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

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

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.

Study Overview

• Status: Completed
• Conditions: Macular Degeneration; Retinal Degeneration; Geographic Atrophy; Dry Age-related Macular Degeneration; Retinal Disease
• Intervention / Treatment: Biological: GEM103

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85020
      • Associated Retina Consultants
    • Phoenix, Arizona, United States, 85053
      • Retinal Consultants of Arizona
  • California
    • Bakersfield, California, United States, 93309
      • California Retina Consultants
    • Beverly Hills, California, United States, 90211
      • Retina Vitreous Associates
    • Oxnard, California, United States, 93036
      • California Retina Consultants
    • Santa Barbara, California, United States, 93103
      • California Retina Consultants
    • Santa Maria, California, United States, 93454
      • California Retina Consultants
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • Midwest Eye Institute
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Pepose Vision Institute
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Western Carolina Retinal Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Time Frame
Change from baseline in aqueous humor biomarker levels (in ng/mL) of complement factors	Up to 8 Weeks
Change from baseline in clinical assessments including BCVA and LLVA scores as assessed by ETDRS Visual Acuity Score in number of letters	Up to 8 Weeks
Change from baseline in clinical assessments including area of GA in mm2 as assessed by fundus imaging	Up to 8 Weeks
Change in concentration of GEM103 in blood samples	Up to 8 Weeks

Collaborators and Investigators

• Sponsor: Gemini Therapeutics, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 19, 2019
• Primary Completion (ACTUAL): October 21, 2020
• Study Completion (ACTUAL): October 21, 2020

Study Registration Dates

• First Submitted: January 6, 2020
• First Submitted That Met QC Criteria: January 28, 2020
• First Posted (ACTUAL): January 29, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 11, 2021
• Last Update Submitted That Met QC Criteria: February 9, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Pathological Conditions, Anatomical; Eye Diseases, Hereditary; Macular Degeneration; Retinal Diseases; Geographic Atrophy; Atrophy; Retinal Degeneration
• Other Study ID Numbers: GEM-CL-10301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No