A Study to Learn More About the Effects and Long-Term Safety of Omaveloxolone (BIIB141) in Children and Teens With Friedreich's Ataxia

Condition(s) studied

Investigational drug(s) / intervention(s)

Omaveloxolone: Administered as specified in the treatment arm.

Placebo: Administered as specified in the treatment arm.

Study summary

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 does the body process omaveloxolone?
* How many participants have adverse events during the study? Adverse events are health problems that may or may not be caused by the study drug.
* Are there any changes in the participants' overall health or heart health? 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. More specifically, researchers will check participants' balance, coordination, movement, and ability to perform daily tasks using the Upright Stability Score (USS). The USS is part of the mFARS questionnaire.

Researchers will also use other questionnaires to learn more about participants' symptoms, quality of life, ability to perform daily living activities, and how severe participants think their disease is.

Researchers will also note any changes as participants go through puberty. Some participants may also be invited to take part in interviews about their experiences during the study or wear devices that measure movement and physical activity during daily life.

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 doctors, and study 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 finish Part 1 may move onto Part 2. During Part 2, participants who are at least 7 years old will be randomly assigned to receive either 150 mg or 250 mg of omaveloxolone once a day for about 104 weeks. Participants younger than 7 years old will receive 150 mg of omaveloxolone once a day for about 104 weeks.
* 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.

Eligibility

Primary outcome measure(s)

• Part 1: Change From Baseline in Upright Stability Score (USS) Subscale E of Modified Friedreich's Ataxia Rating Scale (mFARS) at Week 52 — Baseline, 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 — Baseline (Week 52 of Part 1), 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) — From the first dose of the study drug in Part 2B up to the end of follow-up period in Part 2B (up to Week 104)
• Part 2B: Number of Participants With Change From Baseline in Cardiac Function Assessed by Echocardiogram (ECHO) at Weeks 52 and Week 104 — Baseline (Week 52 of Part 1), Weeks 52 and 104
• Part 2B: Change From Baseline in Height at Weeks 52 and Week 104 — Baseline (Week 52 of Part 1), Weeks 52 and 104
• Part 2B: Change From Baseline in Weight at Weeks 52 and Week 104 — Baseline (Week 52 of Part 1), Weeks 52 and 104
• Part 2B: Change From Baseline in Body Mass Index (BMI) at Weeks 52 and Week 104 — Baseline (Week 52 of Part 1), Weeks 52 and 104
• Part 2B: Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) at Weeks 52 and Week 104 — Baseline (Week 52 of Part 1), Weeks 52 and 104
  The C-SSRS is a low-burden measure of the spectrum of suicidal ideation and behavior that was developed to assess severity and track suicidal events through any treatment of individuals ≥ 6 years of age. The C-SSRS is a clinical interview providing a summary of both ideation and behavior that can be administered by the clinician during any evaluation or risk assessment to identify the level and type of suicidality present. The assessment includes "yes" or "no" responses for 5 questions each, related to suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan) and suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, suicide). Numeric ratings are provided for severity of ideation, from 1 to 5, with 5 being the most severe.
• Part 2B: Percentage of Participants at Each Tanner Stage at Weeks 52 and Week 104 — Baseline (Week 52 of Part 1), Weeks 52 and 104
  Assessment of Tanner stages (a scale of physical development) will be performed by a medical doctor experienced with this assessment. Tanner score ranges from Stage 1 (childhood) to Stage 5 (full physical maturity). Information regarding Tanner staging will be collected at baseline for all participants and will be stopped once the participant reaches Tanner Stage 5 in all gender-appropriate scales.
• Part 2B: Number of Participants at Each Tanner Stage at Weeks 52 and Week 104 — Baseline (Week 52 of Part 1), Weeks 52 and 104
  Assessment of Tanner stages (a scale of physical development) will be performed by a medical doctor experienced with this assessment. Tanner score ranges from Stage 1 (childhood) to Stage 5 (full physical maturity). Information regarding Tanner staging will be collected at baseline for all participants and will be stopped once the participant reaches Tanner Stage 5 in all gender-appropriate scales.

Trial sites (34)

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