A Multiple Dose Study of Repeat Intravitreal Injections of GEM103 in Neovascular Age-related Macular Degeneration

Phase 2

Terminated

• Conditions: Neovascular Age-related Macular Degeneration; Retinal Degeneration; Macular Degeneration; Retinal Disease
• Interventions: Biological: GEM103; Drug: Sham; Drug: Aflibercept

• Registration Number: NCT04684394
• Lead Sponsor: Gemini Therapeutics, Inc.

Brief Summary

This study is designed to investigate the safety and tolerability of GEM103 IVT injection + standard of care vs. sham + standard of care.

Detailed Description

This is a Phase 2a, multi-center, multiple dose study in subjects with Neovascular Age-related Macular Degeneration (nAMD) to investigate the safety and tolerability of GEM103 IVT injection + standard of care vs. sham + standard of care.

Subjects will undergo clinical and ophthalmic assessments for determination of inclusion in the study and who meet all eligibility criteria will be enrolled.

Study Timeline

• Study First Submitted: 2020-12-21
• Study First Submitted QC: 2020-12-21
• Study First Posted: 2020-12-24
• Study Start: 2020-12-29
• Primary Completion: 2022-01-10
• Study Completion: 2022-02-18
• Status Verified: 2022-03
• Results First Submitted: 2022-10-04
• Results First Submitted QC: 2022-10-04
• Last Update Submitted: 2022-10-04
• Results First Posted: 2022-10-31
• Last Update Posted: 2022-10-31

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. At least 50 years old at the time of signed informed consent

2. Choroidal neovascularization (CNV) related to nAMD with the following features, as determined by the Image Reading Center

   1. Maximum CNV lesion size of 12 disc areas
   2. Subretinal hemorrhage less than or equal to (<=) 50% of lesion size

3. On aflibercept treatment prior to Day 1

4. Best Corrected Visual Acuity (BCVA) in the study eye between 24 to 75 letters using EDTRS

Exclusion Criteria

1. Presence of the following ocular conditions in the study eye:

   1. Any active ocular disease or condition that impact the subject to participate in the study or be a contraindication of IVT injections
   2. Any intraocular surgery
   3. Aphakia or complete absence of the posterior capsule
   4. Prior corneal transplant
   5. Scar or fibrosis greater than or equal to (>=) 50% of CNV lesion or involving center of fovea

2. Presence of any of the following ocular conditions in either eye:

   1. History of herpetic infection, idiopathic polypoidal choroidal vasculopathy (PCV), pathologic myopia, central serous chorioretinopathy (CSCR), adult onset foveal pattern dystrophy
   2. Concurrent disease that could require medical or surgical intervention during the study period
   3. Active/suspected ocular/periocular infection or active intraocular inflammation
   4. History of idiopathic or autoimmune-associated uveitis

3. Any prior or ongoing medical condition 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. Has experienced a cardiovascular or cerebrovascular event within 12 months of informed consent

5. Females must not be pregnant or lactating

6. Current use of medications known to be toxic to the lens, retina or optic nerve

7. Use of any investigational new drug or other experimental treatment in the last 6 months prior to Day 1, and/or receipt of any prior gene therapy or ocular device implantation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SoC + Sham	Sham	Participants were administered SoC therapy defined as aflibercept (2mg/50mcL) first, followed by the Sham injection 15 minutes later. Administration occurred EOM for a total of 6 doses during the 12-month study period.
SoC + GEM103	GEM103	Participants were administered SoC therapy defined as aflibercept (2 milligram \[mg\]/50 microliter \[mcL\]) first, followed by GEM103 (500 microgram \[mcg\]/50mcL) 15 minutes later. Administration occurred every other month (EOM) for a total of 6 doses during the 12-month study period.
SoC + GEM103	Aflibercept	Participants were administered SoC therapy defined as aflibercept (2 milligram \[mg\]/50 microliter \[mcL\]) first, followed by GEM103 (500 microgram \[mcg\]/50mcL) 15 minutes later. Administration occurred every other month (EOM) for a total of 6 doses during the 12-month study period.
SoC + Sham	Aflibercept	Participants were administered SoC therapy defined as aflibercept (2mg/50mcL) first, followed by the Sham injection 15 minutes later. Administration occurred EOM for a total of 6 doses during the 12-month study period.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Non-ocular TEAEs	Baseline up to Week 48	An adverse event (AE) was defined as any untoward medical occurrence or worsening of a pre-existing condition in a participant administered a pharmaceutical product during the study, whether related or not to the study medication. TEAEs were defined as AE that occurred on or after the date and time of study drug administration or those that first occurred pre-dose but worsened by increase in occurrence or severity after study drug administration. Number of participants with non-ocular TEAEs were reported.
Number of Participants With Ocular Treatment-emergent Adverse Events (TEAEs)	Baseline up to Week 48	An adverse event (AE) was defined as any untoward medical occurrence or worsening of a pre-existing condition in a participant administered a pharmaceutical product during the study, whether related or not to the study medication. TEAEs were defined as AE that occurred on or after the date and time of study drug administration or those that first occurred pre-dose but worsened by increase in occurrence or severity after study drug administration. Number of participants with ocular TEAEs in study eye and fellow eye were reported.
Number of Participants With Abnormal Ophthalmic Examination Findings	Baseline up to Week 48	Ophthalmoscopy examination was performed in each eye with findings reported for Vitreous, Optic Nerve, Macula, Retina Periphery. Lens Status and Opacification (Phakic and Pseudophakic) was also performed. Nuclear Cataract, Cortical Cataract, and Posterior Subcapsular Cataract categories was further summarized by severity grade. Ocular biomicroscopic examination was performed with findings reported for Lids/Lashes, Conjunctiva, Cornea, Anterior Chamber, and Iris/Pupil.
Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Low Luminance Visual Acuity (LLVA)	Baseline up to Week 48	Visual function assessments included LLVA assessment in each eye by ETDRS letters. LLVA was measured on the ETDRS chart at a starting distance of 4 meters. The letter score ranges from 0 (worse score) to 100 (best score), and a gain in LLVA from baseline indicates an improvement in visual acuity. For each participant, an average value was calculated across the three visits, and this averaged value was used to determine if the endpoint was met. The results were summarized as the percentage of participants with increase in LLVA with \>=15, \>=10, \>=5 letters from the baseline per treatment arm who met the endpoint.
Mean Change From Baseline in Minnesota Low-vision Reading (MNRead) Test at Week 48	Baseline, Week 48	The MNRead acuity cards are continuous-text reading acuity cards suitable for measuring the reading acuity and reading speed of normal and low-vision participants. Formula for reading speed words per minute (wpm): reading speed is equal to 60\*(10 - errors)/ (time in seconds). A negative change from baseline indicates a decrease in the reading speed; disease worsening.
Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Best Corrected Visual Acuity (BCVA)	Baseline up to Week 48	Visual function assessments included BCVA assessment in each eye by Early Treatment Diabetic Retinopathy Study (ETDRS) letters. BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The letter score ranges from 0 (worse score) to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average value was calculated across the three visits, and this averaged value was used to determine if the endpoint was met. The results were summarized as the percentage of participants with increase in BCVA with greater than or equal to (\>=)15, \>=10, \>=5 letters from the baseline per treatment arm who met the endpoint.

Secondary Outcome Measures

Name	Time	Method
Mean Change From Baseline in Macular Atrophy (MA) Assessed by Fundus Autofluorescence (FAF)	Baseline up to Week 48	MA lesion area was measured in millimeters squared (mm\^2) by FAF in each eye. The change in MA lesion area was measured by FAF and analysis of FAF images was performed by the central reading center. A positive change from baseline indicates an increase in size of MA lesion area (worsening; disease progression).
Change From Baseline in Total Complement Factor H (CFH) Concentration in Aqueous Humor	Baseline, Week 32	Observed continuous total CFH concentration level in aqueous humor (ng/mL) was analyzed in study eye only by type of biological matrix by treatment group using descriptive statistics. Change from baseline in total CFH Concentration in aqueous humor at Week 32 was reported.
Mean Change From Baseline in Early Treatment of Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) at Week 48	Baseline, Week 48	BCVA was measured on the ETDRS chart at a starting distance of 4 meters in each eye. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was used to determine if the endpoint was met. All items were transformed on to total score ranges from 0 to 100 (best score). A negative change indicates no improvement in the condition.

Trial Locations

Locations (23)

Gemini Clinical Trial Site 18; 🇺🇸 Winter Haven, Florida, United States

Gemini Clinical Trial Site 7; 🇺🇸 Pinellas Park, Florida, United States

Gemini Clinical Trial Site 2; 🇺🇸 Asheville, North Carolina, United States

Gemini Clinical Trial Site 3; 🇺🇸 Dallas, Texas, United States

Gemini Clinical Trial Site 17; 🇺🇸 Huntington Beach, California, United States

Gemini Clinical Trial Site 5; 🇺🇸 Miami, Florida, United States

Gemini Clinical Trial Site 13; 🇺🇸 Beaufort, South Carolina, United States

Gemini Clinical Trial Site 1; 🇺🇸 Reno, Nevada, United States

Gemini Clinical Trial Site 16; 🇺🇸 Phoenix, Arizona, United States

Gemini Clinical Trial Site 6; 🇺🇸 Cincinnati, Ohio, United States

Gemini Clinical Trial Site 21; 🇺🇸 San Antonio, Texas, United States

Gemini Clinical Trial Site 14; 🇺🇸 San Antonio, Texas, United States

Gemini Clinical Trial Site 20; 🇺🇸 Sarasota, Florida, United States

Gemini Clinical Trial Site 8; 🇺🇸 Stuart, Florida, United States

Gemini Clinical Trial Site 19; 🇺🇸 Indianapolis, Indiana, United States

Gemini Clinical Trial Site 23; 🇺🇸 Worcester, Massachusetts, United States

Gemini Clinical Trial Site 22; 🇺🇸 Royal Oak, Michigan, United States

Gemini Clinical Trial Site 12; 🇺🇸 Pasadena, California, United States

Gemini Clinical Trial Site 11; 🇺🇸 Campbell, California, United States

Gemini Clinical Trial Site 9; 🇺🇸 Encino, California, United States

Gemini Clinical Trial Site 4; 🇺🇸 Hagerstown, Maryland, United States

Gemini Clinical Trial Site 10; 🇺🇸 Eugene, Oregon, United States

Gemini Clinical Trial Site 15; 🇺🇸 Charlotte, North Carolina, United States