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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00877032
First received: April 6, 2009
Last updated: March 20, 2015
Last verified: March 2015
  Purpose

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


Condition Intervention Phase
Age-Related Maculopathy
Age-Related Maculopathies
Eye Diseases
Retinal Degeneration
Macular Degeneration
Biological: RN6G
Biological: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Incidence and Severity of Ocular Adverse Events (AEs) [ Time Frame: Baseline up to Day 168 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    Participants tested positive for anti-drug anti-body on at least one or more occasions were reported.


Enrollment: 57
Study Start Date: April 2009
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00877032

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

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00877032     History of Changes
Other Study ID Numbers: B1181001
Study First Received: April 6, 2009
Results First Received: March 20, 2015
Last Updated: March 20, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Phase 1
Dry Age Related Macular Degeneration
RN6G

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

ClinicalTrials.gov processed this record on April 26, 2015