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

Macular Degeneration Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00877032
• Other study ID #: B1181001
• Status: Completed
• Phase: Phase 1
• First received: April 6, 2009
• Last updated: March 20, 2015
• Start date: April 2009
• Est. completion date: July 2011

Study information

• Verified date: March 2015
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Age-Related Maculopathies
• Age-Related Maculopathy
• Eye Diseases
• Macular Degeneration
• Retinal Degeneration

Intervention

Biological:
• RN6G
intravenous, single dose, dose ranging from 0.3mg/kg up to a maximum of 40 mg/kg.
• Placebo
intravenous, single dose with experimental dose.

Locations

Country	Name	City	State
United States	EZ Pass Rx	Bountiful	Utah
United States	Amir Hedayati-Rad, MD	Glendale	California
United States	United Medical Imaging	Inglewood	California
United States	United Medical Research Institute	Inglewood	California
United States	Jasper Clinic, Inc.	Kalamazoo	Michigan
United States	Jonathan Rowe, MD	Kalamazoo	Michigan
United States	Ronald VanderLugt, MD	Kalamazoo	Michigan
United States	California Pharmacy and Compounding Center	Newport Beach	California
United States	Dedicated Phase 1	Phoenix	Arizona
United States	Insight Diagnostic Imaging Center	Phoenix	Arizona
United States	Retinal Consultants of AZ	Phoenix	Arizona
United States	Lifetree Clinical Research	Salt Lake City	Utah
United States	Rocky Mountain Eye Care Associates, LC	Salt Lake City	Utah
United States	Western Neurological Associates	Salt Lake City	Utah
United States	CEDRA Clinical Research, LLC	San Antonio	Texas
United States	Medical Center Ophthalmology Associates	San Antonio	Texas
United States	Medical Center Ophthalmology Associates	San Antonio	Texas
United States	Retinal Consultants of San Antonio	San Antonio	Texas
United States	Specialty MRI	San Antonio	Texas
United States	Village Drive Imaging Center	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and Severity of Ocular Adverse Events (AEs)	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	Yes
Primary	Incidence and Severity of Systemic Adverse Events (AEs)	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	Yes
Secondary	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of RN6G	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	No
Secondary	Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of RN6G	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	No
Secondary	Maximum Observed Plasma Concentration (Cmax) of RN6G	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	No
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of RN6G	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	No
Secondary	Volume of Distribution (Vd) of RN6G	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	No
Secondary	Clearance (CL) of RN6G	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	No
Secondary	Mean Residence Time (MRT) of RN6G	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	No
Secondary	Plasma Terminal Half-life (t1/2) of RN6G	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	No
Secondary	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	No
Secondary	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	No
Secondary	Area Under the Curve From Time Zero to Day 165 [AUC (0-165d)] of Amyloid (A) Beta(1-X)	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	No
Secondary	Number of Participants With Anti-Drug Anti-body	Participants tested positive for anti-drug anti-body on at least one or more occasions were reported.	Baseline up to Day 168	Yes

External Links

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