Omaveloxolone for Friedreich's Ataxia

(BRAVE Trial)

Recruiting at 32 trial locations

Overseen By Patient Navigator

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Biogen

Disqualifiers: Diabetes, Heart disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 15

255 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called BIIB141, or omaveloxolone, to assess its effects on children and teens with Friedreich's Ataxia (FA), a condition affecting movement and balance. The trial aims to evaluate the drug's impact on symptoms and overall health, including heart and puberty changes. It targets children and teens aged 2 to 15 diagnosed with FA. Participants will receive either the drug or a placebo (a harmless pill with no active drug) for up to 52 weeks in the first part, then continue or start the drug for up to 104 weeks in the second part. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that omaveloxolone, also known as SKYCLARYS®, is generally safe for individuals with Friedreich's ataxia aged 16 and older. In a study involving 103 patients, a 150 mg dose of omaveloxolone proved as safe as a placebo, a harmless pill used for comparison. This study included 24 teenagers.

While additional safety information is being gathered, omaveloxolone has already received approval for older teens and adults with this condition, indicating it has passed significant safety evaluations for them. However, since this study focuses on younger children and teens, researchers are closely monitoring for any new safety concerns in this age group. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Friedreich's Ataxia?

Omaveloxolone is unique because it targets the underlying oxidative stress and mitochondrial dysfunction seen in Friedreich's Ataxia, providing a new approach compared to existing treatments. Unlike the standard of care, which often focuses on symptom management through physical therapy and medications like idebenone, omaveloxolone acts by activating the Nrf2 pathway, offering potential disease-modifying effects. Researchers are excited about this treatment because it might not only improve symptoms but also slow down the progression of the disease, offering hope for a more comprehensive management strategy for patients.

What is the effectiveness track record for omaveloxolone in treating Friedreich's Ataxia?

Research has shown that omaveloxolone can slow the progression of Friedreich's Ataxia, a disease affecting movement and coordination. One study found that patients taking omaveloxolone had less difficulty moving after 48 weeks compared to those not taking the drug. Another study reported a 55% reduction in the mFARS score, which measures disease severity. This suggests that omaveloxolone can improve daily activities and overall stability for individuals with this condition. Additionally, it has been found safe and well-tolerated in adults with Friedreich's Ataxia. Participants in this trial will receive either omaveloxolone or a placebo in Part 1, and those who complete Part 1 may receive omaveloxolone in Part 2. ^{3 4 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Biogen

Are You a Good Fit for This Trial?

This trial is for children and teens aged 2 to 15 with Friedreich's Ataxia. It aims to understand the effects and safety of BIIB141 (Omaveloxolone) in this age group, as it's currently approved only for those over 16. Participants will be monitored for changes in symptoms, overall health, heart health, and puberty development.

Inclusion Criteria

Participants have completed Part 1 RCT of the study and no discontinuation criteria have been met

My child is between 7 and 16 years old with a specific balance score.

Safety and tolerability data from Part 1 RCT are supportive of continuation in the judgement of the investigator

Exclusion Criteria

If BNP is > 200 pg/mL at the previous visit assessment, Part 2 Day 1 should be delayed until BNP is < 200 pg/mL

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

Glycosylated hemoglobin A1C (HbA1c) > 11%

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment Part 1

Participants receive either BIIB141 or placebo once a day for up to 52 weeks

52 weeks

10 visits (in-person), 1 phone call at Week 2

Open-label Extension Part 2

Participants continue or start BIIB141 for up to 104 weeks

104 weeks

Visits at Weeks 4, 8, 12, 26, and every 26 weeks thereafter, 1 phone call at Week 2

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 final phone call 31 days after last dose

What Are the Treatments Tested in This Trial?

Interventions

• BIIB141

Trial Overview The study tests Omaveloxolone against a placebo over approximately three years. Part one involves daily doses at home with periodic research center visits; participants then continue or switch to Omaveloxolone in part two. The focus is on symptom management, long-term safety, and how the body processes the drug.

How Is the Trial Designed?

Group I: Part 2 OLE: Omaveloxolone Experimental Treatment 1 Intervention

Participants who complete Part 1 of the study and are eligible will receive a single oral dose of omaveloxolone, QD for up to 104 weeks in the Part 2 OLE study.

Group II: Part 1 RCT: Omaveloxolone Experimental Treatment 1 Intervention

Participants will receive a single oral dose of omaveloxolone once a day (QD) for up to 52 weeks in Part 1 of the study.

Group III: Part 1 RCT: Placebo Placebo Group 1 Intervention

Participants will receive placebo, orally, QD for up to 52 weeks in Part 1 of the study.

Who Is Running the Clinical Trial?

Biogen

Lead Sponsor

Trials

655

Recruited

468,000+

Daniel Quirk

Biogen

Chief Medical Officer

MD

Christopher A. Viehbacher

Biogen

Chief Executive Officer since 2022

Graduated from Queen's University, Kingston, Ontario, Canada

Published Research Related to This Trial

Omaveloxolone (SKYCLARYS™) is an orally active drug that enhances antioxidant activity by activating the Nrf2 pathway, which is crucial for combating oxidative stress and mitochondrial dysfunction in patients with Friedreich's ataxia.

Approved in February 2023, omaveloxolone represents a significant advancement in treating Friedreich's ataxia, particularly for adults and adolescents aged 16 and older, by targeting the underlying cellular damage associated with the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omaveloxolone: First Approval. Lee, A.[2023]

In a Phase 2 study involving 69 patients with Friedreich ataxia, omaveloxolone was found to be well tolerated with mostly mild adverse effects, indicating a favorable safety profile.

At a dose of 160 mg/day, omaveloxolone significantly improved neurological function as measured by the modified Friedreich Ataxia Rating Scale (mFARS), particularly in patients without musculoskeletal foot deformity, suggesting its potential efficacy in treating this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia. Lynch, DR., Farmer, J., Hauser, L., et al.[2022]

In a phase 2 trial involving 103 patients with Friedreich ataxia, omaveloxolone significantly improved neurological function compared to placebo, with a notable difference in modified Friedreich's Ataxia Rating Scale scores after 48 weeks.

Omaveloxolone was generally safe and well tolerated, although some patients experienced transient increases in liver enzymes and common side effects like headache, nausea, and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study). Lynch, DR., Chin, MP., Delatycki, MB., et al.[2023]

Omaveloxolone, a synthetic compound that activates the Nrf2 pathway, showed a dose-linear pharmacokinetic profile in monkeys, indicating predictable absorption and distribution in key tissues like the liver, lung, and brain after oral administration.

In Friedreich's ataxia patients, doses of omaveloxolone starting at 80 mg led to significant improvements in neurological function, with plasma levels correlating with those that effectively activated Nrf2 in monkeys, suggesting its potential efficacy in treating this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of the novel Nrf2 activator omaveloxolone in primates. Reisman, SA., Gahir, SS., Lee, CI., et al.[2022]

Citations

1. neurologylive.com neurologylive.com/view/long-term-data-suggest-friedreich-ataxia-agent-omaveloxolone-slows-disease-progression-over-4-years

Long-Term Data Suggest Friedreich Ataxia Agent ... Omaveloxolone treatment in FA patients resulted in slower disease progression, with improved mFARS and FA-ADL scores over four years compared to ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12579712/

Early experience on omaveloxolone in adult patients with ... Omaveloxolone seems to be safe and well-tolerated in adult FRDA patients in the real-life setting. No neurological progression was reported with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06054893

NCT06054893 | A Study to Find Out How BIIB141 ... The part 1 primary objective of the study is to evaluate the pharmacokinetics (PK) of omaveloxolone following administration of a single dose in 3 age cohorts ( ...

4. skyclarys.com skyclarys.com/en-us/home/why-skyclarys/efficacy.html

Clinical Trial Results - SKYCLARYS® (omaveloxolone ... Patients taking SKYCLARYS had less physical impairment after 48 weeks of treatment compared with untreated patients in the clinical trial.

5. ojrd.biomedcentral.com ojrd.biomedcentral.com/articles/10.1186/s13023-024-03474-6

Safety and efficacy of omaveloxolone v/s placebo for the ... Overall, in a research analysis performed by the same group of researchers on the MOXIe study demonstrated a reduction of mFARS by 55% in the ...

6. curefa.org curefa.org/clinical-studies/observational-multinational-post-marketing-registry-of-omaveloxolone-treated-patients-with-friedreichs-ataxia/

A Study to Learn More About the Long-Term Safety of ... In this study, researchers will learn more about the safety of BIIB141, also known as omaveloxolone or SKYCLARYS®, in people with Friedreich's ataxia (FA).

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40533692/

Characteristics of Adverse Events and Clinical Risks ... Omaveloxolone, the first approved therapeutic agent for Friedreich ataxia (FRDA), currently has limited real-world safety data available.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/216718Orig1s000SumR.pdf

216718Orig1s000 SUMMARY REVIEW - accessdata.fda.gov A total of 103 patients provided safety data of 150 mg omaveloxolone compared to placebo. This included 24 adolescent patients age ≥ 16 ...