Clinical trial NCT04246866: First in Human Study to Evaluate the Safety and Tolerability of GEM103 in Geographic Atrophy Secondary to Dry Age Related Macular Degeneration
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Dry Age-related Macular Degeneration
Geographic Atrophy
Macular Degeneration
Retinal Disease
Retinal Degeneration
Lead sponsor: Gemini Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-01-29
Enrollment: 12
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. At least 50 years old at the time of signed informed consent
2. Able to cooperate sufficiently for adequate ophthalmic visual function testing and anatomic assessment and provide informed consent prior to initiation of any study procedure
3. Best corrected visual acuity (BCVA) in study eye between 5-45 letters
4. Confirmed diagnosis of central GA in the study eye and eligible total GA lesion size

Exclusion Criteria:

1. 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)
2. 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
3. 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
4. Female subjects must not be pregnant or lactating
5. Current use of medications known to be toxic to the lens, retina, or optic nerve

Primary outcomes:
measure: Incidence and severity of AEs/SAEs following drug administration
timeFrame: Up to 8 Weeks
Secondary outcomes:
measure: GEM103 concentrations in ocular fluids
timeFrame: Up to 8 Weeks
measure: Changes in complement factor levels compared to baseline after drug administration
timeFrame: Up to 8 Weeks
Other outcomes:
measure: Change from baseline in aqueous humor biomarker levels (in ng/mL) of complement factors
timeFrame: Up to 8 Weeks
measure: Change from baseline in clinical assessments including BCVA and LLVA scores as assessed by ETDRS Visual Acuity Score in number of letters
timeFrame: Up to 8 Weeks
measure: Change from baseline in clinical assessments including area of GA in mm2 as assessed by fundus imaging
timeFrame: Up to 8 Weeks
measure: Change in concentration of GEM103 in blood samples
timeFrame: Up to 8 Weeks
Locations:
city: Phoenix
country: United States
facility: Associated Retina Consultants
state: Arizona
city: Phoenix
country: United States
facility: Retinal Consultants of Arizona
state: Arizona
city: Bakersfield
country: United States
facility: California Retina Consultants
state: California
city: Beverly Hills
country: United States
facility: Retina Vitreous Associates
state: California
city: Oxnard
country: United States
facility: California Retina Consultants
state: California
city: Santa Barbara
country: United States
facility: California Retina Consultants
state: California
city: Santa Maria
country: United States
facility: California Retina Consultants
state: California
city: Augusta
country: United States
facility: Southeast Retina Center
state: Georgia
city: Indianapolis
country: United States
facility: Midwest Eye Institute
state: Indiana
city: Chesterfield
country: United States
facility: Pepose Vision Institute
state: Missouri
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Asheville
country: United States
facility: Western Carolina Retinal Associates
state: North Carolina
Study officials:
References:
citation: Khanani AM, Maturi RK, Bagheri N, Bakall B, Boyer DS, Couvillion SS, Dhoot DS, Holekamp NM, Jamal KN, Marcus DM, Pieramici D, Aziz AA, Patki KC, Bridges WZ Jr, Barone SB. A Phase I, Single Ascending Dose Study of GEM103 (Recombinant Human Complement Factor H) in Patients with Geographic Atrophy. Ophthalmol Sci. 2022 Apr 11;2(2):100154. doi: 10.1016/j.xops.2022.100154. eCollection 2022 Jun.