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

NCT04577352 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: PTC743-NEU-003-FA
• Study Type: interventional
• Target: 146
• Locations: 9 countries
• Sites: 14

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).

Conditions

Friedreich Ataxia

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in the mFARS Score at Week 72 - Modified Intent-to-treat (mITT) Analysis Set

  mFARS is a 93-item scale; comprised of neurologic component of FARS. For each item, responses categorize the corresponding neurological finding, with a score ranging from 0 to 3, 4, or 5 with 0 being normal and higher numbers indicative of greater impairment. Total mFARS scores for each subscale: bulbar (0 to 5), upper limb coordination (0 to 36), lower limb coordination (0 to 16), and upright stability (0 to 36). mFARS total score was a composite score of all 4 subscales, ranging from 0 (normal) to 93 (greater impairment). A lower score = better neurological function. Missing data was imputed using pattern mix model multiple imputation. Least square (LS) mean and standard error (SE) was calculated using mixed-model repeated measures (MMRM).

  Baseline, Week 72

• Change From Baseline in the mFARS Score at Week 72 - Intent-to-treat (ITT) Analysis Set

  mFARS is a 93-item scale; comprised of neurologic component of FARS. For each item, responses categorize the corresponding neurological finding, with a score ranging from 0 to 3, 4, or 5 with 0 being normal and higher numbers indicative of greater impairment. Total mFARS scores for each subscale: bulbar (0 to 5), upper limb coordination (0 to 36), lower limb coordination (0 to 16), and upright stability (0 to 36). mFARS total score was a composite score of all 4 subscales, ranging from 0 (normal) to 93 (greater impairment). A lower score = better neurological function. Missing data was imputed using pattern mix model multiple imputation. LS mean and SE was calculated using MMRM.

  Baseline, Week 72

Secondary Outcomes (6)

• Change From Baseline in Friedreich Ataxia Rating Scale Activities of Daily Living (FARS-ADL) Score at Week 72 - mITT Analysis Set

  Baseline, Week 72

• Change From Baseline in FARS-ADL Score at Week 72 - ITT Analysis Set

  Baseline, Week 72

• Change From Baseline in 1-Minute Walk Test (1MWT) at Week 72 - mITT Analysis Set

  Baseline, Week 72

• Change From Baseline in 1MWT at Week 72 - ITT Analysis Set

  Baseline, Week 72

• Number of Falls Per 28 Days Over Every 24-Week Period - mITT Analysis Set

  Week 1-24, Week 25-48, and Week 49-72

Other Outcomes (4)

• Change From Baseline in the Upright Stability Subscale of the mFARS at Week 72 - mITT Analysis Set

  Baseline, Week 72

• Change From Baseline in the Upright Stability Subscale of the mFARS at Week 72 - ITT Analysis Set

  Baseline, Week 72

• Change From Baseline in the Modified Fatigue Impact Scale (MFIS) Score at Week 72 - mITT Analysis Set

  Baseline, Week 72

Study Arms (2)

Vatiquinone

EXPERIMENTAL

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.

Drug: Vatiquinone

Placebo

PLACEBO COMPARATOR

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.

Drug: Vatiquinone; Drug: Placebo

Interventions

Vatiquinone DRUG

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

Placebo; Vatiquinone

Placebo DRUG

Placebo will be administered per schedule specified in the arm.

Placebo

Eligibility Criteria

• Age: 7 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• Illicit drug use 30 days prior to screening and during the study is prohibited.

Sponsors & Collaborators

• PTC Therapeutics: lead

Study Sites (14)

UCLA

Los Angeles, California, 90095, United States

Location

University of Florida

Gainesville, Florida, 32608, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Murdoch Children's Research Institute

Parkville, Victoria, 3052, Australia

Location

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

São Paulo, 13083-887, Brazil

Location

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

Montreal, Quebec, H2X 0A9, Canada

Location

CHU Sainte-Justine

Montreal, Quebec, H3T1C5, Canada

Location

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

Paris, 75646, France

Location

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

Tübingen, 72076, Germany

Location

Ospedale Pediatrico Bambino Gesu' IRCCS

Roma, 00165, Italy

Location

CBR Neurogenetic Research Clinic, University of Auckland

Auckland, 1023, New Zealand

Location

Hospital Sant Joan de Déu Barcelona Unidad de Enfermedades Neuromusculares

Barcelona, 08950, Spain

Location

MeSH Terms

Conditions

Friedreich Ataxia

Interventions

alpha-tocotrienol quinone

Condition Hierarchy (Ancestors)

Spinocerebellar Degenerations; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Patient Advocacy
• Organization: PTC Therapeutics, Inc.

medinfo@ptcbio.com

1-866-562-4620

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2020
• First Posted: October 6, 2020
• Study Start: December 17, 2020
• Primary Completion: April 4, 2023
• Study Completion: October 2, 2023
• Last Updated: April 13, 2026
• Results First Posted: April 8, 2026

Record last verified: 2024-06

Locations

DE (1); ES (1); AU (1); IT (1); BR (1); US (5); NZ (1); FR (1); CA (2)