Phase 3 Randomized, Double-Blind, Placebo-Controlled Study of Omaveloxolone in Pediatric Friedreich’s Ataxia Patients Aged 2 to <16 Years

The primary objective of this study is to evaluate the efficacy of omaveloxolone in patients with Friedreich’s ataxia at week 52. The secondary objectives include:

• Assessment of safety and tolerability through week 52 and during long-term administration.
• Evaluation of pharmacokinetics by measuring plasma concentration following single and multiple doses.
• Investigation of pharmacodynamics.
• Determination of efficacy following long-term use.

This clinical trial involves a total of 199 participants diagnosed with Friedreich’s ataxia. The study population consists of both male and female patients who are considered vulnerable. For the first stage of the study, subjects must be between 2 and 16 years of age at the time of informed consent. Inclusion requires a genetically confirmed diagnosis, specifically characterized by a homozygous GAA repeat expansion in intron-1 of the frataxin gene, or a combination of a GAA repeat expansion in one allele with point mutations, deletions, or other non-GAA expansion mutations in the opposite allele. Additionally, participants must be symptomatic. The second stage of the study includes individuals who have successfully completed the initial randomized controlled trial without meeting any discontinuation criteria, provided that the investigator deems the safety and tolerability data sufficient for continued participation.

This Phase 3 study is a two-part, randomized, double-blind, placebo-controlled trial and an open-label extension designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of omaveloxolone in individuals with Friedreich’s ataxia aged 2 to less than 16 years. Part 1 focuses on evaluating efficacy at Week 52, while Part 2 assesses the long-term safety and tolerability of the investigational product. Participants must have a genetically confirmed diagnosis and be symptomatic. The sequence of the study involves an initial screening period followed by the randomized controlled phase. Upon successful completion of Part 1, and provided no discontinuation criteria are met and the investigator deems it appropriate based on safety data, participants may transition to the open-label extension in Part 2. The primary efficacy endpoint for Part 1 is the change from baseline in the modified Friedreich’s ataxia rating scale. Early termination from the study may occur if specific discontinuation criteria are met during the initial phase.

The experimental treatment consists of omaveloxolone administered as 50 mg hard capsules. This medication is intended for oral administration in participants diagnosed with Friedreich ataxia.

The control group receives a placebo in the form of matching hard capsules.

The efficacy of omaveloxolone in participants with Friedreich’s ataxia will be evaluated through multiple endpoints. In Part 1, the primary efficacy endpoint is the change from baseline in the Unified Scale Score, specifically the modified Friedreich’s Ataxia Rating Scale (mFARS), measured at Week 52. Secondary efficacy assessments include changes from baseline in the Friedreich Ataxia Activities of Daily Living (FA-ADL), the Friedreich Ataxia Health Index (FA-HI), and the Patient Global Impression of Severity (PGI-S) and Clinician Global Impression of Severity (CGI-S).

Additional efficacy parameters assessed during Part 1 include changes from baseline in echocardiography (ECHO), height, weight, Body Mass Index (BMI), the Columbia-Suicide Severity Rating Scale (C-SSRS), and the Tanner scale. During Part 2, the open-label extension, efficacy is assessed via changes from baseline in mFARS, FA-ADL, FA-HI, PGI-S, and CGI-S.