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

NCT04684394 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: GEM-CL-10311
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 23

Brief Summary

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

Conditions

Neovascular Age-related Macular Degeneration; Retinal Disease; Retinal Degeneration; Macular Degeneration

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Ocular Treatment-emergent Adverse Events (TEAEs)

  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.

  Baseline up to Week 48

• Number of Participants With Non-ocular TEAEs

  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.

  Baseline up to Week 48

• Number of Participants With Abnormal Ophthalmic Examination Findings

  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.

  Baseline up to Week 48

• Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Best Corrected Visual Acuity (BCVA)

  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.

  Baseline up to Week 48

• Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Low Luminance Visual Acuity (LLVA)

  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.

  Baseline up to Week 48

• Mean Change From Baseline in Minnesota Low-vision Reading (MNRead) Test at 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.

  Baseline, Week 48

Secondary Outcomes (3)

• Change From Baseline in Total Complement Factor H (CFH) Concentration in Aqueous Humor

  Baseline, Week 32

• Mean Change From Baseline in Early Treatment of Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) at Week 48

  Baseline, Week 48

• Mean Change From Baseline in Macular Atrophy (MA) Assessed by Fundus Autofluorescence (FAF)

  Baseline up to Week 48

Study Arms (2)

SoC + GEM103

EXPERIMENTAL

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.

Biological: GEM103; Drug: Aflibercept

SoC + Sham

SHAM COMPARATOR

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.

Drug: Aflibercept; Drug: Sham

Interventions

GEM103 BIOLOGICAL

GEM103 500 mcg/50 mcL intravitreal injection

SoC + GEM103

Aflibercept DRUG

Aflibercept 2 mg/50 mcL (SOC) intravitreal injection Sham intravitreal injection

SoC + GEM103; SoC + Sham

Sham DRUG

Sham intravitreal injection

SoC + Sham

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 50 years old at the time of signed informed consent
• Choroidal neovascularization (CNV) related to nAMD with the following features, as determined by the Image Reading Center
• Maximum CNV lesion size of 12 disc areas
• Subretinal hemorrhage less than or equal to (\<=) 50% of lesion size
• On aflibercept treatment prior to Day 1
• Best Corrected Visual Acuity (BCVA) in the study eye between 24 to 75 letters using EDTRS

You may not qualify if:

• Presence of the following ocular conditions in the study eye:
• Any active ocular disease or condition that impact the subject to participate in the study or be a contraindication of IVT injections
• Any intraocular surgery
• Aphakia or complete absence of the posterior capsule
• Prior corneal transplant
• Scar or fibrosis greater than or equal to (\>=) 50% of CNV lesion or involving center of fovea
• Presence of any of the following ocular conditions in either eye:
• History of herpetic infection, idiopathic polypoidal choroidal vasculopathy (PCV), pathologic myopia, central serous chorioretinopathy (CSCR), adult onset foveal pattern dystrophy
• Concurrent disease that could require medical or surgical intervention during the study period
• Active/suspected ocular/periocular infection or active intraocular inflammation
• History of idiopathic or autoimmune-associated uveitis
• 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
• Has experienced a cardiovascular or cerebrovascular event within 12 months of informed consent
• Females must not be pregnant or lactating
• Current use of medications known to be toxic to the lens, retina or optic nerve

Sponsors & Collaborators

• Gemini Therapeutics, Inc.: lead

Study Sites (23)

Gemini Clinical Trial Site 16

Phoenix, Arizona, 85021, United States

Location

Gemini Clinical Trial Site 11

Campbell, California, 95008, United States

Location

Gemini Clinical Trial Site 9

Encino, California, 91436, United States

Location

Gemini Clinical Trial Site 17

Huntington Beach, California, 92647, United States

Location

Gemini Clinical Trial Site 12

Pasadena, California, 91107, United States

Location

Gemini Clinical Trial Site 5

Miami, Florida, 33143, United States

Location

Gemini Clinical Trial Site 7

Pinellas Park, Florida, 33782, United States

Location

Gemini Clinical Trial Site 20

Sarasota, Florida, 34239, United States

Location

Gemini Clinical Trial Site 8

Stuart, Florida, 34994, United States

Location

Gemini Clinical Trial Site 18

Winter Haven, Florida, 33880, United States

Location

Gemini Clinical Trial Site 19

Indianapolis, Indiana, 46290, United States

Location

Gemini Clinical Trial Site 4

Hagerstown, Maryland, 21740, United States

Location

Gemini Clinical Trial Site 23

Worcester, Massachusetts, 01605, United States

Location

Gemini Clinical Trial Site 22

Royal Oak, Michigan, 48073, United States

Location

Gemini Clinical Trial Site 1

Reno, Nevada, 89502, United States

Location

Gemini Clinical Trial Site 2

Asheville, North Carolina, 28803, United States

Location

Gemini Clinical Trial Site 15

Charlotte, North Carolina, 28210, United States

Location

Gemini Clinical Trial Site 6

Cincinnati, Ohio, 45219, United States

Location

Gemini Clinical Trial Site 10

Eugene, Oregon, 97401, United States

Location

Gemini Clinical Trial Site 13

Beaufort, South Carolina, 29902, United States

Location

Gemini Clinical Trial Site 3

Dallas, Texas, 75231, United States

Location

Gemini Clinical Trial Site 21

San Antonio, Texas, 78240, United States

Location

Gemini Clinical Trial Site 14

San Antonio, Texas, 78247, United States

Location

MeSH Terms

Conditions

Retinal Diseases; Retinal Degeneration; Macular Degeneration

Interventions

aflibercept; salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Eye Diseases; Eye Diseases, Hereditary

Results Point of Contact

• Title: Gemini Therapeutics, Inc.
• Organization: Gemini Therapeutics, Inc.

clinicaltrials@geminitherapeutics.com

617-401-4401

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2020
• First Posted: December 24, 2020
• Study Start: December 29, 2020
• Primary Completion: January 10, 2022
• Study Completion: February 18, 2022
• Last Updated: October 31, 2022
• Results First Posted: October 31, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (23)