In this study, researchers will learn more about omaveloxolone, also known as BIIB141 or SKYCLARYS®. Omaveloxolone is already approved for people with Friedreich's Ataxia (FA) who are 16 years of age or older. However, it is not yet available for younger teens and children. The main goal of this study is to learn how omaveloxolone affects symptoms of FA and its safety in younger participants between the ages of 2 and 15 years old.
The main questions researchers want to answer in this study are:
* How does omaveloxolone affect the participants' FA symptoms? * How many participants have adverse events during the study? * Are there any changes in the participants' overall health or heart health? Adverse events are health problems that may or may not be caused by the study drug.
Researchers will use the modified Friedreich's Ataxia Rating Scale (mFARS) to test nerve function. The mFARS tests movement ability, balance, coordination, speech, and arm and leg functions.
They will also use a number of questionnaires to learn more about participants' quality of life, muscle strength, and ability to perform daily tasks. Researchers will also note any changes as participants go through puberty.
Finally, researchers will learn more about how the body processes omaveloxolone in children and teenagers.
This study will be done in 2 parts as follows:
* Participants will be screened for up to 4 weeks to check if they can join the study. * In Part 1, participants will be randomly assigned to take either omaveloxolone or a placebo by mouth once a day for about 1 year. A placebo looks like the study drug but contains no real medicine. * Part 1 will be double blind. This means that the participants, study doctor, and site staff will not know if the participants are receiving omaveloxolone or a placebo. * Including screening, participants will have up to 9 clinic visits and 1 phone call during Part 1. If a participant does not join Part 2, they will have another safety follow-up phone call a month after their last dose of omaveloxolone. * Participants who complete Part 1 will move onto Part 2 where everyone will receive omaveloxolone for about 2 years. * During Part 2, participants will have up to 8 clinic visits and 1 phone call. Participants will also have a follow-up phone call about a month after they stop taking omaveloxolone. * In total, participants will have up to 17 clinic visits and 3 phone calls. Each participant will be in the study for up to 3 years.
Diagnosed with genetically confirmed Friedreich's Ataxia (FA), i.e., homozygous for guanine-adenine-adenine (GAA) repeat expansion in intron-1 of the frataxin gene, or GAA repeat expansion in 1 allele and with point mutations or deletions, or other non-GAA expansion mutations in the other allele.
Symptomatic for FA as confirmed by clinician assessment. a. Children 7 to < 16 years must also have an upright stability score (USS) score of 10 to ≤ 34 at baseline
Glycosylated hemoglobin A1C (HbA1c) > 11%
B-type natriuretic peptide (BNP) > 200 picograms per milliliter (pg/mL) at screening
Ejection fraction (EF) < 40% [based on echocardiogram (ECHO) performed at screening visit]
Clinically significant cardiac disease except mild to moderate cardiomyopathy
Parallel
Omaveloxolone
DrugAdministered as specified in the treatment arm.
Placebo
DrugAdministered as specified in the treatment arm.
Part 1: Change From Baseline in Upright Stability Score (USS) Subscale E of Modified Friedreich's Ataxia Rating Scale (mFARS) at Week 52
The mFARS is a validated and sensitive rating scale that was developed to quantitatively assess the severity of the neurologic features of FA in adults and adolescents. Scores on the mFARS range from 0 to 93, with lower scores indicating better neurological function. The subscales of the mFARS assessment and maximum score for each subscale are: bulbar function (Subscale A; 2 assessments of speech and cough; maximum score = 5), upper limb coordination (Subscale B; 5 assessments of coordination of movement and function in arms and hands with each limb scored individually; maximum score = 36), lower limb coordination (Subscale C; 2 assessments of coordination of movement and function of lower limbs with each limb scored individually; maximum score = 16), and upright stability (USS, Subscale E; 9 assessments of sitting posture, stance, tandem walk, and gait assessments; maximum score = 36).
Part 2A: Change From Baseline in USS Subscale E of mFARS at Week 52
The mFARS is a validated and sensitive rating scale that was developed to quantitatively assess the severity of the neurologic features of FA in adults and adolescents. Scores on the mFARS range from 0 to 93, with lower scores indicating better neurological function. The subscales of the mFARS assessment and maximum score for each subscale are: bulbar function (Subscale A; 2 assessments of speech and cough; maximum score = 5), upper limb coordination (Subscale B; 5 assessments of coordination of movement and function in arms and hands with each limb scored individually; maximum score = 36), lower limb coordination (Subscale C; 2 assessments of coordination of movement and function of lower limbs with each limb scored individually; maximum score = 16), and upright stability (USS, Subscale E; 9 assessments of sitting posture, stance, tandem walk, and gait assessments; maximum score = 36).
Part 2B: Number of Participants With Treatment-Emergent Adverse Event (TEAE) and Treatment-Emergent Serious Adverse Event (TESAE)
Part 2B: Number of Participants With Change From Baseline in Cardiac Function Assessed by Echocardiogram (ECHO) at Weeks 52 and Week 104
Part 1: Change From Baseline in Friedreich's Ataxia-Health Index (FA-HI) at Week 52
The FA-HI is a participant reported survey that assesses overall disease burden on a 100-point scale, with 0 representing no disease burden and 100 representing the maximum level of disease burden containing 113 symptoms questions representing 18 symptomatic subscales.
Part 1: Change From Baseline in Modified Friedreich's Ataxia Rating Scale (mFARS) at Week 52
The mFARS is a validated and sensitive rating scale that was developed to quantitatively assess the severity of the neurologic features of FA in adults and adolescents. Scores on the mFARS range from 0 to 93, with lower scores indicating better neurological function. The subscales of the mFARS assessment and maximum score for each subscale are: bulbar function (Subscale A; 2 assessments of speech and cough; maximum score = 5), upper limb coordination (Subscale B; 5 assessments of coordination of movement and function in arms and hands with each limb scored individually; maximum score = 36), lower limb coordination (Subscale C; 2 assessments of coordination of movement and function of lower limbs with each limb scored individually; maximum score = 16), and upright stability (USS, Subscale E; 9 assessments of sitting posture, stance, tandem walk, and gait assessments; maximum score = 36).
Part 1: Change From Baseline in Patient Global Impressions-Severity (PGI-S) at Week 52
PGI-S will be conducted for participants 7 to \< 16 years of age. These are clinically meaningful outcome measures that are participant-relevant across all age groups and disease severities for this population. PGI -S is a 1-item questionnaire where the response is recorded on a 4-point scale scored as: 1-normal, 2-mild, 3-moderate, or 4-severe.
Part 1: Change From Baseline in Clinical Global Impressions-Severity (CGI-S) at Week 52
The CGI-S will be conducted for all enrolled participants, 2 to \< 16 years of age. The CGI-S rating evaluates the severity of individual symptoms and treatment response in participants with mental disorders. The CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment. A rating of 1 is considered normal, or with the least severe symptoms, a rating of 7 is extremely ill, or the worst symptoms.
