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

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

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

Study Overview

• Status: Enrolling by invitation
• Conditions: Stargardt Disease; Stargardt Macular Degeneration; Stargardt Macular Dystrophy; Autosomal Recessive Stargardt Disease 1 (ABCA4-related)
• Intervention / Treatment: Drug: ALK-001; Drug: Placebo

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 Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85020
      • Alkeus Site
  • California
    • Los Angeles, California, United States, 90095
      • Alkeus Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Alkeus Site
  • Florida
    • Gainesville, Florida, United States, 32601
      • Alkeus Site
    • Miami, Florida, United States, 33136
      • Alkeus Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Alkeus Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Alkeus Site
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Alkeus Site
  • New York
    • New York, New York, United States, 10032
      • Alkeus Site
    • Westbury, New York, United States, 11590
      • Alkeus Site
  • Texas
    • Houston, Texas, United States, 77025
      • Alkeus Site
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Alkeus Site
  • Washington
    • Silverdale, Washington, United States, 98383
      • Alkeus Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Alkeus Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALK-001; Daily, oral administration of one capsule. See details below.	Drug: ALK-001; Daily, oral administration for 24 months; Other Names: C20-D3-Retinyl Acetate; C20 Deuterated vitamin A
Placebo Comparator: Placebo; Daily, oral administration of one capsule. See details below.	Drug: Placebo; Daily, oral administration for 24 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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
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	Combination of changes in atrophic lesion size, best corrected visual acuity (BCVA), and ocular assessments.	From baseline to 24 months

Collaborators and Investigators

• Sponsor: Alkeus Pharmaceuticals, Inc.
• Investigators: Study Director: Leonide Saad, PhD, Alkeus Pharmaceuticals, Inc.; Study Director: Hendrik Scholl, MD, University of Basel

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

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Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: March 9, 2015
• First Submitted That Met QC Criteria: March 27, 2015
• First Posted (Estimated): March 30, 2015

Study Record Updates

• Last Update Posted (Actual): April 27, 2025
• Last Update Submitted That Met QC Criteria: April 24, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Eye Diseases; Eye Diseases, Hereditary; Retinal Diseases; Retinal Degeneration; Stargardt Disease; Macular Degeneration; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Micronutrients; Protective Agents; Vitamins; Adjuvants, Immunologic; Anticarcinogenic Agents; Vitamin A; Retinol acetate
• Other Study ID Numbers: ALK001-P1002; R01FD004098 (U.S. FDA Grant/Contract); R01FD006016 (Other Grant/Funding Number: FDA OOPD); R01FD006316 (U.S. FDA Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No