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

Official title

A Phase 3 Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Omaveloxolone (BIIB141) in Participants With Friedreich's Ataxia Aged 2 to < 16 Years

Overview

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.

Detailed description

The primary objective of Part 1 is to evaluate the efficacy of omaveloxolone as measured by upright stability score (USS) and the secondary objectives are to evaluate the efficacy of omaveloxolone as measured by additional secondary efficacy outcomes, safety of omaveloxolone and the plasma concentration of omaveloxolone after single and multiple dose administration.

The primary objective of Part 2A is to evaluate the efficacy of omaveloxolone and the secondary objectives are to characterize the efficacy of omaveloxolone as measured by additional secondary outcomes, evaluate the safety and tolerability of omaveloxolone and plasma concentration of omaveloxolone after single and multiple dose administration.

The primary objective for Part 2B is to evaluate the safety and tolerability of long-term omaveloxolone use and the secondary objective is to evaluate the efficacy of omaveloxolone following long-term use.

Interventions

• Drug Omaveloxolone
  Administered as specified in the treatment arm.
• Drug Placebo
  Administered as specified in the treatment arm.

Primary outcome measures

• Part 1: Change From Baseline in Upright Stability Score (USS) Subscale E of Modified Friedreich's Ataxia Rating Scale (mFARS) at Week 52 [Time frame: Baseline, Week 52]
• Part 2A: Change From Baseline in USS Subscale E of mFARS at Week 52 [Time frame: Baseline (Week 52 of Part 1), Week 52]
• Part 2B: Number of Participants With Treatment-Emergent Adverse Event (TEAE) and Treatment-Emergent Serious Adverse Event (TESAE) [Time frame: 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 [Time frame: Baseline (Week 52 of Part 1), Weeks 52 and 104]
• Part 2B: Change From Baseline in Height at Weeks 52 and Week 104 [Time frame: Baseline (Week 52 of Part 1), Weeks 52 and 104]
• Part 2B: Change From Baseline in Weight at Weeks 52 and Week 104 [Time frame: 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 [Time frame: 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 [Time frame: Baseline (Week 52 of Part 1), Weeks 52 and 104]
• Part 2B: Percentage of Participants at Each Tanner Stage at Weeks 52 and Week 104 [Time frame: Baseline (Week 52 of Part 1), Weeks 52 and 104]
• Part 2B: Number of Participants at Each Tanner Stage at Weeks 52 and Week 104 [Time frame: Baseline (Week 52 of Part 1), Weeks 52 and 104]

Secondary outcome measures (12)

• Part 1: Change From Baseline in Friedreich's Ataxia-Health Index (FA-HI) at Week 52 [Time frame: Baseline, Week 52]
• Part 1: Change From Baseline in Modified Friedreich's Ataxia Rating Scale (mFARS) at Week 52 [Time frame: Baseline, Week 52]
• Part 1: Change From Baseline in Patient Global Impressions-Severity (PGI-S) at Week 52 [Time frame: Baseline, Week 52]
• Part 1: Change From Baseline in Clinical Global Impressions-Severity (CGI-S) at Week 52 [Time frame: Baseline, Week 52]
• Part 1: Change From Baseline in Friedreich's Ataxia-Activities of Daily Living (FA-ADL) [Time frame: Baseline, Week 52]
• Part 1: Number of Participants With Treatment-Emergent Adverse Event (TEAE) and Treatment-Emergent Serious Adverse Event (TESAE) [Time frame: From first dose of study drug up to end of follow up period in Part 1 (up to Week 52)]
• Part 1: Number of Participants With Change From Baseline in Cardiac Function Assessed by ECHO at Week 52 [Time frame: Baseline, Week 52]
• Part 1: Change From Baseline in Height at Week 52 [Time frame: Baseline, Week 52]
• Part 1: Change From Baseline in Weight at Week 52 [Time frame: Baseline, Week 52]
• Part 1: Change From Baseline in Body Mass Index (BMI) at Week 52 [Time frame: Baseline, Week 52]
• Part 1: Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) at Week 52 [Time frame: Baseline, Week 52]
• Part 1: Percentage of Participants at Each Tanner Stage at Week 52 [Time frame: Baseline, Week 52]

Eligibility criteria

Part 1: Key inclusion criteria:

• 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

Part 1: Key exclusion criteria:

• 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

Part 2A: Eligibility criteria:

• They have completed Part 1 of the study and no discontinuation criteria have been met.
• Safety and tolerability data from Part 1 are supportive of continuation in the judgement of the investigator.

Part 2B: Eligibility criteria:

• Participants have completed Part 1 of the study and no discontinuation criteria have been met.
• Safety and tolerability data from Part 1 are supportive of continuation in the judgement of the Investigator.

Note: Other protocol-defined Inclusion/Exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 7 centers

• UCLA Neurology Outpatient Clinic at Westwood — Los Angeles
• Norman Fixel Institute for Neurological Diseases UF Health — Gainesville
• USF Health Morsani College of Medicine Department of Neurology — Tampa
• Children's Hospital of Philadelphia - Buerger Center for Advanced Pediatric Care - PIN — Philadelphia
• St. Jude Children's Research Hospital - PIN — Memphis
• CHKD's Health Center - South Campus - PIN — Norfolk
• Seattle Children's Hospital — Seattle

Brazil · 3 centers

• L2 Ip - Instituto de Pesquisas Clinicas Ltda - ME — Brasília
• University of Campinas (UNICAMP) School of Medical Sciences — Campinas
• PSEG Centro de Pesquisa Clinica — São Paulo

Germany · 3 centers

• Universitätsklinikum Aachen — Aachen
• UKGM - Universitätsklinikum Giessen und Marburg GmbH - Standort Gießen — Giessen
• Universitätsklinikum Hamburg Eppendorf — Hamburg

Italy · 3 centers

• Ospedale Pediatrico Bambino Gesù IRCCS — Rome
• IRCCS Eugenio Medea - Polo. Scientifico Veneto — Conegliano
• Fondazione IRCCS Istituto Neurologico Carlo Besta — Milan

United Kingdom · 3 centers

• University College Hospital - PPDS — London
• John Radcliffe Hospital — Oxford
• Sheffield Children's Hospital - PPDS — Sheffield

Australia · 2 centers

• Sydney Children's Hospital — Randwick
• Murdoch Childrens Research Institute (MCRI) — Parkville

Canada · 2 centers

• McGill University — Montreal
• CHU de Quebec -Universite Laval — Québec

France · 2 centers

• CHU de Montpellier- Hôpital Gui De Chauliac — Montpellier
• AP-HP - Hôpital Armand Trousseau — Paris

Spain · 2 centers

• Hospital Sant Joan de Deu - PIN — Espluges de Llobregat
• Hospital Universitario La Paz - PPDS — Madrid

Austria · 1 center

• Universitätsklinikum Innsbruck — Innsbruck

Denmark · 1 center

• Rigshospitalet - Juliane Marie Centret (JMC) Copenhagen — Copenhagen

India · 1 center

• All India Institute of Medical Sciences (AIIMS) - New Delhi — New Delhi

Ireland · 1 center

• CHI at Temple Street — Dublin

Netherlands · 1 center

• Radboud Universitair Medisch Centrum — Nijmegen

Saudi Arabia · 1 center

• King Faisal Specialist Hospital & Research Centre — Riyadh

Turkey (Türkiye) · 1 center

• Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi — Istanbul

Identifiers

NCT: NCT06953583 · 296FA301 · 2025-520896-13

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗