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

Primary Purpose

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

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
GEM103
Aflibercept
Sham
Sponsored by
Gemini Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neovascular Age-related Macular Degeneration

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Gemini Clinical Trial Site 16
  • Gemini Clinical Trial Site 11
  • Gemini Clinical Trial Site 9
  • Gemini Clinical Trial Site 17
  • Gemini Clinical Trial Site 12
  • Gemini Clinical Trial Site 5
  • Gemini Clinical Trial Site 7
  • Gemini Clinical Trial Site 20
  • Gemini Clinical Trial Site 8
  • Gemini Clinical Trial Site 18
  • Gemini Clinical Trial Site 19
  • Gemini Clinical Trial Site 4
  • Gemini Clinical Trial Site 23
  • Gemini Clinical Trial Site 22
  • Gemini Clinical Trial Site 1
  • Gemini Clinical Trial Site 2
  • Gemini Clinical Trial Site 15
  • Gemini Clinical Trial Site 6
  • Gemini Clinical Trial Site 10
  • Gemini Clinical Trial Site 13
  • Gemini Clinical Trial Site 3
  • Gemini Clinical Trial Site 21
  • Gemini Clinical Trial Site 14

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

SoC + GEM103

SoC + Sham

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
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.
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.
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.
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.
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.

Secondary Outcome Measures

Change From Baseline in Total Complement Factor H (CFH) Concentration in Aqueous Humor
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
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.
Mean Change From Baseline in Macular Atrophy (MA) Assessed by Fundus Autofluorescence (FAF)
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).

Full Information

First Posted
December 21, 2020
Last Updated
October 4, 2022
Sponsor
Gemini Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04684394
Brief Title
A Multiple Dose Study of Repeat Intravitreal Injections of GEM103 in Neovascular Age-related Macular Degeneration
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision
Study Start Date
December 29, 2020 (Actual)
Primary Completion Date
January 10, 2022 (Actual)
Study Completion Date
February 18, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gemini Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neovascular Age-related Macular Degeneration, Retinal Disease, Retinal Degeneration, Macular Degeneration

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SoC + GEM103
Arm Type
Experimental
Arm Description
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.
Arm Title
SoC + Sham
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
GEM103
Intervention Description
GEM103 500 mcg/50 mcL intravitreal injection
Intervention Type
Drug
Intervention Name(s)
Aflibercept
Intervention Description
Aflibercept 2 mg/50 mcL (SOC) intravitreal injection Sham intravitreal injection
Intervention Type
Drug
Intervention Name(s)
Sham
Intervention Description
Sham intravitreal injection
Primary Outcome Measure Information:
Title
Number of Participants With Ocular Treatment-emergent Adverse Events (TEAEs)
Description
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.
Time Frame
Baseline up to Week 48
Title
Number of Participants With Non-ocular TEAEs
Description
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.
Time Frame
Baseline up to Week 48
Title
Number of Participants With Abnormal Ophthalmic Examination Findings
Description
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.
Time Frame
Baseline up to Week 48
Title
Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Best Corrected Visual Acuity (BCVA)
Description
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.
Time Frame
Baseline up to Week 48
Title
Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Low Luminance Visual Acuity (LLVA)
Description
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.
Time Frame
Baseline up to Week 48
Title
Mean Change From Baseline in Minnesota Low-vision Reading (MNRead) Test at Week 48
Description
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.
Time Frame
Baseline, Week 48
Secondary Outcome Measure Information:
Title
Change From Baseline in Total Complement Factor H (CFH) Concentration in Aqueous Humor
Description
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.
Time Frame
Baseline, Week 32
Title
Mean Change From Baseline in Early Treatment of Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) at Week 48
Description
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.
Time Frame
Baseline, Week 48
Title
Mean Change From Baseline in Macular Atrophy (MA) Assessed by Fundus Autofluorescence (FAF)
Description
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).
Time Frame
Baseline up to Week 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 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
Facility Information:
Facility Name
Gemini Clinical Trial Site 16
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85021
Country
United States
Facility Name
Gemini Clinical Trial Site 11
City
Campbell
State/Province
California
ZIP/Postal Code
95008
Country
United States
Facility Name
Gemini Clinical Trial Site 9
City
Encino
State/Province
California
ZIP/Postal Code
91436
Country
United States
Facility Name
Gemini Clinical Trial Site 17
City
Huntington Beach
State/Province
California
ZIP/Postal Code
92647
Country
United States
Facility Name
Gemini Clinical Trial Site 12
City
Pasadena
State/Province
California
ZIP/Postal Code
91107
Country
United States
Facility Name
Gemini Clinical Trial Site 5
City
Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Gemini Clinical Trial Site 7
City
Pinellas Park
State/Province
Florida
ZIP/Postal Code
33782
Country
United States
Facility Name
Gemini Clinical Trial Site 20
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34239
Country
United States
Facility Name
Gemini Clinical Trial Site 8
City
Stuart
State/Province
Florida
ZIP/Postal Code
34994
Country
United States
Facility Name
Gemini Clinical Trial Site 18
City
Winter Haven
State/Province
Florida
ZIP/Postal Code
33880
Country
United States
Facility Name
Gemini Clinical Trial Site 19
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46290
Country
United States
Facility Name
Gemini Clinical Trial Site 4
City
Hagerstown
State/Province
Maryland
ZIP/Postal Code
21740
Country
United States
Facility Name
Gemini Clinical Trial Site 23
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01605
Country
United States
Facility Name
Gemini Clinical Trial Site 22
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Facility Name
Gemini Clinical Trial Site 1
City
Reno
State/Province
Nevada
ZIP/Postal Code
89502
Country
United States
Facility Name
Gemini Clinical Trial Site 2
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28803
Country
United States
Facility Name
Gemini Clinical Trial Site 15
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28210
Country
United States
Facility Name
Gemini Clinical Trial Site 6
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Gemini Clinical Trial Site 10
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97401
Country
United States
Facility Name
Gemini Clinical Trial Site 13
City
Beaufort
State/Province
South Carolina
ZIP/Postal Code
29902
Country
United States
Facility Name
Gemini Clinical Trial Site 3
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Gemini Clinical Trial Site 21
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78240
Country
United States
Facility Name
Gemini Clinical Trial Site 14
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78247
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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