Clinical trial NCT01003691: Safety And Tolerability Study Of RN6G In Subjects With Advanced Dry, Age-Related Macular Degeneration Including Geographic Atrophy
Official title: A PHASE 1, DOUBLE-MASKED, PLACEBO-CONTROLLED STUDY EVALUATING THE SAFETY, TOLERABILITY, IMMUNOGENICITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF MULTIPLE ESCALATING DOSAGES OF RN6G (PF-04382923) IN SUBJECTS WITH ADVANCED DRY, AGE-RELATED MACULAR DEGENERATION (AMD) INCLUDING GEOGRAPHIC ATROPHY
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Age-Related Maculopathy
Age-Related Maculopathies
Eye Diseases
Retinal Degeneration
Macular Degeneration
Keywords: Phase 1b Advanced Dry Age-Related Macular Degeneration RN6G
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2009-10-29
Enrollment: 24
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and tolerability of multiple doses of RN6G in subjects with advanced dry, age-related macular degeneration including geographic atrophy.


Eligibility criteria: Inclusion Criteria:

* Be of non-child bearing potential
* Diagnosis of dry AMD including uni- or multi-focal geographic atrophy without foveal involvement
* BCVA of 20/50 or better in the study eye

Exclusion Criteria:

* Evidence of ocular disease other than advanced AMD or GA in the study eye
* History or diagnosis of exudative (wet) AMD, with subretinal or choroidal neovascular lesions in the study eye
* Presence of disease or condition that might compromise the cardiovascular, hematological, renal, hepatic, pulmonary, endocrine, central nervous immune, or gastrointestinal system
* Requires ocular or systemic medications that are known to be toxic to the lens, retina or optic nerve

Primary outcomes:
measure: Number of Participants With Toxicity or Intolerable Dose Criteria
timeFrame: Baseline up to Day 304/End of Treatment (ET)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Categorized by Severity
timeFrame: Baseline up to Day 304/ET
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs): All Causalities and TEAEs Categorized by Causal Relationship to Study Drug
timeFrame: Baseline up to Day 304/ET
measure: Number of Participants With Ocular Treatment Emergent Adverse Events (TEAEs) Categorized by Severity
timeFrame: Baseline up to Day 304/ET
measure: Number of Participants With Ocular Treatment Emergent Adverse Events (TEAEs) Categorized by Causal Relationship to Study Drug
timeFrame: Baseline up to Day 304/ET
measure: Number of Participants With Systemic Treatment Emergent Adverse Events (TEAEs) Categorized by Severity
timeFrame: Baseline up to Day 304/ET
measure: Number of Participants With Systemic Treatment Emergent Adverse Events (TEAEs) Categorized by Causal Relationship to Study Drug
timeFrame: Baseline up to Day 304/ET
measure: Number of Participants With Positive Anti-Drug-Antibodies (ADA) and Neutralizing Antibodies (Nab)
timeFrame: Baseline up to Day 304/ET
Secondary outcomes:
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of RN6G (PF-04382923)
timeFrame: Pre-dose: 0 hour on Day 1, 28, 56, 84,112,140; Post-dose: 1, 2, 4, 24, 168, 336 hours on Day 1 and 1, 2, 4, 24, 336, 672 hours on Day 140
measure: Maximum Observed Plasma Concentration (Cmax) of RN6G (PF-04382923)
timeFrame: Pre-dose: 0 hour on Day 1, 28, 56, 84,112,140; Post-dose: 1, 2, 4, 24, 168, 336 hours on Day 1 and 1, 2, 4, 24, 336, 672, 1992, 3936 hours on Day 140
measure: Minimum Observed Plasma Trough Concentration (Cmin) of RN6G (PF-04382923)
timeFrame: Pre-dose: 0 hour on Day 1, 28, 56, 84,112,140; Post-dose: 1, 2, 4, 24, 336, 672, 1992, 3936 hours on Day 140
measure: Plasma Concentration (Css) at Steady State of RN6G (PF-04382923)
timeFrame: Pre-dose: 0 hour on Day 1, 28, 56, 84,112,140; Post-dose: 1, 2, 4, 24, 336, 672, 1992, 3936 hours on Day 140
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RN6G (PF-04382923)
timeFrame: Pre-dose: 0 hour on Day 1, 28, 56, 84,112,140; Post-dose: 1, 2, 4, 24, 168, 336 hours on Day 1 and 1, 2, 4, 24, 336, 672, 1992, 3936 hours on Day 140
measure: Volume of Distribution at Steady State (Vss) of RN6G (PF-04382923)
timeFrame: Pre-dose: 0 hour on Day 1, 28, 56, 84,112,140; Post-dose: 1, 2, 4, 24, 336, 672, 1992, 3936 hours on Day 140
measure: Mean Residence Time (MRT) of RN6G (PF-04382923)
timeFrame: Pre-dose: 0 hour on Day 1, 28, 56, 84,112,140; Post-dose: 1, 2, 4, 24, 336, 672, 1992, 3936 hours on Day 140
measure: Systemic Clearance (CL) of RN6G (PF-04382923)
timeFrame: Pre-dose: 0 hour on Day 1, 28, 56, 84,112,140; Post-dose: 1, 2, 4, 24, 336, 672, 1992, 3936 hours on Day 140
measure: Plasma Decay Half-Life (t1/2) of RN6G (PF-04382923)
timeFrame: Pre-dose: 0 hour on Day 1, 28, 56, 84,112,140; Post-dose: 1, 2, 4, 24, 336, 672, 1992, 3936 hours on Day 140
measure: Change From Baseline in Plasma Total Amyloid (A) Beta (1-X) Concentration at Day 1, 2, 7, 14, 19, 28, 45, 56, 75, 84, 103, 112, 131, 140, 141, 154, 168, 224, 304/ET
timeFrame: Baseline, Day 1 (1 hour, 2 hours, 4 hours post dose), 2, 7, 14, 19, 28, 45, 56, 75, 84, 103, 112, 131, 140 (predose, 1 hour, 2 hours, 4 hours post dose), 141, 154, 168, 224, 304/ET
measure: Percent Change From Baseline in Plasma Total Amyloid (A) Beta (1-X) Concentration at Day 1, 2, 7, 14, 19, 28, 45, 56, 75, 84, 103, 112, 131, 140, 141, 154, 168, 224, 304/ET
timeFrame: Day 1 (1 hour , 2 hours, 4 hours post dose), 2, 7, 14, 19, 28, 45, 56, 75, 84, 103, 112, 131, 140 (predose, 1 hour, 2 hours, 4 hours post dose), 141, 154, 168, 224, 304/ET
measure: Change From Baseline in Plasma Amyloid (A) Beta (1-40) Concentration at Day 1, 2, 7, 14, 19, 28, 45, 56, 75, 84, 103, 112, 131, 140, 141, 154, 168, 224, 304/ET
timeFrame: Baseline, Day 1 (1 hour , 2 hours, 4 hours post dose), 2, 7, 14, 19, 28, 45, 56, 75, 84, 103, 112, 131, 140 (predose, 1 hour, 2 hours, 4 hours post dose), 141, 154, 168, 224, 304/ET
measure: Percent Change From Baseline in Plasma Amyloid (A) Beta (1-40) Concentrations at Day 1, 2, 7, 14, 19, 28, 45, 56, 75, 84, 103, 112, 131, 140, 141, 154, 168, 224, 304/ET
timeFrame: Day 1 (1 hour, 2 hours, 4 hours post dose), 2, 7, 14, 19, 28, 45, 56, 75, 84, 103, 112, 131, 140 (predose, 1 hour, 2 hours, 4 hours post dose), 141, 154, 168, 224, 304/ET
measure: Change From Baseline in Plasma Amyloid (A) Beta (1-42) Concentration at Day 1, 2, 7, 14, 19, 28, 45, 56, 75, 84, 103, 112, 131, 140, 141, 154, 168, 224, 304/ET
timeFrame: Baseline, Day 1 (1 hour, 2 hours, 4 hours post dose), 2, 7, 14, 19, 28, 45, 56, 75, 84, 103, 112, 131, 140 (predose, 1 hour, 2 hours, 4 hours post dose), 141, 154, 168, 224, 304/ET
measure: Percent Change From Baseline in Plasma Amyloid (A) Beta (1-42) Concentrations at Day 1, 2, 7, 14, 19, 28, 45, 56, 75, 84, 103, 112, 131, 140, 141, 154, 168, 224, 304/ET
timeFrame: Day 1 (1 hour, 2 hours, 4 hours post dose), 2, 7, 14, 19, 28, 45, 56, 75, 84, 103, 112, 131, 140 (predose, 1 hour, 2 hours, 4 hours post dose), 141, 154, 168, 224, 304/ET
measure: Change From Baseline in Vital Signs at Day 1, 2, 7, 14, 19, 28, 45, 56, 75, 84, 103, 112, 131, 140, 141, 154, 168, 224, 304/ET: Systolic and Diastolic Blood Pressure
timeFrame: Baseline, 1 and 4 hour (H) post-dose on Day 1; 24 H post-dose on Days 2 and 141; pre-dose and 4 - 8 H post-dose on Days 28, 56, 84, 112; pre-dose and 1, 4 H post-dose on Day 140; Day 7, 14, 19, 45, 75, 103;131, 141, 154 168, 224 and 304/ET
measure: Change From Baseline in Vital Signs at Day 1, 2, 7, 14, 19, 28, 45, 56, 75, 84, 103, 112, 131, 140, 141, 154, 168, 224, 304/ET: Pulse Rate
timeFrame: Baseline, 1 and 4 H post-dose on Day 1; 24 H post-dose on Days 2 and 141; pre-dose and 4 - 8 H post-dose on Days 28, 56, 84, 112; pre-dose and 1, 4 H post-dose on Day 140; Day 7, 14, 19, 45, 75, 103;131, 141, 154 168, 224 and 304/ET
measure: Change From Baseline in Vital Signs at Day 1, 2, 7, 14, 19, 28, 45, 56, 75, 84, 103, 112, 131, 140, 141, 154, 168, 224, 304/ET: Temperature
timeFrame: Baseline, 1 and 4 H post-dose on Day 1; 24 H post-dose on Days 2 and 141; pre-dose and 4 - 8 H post-dose on Days 28, 56, 84, 112; pre-dose and 1, 4 H post-dose on Day 140; Day 7, 14, 19, 45, 75, 103;131, 141, 154 168, 224 and 304/ET
measure: Change From Baseline in Vital Signs at Day 1, 2, 7, 14, 19, 28, 45, 56, 75, 84, 103, 112, 131, 140, 141, 154, 168, 224, 304/ET: Weight
timeFrame: Baseline, 1 and 4 H post-dose on Day 1; 24 H post-dose on Days 2 and 141; pre-dose and 4 - 8 H post-dose on Days 28, 56, 84, 112; pre-dose and 1, 4 H post-dose on Day 140; Day 7, 14, 19, 45, 75, 103;131, 141, 154 168, 224 and 304/ET
measure: Change From Baseline Electrocardiogram (ECG) 12-lead at Day 1, 28, 56, 84, 112, 140, 168, 224, 304/ET
timeFrame: Baseline, 1 and 4 H post-dose on Day 1; pre-dose on Days 28, 56, 84, 112; pre-dose and 1, 4 H post-dose on Day 140; Day 168, 224 and 304/ET
measure: Change From Baseline in Heart Rate at Day 1, 28, 56, 84, 112, 140, 168, 224, 304/ET
timeFrame: Baseline, 1 and 4 H post-dose on Day 1; pre-dose on Days 28, 56, 84, 112; pre-dose and 1, 4 H post-dose on Day 140; Day 168, 224 and 304/ET
measure: Change From Baseline in Bilirubin, Direct Bilirubin, Blood Urea Nitrogen, Creatinine, Uric Acid, Calcium, Phosphate, Glucose, Cholesterol, Triglycerides, Immunoglobulin G, Immunoglobulin A, Immunoglobulin M at Day 28, 56, 84, 112, 140, 168, 224, 304/ET
timeFrame: Baseline, Day 28, 56, 84, 112, 140, 168, 224, 304/ET
measure: Change From Baseline in Laboratory Assessments: Protein, Albumin, Hemoglobin at Day 28, 56, 84, 112, 140, 168, 224, 304/ET
timeFrame: Baseline, Day 28, 56, 84, 112, 140, 168, 224, 304/ET
measure: Change From Baseline in Laboratory Assessments: Aspartate Aminotransferase, Creatine Kinase, Alanine Aminotransferase, Gamma Glutamyl Transferase (GGT), Lactate Dehydrogenase, Alkaline Phosphatase at Day 28, 56, 84, 112, 140, 168, 224, 304/ET
timeFrame: Baseline, Day 28, 56, 84, 112, 140, 168, 224, 304/ET
measure: Change From Baseline in Laboratory Assessments: Sodium, Potassium, Chloride, Bicarbonate, Magnesium at Day 28, 56, 84, 112, 140, 168, 224, 304/ET
timeFrame: Baseline, Day 28, 56, 84, 112, 140, 168, 224, 304/ET
measure: Change From Baseline in Laboratory Assessments: Hematocrit at Day 28, 56, 84, 112, 140, 168, 224, 304/ET
timeFrame: Baseline, Day 28, 56, 84, 112, 140, 168, 224, 304/ET
measure: Change From Baseline in Laboratory Assessments: Red Blood Cells (RBCs) at Day 28, 56, 84, 112, 140, 168, 224, 304/ET
timeFrame: Baseline, Day 28, 56, 84, 112, 140, 168, 224, 304/ET
measure: Change From Baseline in Laboratory Assessments: Platelets, White Blood Cells (WBCs), Neutrophils (Absolute), Eosinophils (Absolute), Basophils (Absolute), Lymphocytes (Absolute), Monocytes (Absolute) at Day 28, 56, 84, 112, 140, 168, 224, 304/ET
timeFrame: Baseline, Day 28, 56, 84, 112, 140, 168, 224, 304/ET
measure: Change From Baseline in Laboratory Assessments: Prothrombin Time (PT), Partial Thromboplastin Time at Day 28, 56, 84, 112, 140, 168, 224, 304/ET
timeFrame: Baseline, Day 28, 56, 84, 112, 140, 168, 224, 304/ET
measure: Change From Baseline in Laboratory Assessments: Urine Specific Gravity at Day 28, 56, 84, 112, 140, 168, 224, 304/ET
timeFrame: Baseline, Day 28, 56, 84, 112, 140, 168, 224, 304/ET
measure: Change From Baseline in Laboratory Assessments: Urine pH at Day 28, 56, 84, 112, 140, 168, 224, 304/ET
timeFrame: Baseline, Day 28, 56, 84, 112, 140, 168, 224, 304/ET
measure: Change From Baseline in Laboratory Assessments: Beta Interleukin-1, Interleukin-6, Alpha Tumor Necrosis Factor, Interferon (Gamma) at Day 28, 56, 84, 112, 140
timeFrame: Baseline, Day 28, 56, 84, 112, 140
measure: Change From Baseline in Laboratory Assessments: Component of Complement (C3A, C5B-9) at Day 28, 56, 84, 112, 140
timeFrame: Baseline, Day 28, 56, 84, 112, 140
measure: Change From Baseline in Laboratory Assessments: Cluster of Differentiation 4 (C4D) at Day 28, 56, 84, 112, 140
timeFrame: Baseline, Day 28, 56, 84, 112, 140
measure: Change From Baseline in Prothrombin Time (PT) International Normalized Ratio (INR) at Day 28, 56, 84, 112, 140, 168, 224, 304/ET
timeFrame: Baseline, Day 28, 56, 84, 112, 140, 168, 224, 304/ET
measure: Change From Electrocardiogram (ECG): QTcF Interval (Fridericia's Correction) at Day 1, 28, 56, 84, 112, 140, 168, 224, 304/ET
timeFrame: Baseline, 1 and 4 H post-dose on Day 1; pre-dose on Days 28, 56, 84, 112; pre-dose and 1, 4 H post-dose on Day 140; Day 168, 224 and 304/ET
Other outcomes:
Locations:
city: Campbell
country: United States
facility: Retinal Diagnostic Center
state: California
city: Los Gatos
country: United States
facility: American Institute of Research (Administrative Only)
state: California
city: San Jose
country: United States
facility: Neurology Center Rai Kumar
state: California
city: San Jose
country: United States
facility: Harmeet Sachdev, MD, FAAN
state: California
city: San Jose
country: United States
facility: Santa Clara Drug
state: California
city: Tampa
country: United States
facility: Retina Associates of Florida, PA
state: Florida
city: Tampa
country: United States
facility: Hoye's Pharmacy
state: Florida
city: Augusta
country: United States
facility: Ranjit K. Sethi, MD, PC
state: Georgia
city: Augusta
country: United States
facility: Clinical Specialists, LLC
state: Georgia
city: Augusta
country: United States
facility: Southeast Retina Center, PC
state: Georgia
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: West Columbia
country: United States
facility: Hawthorne Pharmacy
state: South Carolina
city: West Columbia
country: United States
facility: Jay Markowitz and Associates
state: South Carolina
city: West Columbia
country: United States
facility: Palmetto Retina Center, LLC
state: South Carolina
city: West Columbia
country: United States
facility: South Carolina Neurological
state: South Carolina
city: Abilene
country: United States
facility: National Central Pharmacy
state: Texas
city: Abilene
country: United States
facility: Abilene Surgery Center
state: Texas
city: Abilene
country: United States
facility: Heart and Vascular Institute
state: Texas
city: Abilene
country: United States
facility: Retina Research Institute of Texas
state: Texas
city: Austin
country: United States
facility: Brian B. Berger, MD, PA
state: Texas
city: Austin
country: United States
facility: Retina Research Center, PLLC
state: Texas
city: Austin
country: United States
facility: Sleep Medicine Consultants
state: Texas
city: Cedar Park
country: United States
facility: Specialty Compounding
state: Texas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: