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

NCT02402660 | Enrolling By Invitation Phase 2 DMC FDA Drug

• 4 other identifiers: ALK001-P1002R01FD004098R01FD006016R01FD006316
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 14

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Effects of ALK-001 on the progression of Stargardt disease

  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

Study Arms (2)

ALK-001

EXPERIMENTAL

Daily, oral administration of one capsule. See details below.

Drug: ALK-001

Placebo

PLACEBO COMPARATOR

Daily, oral administration of one capsule. See details below.

Drug: Placebo

Interventions

ALK-001 DRUG

Daily, oral administration for 24 months

Also known as: C20-D3-Retinyl Acetate, C20 Deuterated vitamin A

ALK-001

Placebo DRUG

Daily, oral administration for 24 months

Placebo

Eligibility Criteria

• Age: 8 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Alkeus Pharmaceuticals, Inc.: lead

Study Sites (14)

Alkeus Site

Phoenix, Arizona, 85020, United States

Location

Alkeus Site

Los Angeles, California, 90095, United States

Location

Alkeus Site

Aurora, Colorado, 80045, United States

Location

Alkeus Site

Gainesville, Florida, 32601, United States

Location

Alkeus Site

Miami, Florida, 33136, United States

Location

Alkeus Site

Indianapolis, Indiana, 46202, United States

Location

Alkeus Site

Baltimore, Maryland, 21287, United States

Location

Alkeus Site

Grand Rapids, Michigan, 49546, United States

Location

Alkeus Site

New York, New York, 10032, United States

Location

Alkeus Site

Westbury, New York, 11590, United States

Location

Alkeus Site

Houston, Texas, 77025, United States

Location

Alkeus Site

Salt Lake City, Utah, 84132, United States

Location

Alkeus Site

Silverdale, Washington, 98383, United States

Location

Alkeus Site

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (7)

• Ma L, Kaufman Y, Zhang J, Washington I. C20-D3-vitamin A slows lipofuscin accumulation and electrophysiological retinal degeneration in a mouse model of Stargardt disease. J Biol Chem. 2011 Mar 11;286(10):7966-7974. doi: 10.1074/jbc.M110.178657. Epub 2010 Dec 14.

  PMID: 21156790 BACKGROUND

• Kaufman Y, Ma L, Washington I. Deuterium enrichment of vitamin A at the C20 position slows the formation of detrimental vitamin A dimers in wild-type rodents. J Biol Chem. 2011 Mar 11;286(10):7958-7965. doi: 10.1074/jbc.M110.178640. Epub 2010 Nov 12.

  PMID: 21075840 BACKGROUND

• Mihai DM, Jiang H, Blaner WS, Romanov A, Washington I. The retina rapidly incorporates ingested C20-D(3)-vitamin A in a swine model. Mol Vis. 2013 Jul 25;19:1677-83. Print 2013.

  PMID: 23914132 BACKGROUND

• Charbel Issa P, Barnard AR, Herrmann P, Washington I, MacLaren RE. Rescue of the Stargardt phenotype in Abca4 knockout mice through inhibition of vitamin A dimerization. Proc Natl Acad Sci U S A. 2015 Jul 7;112(27):8415-20. doi: 10.1073/pnas.1506960112. Epub 2015 Jun 23.

  PMID: 26106163 BACKGROUND

• Saad L, Washington I. Can Vitamin A be Improved to Prevent Blindness due to Age-Related Macular Degeneration, Stargardt Disease and Other Retinal Dystrophies? Adv Exp Med Biol. 2016;854:355-61. doi: 10.1007/978-3-319-17121-0_47.

  PMID: 26427432 BACKGROUND

• Zhang D, Robinson K, Washington I. C20D3-Vitamin A Prevents Retinal Pigment Epithelium Atrophic Changes in a Mouse Model. Transl Vis Sci Technol. 2021 Dec 1;10(14):8. doi: 10.1167/tvst.10.14.8.

  PMID: 34878528 BACKGROUND

• Zhang D, Robinson K, Saad L, Washington I. Vitamin A cycle byproducts impede dark adaptation. J Biol Chem. 2021 Sep;297(3):101074. doi: 10.1016/j.jbc.2021.101074. Epub 2021 Aug 12.

  PMID: 34391781 BACKGROUND

Related Links

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MeSH Terms

Conditions

Stargardt Disease

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Macular Degeneration; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2015
• First Posted: March 30, 2015
• Study Start: August 1, 2015
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: April 27, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)