Phase 1 N=24 Randomized Quadruple-blind Treatment

Safety And Tolerability Study Of RN6G In Subjects With Advanced Dry, Age-Related Macular Degeneration Including Geographic Atrophy

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

Bottom Line

View on ClinicalTrials.gov: NCT01003691 ↗

Enrolled (actual)

Serious AEs

8.3%

Results posted

May 2022

Primary outcome: Primary: Number of Participants With Toxicity or Intolerable Dose Criteria — 0; 0; 0; 0 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: RN6G (Biological); Placebo (Biological)
Age: Adult, Older Adult · 60+ yrs
Sex: All
Sponsor: Pfizer
Primary completion: Mar 2013

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Toxicity or Intolerable Dose Criteria	0; 0; 0; 0	—
PRIMARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) Categorized by Severity	1; 3; 0; 0; 5; 3	—
PRIMARY Number of Participants With Treatment Emergent Adverse Events (TEAEs): All Causalities and TEAEs Categorized by Causal Relationship to Study Drug	6; 6; 6; 6; 0; 0	—
PRIMARY Number of Participants With Ocular Treatment Emergent Adverse Events (TEAEs) Categorized by Severity	4; 4; 0; 2; 0; 0	—
PRIMARY Number of Participants With Ocular Treatment Emergent Adverse Events (TEAEs) Categorized by Causal Relationship to Study Drug	0; 0; 0; 0; 4; 4	—
PRIMARY Number of Participants With Systemic Treatment Emergent Adverse Events (TEAEs) Categorized by Severity	1; 3; 0; 0; 5; 3	—
PRIMARY Number of Participants With Systemic Treatment Emergent Adverse Events (TEAEs) Categorized by Causal Relationship to Study Drug	2; 0; 0; 0; 4; 6	—
PRIMARY Number of Participants With Positive Anti-Drug-Antibodies (ADA) and Neutralizing Antibodies (Nab)	0; 0; 0; 0	—
SECONDARY Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of RN6G (PF-04382923)	NA; NA; 50230; 140300; 213200	—
SECONDARY Maximum Observed Plasma Concentration (Cmax) of RN6G (PF-04382923)	142.9; 283.4; 524.1; 185.1; 439.8; 691.7	—
SECONDARY Minimum Observed Plasma Trough Concentration (Cmin) of RN6G (PF-04382923)	38.43; 119.7; 201.5	—
SECONDARY Plasma Concentration (Css) at Steady State of RN6G (PF-04382923)	74.75; 208.7; 317.2	—
SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of RN6G (PF-04382923)	1.49; 2.06; 2.17; 1.77; 2.05; 1.32	—
SECONDARY Volume of Distribution at Steady State (Vss) of RN6G (PF-04382923)	79.52; 88.04; 78.45	—
SECONDARY Mean Residence Time (MRT) of RN6G (PF-04382923)	818.1; 1274; 1121	—
SECONDARY Systemic Clearance (CL) of RN6G (PF-04382923)	0.09954; 0.07129; 0.07036	—
SECONDARY Plasma Decay Half-Life (t1/2) of RN6G (PF-04382923)	25.14; 42.00; 38.10	—
SECONDARY 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	371.8; 1596.8; 200.0; 386.5; 3340.5; 3205.5	—
SECONDARY 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	1194.4; 1032.9; 1973.6; 3.8; 1835.9; 1682.9	—
SECONDARY 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	160.4; 199.7; 209.2; 224.3; 1271.3; 1306.4	—
SECONDARY 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	838.8; 660.9; 752.8; 0.4; 1283.4; 1051.5	—
SECONDARY 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	34.0; 67.3; 46.9; 61.4; 65.3; 72.4	—
SECONDARY 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	199.0; 163.7; 340.2; -7.0; 257.8; 254.3	—
SECONDARY 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	128.0; 128.7; 127.3; 125.3; 11.3; -5.7	—
SECONDARY 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	64.2; 62.8; 66.5; 66.7; 1.7; -1.8	—
SECONDARY 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	36.40; 36.72; 36.87; 36.72; 0.30; 0.10	—
SECONDARY 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	81.74; 85.85; 78.58; 80.14; 0.25; -0.05	—
SECONDARY Change From Baseline Electrocardiogram (ECG) 12-lead at Day 1, 28, 56, 84, 112, 140, 168, 224, 304/ET	939.28; 962.44; 918.39; 928.33; 4.06; 24.94	—
SECONDARY Change From Baseline in Heart Rate at Day 1, 28, 56, 84, 112, 140, 168, 224, 304/ET	64.94; 63.17; 66.06; 65.44; -0.33; -1.67	—
SECONDARY 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	0.48; 0.58; 0.47; 0.52; -0.05; -0.12	—
SECONDARY Change From Baseline in Laboratory Assessments: Protein, Albumin, Hemoglobin at Day 28, 56, 84, 112, 140, 168, 224, 304/ET	7.07; 6.93; 6.97; 6.77; -0.25; -0.25	—
SECONDARY 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	22.2; 21.2; 25.5; 19.5; -1.2; -1.0	—
SECONDARY Change From Baseline in Laboratory Assessments: Sodium, Potassium, Chloride, Bicarbonate, Magnesium at Day 28, 56, 84, 112, 140, 168, 224, 304/ET	140.0; 137.8; 140.0; 141.7; -2.3; -0.3	—
SECONDARY Change From Baseline in Laboratory Assessments: Hematocrit at Day 28, 56, 84, 112, 140, 168, 224, 304/ET	41.70; 41.28; 40.78; 40.87; -1.18; -0.67	—
SECONDARY Change From Baseline in Laboratory Assessments: Red Blood Cells (RBCs) at Day 28, 56, 84, 112, 140, 168, 224, 304/ET	4.45; 4.48; 4.42; 4.43; -0.10; -0.07	—
SECONDARY 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	187.5; 209.3; 198.7; 204.2; 1.2; -10.7	—
SECONDARY Change From Baseline in Laboratory Assessments: Prothrombin Time (PT), Partial Thromboplastin Time at Day 28, 56, 84, 112, 140, 168, 224, 304/ET	11.82; 11.53; 11.10; 11.90; -0.55; -0.02	—
SECONDARY Change From Baseline in Laboratory Assessments: Urine Specific Gravity at Day 28, 56, 84, 112, 140, 168, 224, 304/ET	1.0197; 1.0150; 1.0138; 1.0242; -0.0018; 0.0012	—
SECONDARY Change From Baseline in Laboratory Assessments: Urine pH at Day 28, 56, 84, 112, 140, 168, 224, 304/ET	6.33; 5.92; 6.00; 6.00; -0.17; 0.42	—
SECONDARY Change From Baseline in Laboratory Assessments: Beta Interleukin-1, Interleukin-6, Alpha Tumor Necrosis Factor, Interferon (Gamma) at Day 28, 56, 84, 112, 140	0.00; 0.00; 0.32; 0.00; 0.00; 0.00	—
SECONDARY Change From Baseline in Laboratory Assessments: Component of Complement (C3A, C5B-9) at Day 28, 56, 84, 112, 140	970.3; 928.0; 1465.8; 1813.0; 560.2; 447.5	—
SECONDARY Change From Baseline in Laboratory Assessments: Cluster of Differentiation 4 (C4D) at Day 28, 56, 84, 112, 140	2.692; 3.720; 1.078; -1.720; -1.503; -1.320	—
SECONDARY Change From Baseline in Prothrombin Time (PT) International Normalized Ratio (INR) at Day 28, 56, 84, 112, 140, 168, 224, 304/ET	0.995; 0.972; 0.933; 1.017; -0.047; -0.003	—
SECONDARY Change From Electrocardiogram (ECG): QTcF Interval (Fridericia's Correction) at Day 1, 28, 56, 84, 112, 140, 168, 224, 304/ET	414.22; 427.89; 420.56; 412.06; 0.56; -1.50	—

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

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Data sourced from ClinicalTrials.gov (NCT01003691). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.