Geographic Atrophy, Macular Degeneration
Conditions
Brief summary
This study will assess the safety and efficacy of the brimonidine intravitreal implant in participants with geographic atrophy due to age-related macular degeneration.
Interventions
DRUG400 µg Brimonidine Implant
400 µg brimonidine implant in the study eye using Brimo DDS® applicator on Day 1, and every 3 months through Month 21.
OTHERSham
Sham treatment with needleless applicator (no implant) to the study eye on Day 1, and every 3 months through Month 21.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Geographic atrophy due to age-related macular degeneration in the study eye * Visual acuity better than or equal to 20/125 Snellen equivalent in the study eye and 20/200 Snellen equivalent in the fellow eye.
Exclusion criteria
* Cataract surgery or Laser-Assisted in situ Keratomileusis (LASIK) in the study eye in the last 3 months * Infections in either eye in the last 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Geographic Atrophy (GA) Lesion Area of the Study Eye as Assessed by Fundus Autofluorescence (FAF) at Month 24 | Baseline (Day 1) to Month 24 | GA lesion area was measured in mm\^2 by FAF in the study eye and was quantified by the central reading center. The study eye was defined as the eye that met inclusion/exclusion criteria with the worst standard Best Correct Visual Acuity (BCVA). If the BCVA in both eyes was similar the right eye was selected as the study eye. A positive change from baseline indicates an increase in size of GA lesion area (worsening; disease progression). Mixed model for repeated measures (MMRM) was used for analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Standard Best Corrected Visual Acuity (BCVA) Score as Assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) Chart at Month 24 | Baseline (Day 1) to Month 24 | BCVA was measured using an eye chart (ETDRS) and was reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The study eye was defined as the eye that met inclusion/exclusion criteria with the worst standard BCVA. If the BCVA in both eyes was similar the right eye was selected as the study eye. A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening. MMRM was used for analysis. |
| Change From Baseline in Low Luminance BCVA Score as Assessed by ETDRS Chart at Month 24 | Baseline (Day 1) to Month 24 | Low Luminance BCVA was measured by placing a 2.0 log unit neutral density filter over the best correction for that eye and having the participant read the normally illuminated ETDRS chart and was reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The study eye was defined as the eye that met inclusion/exclusion criteria with the worst standard BCVA. If the BCVA in both eyes was similar the right eye was selected as the study eye. A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening. MMRM was used for analysis. |
Other
| Measure | Time frame |
|---|---|
| Change From Baseline in Retinal Sensitivity in the Study Eye | Baseline (Day 1) to Month 24 |
Countries
Australia, France, Germany, Italy, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 400 µg Brimonidine Implant 400 µg brimonidine implant in the study eye, administered by intravitreal injections using the Brimonidine Drug Delivery System (Brimo DDS®) applicator every 3 months from Baseline (Day 1) through Month 21. | 154 |
| Sham Sham treatment (control) in the study eye, administered by intravitreal injections using a needleless DDS applicator every 3 months from Baseline (Day 1) through Month 21. | 156 |
| Total | 310 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 14 |
| Overall Study | Lack of Efficacy | 4 | 3 |
| Overall Study | Lost to Follow-up | 6 | 4 |
| Overall Study | Other Miscellaneous Reasons | 3 | 4 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Study Terminated by Sponsor | 87 | 80 |
| Overall Study | Withdrawal by Subject | 9 | 11 |
Baseline characteristics
| Characteristic | 400 µg Brimonidine Implant | Sham | Total |
|---|---|---|---|
| Age, Continuous | 76.9 years STANDARD_DEVIATION 7.89 | 77.0 years STANDARD_DEVIATION 7.24 | 76.9 years STANDARD_DEVIATION 7.56 |
| Geographic Atrophy (GA) Lesion Area by Fundus Autofluorescence (FAF) | 5.1611 millimeters squared (mm^2) STANDARD_DEVIATION 3.7016 | 5.4761 millimeters squared (mm^2) STANDARD_DEVIATION 3.5961 | 5.3212 millimeters squared (mm^2) STANDARD_DEVIATION 3.6457 |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 153 Participants | 156 Participants | 309 Participants |
| Sex: Female, Male Female | 101 Participants | 91 Participants | 192 Participants |
| Sex: Female, Male Male | 53 Participants | 65 Participants | 118 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 154 | 6 / 156 |
| other Total, other adverse events | 79 / 154 | 61 / 156 |
| serious Total, serious adverse events | 48 / 154 | 37 / 156 |
Outcome results
Primary
Change From Baseline in Geographic Atrophy (GA) Lesion Area of the Study Eye as Assessed by Fundus Autofluorescence (FAF) at Month 24
GA lesion area was measured in mm\^2 by FAF in the study eye and was quantified by the central reading center. The study eye was defined as the eye that met inclusion/exclusion criteria with the worst standard Best Correct Visual Acuity (BCVA). If the BCVA in both eyes was similar the right eye was selected as the study eye. A positive change from baseline indicates an increase in size of GA lesion area (worsening; disease progression). Mixed model for repeated measures (MMRM) was used for analysis.
Time frame: Baseline (Day 1) to Month 24
Population: Participants from the mITT population, all randomized and treated participants with baseline and at least 1 postbaseline assessment for GA lesion area by FAF, with data available for analysis at Month 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 400 µg Brimonidine Implant | Change From Baseline in Geographic Atrophy (GA) Lesion Area of the Study Eye as Assessed by Fundus Autofluorescence (FAF) at Month 24 | 3.1455 mm^2 | Standard Error 0.1377 |
| Sham | Change From Baseline in Geographic Atrophy (GA) Lesion Area of the Study Eye as Assessed by Fundus Autofluorescence (FAF) at Month 24 | 3.5044 mm^2 | Standard Error 0.1359 |
p-value: 0.04795% CI: [-0.7132, -0.0047]MMRM
Secondary
Change From Baseline in Low Luminance BCVA Score as Assessed by ETDRS Chart at Month 24
Low Luminance BCVA was measured by placing a 2.0 log unit neutral density filter over the best correction for that eye and having the participant read the normally illuminated ETDRS chart and was reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The study eye was defined as the eye that met inclusion/exclusion criteria with the worst standard BCVA. If the BCVA in both eyes was similar the right eye was selected as the study eye. A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening. MMRM was used for analysis.
Time frame: Baseline (Day 1) to Month 24
Population: Participants from the mITT population, all randomized and treated participants with baseline and at least 1 postbaseline assessment for GA lesion area by FAF, with data available for analysis for this outcome measure at Month 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 400 µg Brimonidine Implant | Change From Baseline in Low Luminance BCVA Score as Assessed by ETDRS Chart at Month 24 | -8.1 letters read correctly | Standard Error 1 |
| Sham | Change From Baseline in Low Luminance BCVA Score as Assessed by ETDRS Chart at Month 24 | -6.7 letters read correctly | Standard Error 1 |
p-value: 0.30195% CI: [-4.2, 1.3]MMRM
Secondary
Change From Baseline in Standard Best Corrected Visual Acuity (BCVA) Score as Assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) Chart at Month 24
BCVA was measured using an eye chart (ETDRS) and was reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The study eye was defined as the eye that met inclusion/exclusion criteria with the worst standard BCVA. If the BCVA in both eyes was similar the right eye was selected as the study eye. A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening. MMRM was used for analysis.
Time frame: Baseline (Day 1) to Month 24
Population: Participants from the mITT population, all randomized and treated participants with baseline and at least 1 postbaseline assessment for GA lesion area by FAF, with data available for analysis for this outcome measure at Month 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 400 µg Brimonidine Implant | Change From Baseline in Standard Best Corrected Visual Acuity (BCVA) Score as Assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) Chart at Month 24 | -10.9 letters read correctly | Standard Error 1 |
| Sham | Change From Baseline in Standard Best Corrected Visual Acuity (BCVA) Score as Assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) Chart at Month 24 | -9.7 letters read correctly | Standard Error 1 |
p-value: 0.3995% CI: [-3.9, 1.5]MMRM
Other Pre-specified
Change From Baseline in Retinal Sensitivity in the Study Eye
Time frame: Baseline (Day 1) to Month 24