Phase 2 Tolerability and Effects of ALK-001 on Stargardt Disease

Study Overview
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Brief Summary
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The purpose of this study is to determine the long term safety and tolerability of ALK-001 (C20-D3-retinyl acetate), and to explore the effects of ALK-001 on the progression of Stargardt disease in patients between the ages of 8 and 70 years old. Funding Source - FDA OOPD

Detailed Description
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This study evaluates the effects of orally-administered ALK-001 on the progression of Stargardt disease (ABCA4-related). Stargardt disease is a rare genetic disorder that leads to damage to the retina and results in legal blindness. Stargardt disease is caused by a defective ABCA4 gene, which affects the processing of vitamin A in the eye and leads to the formation of toxic vitamin A aggregates (called vitamin A dimers) in the eye. Vitamin A dimers are thought to contribute to vision loss in Stargardt disease. ALK-001, the investigational drug, is a chemically-modified vitamin A designed as a replacement of vitamin A to prevent the formation of toxic vitamin A dimers in the eye. Trial participants will receive either ALK-001 or placebo, and follow-up visits will take place periodically for up to 24 months. There is currently no treatment for Stargardt disease.

Official Title
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A Phase 2 Multicenter, Double-Masked, Randomized, Placebo-Controlled Study to Investigate the Long Term Safety, Tolerability, Pharmacokinetics and Effects of ALK-001 on the Progression of Stargardt Disease

Conditions
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Stargardt Disease, Stargardt Macular Degeneration, Stargardt Macular Dystrophy, Autosomal Recessive Stargardt Disease 1 (ABCA4-related)

Intervention / Treatment
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* Drug: ALK-001
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Simplified Inclusion Criteria: Male or female between 8 and 70 years old (inclusive), with any visual acuity Has a clinical diagnosis of typical autosomal recessive Stargardt macular dystrophy (STGD1) Has provided a genetic report indicating at least two ABCA4 disease-causing mutations. When only one ABCA4 disease-causing mutation is reported, sponsor's permission will be required. At least one eye (called the primary study eye) must have at least one well-demarcated area of significantly reduced autofluorescence as imaged by fundus autofluorescence (FAF), have decreased retinal sensitivity as measured by microperimetry, or have maculopathy expected to progress over the duration of the study Primary study eye must have clear ocular media and adequate pupillary dilation, including no allergy to dilating eyedrops, to permit good quality retinal imaging Healthy as judged by investigator Able and willing to comply with study requirements, restrictions and instructions and is likely to complete the 24-month study Has signed and dated the informed consent forms (or assent where appropriate) to participate Female of childbearing potential has signed the informed consent about birth defects or attestation on contraception requirements Main Exclusion Criteria: Has taken disallowed items (supplement containing vitamin A or beta-carotene, liver-based products, or prescription oral retinoid medications) over the past 30 days Is lactating, pregnant, or has a positive serum or urine pregnancy test at screening or at randomization Has concurrent medical condition or history, which in the opinion of the investigator, is likely to prevent compliance with the protocol and/or interfere with absorption of ALK-001 or study procedures Has clinically significant abnormal laboratory result(s) at screening Has active or historical acute or chronic liver disorder Has active or historical ocular disorder in the primary study eye that, in the opinion of the investigator, may confound assessment of the retina morphologically or functionally (this could include for example cataract surgery within the past 6 months, choroidal neovascularization (CNV), glaucoma, recurring uveitis, diabetic retinopathy, other retinal disease, etc.) Has had intraocular surgery or injections in the primary study eye within 90 days of the screening visit Has a clinically significant abnormal electrocardiogram (ECG), or has a corrected QT interval (QTc) that is 450 ms or greater

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALK-001<br>Daily, oral administration of one capsule. See details below. | Drug: ALK-001<br>* Daily, oral administration for 24 months<br>* Other names: C20 Deuterated vitamin A;|
| Placebo Comparator: Placebo<br>Daily, oral administration of one capsule. See details below. | Drug: Placebo<br>* Daily, oral administration for 24 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of 24 months of daily dosing of ALK-001 assessed by Incidence and/or clinically significant changes of a combination of ocular and non-ocular adverse events |  | From baseline to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of ALK-001 on the progression of Stargardt disease | Combination of changes in atrophic lesion size, best corrected visual acuity (BCVA), and ocular assessments. | From baseline to 24 months | 
| Pharmacokinetic profile of ALK-001 derived from the concentrations of ALK-001 and metabolites in plasma |  | Up to 24 months |