A Randomized, Parallel-Arm, Double-Blind, Placebo-Controlled Study With Open-Label Extension to Assess the Efficacy and Safety of Vatiquinone for the Treatment of Friedreich Ataxia (MOVE-FA)
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- PTC Therapeutics
- Enrollment
- 146
- Locations
- 21
- Primary Endpoint
- Change From Baseline in the Modified Friedreich Ataxia Rating Scale (mFARS) Score at Week 72
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 7 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
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.
Intervention: Placebo (Drug)
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.
Intervention: Vatiquinone (Drug)
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.
Intervention: Vatiquinone (Drug)
Outcomes
Primary Outcomes
Change From Baseline in the Modified Friedreich Ataxia Rating Scale (mFARS) Score at Week 72
Time Frame: Baseline, Week 72
Friedreich Ataxia Rating Scale (FARS) is a disease-specific scale that measures progression of neurological effects of FA. The mFARS is a validated and reliable 93- item scale; comprised of the neurologic component of the FARS and evaluates bulbar, upper limb, lower limb, and upright stability/gait function. For each item, responses categorize the corresponding neurological finding, and the findings are assigned a score ranging from 0 to 3, 4, or 5 with 0 being normal and higher numbers indicative of greater impairment.
Change From Baseline in the mFARS Score at Week 72 - Modified Intent-to-treat (mITT) Analysis Set
Time Frame: Baseline, Week 72
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).
Change From Baseline in the mFARS Score at Week 72 - Intent-to-treat (ITT) Analysis Set
Time Frame: Baseline, Week 72
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.
Secondary Outcomes
- Change From Baseline in 1-Minute Walk Test (1MWT) at Week 72(Baseline, Week 72)
- Number of Falls Through Week 72(Baseline through Week 72)
- Change From Baseline in Friedreich Ataxia Rating Scale Activities of Daily Living (FARS-ADL) Score at Week 72(Baseline, Week 72)
- 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)
- Number of Falls Per 28 Days Over Every 24-Week Period - ITT Analysis Set(Week 1-24, Week 25-48, and Week 49-72)