Safety And Tolerability Study Of RN6G In Patients With Dry, Age-Related Macular Degeneration

March 20, 2015 updated by: Pfizer

A Phase I, Double-masked, Placebo-controlled Study Evaluating The Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, And Immunogenicity Of Single Escalating Doses Of Rn6g In Patients With Dry, Age-related Macular Degeneration (Amd)

The purpose of this study is to determine the safety and tolerability of RN6G in patients with dry, age-related macular degeneration.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

57

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85014
        • Retinal Consultants of AZ
      • Phoenix, Arizona, United States, 85013
        • Dedicated Phase 1
      • Phoenix, Arizona, United States, 85015
        • Insight Diagnostic Imaging Center
    • California
      • Glendale, California, United States, 91206
        • Amir Hedayati-Rad, MD
      • Inglewood, California, United States, 90301
        • United Medical Research Institute
      • Inglewood, California, United States, 90301
        • United Medical Imaging
      • Newport Beach, California, United States, 92660
        • California Pharmacy and Compounding Center
    • Michigan
      • Kalamazoo, Michigan, United States, 49007
        • Jasper Clinic, Inc.
      • Kalamazoo, Michigan, United States, 49048
        • Jonathan Rowe, MD
      • Kalamazoo, Michigan, United States, 49048
        • Ronald VanderLugt, MD
    • Texas
      • San Antonio, Texas, United States, 78240
        • Medical Center Ophthalmology Associates
      • San Antonio, Texas, United States, 78240
        • Retinal Consultants of San Antonio
      • San Antonio, Texas, United States, 78217
        • CEDRA Clinical Research, LLC
      • San Antonio, Texas, United States, 78217
        • Village Drive Imaging Center
      • San Antonio, Texas, United States, 78229
        • Specialty MRI
      • San Antonio, Texas, United States, 78233
        • Medical Center Ophthalmology Associates
    • Utah
      • Bountiful, Utah, United States, 84010
        • EZ Pass Rx
      • Salt Lake City, Utah, United States, 84106
        • Lifetree Clinical Research
      • Salt Lake City, Utah, United States, 84107
        • Rocky Mountain Eye Care Associates, LC
      • Salt Lake City, Utah, United States, 84124
        • Western Neurological Associates

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Be of non-childbearing potential.
  • Diagnosis of dry AMD as defined by the Age-Related Eye Disease Study (AREDS, 2005), including uni- or multi-focal GA, without foveal involvement.
  • BCVA of 20/320 or better in the worst eye.

Exclusion Criteria:

  • Diagnosis of exudative (wet) AMD, with subretinal or choroidal neovascular lesions.
  • Diagnosis or history of Alzheimer's disease, dementia or neurodegenerative disorders.
  • Diagnosis or recent history of clinically significant cerebrovascular disease.
  • Uncontrolled hypertension.
  • Uncontrolled Type 1 or Type 2 diabetes mellitus.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm 1
Biological: RN6G
intravenous, single dose, dose ranging from 0.3mg/kg up to a maximum of 40 mg/kg.
Biological: Placebo
intravenous, single dose with experimental dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and Severity of Ocular Adverse Events (AEs)
Time Frame: Baseline up to Day 168
AE: untoward medical occurrence in participant who received study drug without regard to causal relationship. Ocular AE was identified by spontaneous report or ocular examination: early treatment diabetic retinopathy study (ETDRS) best-corrected visual acuity (BCVA); low-luminance BCVA; pupillary light response, extra-ocular muscle movements, external examination of the eyelids and eyelashes, slit-lamp biomicroscopic examination (SLE) of all components of the anterior and posterior segments, intra-ocular pressure (IOP), and dilated ocular fundus examination of the vitreous and retina. AE was assessed according to severity; mild (did not interfere with participant's usual function), moderate (interfered to some extent with participant's usual function) and severe (interfered significantly with participant's usual function). Total number of participants with ocular (related to eye) AEs and severity was reported.
Baseline up to Day 168
Incidence and Severity of Systemic Adverse Events (AEs)
Time Frame: Baseline up to Day 168
AE: untoward medical occurrence in participant who received study drug without regard to causal relationship. Systemic AEs was identified by spontaneous report or physical and neurological examinations changes in vital signs, clinical laboratory abnormalities, 12-lead electrocardiograms (ECG), brain magnetic resonance imaging (MRI). AE was assessed according to severity; mild (did not interfere with participant's usual function), moderate (interfered to some extent with participant's usual function) and severe (interfered significantly with participant's usual function). Total number of participants with systemic (all AEs including eye-related) AEs and severity was reported.
Baseline up to Day 168

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of RN6G
Time Frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
AUC (0 - inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf). Participants who received RN6G were reported.
Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of RN6G
Time Frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t). Participants who received RN6G were reported.
Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Maximum Observed Plasma Concentration (Cmax) of RN6G
Time Frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Participants who received RN6G were reported.
Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Time to Reach Maximum Observed Plasma Concentration (Tmax) of RN6G
Time Frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Participants who received RN6G were reported.
Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Volume of Distribution (Vd) of RN6G
Time Frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Participants who received RN6G were reported and volume was measured as volume/kg of body weight.
Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Clearance (CL) of RN6G
Time Frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
CL is a quantitative measure of the rate at which a drug substance is removed from the body. Participants who received RN6G were reported and clearance was measured as mL/hr/kg of body weight.
Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Mean Residence Time (MRT) of RN6G
Time Frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
MRT was calculated as area under the moment curve from time 0 to extrapolated infinite time (AUMC[0 to inf])/area under the concentration effect curve from time 0 to extrapolated infinite time (AUC[0 to inf]). AUMC (0 to inf)= area under the moment curve from 0 to time t (AUMC 0-t) + [(Ct*tlast )/lamdaz ] + [Ct/(lamdaz )^2 ] where Ct= last measurable concentration, tlast= last measurable time, lamdaz= apparent terminal elimination rate constant. Participants who received RN6G were reported.
Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Plasma Terminal Half-life (t1/2) of RN6G
Time Frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Plasma terminal half-life is the time measured for the plasma concentration to decrease by one half. Participants who received RN6G were reported.
Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Maximum Observed Plasma Concentration (Cmax) of Amyloid (A) Beta(1-X)
Time Frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Amyloid (A) Beta(1-X)
Time Frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Area Under the Curve From Time Zero to Day 165 [AUC (0-165d)] of Amyloid (A) Beta(1-X)
Time Frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 165
AUC (0-165d)= Area under the plasma concentration versus time curve from time zero (pre-dose) to Day 165.
Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 165
Number of Participants With Anti-Drug Anti-body
Time Frame: Baseline up to Day 168
Participants tested positive for anti-drug anti-body on at least one or more occasions were reported.
Baseline up to Day 168

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2009

Primary Completion (ACTUAL)

July 1, 2011

Study Completion (ACTUAL)

July 1, 2011

Study Registration Dates

First Submitted

April 6, 2009

First Submitted That Met QC Criteria

April 6, 2009

First Posted (ESTIMATE)

April 7, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

March 31, 2015

Last Update Submitted That Met QC Criteria

March 20, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B1181001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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