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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 by Alkeus Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Alkeus Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT02402660
First received: March 9, 2015
Last updated: May 25, 2016
Last verified: May 2016
  Purpose
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 12 and 60 years old.

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Alkeus Pharmaceuticals, Inc.:

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 [ Time Frame: From baseline to 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Effects of ALK-001 on the progression of Stargardt disease [ Time Frame: From baseline to 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: August 2015
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

This is a multicenter, randomized, double-masked, parallel group, placebo-controlled study evaluating the effects of ALK-001 administered daily by mouth in subjects with Stargardt disease (ABCA4-related).

Stargardt disease is a rare genetic disorder that leads to damage to the retina and results in legal blindness. The onset of symptoms usually occurs during one's teenage years, although symptoms can appear in children as young as 4 years old. There is currently no treatment for Stargardt.

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 is a chemically-modified vitamin A designed as a replacement of vitamin A. ALK-001 has been changed specifically to prevent the formation of toxic vitamin A dimers in the eye, without altering the normal processing of vitamin A to enable vision.

Trial participants will be randomly assigned to receive ALK-001 (30 subjects) or placebo (20 subjects) for one year. After one year of treatment, half of the participants (10 subjects) receiving placebo will be randomly crossed over to receive ALK-001 for the following 12 months, while the remaining 10 subjects will continue on the placebo. All subjects initially receiving ALK-001 will remain on the same treatment for 12 months.

Follow-up visits will take place 4 and 8 weeks after the initiation of treatment to assess safety and tolerability, then after 6, 9, 12, 15, 18, 21 and 24 months to assess the safety, tolerability and effects of ALK-001 on the progression of Stargardt disease.

The study is double-masked so that neither the participants, the clinical staff, nor the sponsor, are aware of the treatment allocation (ALK-001 or placebo). A Data Safety Monitoring Board (DSMB) will review safety and efficacy data throughout the study.

  Eligibility

Ages Eligible for Study:   12 Years to 60 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Simplified Inclusion Criteria:

  • Male or female between 12 and 60 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)
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02402660

Contacts
Contact: Leonide Saad, PhD 800-287-2755 trials@alkeus.com

Locations
United States, California
University of California Los Angeles - Jules Stein Eye Institute Recruiting
Los Angeles, California, United States, 90095
Principal Investigator: Michael Gorin, MD, PhD         
Sub-Investigator: Steven Nusinowitz, PhD         
United States, Florida
Vitreoretinal Associates Recruiting
Gainesville, Florida, United States, 32607
Principal Investigator: Christine Kay, MD         
Sub-Investigator: Jing Zhang, MD         
University of Miami - Bascom Palmer Eye Institute Recruiting
Miami, Florida, United States, 33136
Principal Investigator: Byron Lam, MD         
United States, Maryland
Johns Hopkins - Wilmer Eye Institute Recruiting
Baltimore, Maryland, United States, 21287
Principal Investigator: Hendrik Scholl, MD         
Sub-Investigator: Mahmood Shah, MD         
United States, New York
Columbia University Medical Center - Harkness Eye Institute Recruiting
New York, New York, United States, 10032
Principal Investigator: Stephen Tsang, MD, PhD         
Sub-Investigator: Srilaxmi Bearelly, MD         
United States, Utah
University of Utah - Moran Eye Institute Recruiting
Salt Lake City, Utah, United States, 84132
Principal Investigator: Paul Bernstein, MD, PhD         
United States, Wisconsin
Medical College of Wisconsin - Eye Institute Recruiting
Milwaukee, Wisconsin, United States, 53226
Principal Investigator: Kimberly Stepien, MD         
Sponsors and Collaborators
Alkeus Pharmaceuticals, Inc.
Investigators
Study Director: Leonide Saad, PhD Alkeus Pharmaceuticals, Inc.
  More Information

Additional Information:
Publications:
Responsible Party: Alkeus Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02402660     History of Changes
Other Study ID Numbers: ALK001-P1002  FDA OOPD 
Study First Received: March 9, 2015
Last Updated: May 25, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases

ClinicalTrials.gov processed this record on July 24, 2016