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

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

Official Title
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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)

Conditions
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Age-Related Maculopathy, Age-Related Maculopathies, Eye Diseases, Retinal Degeneration, Macular Degeneration

Intervention / Treatment
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* Biological: RN6G
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Biological: RN6G<br>* intravenous, single dose, dose ranging from 0.3mg/kg up to a maximum of 40 mg/kg.<br>Biological: Placebo<br>* intravenous, single dose with experimental dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Dry Age Related Macular Degeneration, RN6G