Clinical trial NCT04239625: Open-Label Extension: Tolerability and Effects of ALK-001 on Stargardt Disease (TEASE)
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Stargardt Disease
Stargardt Macular Degeneration
Stargardt Macular Dystrophy
Autosomal Recessive Stargardt Disease 1 (ABCA4-related)
Lead sponsor: Alkeus Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-01-27
Enrollment: 200
Sex: ALL
Minimum age (years): 8
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this open-label, multicenter study is to determine the long-term safety, pharmacokinetics and effects of ALK-001 (C20-D3-retinyl acetate) on the progression of Stargardt disease. This study is an extension of NCT02402660 and enrolls participants who are at least 8 years old. Enrollment is by invitation only.

Funding Source - FDA OOPD


Eligibility criteria: Simplified Inclusion Criteria:

* Clinical diagnosis of Stargardt disease (STGD1)
* Has at least two ABCA4 disease-causing mutations, unless authorized by sponsor
* Has a best-corrected visual acuity (BCVA) greater than approximately 20/160 in at least one eye
* 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 been invited to participate in this extension, and has signed and dated the informed consent forms (or assent where appropriate) to participate
* Female of childbearing potential has signed the attestation on contraception requirements

Simplified Exclusion Criteria:

* Is lactating or pregnant
* Has a medical condition likely to prevent compliance with the protocol and/or interfere with absorption of ALK-001 or performance of study procedures
* Has abnormal laboratory result(s) at screening
* Has an ocular disorder that may confound ocular assessments
* Has a history of ocular intervention within 90 days of screening

Primary outcomes:
measure: Safety and tolerability of ALK-001 assessed by incidence and/or clinically-significant changes of a combination of ocular and non-ocular adverse events
timeFrame: From baseline to 24 months
measure: Pharmacokinetic profile of ALK-001 derived from the concentrations of ALK-001 and metabolites in plasma
timeFrame: Up to 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Alkeus Site
state: Arizona
city: Los Angeles
country: United States
facility: Alkeus Site
state: California
city: Aurora
country: United States
facility: Alkeus Site
state: Colorado
city: Gainesville
country: United States
facility: Alkeus Site
state: Florida
city: Indianapolis
country: United States
facility: Alkeus Site
state: Indiana
city: Grand Rapids
country: United States
facility: Alkeus Site
state: Michigan
city: Westbury
country: United States
facility: Alkeus Site
state: New York
city: Silverdale
country: United States
facility: Alkeus Site
state: Washington
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.