Clinical trial NCT06953583: A Study to Learn More About the Effects and Long-Term Safety of BIIB141 (Omaveloxolone) in Participants With Friedreich's Ataxia Aged 2 to 15 Years Old
Official title: A Phase 3, 2-Part, Randomized, Double-Blind, Placebo-Controlled Study (Part 1) and Open-Label Extension (Part 2) to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Omaveloxolone (BIIB141) in Participants With Friedreich's Ataxia Aged 2 to < 16 Years
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Friedreich Ataxia
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2025-05-01
Enrollment: 255
Sex: ALL
Minimum age (years): 2
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this study, researchers will learn more about the effects and safety of BIIB141, also known as omaveloxolone or SKYCLARYS®. This drug has been approved, or made available for doctors to prescribe, for people with Friedreich's Ataxia (FA) who are at least 16 years old. But, it is not yet available for children and teens with FA who are younger than 16 years old. The main objective of this study is to learn how BIIB141 works in the body and about its safety in children and teens who are 2 to 15 years old.

The main questions researchers want to answer in this study are:

* How does BIIB141 affect the participants' FA symptoms balance and stability?
* How many participants have medical problems during the study?
* Are there any changes in the participants' overall health during the study?
* Are there any changes in the participants' heart health?
* Are there any changes in how the participants move through puberty? Puberty is the time in someone's life when their body changes from a child to an adult.

Researchers will also learn more about:

- How the body processes BIIB141 in children and teens

This study will be done as follows:

* Participants will be screened to check if they can join the study. The screening period will be up to 28 days, after which participants will check into their study research center.
* There are 2 parts in this study. During Part 1, participants will take either BIIB141 or a placebo once a day.
* In Part 1, participants will take BIIB141 or the placebo in a study research center on Day 1, and then at in-person visits at Week 4, Week 12, Week 26, and Week 52. On all other days, they will take BIIB141 or the placebo at home. Part 1 lasts up to 52 weeks.
* During Part 2, participants from Part 1 will either continue taking BIIB141 or start it if they were taking the placebo. Part 2 will last up to 104 weeks.
* In Part 1, participants will have up to 10 visits to their study research center and a phone call at Week 2. In Part 2, participants will have visits at Weeks 4, 8,12, 26, and every 26 weeks after that until they leave the study, and a phone call at Week 2. There will be a final phone call to check on the participants' health 31 days after their last dose.
* Each participant will be in the study for up to about 3 years

Detailed description: The primary objective of Part 1 randomized controlled trial (RCT) is to evaluate the efficacy of omaveloxolone at Week 52 and the secondary objectives are to evaluate safety of omaveloxolone through Week 52 and the concentration of omaveloxolone after single and multiple dose administration. The primary objective of Part 2 open-label extension (OLE) trial 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.

Eligibility criteria: Part 1 RCT: 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 reported by the participant and/or the parent/caregiver a. Children 7 to \< 16 years must also have an upright stability score (USS) score of 10 to ≤ 34 at baseline

Part 1 RCT: 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 2 OLE: Eligibility criteria:

* Participants have completed Part 1 RCT of the study and no discontinuation criteria have been met
* Safety and tolerability data from Part 1 RCT are supportive of continuation in the judgement of the investigator

  1. If alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or total bilirubin (TBL) are \> 2× upper limit of normal (ULN) at the previous visit assessment, Part 2 Day 1 should be delayed until ALT and AST are \< 1.5× ULN and TBL is \< 2× ULN
  2. If BNP is \> 200 pg/mL at the previous visit assessment, Part 2 Day 1 should be delayed until BNP is \< 200 pg/mL
  3. If any other clinically significant laboratory abnormalities are present based on the previous visit assessments, Part 2 Day 1 should be delayed until the abnormalities are resolved
  4. In the event of intercurrent illness or other change in health status of the participant, additional Part 1 screening assessments may be repeated prior to initiation of Part 2, based on the judgement of the investigator in consultation with the medical monitor

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

Primary outcomes:
measure: Part 1 RCT: Change From Baseline in Upright Stability Score (USS) Subscale E of Modified Friedreich's Ataxia Rating Scale (mFARS)
timeFrame: Baseline, Week 52
measure: Part 2 OLE: Number of Participants With Treatment-Emergent Adverse Event (TEAE) and Treatment-Emergent Serious Adverse Event (TESAE)
timeFrame: From the first dose of the study drug in Part 2 up to the end of follow-up period in Part 2 (up to Week 105)
measure: Part 2 OLE: Number of Participants With Change From Baseline in Cardiac Function Assessed by Echocardiogram (ECHO)
timeFrame: Baseline (Week 52) up to Week 104
measure: Part 2 OLE: Change From Baseline in Height
timeFrame: Baseline (Week 52) up to Week 104
measure: Part 2 OLE: Change From Baseline in Weight
timeFrame: Baseline (Week 52) up to Week 104
measure: Part 2 OLE: Change From Baseline in Body Mass Index (BMI)
timeFrame: Baseline (Week 52) up to Week 104
measure: Part 2 OLE: Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline (Week 52) up to Week 104
measure: Part 2 OLE: Percentage of Participants at Each Tanner Stage
timeFrame: Baseline (Week 52) up to Week 104
measure: Part 2 OLE: Number of Participants at Each Tanner Stage
timeFrame: Baseline (Week 52) up to Week 104
Secondary outcomes:
measure: Part 1 RCT: Change From Baseline in Friedreich's Ataxia-Health Index (FA-HI)
timeFrame: Baseline, Week 52
measure: Part 1 RCT: Change From Baseline in Modified Friedreich's Ataxia Rating Scale (mFARS)
timeFrame: Baseline, Week 52
measure: Part 1 RCT: Change From Baseline in Patient Global Impressions-Severity (PGI-S)
timeFrame: Baseline, Week 52
measure: Part 1 RCT: Change From Baseline in Clinical Global Impressions-Severity (CGI-S)
timeFrame: Baseline, Week 52
measure: Part 1 RCT: Change From Baseline in Friedreich's Ataxia-Activities of Daily Living (FA-ADL)
timeFrame: Baseline, Week 52
measure: Part 1 RCT: Number of Participants With Treatment-Emergent Adverse Event (TEAE) and Treatment-Emergent Serious Adverse Event (TESAE)
timeFrame: From first dose of study drug up to end of follow up period in Part 1 RCT (up to Week 54)
measure: Part 1 RCT: Number of Participants With Change From Baseline in Cardiac Function Assessed by Echocardiogram (ECHO)
timeFrame: Baseline, Weeks 26 and 52
measure: Part 1 RCT: Change From Baseline in Height
timeFrame: Baseline up to Week 52
measure: Part 1 RCT: Change From Baseline in Weight
timeFrame: Baseline up to Week 52
measure: Part 1 RCT: Change From Baseline in Body Mass Index (BMI)
timeFrame: Baseline up to Week 52
measure: Part 1 RCT: Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline up to week 52
measure: Part 1 RCT: Percentage of Participants at Each Tanner Stage
timeFrame: Screening and Week 52
measure: Part 1 RCT: Number of Participants at Each Tanner Stage
timeFrame: Screening and Week 52
measure: Part 1 RCT: Plasma Concentrations of Omaveloxolone
timeFrame: Pre-dose and post-dose on Day 1, Weeks 4, 12 and 26
measure: Part 2 OLE: Change From Baseline in Modified Friedreich's Ataxia Rating Scale (mFARS), Including Upright Stability Score (USS)
timeFrame: Baseline (Week 52) up to Week 104
measure: Part 2 OLE: Change From Baseline in Friedreich's Ataxia-Activities of Daily Living (FA-ADL)
timeFrame: Baseline (Week 52) up to Week 104
measure: Part 2 OLE: Change From Baseline in Friedreich's Ataxia-Health Index (FA-HI)
timeFrame: Baseline (Week 52) up to Week 104
measure: Part 2 OLE: Change From Baseline in Patient Global Impressions-Severity (PGI-S)
timeFrame: Baseline (Week 52) up to Week 104
measure: Part 2 OLE: Change From Baseline in Clinical Global Impressions-Severity (CGI-S)
timeFrame: Baseline (Week 52) up to Week 104
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Neurology Outpatient Clinic at Westwood
state: California
city: Gainesville
country: United States
facility: Norman Fixel Institute for Neurological Diseases UF Health
state: Florida
city: Tampa
country: United States
facility: USF Health Morsani College of Medicine Department of Neurology
state: Florida
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia Buerger Center
state: Pennsylvania
city: Memphis
country: United States
facility: St Jude Children's Research Hospital
state: Tennessee
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughters
state: Virginia
city: Parkville
country: Australia
facility: Murdoch Childrens Research Institute (MCRI)
state: Victoria
city: Innsbruck
country: Austria
facility: Universitätsklinikum Innsbruck
city: Brasília
country: Brazil
facility: L2 Ip - Instituto de Pesquisas Clinicas Ltda - ME
state: Distrito Federal
city: Campinas
country: Brazil
facility: University of Campinas (UNICAMP) School of Medical Sciences
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: PSEG Centro de Pesquisa Clinica
city: Montreal
country: Canada
facility: McGill University
state: Quebec
city: Copenhagen
country: Denmark
facility: Rigshospitalet - Juliane Marie Centret (JMC) Copenhagen
city: Montpellier
country: France
facility: CHU de Montpellier - Hôpital Arnaud de Villeneuve
state: Hérault
city: Paris
country: France
facility: AP-HP - Hôpital Armand Trousseau
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen
city: Giessen
country: Germany
facility: UKGM - Universitätsklinikum Giessen und Marburg GmbH - Standort Gießen
city: Hamburg
country: Germany
facility: UKE Hamburg
city: Dublin
country: Ireland
facility: CHI at Temple Street
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesù IRCCS
state: Lazio
city: Conegliano
country: Italy
facility: IRCCS Eugenio Medea - Polo. Scientifico Veneto
state: Veneto
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta
city: Nijmegen
country: Netherlands
facility: Radboud Universitair Medisch Centrum
city: Espluges De Llobregat
country: Spain
facility: Hospital Sant Joan de Deu
city: Madrid
country: Spain
facility: Hospital Universitario La Paz - PPDS
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital
state: South Yorkshire
city: London
country: United Kingdom
facility: University College London, Institue of Neurology
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: