First in Human Study to Evaluate the Safety and Tolerability of GEM103 in Geographic Atrophy Secondary to Dry Age Related Macular Degeneration

Study Overview
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Brief Summary
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The study is designed to identify the maximum tolerated dose (MTD) for intravitreal (IVT) administration of GEM103 in subjects with geographic atrophy (GA) secondary to dry AMD. Safety and tolerability of a single dose of GEM103 will be assessed based on the occurrence of dose-limiting toxicities (DLTs). Each subject will be followed for safety, pharmacokinetic (PK), clinical, and biomarker evaluations. Three escalating dose cohorts are planned.

Detailed Description
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This is a Phase 1, multicenter, open-label, single-dose, dose-escalation study in subjects with GA secondary to dry AMD to investigate the safety, tolerability, pharmacodynamics (PD), and immunogenicity of IVT injections of GEM103 to a single eye. The study is designed to identify the MTD for IVT administration of GEM103. Safety and tolerability of a single dose of GEM103 will be assessed based on the occurrence of DLTs. Three escalating dose cohorts are planned. Subjects will undergo clinical and ophthalmic assessments for inclusion eligibility into the study. Enrolled subjects will receive GEM103 and be followed for safety, PK, clinical, and biomarker evaluations.

Official Title
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A Phase 1, Multicenter, Open-label, Single-dose, Dose-escalation Study in Patients With Geographic Atrophy (GA) Secondary to Dry Age-related Macular Degeneration (AMD) to Evaluate the Safety, Tolerability, Pharmacodynamics, and Immunogenicity of Intravitreal Injections of GEM103

Conditions
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Dry Age-related Macular Degeneration, Geographic Atrophy, Macular Degeneration, Retinal Disease, Retinal Degeneration

Intervention / Treatment
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* Biological: GEM103


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 50 years old at the time of signed informed consent Able to cooperate sufficiently for adequate ophthalmic visual function testing and anatomic assessment and provide informed consent prior to initiation of any study procedure Best corrected visual acuity (BCVA) in study eye between 5-45 letters Confirmed diagnosis of central GA in the study eye and eligible total GA lesion size Exclusion Criteria: Presence of the following ocular conditions - in the study eye: Exudative AMD or choroidal neovascularization (CNV) Any ocular disease or condition that could impact the subject's ability to participate in the study or be a contraindication to IVT injection Any intraocular surgery (with the exception of intraocular lens replacement surgery more than 3 months prior to consent) Presence of any of the following ocular conditions - in either eye: History of herpetic infection Ongoing treatment with antiangiogenic therapies in the fellow eye or completed treatment in the study eye Any prior or ongoing medical condition (e.g. ocular other than dry AMD, systemic, psychiatric) or clinically significant screening laboratory value that may present a safety risk, interfere with study compliance, interfere with consistent study follow-up, or confound data interpretation throughout the longitudinal follow-up period Female subjects must not be pregnant or lactating Current use of medications known to be toxic to the lens, retina, or optic nerve

Ages Eligible for Study
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Minimum Age: 50 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: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose 1<br>A single dose of GEM103 will be administered via intravitreal injection. This arm will be the lowest dose of GEM103 | Biological: GEM103<br>* GEM103<br>|
| Experimental: Dose 2<br>A single dose of GEM103 will be administered via intravitreal injection. This arm will be the medium dose of GEM103 | Biological: GEM103<br>* GEM103<br>|
| Experimental: Dose 3<br>A single dose of GEM103 will be administered via intravitreal injection. This arm will be a higher dose of GEM103 | Biological: GEM103<br>* GEM103<br>|
| Experimental: Dose 4<br>A single dose of GEM103 will be administered via intravitreal injection. This arm will be the highest (extension) dose of GEM103 | Biological: GEM103<br>* GEM103<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of AEs/SAEs following drug administration |  | Up to 8 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GEM103 concentrations in ocular fluids |  | Up to 8 Weeks | 
| Changes in complement factor levels compared to baseline after drug administration |  | Up to 8 Weeks |