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

Sponsor

Alkeus Pharmaceuticals, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT02402660

Collaborator

(none)

140

Enrollment

Locations

Arms

115

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Stargardt Disease Stargardt Macular Degeneration Stargardt Macular Dystrophy Autosomal Recessive Stargardt Disease 1 (ABCA4-related)	Drug: ALK-001 Drug: Placebo	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

140 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 1, 2015

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Mar 1, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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.
Pharmacokinetic profile of ALK-001 derived from the concentrations of ALK-001 and metabolites in plasma [Up to 24 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

8 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Los Angeles - Jules Stein Eye Institute	Los Angeles	California	United States	90095
2	Vitreoretinal Associates	Gainesville	Florida	United States	32607
3	University of Miami - Bascom Palmer Eye Institute	Miami	Florida	United States	33136
4	Johns Hopkins - Wilmer Eye Institute	Baltimore	Maryland	United States	21287
5	Columbia University Medical Center - Harkness Eye Institute	New York	New York	United States	10032
6	University of Utah - Moran Eye Institute	Salt Lake City	Utah	United States	84132
7	Medical College of Wisconsin - Eye Institute	Milwaukee	Wisconsin	United States	53226