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).
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
146
Vatiquinone will be administered per dose and schedule specified in the arm.
Placebo will be administered per schedule specified in the arm.
UCLA
Los Angeles, California, United States
University of Florida
Gainesville, Florida, United States
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).
Time frame: 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.
Time frame: Baseline, Week 72
Change From Baseline in Friedreich Ataxia Rating Scale Activities of Daily Living (FARS-ADL) Score at Week 72 - mITT Analysis Set
The ADL component of the FARS includes 9 subscales: speech, swallowing, cutting food and handling utensils, dressing, personal hygiene, falling, walking, quality of sitting position, and bladder function. Each of these subscales is rated on a 5-point scale where 0=normal to 4=severe disability/inability to carry out activity independently for a total possible score of 0 to 36, with higher scores representing greater disability/dependency. Missing data was imputed using pattern mix model multiple imputation. LS mean and SE was calculated using MMRM.
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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
...and 4 more locations
Time frame: Baseline, Week 72
Change From Baseline in FARS-ADL Score at Week 72 - ITT Analysis Set
The ADL component of the FARS includes 9 subscales: speech, swallowing, cutting food and handling utensils, dressing, personal hygiene, falling, walking, quality of sitting position, and bladder function. Each of these subscales is rated on a 5-point scale where 0=normal to 4=severe disability/inability to carry out activity independently for a total possible score of 0 to 36, with higher scores representing greater disability/dependency. Missing data was imputed using pattern mix model multiple imputation. LS mean and SE was calculated using MMRM.
Time frame: Baseline, Week 72
Change From Baseline in 1-Minute Walk Test (1MWT) at Week 72 - mITT Analysis Set
The 1MWT is a timed performance test used to measure functional ability, walking endurance, balance, and muscle performance by measuring maximal walking speed in 1 minute. Participants were instructed to walk as quickly as possible for 1 minute without running. Maximal walking speed was measured upon completion of the walk and distance was recorded. The mean change from baseline in the distance the participant walked is reported. Missing data was imputed using pattern mix model multiple imputation. LS mean and SE was calculated using MMRM.
Time frame: Baseline, Week 72
Change From Baseline in 1MWT at Week 72 - ITT Analysis Set
The 1MWT is a timed performance test used to measure functional ability, walking endurance, balance, and muscle performance by measuring maximal walking speed in 1 minute. Participants were instructed to walk as quickly as possible for 1 minute without running. Maximal walking speed was measured upon completion of the walk and distance was recorded. The mean change from baseline in the distance the participant walked is reported. Missing data was imputed using pattern mix model multiple imputation. LS mean and SE was calculated using MMRM.
Time frame: Baseline, Week 72
Number of Falls Per 28 Days Over Every 24-Week Period - mITT Analysis Set
Each participant was required to maintain a fall log, which included the date and time of each fall. Falls as defined by World Health Organization as "inadvertently coming to rest on the ground, floor or other lower level, excluding intentional change in position to rest in furniture, wall or other objects," were reported. Number of falls per 28 days during a time interval was calculated as the number of falls during the period divided by the number of days during the interval, and multiplied by 28. The falls that occurred on or after the first Loss of Ambulation visit were excluded from the analysis.
Time frame: Week 1-24, Week 25-48, and Week 49-72
Number of Falls Per 28 Days Over Every 24-Week Period - ITT Analysis Set
Each participant was required to maintain a fall log, which included the date and time of each fall. Falls as defined by World Health Organization as "inadvertently coming to rest on the ground, floor or other lower level, excluding intentional change in position to rest in furniture, wall or other objects," were reported. Number of falls per 28 days during a time interval was calculated as the number of falls during the period divided by the number of days during the interval, and multiplied by 28. The falls that occurred on or after the first Loss of Ambulation visit were excluded from the analysis.
Time frame: Week 1-24, Week 25-48, and Week 49-72