Age-Related Macular Degeneration, Geographic Atrophy
Conditions
Keywords
Geographic Atrophy, GA, Age-Related Macular Degeneration, AMD
Brief summary
The purpose of this study was to evaluate the safety and efficacy of AL-8309B Ophthalmic Solution versus Vehicle administered as a topical ocular drop for the treatment for geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
Interventions
DRUGAL-8309B Ophthalmic Solution
DRUGAL-8309B Vehicle
Inactive ingredients used as placebo comparator
Sponsors
Alcon Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Willing to give written informed consent, make required study visits, and follow instructions. * Able to administer eye drops or have a caretaker to administer the eye drops. * Study eye: Atrophy secondary to age-related macular degeneration, best corrected visual acuity (BCVA) of 35 letters (20/200 Snellen equivalent) or better, clear ocular media, and adequate pupillary dilation. * Other protocol-defined inclusion criteria may apply.
Exclusion criteria
* Pregnant, nursing, or not using adequate contraception. * Ocular disease in the study eye, other than non-exudative AMD. * History of cataract surgery in either eye within the past 3 months of screening. * History or evidence of serious ocular trauma or intraocular surgery in either eye within the past 6 months of screening. * Any medical condition that would make participation in the trial or adherence to the study schedule difficult or unlikely. * Participation in an investigational drug or device study within 30 days of screening. * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Annualized Lesion Enlargement Rate From Baseline as Assessed With Fundus Autofluorescence Imaging | Baseline, up to Month 30 | The size of the retinal lesion was measured using the Heidelberg Retinal Angiography system at Baseline, Month 6, Month 12, Month 15, Month 18, Month 24, and Month 30. Images were collected in both eyes; however, one eye from each subject was chosen as the study eye, and only data for the study eye were used for the efficacy analysis. Results were estimated from a longitudinal random effects regression model. A greater lesion growth rate may indicate a faster progression of the disease. |
Participant flow
Recruitment details
Subjects were recruited from 48 study centers located in 14 countries.
Pre-assignment details
This reporting group includes all enrolled subjects (772). A subject was considered enrolled if they met all of the inclusion criteria and none of the exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| AL-8309B 1.0% AL-8309B 1.0% Ophthalmic Solution, 1 drop in each eye twice daily for 30 months, up to a maximum of 36 months | 252 |
| AL-8309B 1.75% AL-8309B 1.75% Ophthalmic Solution, 1 drop in each eye twice daily, for 30 months up to a maximum of 36 months | 259 |
| Vehicle AL-8309B Vehicle, 1 drop in each eye twice daily, for 30 months up to a maximum of 36 months | 261 |
| Total | 772 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 21 | 32 | 28 |
| Overall Study | Decision Unrelated to an Adverse Event | 15 | 12 | 17 |
| Overall Study | Did not attend final visit | 2 | 3 | 0 |
| Overall Study | Failed inclusion criteria | 3 | 4 | 0 |
| Overall Study | Lost to Follow-up | 5 | 5 | 5 |
| Overall Study | Noncompliance | 0 | 4 | 4 |
| Overall Study | Protocol Deviation | 1 | 1 | 1 |
| Overall Study | Randomization Error | 2 | 0 | 0 |
| Overall Study | Sponsor Decision | 7 | 11 | 7 |
| Overall Study | Subject Decision | 3 | 2 | 6 |
| Overall Study | Subject Moved | 0 | 4 | 0 |
| Overall Study | Transportation | 0 | 2 | 0 |
| Overall Study | Withdrew Consent | 9 | 6 | 9 |
Baseline characteristics
| Characteristic | AL-8309B 1.75% | Vehicle | AL-8309B 1.0% | Total |
|---|---|---|---|---|
| Age, Continuous | 78.3 years STANDARD_DEVIATION 7.7 | 78.8 years STANDARD_DEVIATION 7.1 | 77.9 years STANDARD_DEVIATION 8 | 78.3 years STANDARD_DEVIATION 7.6 |
| Region of Enrollment Australia | 18 participants | 16 participants | 16 participants | 50 participants |
| Region of Enrollment Austria | 13 participants | 14 participants | 13 participants | 40 participants |
| Region of Enrollment Belgium | 6 participants | 6 participants | 7 participants | 19 participants |
| Region of Enrollment Canada | 1 participants | 0 participants | 1 participants | 2 participants |
| Region of Enrollment France | 27 participants | 29 participants | 28 participants | 84 participants |
| Region of Enrollment Germany | 20 participants | 19 participants | 18 participants | 57 participants |
| Region of Enrollment Ireland | 3 participants | 3 participants | 3 participants | 9 participants |
| Region of Enrollment Israel | 15 participants | 15 participants | 13 participants | 43 participants |
| Region of Enrollment Italy | 15 participants | 14 participants | 12 participants | 41 participants |
| Region of Enrollment Japan | 2 participants | 3 participants | 3 participants | 8 participants |
| Region of Enrollment Portugal | 3 participants | 2 participants | 2 participants | 7 participants |
| Region of Enrollment Switzerland | 21 participants | 21 participants | 21 participants | 63 participants |
| Region of Enrollment United Kingdom | 3 participants | 3 participants | 4 participants | 10 participants |
| Region of Enrollment United States | 112 participants | 116 participants | 111 participants | 339 participants |
| Sex: Female, Male Female | 162 Participants | 147 Participants | 130 Participants | 439 Participants |
| Sex: Female, Male Male | 97 Participants | 114 Participants | 122 Participants | 333 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 207 / 250 | 212 / 258 | 207 / 260 |
| serious Total, serious adverse events | 86 / 250 | 96 / 258 | 85 / 260 |
Outcome results
Primary
Mean Annualized Lesion Enlargement Rate From Baseline as Assessed With Fundus Autofluorescence Imaging
The size of the retinal lesion was measured using the Heidelberg Retinal Angiography system at Baseline, Month 6, Month 12, Month 15, Month 18, Month 24, and Month 30. Images were collected in both eyes; however, one eye from each subject was chosen as the study eye, and only data for the study eye were used for the efficacy analysis. Results were estimated from a longitudinal random effects regression model. A greater lesion growth rate may indicate a faster progression of the disease.
Time frame: Baseline, up to Month 30
Population: This analysis population included all treated subjects. A subject was considered treated if they had a first or last dosing date in the database.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| AL-8309B 1.0% | Mean Annualized Lesion Enlargement Rate From Baseline as Assessed With Fundus Autofluorescence Imaging | 1.725 square millimeters per year |
| AL-8309B 1.75% | Mean Annualized Lesion Enlargement Rate From Baseline as Assessed With Fundus Autofluorescence Imaging | 1.758 square millimeters per year |
| Vehicle | Mean Annualized Lesion Enlargement Rate From Baseline as Assessed With Fundus Autofluorescence Imaging | 1.707 square millimeters per year |