Neovascular Age-Related Macular Degeneration
Conditions
Keywords
Age-related macular degeneration (AMD), Choroidal neovascularization
Brief summary
Phase 2b, multicenter, visual examiner-masked, randomized active-controlled, parallel-arm design study to evaluate the safety and duration of repeated IVT injections of 3 dose levels of GB-102 compared with aflibercept.
Detailed description
Phase 2b, multicenter, visual examiner-masked, randomized active-controlled, parallel-arm design study to evaluate the safety and duration of the effect of GB-102, as measured by time to first rescue treatment across multiple dose levels of GB-102 administered every 6 months as compared to intravitreal (IVT) aflibercept administered every 2 months in subjects with neovascular (wet) age-related macular degeneration who have received prior induction with anti-vascular endothelial growth factor (VEGF) Extension Study: To monitor the safety and duration of effect of IVT GB-102 administered every 6 months compared to IVT aflibercept administered every 2 months in subjects in ALTISSIMO (Core Study) who complete all study visits through Month 12 (Day 360) and who do not require/receive rescue treatment at the Month 12 (Day 360) final study visit
Interventions
DRUGDrug: GB-102
Intravitreal injection of GB-102
DRUGAflibercept
Intravitreal injection of aflibercept (2 mg dose)
Sponsors
Graybug Vision
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Visual examiner-masked
Intervention model description
Parallel-arm design
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males or females ≥ 50 years of age * Presence of a choroidal neovascularization (CNV) lesion secondary to AMD treated with at least 3 prior intravitreal (IVT) injections of an anti-vascular endothelial growth factor (VEGF) agent (aflibercept, bevacizumab, or ranibizumab). * Demonstrated response to prior anti-VEGF treatment since diagnosis * Best-corrected visual acuity (BCVA) of 35 letters or better
Exclusion criteria
* History, within 6 months prior to screening, of any of the following: myocardial infarction, any cardiac event requiring hospitalization, treatment for acute congestive heart failure, transient ischemic attack, or stroke * Uncontrolled hypertension, diabetes mellitus or intraocular pressure (IOP) * Chronic renal disease * Abnormal liver function * Women who are pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Rescue Treatment | Baseline through 12 months | Kaplan-Meier estimate of the median time to first rescue treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Times That at Least One Rescue Criterion is Met | Baseline through 12 months | Assessment of the number of monthly intervals that at least one rescue criterion is met |
| Number of Treatments, Including Both Rescue and Scheduled Study Treatments, During the Study | Baseline through 12 months | Assessment of the number of treatments, including both rescue and scheduled study treatments, that occurred during the study |
| Change From Baseline in Best-corrected Visual Acuity (BCVA) (ETDRS Letter Score) at All Visits | Baseline through 12 months | BCVA = best corrected visual acuity; ETDRS = early treatment of diabetic retinopathy BCVA ETDRS range = 0 (worst) to 100 (best) Assessment of change in BCVA (ETDRS letter score) from baseline at all visits |
| Time to Fulfillment of at Least One Rescue Criterion | 6 months through 12 months | Assessment of time to fulfillment of at least one rescue criterion starting at the Month 6 visit through to the Month 12 visit |
| Frequency of Subjects With BCVA Worse Than 20/200 (Snellen Equivalent) at All Visits | Baseline through 12 months | Assessment of the frequency of subjects with BCVA worse than 20/200 (Snellen equivalent) at all visits A vision score of 20/20 is considered normal. A vision score of 20/200 is considered legally blind. |
| Change From Baseline in Central Subfield Thickness (CST) (μm) at All Visits | Baseline through 12 months | CST = central subfield thickness Assessment of change in CST (μm) measurement from baseline at all visits |
| Frequency of Subjects With Absence of Exudation (Intra-/Sub-retinal Fluid/Cystoid Edema) at at All Visits | Baseline through 12 months | Assessment of the frequency of subjects with absence of exudation (intra-/sub-retinal fluid/cystoid edema) at all visits |
| Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | Baseline through 12 months | BCVA = best corrected visual acuity; ETDRS = early treatment of diabetic retinopathy BCVA ETDRS range = 0 (worst) to 100 (best) Assessment of categorical change in BCVA (ETDRS letter score) from baseline at all visits |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GB-102 1 mg/1 mg Participants receive intravitreal (IVT) GB-102 1 mg in the study eye at Baseline and Month 6 and sham at Months 2, 4, 8 and 10. | 21 |
| GB-102 2 mg/1 mg Participants receive intravitreal (IVT) GB-102 2 mg in the study eye at Baseline, intravitreal (IVT) GB-102 1 mg at Month 6 and sham at Months 2, 4, 8 and 10. | 22 |
| Aflibercept 2 mg Participants receive intravitreal (IVT) aflibercept 2 mg in the study eye at Baseline, Months 2, 4, 6, 8 and 10. | 13 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Core Study | COVID-19 | 0 | 1 | 0 |
| Core Study | Difficulties leaving the house | 0 | 1 | 0 |
| Core Study | Withdrawal by Subject | 1 | 2 | 1 |
| Extension Study | Received Rescue Treatment | 5 | 6 | 5 |
| Extension Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Aflibercept 2 mg | GB-102 1 mg/1 mg | GB-102 2 mg/1 mg |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 54 Participants | 12 Participants | 21 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Age, Continuous | 78.5 years STANDARD_DEVIATION 8.44 | 77.5 years STANDARD_DEVIATION 9.13 | 80 years STANDARD_DEVIATION 8.08 | 77.8 years STANDARD_DEVIATION 8.58 |
| Best Corrected Visual Acuity (ETDRS Letters) | 70.5 ETDRS letters STANDARD_DEVIATION 11.52 | 69.6 ETDRS letters STANDARD_DEVIATION 14.67 | 70.8 ETDRS letters STANDARD_DEVIATION 11.5 | 70.7 ETDRS letters STANDARD_DEVIATION 9.92 |
| Central Subfield Thickness | 221.0 microns STANDARD_DEVIATION 47.42 | 217.5 microns STANDARD_DEVIATION 31.66 | 211.0 microns STANDARD_DEVIATION 47.14 | 232.5 microns STANDARD_DEVIATION 54.37 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants | 13 Participants | 20 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 54 Participants | 12 Participants | 20 Participants | 22 Participants |
| Region of Enrollment United States | 56 participants | 13 participants | 21 participants | 22 participants |
| Sex: Female, Male Female | 36 Participants | 8 Participants | 15 Participants | 13 Participants |
| Sex: Female, Male Male | 20 Participants | 5 Participants | 6 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 22 | 0 / 13 |
| other Total, other adverse events | 20 / 21 | 22 / 22 | 8 / 13 |
| serious Total, serious adverse events | 2 / 21 | 4 / 22 | 1 / 13 |
Outcome results
Primary
Time to First Rescue Treatment
Kaplan-Meier estimate of the median time to first rescue treatment.
Time frame: Baseline through 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GB-102 1 mg/1 mg | Time to First Rescue Treatment | 5 months |
| GB-102 2 mg/1 mg | Time to First Rescue Treatment | 4 months |
| Aflibercept 2 mg | Time to First Rescue Treatment | NA months |
Secondary
Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits
BCVA = best corrected visual acuity; ETDRS = early treatment of diabetic retinopathy BCVA ETDRS range = 0 (worst) to 100 (best) Assessment of categorical change in BCVA (ETDRS letter score) from baseline at all visits
Time frame: Baseline through 12 months
Population: The Full Analysis Set (FAS) will include all randomized subjects who receive at least one dose of study treatment, and complete a baseline and at least one post-baseline visit.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GB-102 1 mg/1 mg | Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | >= -14 to <= -10 letters | 3 Participants |
| GB-102 1 mg/1 mg | Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | >= 5 to <= 9 letters | 2 Participants |
| GB-102 1 mg/1 mg | Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | >= -4 to <= 4 letters | 7 Participants |
| GB-102 1 mg/1 mg | Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | <= -15 letters | 7 Participants |
| GB-102 1 mg/1 mg | Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | >= 15 letters | 0 Participants |
| GB-102 1 mg/1 mg | Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | >= 10 to <= 14 letters | 0 Participants |
| GB-102 1 mg/1 mg | Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | >= -9 to <= -5 letters | 1 Participants |
| GB-102 2 mg/1 mg | Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | >= -4 to <= 4 letters | 8 Participants |
| GB-102 2 mg/1 mg | Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | <= -15 letters | 4 Participants |
| GB-102 2 mg/1 mg | Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | >= -14 to <= -10 letters | 2 Participants |
| GB-102 2 mg/1 mg | Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | >= -9 to <= -5 letters | 1 Participants |
| GB-102 2 mg/1 mg | Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | >= 5 to <= 9 letters | 2 Participants |
| GB-102 2 mg/1 mg | Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | >= 10 to <= 14 letters | 1 Participants |
| GB-102 2 mg/1 mg | Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | >= 15 letters | 0 Participants |
| Aflibercept 2 mg | Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | >= 5 to <= 9 letters | 3 Participants |
| Aflibercept 2 mg | Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | >= -14 to <= -10 letters | 2 Participants |
| Aflibercept 2 mg | Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | >= 15 letters | 0 Participants |
| Aflibercept 2 mg | Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | >= 10 to <= 14 letters | 1 Participants |
| Aflibercept 2 mg | Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | >= -4 to <= 4 letters | 5 Participants |
| Aflibercept 2 mg | Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | >= -9 to <= -5 letters | 1 Participants |
| Aflibercept 2 mg | Categorical Change From Baseline in BCVA (ETDRS Letter Score) at All Visits | <= -15 letters | 0 Participants |
Secondary
Change From Baseline in Best-corrected Visual Acuity (BCVA) (ETDRS Letter Score) at All Visits
BCVA = best corrected visual acuity; ETDRS = early treatment of diabetic retinopathy BCVA ETDRS range = 0 (worst) to 100 (best) Assessment of change in BCVA (ETDRS letter score) from baseline at all visits
Time frame: Baseline through 12 months
Population: The Full Analysis Set (FAS) will include all randomized subjects who receive at least one dose of study treatment, and complete a baseline and at least one post-baseline visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GB-102 1 mg/1 mg | Change From Baseline in Best-corrected Visual Acuity (BCVA) (ETDRS Letter Score) at All Visits | -7.4 letters | Standard Deviation 4.72 |
| GB-102 2 mg/1 mg | Change From Baseline in Best-corrected Visual Acuity (BCVA) (ETDRS Letter Score) at All Visits | -5.1 letters | Standard Deviation 4.37 |
| Aflibercept 2 mg | Change From Baseline in Best-corrected Visual Acuity (BCVA) (ETDRS Letter Score) at All Visits | 1.8 letters | Standard Deviation 0.97 |
Secondary
Change From Baseline in Central Subfield Thickness (CST) (μm) at All Visits
CST = central subfield thickness Assessment of change in CST (μm) measurement from baseline at all visits
Time frame: Baseline through 12 months
Population: The Full Analysis Set (FAS) will include all randomized subjects who receive at least one dose of study treatment, and complete a baseline and at least one post-baseline visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GB-102 1 mg/1 mg | Change From Baseline in Central Subfield Thickness (CST) (μm) at All Visits | 41.7 microns | Standard Deviation 20.69 |
| GB-102 2 mg/1 mg | Change From Baseline in Central Subfield Thickness (CST) (μm) at All Visits | 27.2 microns | Standard Deviation 11.07 |
| Aflibercept 2 mg | Change From Baseline in Central Subfield Thickness (CST) (μm) at All Visits | 7.8 microns | Standard Deviation 15.46 |
Secondary
Frequency of Subjects With Absence of Exudation (Intra-/Sub-retinal Fluid/Cystoid Edema) at at All Visits
Assessment of the frequency of subjects with absence of exudation (intra-/sub-retinal fluid/cystoid edema) at all visits
Time frame: Baseline through 12 months
Population: The Full Analysis Set (FAS) will include all randomized subjects who receive at least one dose of study treatment, and complete a baseline and at least one post-baseline visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GB-102 1 mg/1 mg | Frequency of Subjects With Absence of Exudation (Intra-/Sub-retinal Fluid/Cystoid Edema) at at All Visits | 2 Participants |
| GB-102 2 mg/1 mg | Frequency of Subjects With Absence of Exudation (Intra-/Sub-retinal Fluid/Cystoid Edema) at at All Visits | 3 Participants |
| Aflibercept 2 mg | Frequency of Subjects With Absence of Exudation (Intra-/Sub-retinal Fluid/Cystoid Edema) at at All Visits | 1 Participants |
Secondary
Frequency of Subjects With BCVA Worse Than 20/200 (Snellen Equivalent) at All Visits
Assessment of the frequency of subjects with BCVA worse than 20/200 (Snellen equivalent) at all visits A vision score of 20/20 is considered normal. A vision score of 20/200 is considered legally blind.
Time frame: Baseline through 12 months
Population: The Full Analysis Set (FAS) will include all randomized subjects who receive at least one dose of study treatment, and complete a baseline and at least one post-baseline visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GB-102 1 mg/1 mg | Frequency of Subjects With BCVA Worse Than 20/200 (Snellen Equivalent) at All Visits | 3 Participants |
| GB-102 2 mg/1 mg | Frequency of Subjects With BCVA Worse Than 20/200 (Snellen Equivalent) at All Visits | 1 Participants |
| Aflibercept 2 mg | Frequency of Subjects With BCVA Worse Than 20/200 (Snellen Equivalent) at All Visits | 0 Participants |
Secondary
Number of Times That at Least One Rescue Criterion is Met
Assessment of the number of monthly intervals that at least one rescue criterion is met
Time frame: Baseline through 12 months
Population: The Full Analysis Set (FAS) will include all randomized subjects who receive at least one dose of study treatment, and complete a baseline and at least one post-baseline visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GB-102 1 mg/1 mg | Number of Times That at Least One Rescue Criterion is Met | 5.1 total monthly interval | Standard Error 3.38 |
| GB-102 2 mg/1 mg | Number of Times That at Least One Rescue Criterion is Met | 6.1 total monthly interval | Standard Error 2.86 |
| Aflibercept 2 mg | Number of Times That at Least One Rescue Criterion is Met | 1.1 total monthly interval | Standard Error 1.26 |
Secondary
Number of Treatments, Including Both Rescue and Scheduled Study Treatments, During the Study
Assessment of the number of treatments, including both rescue and scheduled study treatments, that occurred during the study
Time frame: Baseline through 12 months
Population: The Full Analysis Set (FAS) will include all randomized subjects who receive at least one dose of study treatment, and complete a baseline and at least one post-baseline visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GB-102 1 mg/1 mg | Number of Treatments, Including Both Rescue and Scheduled Study Treatments, During the Study | 4 Injections |
| GB-102 2 mg/1 mg | Number of Treatments, Including Both Rescue and Scheduled Study Treatments, During the Study | 4 Injections |
| Aflibercept 2 mg | Number of Treatments, Including Both Rescue and Scheduled Study Treatments, During the Study | 6 Injections |
Secondary
Time to Fulfillment of at Least One Rescue Criterion
Assessment of time to fulfillment of at least one rescue criterion starting at the Month 6 visit through to the Month 12 visit
Time frame: 6 months through 12 months
Population: Full Analysis Set which include all randomized subjects who received at least one dose of study treatment and complete a baseline and at least one post-baseline visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GB-102 1 mg/1 mg | Time to Fulfillment of at Least One Rescue Criterion | 1.5 months |
| GB-102 2 mg/1 mg | Time to Fulfillment of at Least One Rescue Criterion | 2 months |
| Aflibercept 2 mg | Time to Fulfillment of at Least One Rescue Criterion | NA months |