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

October 4, 2022 updated by: Gemini Therapeutics, Inc.

A Multicenter, Multiple-Dose Study in Neovascular Age-related Macular Degeneration (nAMD) to Evaluate the Safety, Tolerability, Pharmacodynamics, Immunogenicity, and Clinical Effect of Repeat Intravitreal (IVT) Injections of GEM103 as an Adjunct to Standard of Care Aflibercept Therapy

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

Study Overview

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 Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Arizona
      • Phoenix, Arizona, United States, 85021
        • Gemini Clinical Trial Site 16
    • California
      • Campbell, California, United States, 95008
        • Gemini Clinical Trial Site 11
      • Encino, California, United States, 91436
        • Gemini Clinical Trial Site 9
      • Huntington Beach, California, United States, 92647
        • Gemini Clinical Trial Site 17
      • Pasadena, California, United States, 91107
        • Gemini Clinical Trial Site 12
    • Florida
      • Miami, Florida, United States, 33143
        • Gemini Clinical Trial Site 5
      • Pinellas Park, Florida, United States, 33782
        • Gemini Clinical Trial Site 7
      • Sarasota, Florida, United States, 34239
        • Gemini Clinical Trial Site 20
      • Stuart, Florida, United States, 34994
        • Gemini Clinical Trial Site 8
      • Winter Haven, Florida, United States, 33880
        • Gemini Clinical Trial Site 18
    • Indiana
      • Indianapolis, Indiana, United States, 46290
        • Gemini Clinical Trial Site 19
    • Maryland
      • Hagerstown, Maryland, United States, 21740
        • Gemini Clinical Trial Site 4
    • Massachusetts
      • Worcester, Massachusetts, United States, 01605
        • Gemini Clinical Trial Site 23
    • Michigan
      • Royal Oak, Michigan, United States, 48073
        • Gemini Clinical Trial Site 22
    • Nevada
      • Reno, Nevada, United States, 89502
        • Gemini Clinical Trial Site 1
    • North Carolina
      • Asheville, North Carolina, United States, 28803
        • Gemini Clinical Trial Site 2
      • Charlotte, North Carolina, United States, 28210
        • Gemini Clinical Trial Site 15
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Gemini Clinical Trial Site 6
    • Oregon
      • Eugene, Oregon, United States, 97401
        • Gemini Clinical Trial Site 10
    • South Carolina
      • Beaufort, South Carolina, United States, 29902
        • Gemini Clinical Trial Site 13
    • Texas
      • Dallas, Texas, United States, 75231
        • Gemini Clinical Trial Site 3
      • San Antonio, Texas, United States, 78240
        • Gemini Clinical Trial Site 21
      • San Antonio, Texas, United States, 78247
        • Gemini Clinical Trial Site 14

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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. 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SoC + 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.
GEM103 500 mcg/50 mcL intravitreal injection

Aflibercept 2 mg/50 mcL (SOC) intravitreal injection

Sham intravitreal injection

Sham Comparator: SoC + 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.

Aflibercept 2 mg/50 mcL (SOC) intravitreal injection

Sham intravitreal injection

Sham intravitreal injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Ocular Treatment-emergent Adverse Events (TEAEs)
Time Frame: 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.
Baseline up to Week 48
Number of Participants With Non-ocular TEAEs
Time Frame: 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.
Baseline up to Week 48
Number of Participants With Abnormal Ophthalmic Examination Findings
Time Frame: 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.
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)
Time Frame: 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.
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)
Time Frame: 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.
Baseline up to Week 48
Mean Change From Baseline in Minnesota Low-vision Reading (MNRead) Test at Week 48
Time Frame: 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.
Baseline, Week 48

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Total Complement Factor H (CFH) Concentration in Aqueous Humor
Time Frame: 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.
Baseline, Week 32
Mean Change From Baseline in Early Treatment of Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) at Week 48
Time Frame: 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.
Baseline, Week 48
Mean Change From Baseline in Macular Atrophy (MA) Assessed by Fundus Autofluorescence (FAF)
Time Frame: 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).
Baseline up to Week 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 29, 2020

Primary Completion (Actual)

January 10, 2022

Study Completion (Actual)

February 18, 2022

Study Registration Dates

First Submitted

December 21, 2020

First Submitted That Met QC Criteria

December 21, 2020

First Posted (Actual)

December 24, 2020

Study Record Updates

Last Update Posted (Actual)

October 31, 2022

Last Update Submitted That Met QC Criteria

October 4, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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