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

Phase 1
Completed
Conditions
Age-Related Maculopathy
Eye Diseases
Age-Related Maculopathies
Retinal Degeneration
Macular Degeneration
Interventions
Biological: RN6G
Biological: Placebo
Registration Number
NCT00877032
Lead Sponsor
Pfizer
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
57
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Arm 1Placebo-
Arm 1RN6G-
Primary Outcome Measures
NameTimeMethod
Incidence and Severity of Ocular Adverse Events (AEs)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.

Incidence and Severity of Systemic Adverse Events (AEs)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.

Secondary Outcome Measures
NameTimeMethod
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of RN6GPre-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.

Maximum Observed Plasma Concentration (Cmax) of RN6GPre-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.

Time to Reach Maximum Observed Plasma Concentration (Tmax) of RN6GPre-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.

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of RN6GPre-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.

Volume of Distribution (Vd) of RN6GPre-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.

Plasma Terminal Half-life (t1/2) of RN6GPre-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.

Area Under the Curve From Time Zero to Day 165 [AUC (0-165d)] of Amyloid (A) Beta(1-X)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.

Clearance (CL) of RN6GPre-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.

Mean Residence Time (MRT) of RN6GPre-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.

Maximum Observed Plasma Concentration (Cmax) of Amyloid (A) Beta(1-X)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)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
Number of Participants With Anti-Drug Anti-bodyBaseline up to Day 168

Participants tested positive for anti-drug anti-body on at least one or more occasions were reported.

Trial Locations

Locations (19)

Dedicated Phase 1

🇺🇸

Phoenix, Arizona, United States

Retinal Consultants of AZ

🇺🇸

Phoenix, Arizona, United States

Insight Diagnostic Imaging Center

🇺🇸

Phoenix, Arizona, United States

California Pharmacy and Compounding Center

🇺🇸

Newport Beach, California, United States

Jonathan Rowe, MD

🇺🇸

Kalamazoo, Michigan, United States

Ronald VanderLugt, MD

🇺🇸

Kalamazoo, Michigan, United States

Specialty MRI

🇺🇸

San Antonio, Texas, United States

Medical Center Ophthalmology Associates

🇺🇸

San Antonio, Texas, United States

Lifetree Clinical Research

🇺🇸

Salt Lake City, Utah, United States

Rocky Mountain Eye Care Associates, LC

🇺🇸

Salt Lake City, Utah, United States

United Medical Imaging

🇺🇸

Inglewood, California, United States

United Medical Research Institute

🇺🇸

Inglewood, California, United States

EZ Pass Rx

🇺🇸

Bountiful, Utah, United States

Jasper Clinic, Inc.

🇺🇸

Kalamazoo, Michigan, United States

Amir Hedayati-Rad, MD

🇺🇸

Glendale, California, United States

CEDRA Clinical Research, LLC

🇺🇸

San Antonio, Texas, United States

Village Drive Imaging Center

🇺🇸

San Antonio, Texas, United States

Retinal Consultants of San Antonio

🇺🇸

San Antonio, Texas, United States

Western Neurological Associates

🇺🇸

Salt Lake City, Utah, United States

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