Macular Degeneration, Neovascular Age-related Macular Degeneration, Retinal Degeneration, Retinal Disease
Conditions
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.
Interventions
BIOLOGICALGEM103
GEM103 500 mcg/50 mcL intravitreal injection
DRUGAflibercept
Aflibercept 2 mg/50 mcL (SOC) intravitreal injection Sham intravitreal injection
DRUGSham
Sham intravitreal injection
Sponsors
Gemini Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 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. |
| 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. |
| 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at multiple sites in the United States from 29 December 2020 to 18 February 2022.
Pre-assignment details
A total of 70 participants were screened of which 20 were screen failure. 50 participants were randomized in 2:1 ratio in this study, of which 34 participants received the GEM103 + aflibercept (SoC) and 16 received the Sham + SoC.
Participants by arm
| Arm | Count |
|---|---|
| SoC + GEM103 Participants were administered SoC therapy defined as aflibercept (2mg/50mcL) first, followed by GEM103 (500mcg/50mcL) 15 minutes later. Administration occurred EOM for a total of 6 doses during the 12-month study period. | 34 |
| 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. | 16 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Study discontinued per Sponsor decision | 25 | 13 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | SoC + GEM103 | SoC + Sham | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 34 Participants | 16 Participants | 50 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants | 16 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 34 Participants | 16 Participants | 50 Participants |
| Sex: Female, Male Female | 20 Participants | 11 Participants | 31 Participants |
| Sex: Female, Male Male | 14 Participants | 5 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 34 | 2 / 16 |
| other Total, other adverse events | 18 / 34 | 9 / 16 |
| serious Total, serious adverse events | 5 / 34 | 4 / 16 |
Outcome results
Primary
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.
Time frame: Baseline, Week 48
Population: The FAS included all randomized participants who received at least 1 dose of study drug (GEM103 or sham). Here, overall number of participants analyzed, and overall number of units analyzed signifies those participants and units respectively who were evaluable for this outcome measure and number of participants and units analyzed signifies those who were evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SoC + GEM103 | Mean Change From Baseline in Minnesota Low-vision Reading (MNRead) Test at Week 48 | Study Eye | -21.41 wpm | Standard Error 7.07 |
| SoC + GEM103 | Mean Change From Baseline in Minnesota Low-vision Reading (MNRead) Test at Week 48 | Fellow Eye | -18.86 wpm | Standard Error 63.209 |
| SoC + GEM103 | Mean Change From Baseline in Minnesota Low-vision Reading (MNRead) Test at Week 48 | Both Eyes | -4.73 wpm | Standard Error 47.397 |
| SoC + Sham | Mean Change From Baseline in Minnesota Low-vision Reading (MNRead) Test at Week 48 | Study Eye | -30.35 wpm | Standard Error 35.707 |
| SoC + Sham | Mean Change From Baseline in Minnesota Low-vision Reading (MNRead) Test at Week 48 | Fellow Eye | -7.88 wpm | Standard Error 43.452 |
| SoC + Sham | Mean Change From Baseline in Minnesota Low-vision Reading (MNRead) Test at Week 48 | Both Eyes | 3.08 wpm | Standard Error 52.499 |
Primary
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.
Time frame: Baseline up to Week 48
Population: The FAS included all participants who received at least 1 dose of study drug/reference therapy (GEM103 or sham). Here overall number of participants analyzed are those who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Cortical Cataract: Moderate in Study Eye | 0 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Pseudophakic in Study Eye | 24 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Cortical Cataract: Moderate in Fellow Eye | 0 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Macula in Fellow Eye | 28 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Cortical Cataract: Severe in Study Eye | 0 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Pseudophakic in Fellow Eye | 23 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Cortical Cataract: Severe in Fellow Eye | 0 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Vitreous in Fellow Eye | 23 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Posterior Subcapsular Cataract: Mild in Study Eye | 0 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Nuclear Cataract: Mild in Study Eye | 1 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Posterior Subcapsular Cataract: Mild in Fellow Eye | 0 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Retina Periphery in Study Eye | 5 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Posterior Subcapsular Cataract: Moderate in Study Eye | 0 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Nuclear Cataract: Mild in Fellow Eye | 2 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Posterior Subcapsular Cataract: Moderate in Fellow Eye | 0 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Optic Nerve in Fellow Eye | 4 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Posterior Subcapsular Cataract: Severe in Study Eye | 0 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Nuclear Cataract: Moderate in Study Eye | 1 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Posterior Subcapsular Cataract: Severe in Fellow Eye | 0 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Retina Periphery in Fellow Eye | 6 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Lids/Lashes findings in Study Eye | 4 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Nuclear Cataract: Moderate in Fellow Eye | 1 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Lids/Lashes findings in Fellow Eye | 5 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Vitreous in Study Eye | 26 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Cornea findings in Study Eye | 8 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Nuclear Cataract: Severe in Study Eye | 2 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Cornea findings in Fellow Eye | 6 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Phakic in Study Eye | 5 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Conjunctiva findings in Study Eye | 2 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Nuclear Cataract: Severe in Fellow Eye | 2 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Conjunctiva findings in Fellow Eye | 2 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Macula in Study Eye | 28 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Iris Pupil findings in Study Eye | 2 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Cortical Cataract: Mild in Study Eye | 1 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Iris Pupil findings in Fellow Eye | 0 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Phakic in Fellow Eye | 6 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Anterior Chamber findings in Study Eye | 1 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Optic Nerve in Study Eye | 4 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Anterior Chamber findings in Fellow Eye | 1 Participants |
| SoC + GEM103 | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Cortical Cataract: Mild in Fellow Eye | 2 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Anterior Chamber findings in Fellow Eye | 0 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Vitreous in Study Eye | 8 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Vitreous in Fellow Eye | 8 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Optic Nerve in Study Eye | 5 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Optic Nerve in Fellow Eye | 6 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Macula in Study Eye | 11 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Macula in Fellow Eye | 12 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Retina Periphery in Study Eye | 2 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Retina Periphery in Fellow Eye | 4 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Phakic in Study Eye | 4 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Phakic in Fellow Eye | 5 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Pseudophakic in Study Eye | 9 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Pseudophakic in Fellow Eye | 8 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Nuclear Cataract: Mild in Study Eye | 1 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Nuclear Cataract: Mild in Fellow Eye | 1 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Nuclear Cataract: Moderate in Study Eye | 3 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Nuclear Cataract: Moderate in Fellow Eye | 4 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Nuclear Cataract: Severe in Study Eye | 0 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Nuclear Cataract: Severe in Fellow Eye | 0 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Cortical Cataract: Mild in Study Eye | 0 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Cortical Cataract: Mild in Fellow Eye | 1 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Cortical Cataract: Moderate in Study Eye | 0 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Cortical Cataract: Moderate in Fellow Eye | 0 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Cortical Cataract: Severe in Study Eye | 0 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Cortical Cataract: Severe in Fellow Eye | 0 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Posterior Subcapsular Cataract: Mild in Study Eye | 0 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Posterior Subcapsular Cataract: Mild in Fellow Eye | 0 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Posterior Subcapsular Cataract: Moderate in Study Eye | 0 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Posterior Subcapsular Cataract: Moderate in Fellow Eye | 0 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Posterior Subcapsular Cataract: Severe in Study Eye | 0 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Posterior Subcapsular Cataract: Severe in Fellow Eye | 0 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Lids/Lashes findings in Study Eye | 2 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Lids/Lashes findings in Fellow Eye | 2 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Cornea findings in Study Eye | 3 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Cornea findings in Fellow Eye | 1 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Conjunctiva findings in Study Eye | 1 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Conjunctiva findings in Fellow Eye | 1 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Iris Pupil findings in Study Eye | 0 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Iris Pupil findings in Fellow Eye | 0 Participants |
| SoC + Sham | Number of Participants With Abnormal Ophthalmic Examination Findings | Participants With Anterior Chamber findings in Study Eye | 0 Participants |
Primary
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.
Time frame: Baseline up to Week 48
Population: The FAS included all randomized participants who received at least 1 dose of study drug (GEM103 or sham).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SoC + GEM103 | Number of Participants With Non-ocular TEAEs | 10 Participants |
| SoC + Sham | Number of Participants With Non-ocular TEAEs | 7 Participants |
Primary
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.
Time frame: Baseline up to Week 48
Population: The FAS included all randomized participants who received at least 1 dose of study drug (GEM103 or sham).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SoC + GEM103 | Number of Participants With Ocular Treatment-emergent Adverse Events (TEAEs) | Participants with Ocular TEAE in Study Eye | 11 Participants |
| SoC + GEM103 | Number of Participants With Ocular Treatment-emergent Adverse Events (TEAEs) | Participants with Ocular TEAE in Fellow Eye | 6 Participants |
| SoC + Sham | Number of Participants With Ocular Treatment-emergent Adverse Events (TEAEs) | Participants with Ocular TEAE in Study Eye | 1 Participants |
| SoC + Sham | Number of Participants With Ocular Treatment-emergent Adverse Events (TEAEs) | Participants with Ocular TEAE in Fellow Eye | 3 Participants |
Primary
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.
Time frame: Baseline up to Week 48
Population: The FAS included all randomized participants who received at least 1 dose of study drug (GEM103 or sham). Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SoC + GEM103 | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Best Corrected Visual Acuity (BCVA) | >=15 Letters in Study Eye | 0 percentage of participants |
| SoC + GEM103 | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Best Corrected Visual Acuity (BCVA) | >=10 Letters in Study Eye | 3.3 percentage of participants |
| SoC + GEM103 | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Best Corrected Visual Acuity (BCVA) | >=5 Letters in Study Eye | 43.3 percentage of participants |
| SoC + GEM103 | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Best Corrected Visual Acuity (BCVA) | >=15 Letters in Fellow Eye | 3.3 percentage of participants |
| SoC + GEM103 | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Best Corrected Visual Acuity (BCVA) | >=10 Letters in Fellow Eye | 6.7 percentage of participants |
| SoC + GEM103 | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Best Corrected Visual Acuity (BCVA) | >=5 Letters in Fellow Eye | 23.3 percentage of participants |
| SoC + Sham | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Best Corrected Visual Acuity (BCVA) | >=10 Letters in Fellow Eye | 15.4 percentage of participants |
| SoC + Sham | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Best Corrected Visual Acuity (BCVA) | >=15 Letters in Study Eye | 0 percentage of participants |
| SoC + Sham | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Best Corrected Visual Acuity (BCVA) | >=15 Letters in Fellow Eye | 7.7 percentage of participants |
| SoC + Sham | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Best Corrected Visual Acuity (BCVA) | >=10 Letters in Study Eye | 0 percentage of participants |
| SoC + Sham | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Best Corrected Visual Acuity (BCVA) | >=5 Letters in Fellow Eye | 15.4 percentage of participants |
| SoC + Sham | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Best Corrected Visual Acuity (BCVA) | >=5 Letters in Study Eye | 15.4 percentage of participants |
Primary
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.
Time frame: Baseline up to Week 48
Population: The FAS included all randomized participants who received at least 1 dose of study drug (GEM103 or sham). Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SoC + GEM103 | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Low Luminance Visual Acuity (LLVA) | >=15 Letters in Study Eye | 6.7 percentage of participants |
| SoC + GEM103 | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Low Luminance Visual Acuity (LLVA) | >=10 Letters in Study Eye | 16.7 percentage of participants |
| SoC + GEM103 | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Low Luminance Visual Acuity (LLVA) | >=5 Letters in Study Eye | 26.7 percentage of participants |
| SoC + GEM103 | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Low Luminance Visual Acuity (LLVA) | >=15 Letters in Fellow Eye | 3.3 percentage of participants |
| SoC + GEM103 | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Low Luminance Visual Acuity (LLVA) | >=10 Letters in Fellow Eye | 6.7 percentage of participants |
| SoC + GEM103 | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Low Luminance Visual Acuity (LLVA) | >=5 Letters in Fellow Eye | 10.0 percentage of participants |
| SoC + Sham | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Low Luminance Visual Acuity (LLVA) | >=10 Letters in Fellow Eye | 0.0 percentage of participants |
| SoC + Sham | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Low Luminance Visual Acuity (LLVA) | >=15 Letters in Study Eye | 0 percentage of participants |
| SoC + Sham | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Low Luminance Visual Acuity (LLVA) | >=15 Letters in Fellow Eye | 0.0 percentage of participants |
| SoC + Sham | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Low Luminance Visual Acuity (LLVA) | >=10 Letters in Study Eye | 7.7 percentage of participants |
| SoC + Sham | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Low Luminance Visual Acuity (LLVA) | >=5 Letters in Fellow Eye | 15.4 percentage of participants |
| SoC + Sham | Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Low Luminance Visual Acuity (LLVA) | >=5 Letters in Study Eye | 53.8 percentage of participants |
Secondary
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.
Time frame: Baseline, Week 32
Population: The biomarker set (BS) included participants with sufficient data to assess biomarker results. Here, overall number of participants analyzed, and overall number of units analyzed signifies those participants and units respectively who were evaluable for this outcome measure and number of units analyzed signifies those who were evaluable for specified categories.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| SoC + GEM103 | Change From Baseline in Total Complement Factor H (CFH) Concentration in Aqueous Humor | 602.890 nanogram per milliliter (ng/mL) |
| SoC + Sham | Change From Baseline in Total Complement Factor H (CFH) Concentration in Aqueous Humor | 156.520 nanogram per milliliter (ng/mL) |
Secondary
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.
Time frame: Baseline, Week 48
Population: The FAS included all randomized participants who received at least 1 dose of study drug (GEM103 or sham). Here, overall number of participants analyzed, and overall number of units analyzed signifies those participants and units respectively who were evaluable for this outcome measure and number of units analyzed signifies those who were evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SoC + GEM103 | Mean Change From Baseline in Early Treatment of Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) at Week 48 | Study Eye | 1.0 ETDRS letters | Standard Deviation 8.44 |
| SoC + GEM103 | Mean Change From Baseline in Early Treatment of Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) at Week 48 | Fellow Eye | 0.0 ETDRS letters | Standard Deviation 11.05 |
| SoC + Sham | Mean Change From Baseline in Early Treatment of Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) at Week 48 | Study Eye | -0.4 ETDRS letters | Standard Deviation 5.24 |
| SoC + Sham | Mean Change From Baseline in Early Treatment of Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) at Week 48 | Fellow Eye | 0.7 ETDRS letters | Standard Deviation 8.1 |
Secondary
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).
Time frame: Baseline up to Week 48
Population: The FAS included all randomized participants who received at least 1 dose of study drug (GEM103 or sham). Here, overall number of participants analyzed, and overall number of units analyzed signifies those participants and units respectively who were evaluable for this outcome measure and number of units analyzed signifies those who were evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| SoC + GEM103 | Mean Change From Baseline in Macular Atrophy (MA) Assessed by Fundus Autofluorescence (FAF) | Study Eye | 2.170 millimeters squared (mm^2) |
| SoC + GEM103 | Mean Change From Baseline in Macular Atrophy (MA) Assessed by Fundus Autofluorescence (FAF) | Fellow Eye | 2.430 millimeters squared (mm^2) |