frame: Baseline, Month 9, Month 12, Month 15, and End of Study ] [ Designated as safety issue: No ]
    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.

  • Percentage Change From Baseline in Contrast Sensitivity at 9, 12, 15 Months and End of Study [ Time Frame: Baseline, Month 9, Month 12, Month 15, and End of Study ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Month 9, Month 12, Month 15, and End of Study ] [ Designated as safety issue: No ]
    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 Acuity at 9, 12, 15 Months and End of Study [ Time Frame: Baseline, Month 9, Month 12, Month 15, and End of Study ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Month 9, Month 12, Month 15, and End of Study ] [ Designated as safety issue: No ]
    Reading Acuity was measured using the Radner reading charts and expressed in terms of logRAD.

  • Percentage Change From Baseline in Reading Acuity at 9, 12, 15 Months and End of Study [ Time Frame: Baseline, Month 9, Month 12, Month 15, and End of Study ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Month 9, Month 12, Month 15, and End of Study ] [ Designated as safety issue: No ]
    The critical print size is the smallest print size at which participants can read with their maximum reading speed.

  • Change From Placebo in Critical Print Size Reading at 9, 12, 15 Months and End of Study [ Time Frame: Baseline, Month 9, Month 12, Month 15, and End of Study ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 85 and Day 169 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Abnormal Change From Baseline in Vital Signs [ Time Frame: Screening, Days 28, 57, 85, 113, 141, and 169 ] [ Designated as safety issue: Yes ]
    Vital sign assessments include: supine systolic and diastolic blood pressure, pulse rate and body temperature.

  • Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings [ Time Frame: Days 28, 57, 85, 113 and 169 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Day 57 and Day 169 ] [ Designated as safety issue: Yes ]
    The number of participants with positive ADA was to be summarized for each treatment arm.

  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) According to Seriousness [ Time Frame: Days 28, 57, 85, 113, 141 and 169 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Treatment-Related TEAEs [ Time Frame: Days 28, 57, 85, 113, 141 and 169 ] [ Designated as safety issue: Yes ]
    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.

  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449 ] [ Designated as safety issue: No ]
  • Minimum Observed Plasma Trough Concentration (Cmin) [ Time Frame: Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Clearance at Steady State (CLss) [ Time Frame: Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449 ] [ Designated as safety issue: No ]
    Steady state total body clearance equals infusion rate (zero order) divided by steady state plasma concentration of study drug (R0/Css)

  • Accumulation Ratio (Rac) for AUCt [ Time Frame: Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449 ] [ Designated as safety issue: No ]
  • Plasma Population PK Parameters [ Time Frame: Days 1, 28, 57, 85, 169, 253, 281, 309, 337 and 449 ] [ Designated as safety issue: No ]
    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 Total Amyloid Beta (A-Beta) 1-x Plasma Concentration at End of Study (Day 449) [ Time Frame: Baseline, Day 449 ] [ Designated as safety issue: No ]
    Concentration of total amino acid peptide, known as A-Beta 1-x, in plasma.

  • Change From Baseline in Amyloid Beta (A-Beta) 1-40 Plasma Concentration at End of Study (Day 449) [ Time Frame: Baseline, Day 449 ] [ Designated as safety issue: No ]
    Concentration of amino acid peptide, known as A-Beta 1-40, in plasma.

  • Change From Baseline in Amyloid Beta (A-Beta) 1-42 Plasma Concentration at End of Study (Day 449) [ Time Frame: Baseline, Day 449 ] [ Designated as safety issue: No ]
    Concentration of amino acid peptide, known as A-Beta 1-42, in plasma.


Enrollment: 10
Study Start Date: August 2012
Study Completion Date: October 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Placebo Comparator: Placebo Biological: Placebo
Intravenous, 11 doses, 30 minute infusion

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.
  Eligibility

Ages Eligible for Study:   60 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01577381

  Show 83 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01577381     History of Changes
Other Study ID Numbers: B1181003  2012-000823-42 
Study First Received: April 11, 2012
Results First Received: December 9, 2015
Last Updated: February 16, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Phase 2
Advanced Dry Age-Related Macular Degeneration
Geographic Atrophy
RN6G

Additional relevant MeSH terms:
Geographic Atrophy
Macular Degeneration
Eye Diseases
Retinal Degeneration
Retinal Diseases

ClinicalTrials.gov processed this record on May 24, 2016