EPI-743 in Friedreich's Ataxia Point Mutations

A Phase 2A Clinical Trial of EPI-743 (Vincerinone™) on Visual Function in Friedreich's Ataxia Patients With Point Mutations

The purpose of this study is to evaluate the effects of EPI-743 in patients with Friedreich's Ataxia point mutations

Study Overview

• Status: Completed
• Conditions: Friedreich's Ataxia
• Intervention / Treatment: Drug: EPI-743

Detailed Description

The primary objective of this study is to investigate whether treatment with EPI-743 has a discernible impact on visual function-including visual acuity, visual fields and color vision as well as on any of a number of functional and subject/clinician-rated scales relevant in the treatment of Friedreich's ataxia, and to determine the safety of treatment with EPI-743.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of genetically confirmed Friedreich's ataxia point mutation.
2. Visual acuity at baseline more than 15 letters on high contrast EDTRS at four meters.
3. FARS score of 20 to 90.
4. Male or female between 18 and 65 years of age.
5. Agreement to use contraception if within reproductive years
6. Hormone replacement therapy, if used, must remain stable for the duration of the study.
7. Willingness and ability to comply with study procedures.
8. Willingness and ability to arrive at study site metropolitan area day prior to evaluations.
9. Abstention from use of dietary supplements and non-prescribed medications at least 30 days prior to initiation of treatment and for the duration of the study. This would specifically include idebenone, Coenzyme Q10 and vitamin E.
10. Abstention from foods or beverages or bars fortified with Coenzyme Q10, vitamin E, super fortified functional foods or beverages at least 30 days prior to initiation of treatment and for the duration of the study.
11. Abstention from use of other investigative or non-approved drugs within 30 days of enrollment and for the duration of the study.
12. Subject can swallow multiple size 0 capsules.
13. Subject has voluntarily signed an IRB approved informed consent form to participate in the study after all relevant aspects of the study have been explained and discussed with the subject.

Exclusion Criteria:

1. Allergy to EPI-743 or sesame oil or nuts.
2. Clinically significant bleeding condition or abnormal PT/PTT INR (INR > two; PTT > two-times normal).
3. Liver insufficiency with LFTs greater than three-times upper normal limit at screening.
4. Renal insufficiency with creatinine > 1.5 at screening.
5. Fat malabsorption syndromes.
6. Any other respiratory chain diseases of the mitochondria or inborn errors of metabolism.
7. Any other ophthalmologic conditions.
8. Clinically significant cardiomyopathy with ejection fraction < 40 percent at screening.
9. Clinically significant arrhythmia within past two years requiring treatment.
10. Surgery planned through the duration of the study, including follow-up.
11. Pregnancy or breastfeeding.
12. Anticoagulant therapy within 30 days of enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EPI-743; EPI-743, oral, 400mg three times daily for 3 months	Drug: EPI-743; EPI-743 (alpha-tocotrienol quinone) is a small molecule therapeutic that was rationally designed to replete reduced glutathione through NQO1-catalyzed electron transfer from NADPH.; Other Names: Vincerinone, alpha-tocotrienol quinone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual function	Low contrast acuity	3 months
Safety parameters	Clinical and laboratory safety parameters	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual function	Visual fields as assessed by Humphrey 30-2 exam; High contrast visual acuity	3 months
Neurologic function	Friedreich's Ataxia Rating Scale	3 months
Physical function	25-foot walk (for subjects capable of completing the test on enrollment);	3 months
Health related quality of life	Patient report via rating scale	3 months
Activities of Daily Living	Patient report via rating scale	3 months
Cardiac indices	Echocardiogram	3 months
Upper extremity function	9 hole peg test	3 months
Disease biomarkers	Glutathione cycle components	3 months

Collaborators and Investigators

• Sponsor: University of South Florida
• Collaborators: Friedreich's Ataxia Research Alliance; Edison Pharmaceuticals Inc

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: October 10, 2013
• First Submitted That Met QC Criteria: October 10, 2013
• First Posted (Estimate): October 14, 2013

Study Record Updates

• Last Update Posted (Estimate): June 29, 2016
• Last Update Submitted That Met QC Criteria: June 28, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Friedreich's ataxia point mutation
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Neurodegenerative Diseases; Dyskinesias; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Mitochondrial Diseases; Cerebellar Diseases; Spinocerebellar Degenerations; Ataxia; Cerebellar Ataxia; Friedreich Ataxia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Tocotrienols; Tocotrienol, alpha
• Other Study ID Numbers: EPI-743 PM