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

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ClinicalTrials.gov Identifier: NCT02402660
Recruitment Status : Recruiting
First Posted : March 30, 2015
Last Update Posted : January 16, 2018
Sponsor:
Information provided by (Responsible Party):
Alkeus Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE March 9, 2015
First Posted Date  ICMJE March 30, 2015
Last Update Posted Date January 16, 2018
Study Start Date  ICMJE August 2015
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 27, 2015)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02402660 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2015)
  • Effects of ALK-001 on the progression of Stargardt disease [ Time Frame: 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 [ Time Frame: Up to 24 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2015)
  • Effects of ALK-001 on the progression of Stargardt disease [ Time Frame: From baseline to 24 months ]
    Combination of changes in atrophic lesion size, best corrected visual acuity (BCVA), and ocular assessments.
  • Pharmacokinetics of ALK-001 [ Time Frame: Up to 24 months ]
    Pharmacokinetic profile derived from plasma concentrations of ALK-001 and metabolites.
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 2 Tolerability and Effects of ALK-001 on Stargardt Disease
Official Title  ICMJE 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
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 12 and 60 years old.

Funding Source - FDA OOPD

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.

Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Stargardt Disease
  • Stargardt Macular Degeneration
  • Stargardt Macular Dystrophy
  • Autosomal Recessive Stargardt Disease 1 (ABCA4-related)
Intervention  ICMJE
  • Drug: ALK-001
    Daily, oral administration for 24 months
    Other Names:
    • C20-D3-Retinyl Acetate
    • C20 Deuterated vitamin A
  • Drug: Placebo
    Daily, oral administration for 24 months
Study Arms
  • Experimental: ALK-001
    Daily, oral administration of one capsule. See details below.
    Intervention: Drug: ALK-001
  • Placebo Comparator: Placebo
    Daily, oral administration of one capsule. See details below.
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 27, 2015)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date December 2019
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender
Sexes Eligible for Study: All
Ages 12 Years to 60 Years   (Child, Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE
Contact: Leonide Saad, PhD 800-287-2755 trials@alkeus.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02402660
Other Study ID Numbers  ICMJE ALK001-P1002
R01FD004098 ( U.S. FDA Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Alkeus Pharmaceuticals, Inc.
Study Sponsor  ICMJE Alkeus Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Hendrik Scholl, MD University of Basel
Study Director: Leonide Saad, PhD Alkeus Pharmaceuticals, Inc.
PRS Account Alkeus Pharmaceuticals, Inc.
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP