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

Overview

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

Full Title of Study: “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)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Prevention
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: July 2011

Interventions

  • 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.

Arms, Groups and Cohorts

  • Experimental: Arm 1

Clinical Trial Outcome Measures

Primary Measures

  • 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.
  • 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.

Secondary Measures

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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
  • 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
  • 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.
  • 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.

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Pfizer
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Pfizer CT.gov Call Center, Study Director, Pfizer

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