A Study to Assess the Efficacy and Safety of Vatiquinone for the Treatment of Participants With Friedreich Ataxia

NCT ID: NCT04577352

Last Updated: 2024-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 146 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-17
• Study Completion Date: 2023-10-02

Brief Summary

The primary objective of the study is to evaluate the efficacy (using the modified Friedreich Ataxia Rating Scale [mFARS]) and safety of vatiquinone in participants with Friedreich ataxia (FA).

Detailed Description

During the double-blind, placebo-controlled phase, participants will be stratified by baseline mFARS score (<40 versus ≥40), age of disease onset (<14 versus ≥14), and age at screening (≤21 years or >21 years) and randomized to receive either vatiquinone or placebo using interactive response technology (IRT). Following completion of the randomized, double-blind, placebo-controlled phase (72 weeks), participants will enter into an open-label extension phase (24 weeks) during which they will receive open-label treatment with vatiquinone at the dose they received in the randomized phase of the study (for participants entering the extension phase who initially received placebo, the dose of vatiquinone will be determined based on age and weight) and then a safety follow-up (approximately 30 days [±5 days] after last dose or termination visit, whichever is later).

The primary efficacy analysis will be based on change from baseline in mFARS score of participants between 7 and 21 years old. In order to explore the treatment efficacy and safety, approximately an additional 20 participants >21 years of age will be randomized for a total of approximately 126 participants.

Conditions

Friedreich Ataxia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Vatiquinone

Participants will receive vatiquinone capsule at a dose of either 200 milligrams (mg) orally 3 times a day (TID) if ˂12 years of age and weighing ˂25 kilograms (kg) or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 72 weeks during the placebo-controlled phase and for 24 weeks during the open-label extension phase.

Group Type: EXPERIMENTAL

Vatiquinone

Intervention Type: DRUG

Vatiquinone will be administered per dose and schedule specified in the arm.

Placebo

Participants will receive placebo matching to vatiquinone (per age and weight) orally TID for 72 weeks during the placebo-controlled phase and vatiquinone at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 24 weeks during the open-label extension phase.

Group Type: PLACEBO_COMPARATOR

Vatiquinone

Intervention Type: DRUG

Vatiquinone will be administered per dose and schedule specified in the arm.

Placebo

Intervention Type: DRUG

Placebo will be administered per schedule specified in the arm.

Interventions

Vatiquinone

Vatiquinone will be administered per dose and schedule specified in the arm.

Intervention Type: DRUG

Placebo

Placebo will be administered per schedule specified in the arm.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• mFARS ≥20 to ≤70 at baseline
• Must be able to ambulate at least 10 feet in 1 minute with or without assistance (non-wheelchair).
• Friedreich ataxia diagnosis (homozygous for guanine-adenine-adenine [GAA] repeat expansion in intron-1 of frataxin [FXN] gene), confirmed by clinical testing (Note: size of GAA repeat is not required for eligibility)
• Consent to comply with study procedures. For participants under the age of 18 (or age of consent), parent(s)/legal guardian(s) of the participant must agree to comply with the requirements of the study, including the need for frequent and prolonged follow up; parent(s)/legal guardian(s) with custody of the participant must give their consent for participant to enroll in the study.
• Difference in the mFARS at screening and baseline of no more than 4 points.
• Must be able to abstain from anticoagulants and any aspirin (including 81 mg) for 30 days prior to the baseline visit and for the duration of the study; any possible discontinuation of anticoagulants should be monitored and indicated by a specialist (for example, cardiologist, neurologist, or hematologist) and discontinuation will be noted by the prescribing physician.
• Must be able to abstain from potent cytochrome P450 (CYP) 3A4 inducers/inhibitors (for example, ketoconazole, rifampin, St. John's wort, grapefruit juice or any grapefruit product) for at least 30 days prior to enrollment
• Must be able to swallow capsules
• Males and females of childbearing potential must be willing to use an effective method of contraception from the time consent is signed until 30 days after the last dose of study drug or early termination visit. Male participants must agree not to donate sperm during the study and for at least 30 days after the last dose of study drug or early termination visit.

Exclusion Criteria

• Individuals with clinical diagnosis of FA who have point mutations or deletions or other non-GAA expansion mutations
• Previous treatment with vatiquinone
• Allergy to vatiquinone, sesame oil, gelatin (bovine and/or porcine), titanium dioxide, or red iron oxide
• Ejection fraction <50%
• Uncontrolled diabetes (glycated hemoglobin [HbA1c] >7.0%) at the time of screening
• Has current suicidal ideation based on Columbia-Suicide Severity Rating Scale (C-SSRS) within 3 months prior to screening or between screening and baseline at the baseline visit or suicidal behavior within the last year at the screening visit or between screening and baseline at the baseline visit
• Pregnant or lactating participants or those sexually active participants who are unwilling to comply with proper birth control methods; females of childbearing potential must have a negative pregnancy test at screening and during the baseline visit
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2 * upper limit of normal (ULN) at time of screening
• International normalized ratio (INR) ≥1.5 * ULN at time of screening or clinically significant (CS) bleeding, as determined by the investigator
• Serum creatinine ≥1.5 * ULN at time of screening
• Comorbidities that may confound study results (for example, fat malabsorption syndrome, other mitochondrial disorder) in the opinion of the investigator
• Participation in any other interventional clinical trial or received any investigational drug in any other clinical trial within 60 days prior to the baseline visit. Participants may be rescreened after the exclusionary period of 60 days has passed.
• Concomitant use of interventional coenzyme Q10 (CoQ10), vitamin E, or any approved or non-approved medication for FA within 30 days prior to the screening visit. These prohibited medications can be discontinued at the screening visit; if this is the case, the mFARS assessment must be repeated to confirm inclusion eligibility after a minimum of 30 days post-discontinuation and there must be no more than a 4-point difference in mFARS assessed from the post-discontinuation visit to the baseline visit.
• Illicit drug use 30 days prior to screening and during the study is prohibited.

• Minimum Eligible Age: 7 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PTC Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UCLA

Los Angeles, California, United States

University of Florida

Gainesville, Florida, United States

University of South Florida

Tampa, Florida, United States

University of Iowa

Iowa City, Iowa, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Murdoch Children's Research Institute

Parkville, Victoria, Australia

University of Campinas (UNICAMP) - School of Medical Sciences, Dept of Neurology

São Paulo, , Brazil

Centre de Recherche du Centre Hospitalier de l'Université de Montreal (CRCHUM)

Montreal, Quebec, Canada

CHU Sainte-Justine

Montreal, Quebec, Canada

Hôpital Pitié-Salpêtrière, Institut du Cerveau (Paris Brain Institute)

Paris, , France

Department of Neurology and Hertie-Institute for Clinical Brain Research German Center of Neurodegenerative Diseases (DZNE)

Tübingen, , Germany

Ospedale Pediatrico Bambino Gesu' IRCCS

Roma, , Italy

CBR Neurogenetic Research Clinic, University of Auckland

Auckland, , New Zealand

Hospital Sant Joan de Déu Barcelona Unidad de Enfermedades Neuromusculares

Barcelona, , Spain

Countries

United States; Australia; Brazil; Canada; France; Germany; Italy; New Zealand; Spain

Other Identifiers

PTC743-NEU-003-FA

Identifier Type: -

Identifier Source: org_study_id