Clinical trial NCT04577352: A Study to Assess the Efficacy and Safety of Vatiquinone for the Treatment of Participants With Friedreich Ataxia
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Friedreich Ataxia
Lead sponsor: PTC Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-10-06
Enrollment: 146
Sex: ALL
Minimum age (years): 7
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change From Baseline in the Modified Friedreich Ataxia Rating Scale (mFARS) Score at Week 72
timeFrame: Baseline, Week 72
Secondary outcomes:
measure: Change From Baseline in Friedreich Ataxia Rating Scale Activities of Daily Living (FARS-ADL) Score at Week 72
timeFrame: Baseline, Week 72
measure: Change From Baseline in 1-Minute Walk Test (1MWT) at Week 72
timeFrame: Baseline, Week 72
measure: Number of Falls Through Week 72
timeFrame: Baseline through Week 72
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Parkville
country: Australia
facility: Murdoch Children's Research Institute
state: Victoria
city: São Paulo
country: Brazil
facility: University of Campinas (UNICAMP) - School of Medical Sciences, Dept of Neurology
city: Montreal
country: Canada
facility: Centre de Recherche du Centre Hospitalier de l'Université de Montreal (CRCHUM)
state: Quebec
city: Montréal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
city: PARIS cedex
country: France
facility: Hôpital Pitié-Salpêtrière, Institut du Cerveau (Paris Brain Institute)
city: Tuebingen
country: Germany
facility: Department of Neurology and Hertie-Institute for Clinical Brain Research German Center of Neurodegenerative Diseases (DZNE)
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesu' IRCCS
city: Auckland
country: New Zealand
facility: CBR Neurogenetic Research Clinic, University of Auckland
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu Barcelona Unidad de Enfermedades Neuromusculares
Study officials:
References: