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

Phase 2

• Conditions: Stargardt Macular Dystrophy; Autosomal Recessive Stargardt Disease 1 (ABCA4-related); Stargardt Disease; Stargardt Macular Degeneration
• Interventions: Drug: ALK-001; Drug: Placebo

• Registration Number: NCT02402660
• Lead Sponsor: Alkeus Pharmaceuticals, Inc.

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2015-03-09
• Study First Submitted QC: 2015-03-27
• Study First Posted: 2015-03-30
• Study Start: 2015-08
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-24
• Last Update Posted: 2025-04-27
• Primary Completion: 2026-06-30
• Study Completion: 2026-11-30

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 160

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ALK-001	ALK-001	Daily, oral administration of one capsule. See details below.
Placebo	Placebo	Daily, oral administration of one capsule. See details below.

Primary Outcome Measures

Name	Time	Method
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

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

Trial Locations

Locations (1)

Alkeus Site; 🇺🇸 Milwaukee, Wisconsin, United States