EPI-743 in Friedreich's Ataxia Point Mutations

• ClinicalTrials.gov Identifier: NCT01962363
• Recruitment Status: Completed
• First Posted: October 14, 2013
• Last Update Posted: June 29, 2016
• Sponsor: University of South Florida
• Collaborators: Edison Pharmaceuticals Inc; Friedreich's Ataxia Research Alliance
• Information provided by (Responsible Party): University of South Florida

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Friedreich's Ataxia	Drug: EPI-743	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2A Clinical Trial of EPI-743 (Vincerinone™) on Visual Function in Friedreich's Ataxia Patients With Point Mutations
• Study Start Date: October 2013
• Actual Primary Completion Date: June 2016
• Actual Study Completion Date: June 2016

Arms and Interventions

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 Name: Vincerinone, alpha-tocotrienol quinone

Outcome Measures

Primary Outcome Measures :

1. Visual function [ Time Frame: 3 months ]
   Low contrast acuity
2. Safety parameters [ Time Frame: 3 months ]
   Clinical and laboratory safety parameters

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Florida

University of South Florida

Tampa, Florida, United States, 33612

Sponsors and Collaborators

University of South Florida

Edison Pharmaceuticals Inc

Friedreich's Ataxia Research Alliance

Investigators

• Principal Investigator: Theresa A Zesiewicz, MD; University of South Florida

More Information

• Responsible Party: University of South Florida
• ClinicalTrials.gov Identifier: NCT01962363
• Other Study ID Numbers: EPI-743 PM
• First Posted: October 14, 2013
• Last Update Posted: June 29, 2016
• Last Verified: June 2016

Keywords provided by University of South Florida:

Friedreich's ataxia point mutation

Additional relevant MeSH terms:

Ataxia; Cerebellar Ataxia; Friedreich Ataxia; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Spinocerebellar Degenerations; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Mitochondrial Diseases; Metabolic Diseases; Tocotrienols; Tocotrienol, alpha; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Vitamins; Micronutrients