Age Related Macular Degeneration, AMD, Atrophy, Geographic, Geographic Atrophy
Conditions
Brief summary
This is a double-masked, multicenter, randomized, placebo-controlled clinical trial, evaluating the efficacy and safety of ALK-001 in participants with Geographic Atrophy (GA) secondary to age-related macular degeneration (AMD). Up to 200 participants will receive ALK-001 while up to 100 participants will receive a placebo.
Detailed description
There is no oral treatment available for Geographic Atrophy secondary to AMD. AMD is characterized by an age-related degeneration of the retina. The root cause for this degeneration or why some people develop AMD while others do not, is unknown. Over 20 years ago, it was hypothesized that the dimerization of vitamin A may be a significant contributor to the etiology of AMD. The eye indeed uses vitamin A as a cofactor to sense light, and a striking chemical signature of the aging and degenerating retina is the accumulation of vitamin A dimers in the retinal pigment epithelium (RPE) and the underlying Bruch's membrane. In rodent models, high levels of vitamin A dimers correlate with poor retinal health, and a variety of mechanisms have been proposed by which vitamin A dimers may induce retinal toxicity. It has been argued that these mechanisms participate in the development and progression of AMD. ALK-001, the study drug, is a modified form of vitamin A. When taken once a day as a capsule, it replaces natural vitamin A in the body with one that forms vitamin A dimers more slowly. This study will measure the extent to which treatment with ALK-001 slows the progression of Geographic Atrophy.
Interventions
DRUGALK-001 oral capsule
Daily administration for 24 months
DRUGPlacebo oral capsule
Daily administration for 24 months
Sponsors
Alkeus Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Major Inclusion Criteria: \- At least one eye with geographic atrophy secondary to dry age-related macular degeneration (AMD) Major
Exclusion criteria
\- Medical condition, which may interfere with the progression of GA, prevent performance of study procedures, compliance with protocol, or continuous participation in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Growth Rate of GA Lesions, as Assessed by Fundus Autofluorescence (FAF) | Baseline to 24 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Baseline to 24 months | — |
| Changes in Visual Acuity | Baseline to 24 months | Changes in LLVA and BCVA |
Countries
United States
Participant flow
Pre-assignment details
Target enrollment was 200 participants but ultimately only 198 were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| ALK-001 Capsule
ALK-001 oral capsule: Daily administration for 24 months | 135 |
| Placebo Capsule
Placebo oral capsule: Daily administration for 24 months | 63 |
| Total | 198 |
Baseline characteristics
| Characteristic | Total | Placebo | ALK-001 |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 190 Participants | 60 Participants | 130 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 3 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 4 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 192 Participants | 59 Participants | 133 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 198 participants | 63 participants | 135 participants |
| Sex: Female, Male Female | 136 Participants | 45 Participants | 91 Participants |
| Sex: Female, Male Male | 62 Participants | 18 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 135 | 1 / 63 |
| other Total, other adverse events | 59 / 135 | 34 / 63 |
| serious Total, serious adverse events | 26 / 135 | 14 / 63 |
Outcome results
Primary
Growth Rate of GA Lesions, as Assessed by Fundus Autofluorescence (FAF)
Time frame: Baseline to 24 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ALK-001 | Growth Rate of GA Lesions, as Assessed by Fundus Autofluorescence (FAF) | 1.62 mm2/year | Standard Error 0.081 |
| Placebo | Growth Rate of GA Lesions, as Assessed by Fundus Autofluorescence (FAF) | 1.87 mm2/year | Standard Error 0.116 |
Secondary
Changes in Visual Acuity
Changes in LLVA and BCVA
Time frame: Baseline to 24 months
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ALK-001 | Changes in Visual Acuity | LLVA | -3.896 letters | Standard Error 1.316 |
| ALK-001 | Changes in Visual Acuity | BCVA | -6.862 letters | Standard Error 1.251 |
| Placebo | Changes in Visual Acuity | LLVA | -8.298 letters | Standard Error 1.835 |
| Placebo | Changes in Visual Acuity | BCVA | -10.161 letters | Standard Error 1.771 |
Secondary
Number of Participants With Adverse Events
Time frame: Baseline to 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALK-001 | Number of Participants With Adverse Events | 97 Participants |
| Placebo | Number of Participants With Adverse Events | 52 Participants |