Omaveloxolone for Friedreich's Ataxia

(BOLD Trial)

Overseen By Global Biogen Clinical Trial Center

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Reata Pharmaceuticals, Inc.

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Uncontrolled diabetes, Heart disease, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the drug omaveloxolone works in children and teens with Friedreich's Ataxia (FA), a condition affecting movement and coordination. Researchers aim to understand how the body processes the drug and monitor changes in health, including heart health and development through puberty. Participants take the drug in different age-based groups, and researchers observe its effects over time. Children and teens ages 2 to 15 with confirmed FA, who do not have uncontrolled diabetes or severe heart issues, might be suitable for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that participants do not take certain medications that affect liver enzymes, like some antibiotics and antifungals, within 7 days before starting the study and during participation. If you're on these medications, you may need to stop them, but the protocol doesn't specify about other medications.

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 well-tolerated by people with Friedreich's Ataxia (FA). In a study involving 165 patients, including some teenagers, researchers closely monitored the safety of a 150 mg daily dose. The results showed that this treatment is usually safe, with most participants experiencing only mild side effects like headaches or stomach discomfort, common with many medications.

Omaveloxolone is already approved for individuals 16 years and older with FA, indicating it has passed significant safety tests for this age group. Researchers are now examining its effects in younger children and teens aged 2 to 15 years to ensure safety for them as well.

Overall, current evidence supports the safety of omaveloxolone for treating Friedreich's Ataxia, with careful monitoring. ^{1 2 3 4 5}

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

Researchers are excited about omaveloxolone for Friedreich's Ataxia because it offers a unique approach compared to current treatments. While existing options mainly focus on symptom management, omaveloxolone targets the root of the disease by activating the Nrf2 pathway. This pathway may help reduce oxidative stress and inflammation, potentially slowing disease progression. Additionally, omaveloxolone's oral administration makes it a convenient option compared to more invasive treatments. This novel mechanism and ease of use are why there's a buzz around this new treatment.

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

Studies have shown that omaveloxolone effectively treats Friedreich's ataxia, a rare genetic disease affecting the nervous system and movement. Research from the MOXIe study demonstrated that patients taking omaveloxolone improved their symptoms by 55% more, as measured by mFARS scores, compared to those on a placebo. This indicates greater improvement with omaveloxolone than without it. Omaveloxolone is currently the only FDA-approved treatment for Friedreich's ataxia, underscoring its effectiveness and safety for individuals aged 16 and older. The trial aims to explore its effects in younger patients, with different cohorts receiving varying doses based on age and Bayesian population pharmacokinetics analyses. ^{1 3 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 aged 2 to less than 16 with genetically confirmed Friedreich's Ataxia (FA). Participants must be able to follow the study plan, use birth control if of childbearing potential, and not have certain infections or recent participation in other trials. They should also have a heart function above a set threshold.

Inclusion Criteria

Be male or female and ≥2 years of age and <16 years of age

Be willing and able to cooperate with all aspects of the protocol

You have a confirmed genetic diagnosis of Fanconi anemia.

Exclusion Criteria

Have any abnormal laboratory test value or CS pre-existing medical condition that, in the opinion of the investigator, would put the patient at risk by study participation

Have a cognitive impairment that may preclude ability to comply with study procedures, in the opinion of the investigator

You have had strong thoughts of hurting yourself in the past 30 days, or have attempted to hurt yourself in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Part 1 Treatment

Participants receive a single dose of BIIB141 based on age group

1 day

1 visit (in-person)

Part 2 Treatment

Participants continue to take BIIB141 daily at home with periodic visits for monitoring

Up to 240 weeks

Visits at Week 4, Week 12, Week 24, and every 24 weeks; phone calls at Week 2, Week 8, and Week 18

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Omaveloxolone

Trial Overview The trial is testing Omaveloxolone in pediatric patients with FA. It's an open-label study divided into three parts based on age groups, assessing safety, tolerability, and how the body processes the drug after a single dose.

How Is the Trial Designed?

Group I: Part 1 and 2: Cohort C2 Experimental Treatment 1 Intervention

Cohort C2 will contain participants 2 to \<7 years of age. Participants will receive a single oral dose of omaveloxolone, capsule, at a dosage level determined by a Bayesian popPK analysis using the data from Cohorts A1, A2, A3, B1, B2, and C1 to select the dose in part 1, followed by the same dose in part 2 up to week 240 or commercial availability whichever comes first. The dose in part 2 may be adjusted as per additional safety and Bayesian popPK analyses.

Group II: Part 1 and 2: Cohort C1 Experimental Treatment 1 Intervention

Cohort C1 will contain participants 2 to \<7 years of age. Participants will receive a single oral dose of omaveloxolone, capsule, at a dosage level determined by a Bayesian popPK analysis using the data from cohorts A1, A2, and B1 to select the dose in part 1, followed by the same dose in part 2 up to week 240 or commercial availability whichever comes first. The dose in part 2 may be adjusted as per additional safety and Bayesian popPK analyses.

Group III: Part 1 and 2: Cohort B2 Experimental Treatment 1 Intervention

Cohort B2 will contain participants 7 to \<12 years of age and will initiate in parallel with Cohort A3. Participants will receive a single oral dose of omaveloxolone, capsule, at a dosage level determined by a Bayesian popPK analysis using the data from cohorts A1, A2, and B1 to select the dose in part 1, followed by the same dose in part 2 up to week 240 or commercial availability whichever comes first. The dose in part 2 may be adjusted as per additional safety and Bayesian popPK analyses.

Group IV: Part 1 and 2: Cohort B1 Experimental Treatment 1 Intervention

Cohort B1 will contain participants 7 to \<12 years of age and will initiate in parallel with Cohort A2. Participants will receive a single oral dose of omaveloxolone, capsule, at a dosage level determined by a Bayesian popPK analysis using the data from Cohort A1 to select the dose in part 1, followed by the same dose in part 2 up to week 240 or commercial availability whichever comes first. The dose in part 2 may be adjusted as per additional safety and Bayesian popPK analyses.

Group V: Part 1 and 2: Cohort A3 Experimental Treatment 1 Intervention

Cohort A3 will contain participants 12 to \<16 years of age. Participants will receive a single oral dose of omaveloxolone, capsule, at a dosage level determined by a Bayesian popPK analysis using the data from cohorts A1, A2, and B1 to select the dose in part 1, followed by the same dose in part 2 up to week 240 or commercial availability whichever comes first. The dose in part 2 may be adjusted as per additional safety and Bayesian popPK analyses.

Group VI: Part 1 and 2: Cohort A2 Experimental Treatment 1 Intervention

Cohort A2 will contain participants 12 to \<16 years of age. Participants will receive a single oral dose of omaveloxolone, capsule, at a dosage level determined by a Bayesian popPK analysis using the data from Cohort A1 to select the dose in part 1, followed by the same dose in part 2 up to week 240 or commercial availability whichever comes first. The dose in part 2 may be adjusted as per additional safety and Bayesian popPK analyses.

Group VII: Part 1 and 2: Cohort A1 Experimental Treatment 1 Intervention

Cohort A1 will contain participants 12 to \<16 years of age. Participants will receive a single oral dose of omaveloxolone, 150 milligrams (mg), capsule, on Day 1 of the treatment period of part 1, followed by the same dose in part 2 up to week 240 or commercial availability whichever comes first. The dose in part 2 may be adjusted as per additional safety and Bayesian population pharmacokinetics (popPK) analyses.

Omaveloxolone is already approved in United States, European Union for the following indications:

Approved in United States as Skyclarys for:

• Friedreich's ataxia

Approved in European Union as Skyclarys for:

• Friedreich's ataxia

Who Is Running the Clinical Trial?

Reata Pharmaceuticals, Inc.

Lead Sponsor

Trials

52

Recruited

6,900+

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

Reata, a wholly owned subsidiary of Biogen

Lead Sponsor

Trials

52

Recruited

7,400+

Published Research Related to This Trial

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]

Friedreich ataxia (FRDA) is a neurodegenerative disorder with no approved therapies, but increasing Nrf2 activity may help slow disease progression.

Recent clinical trials suggest that omaveloxolone, which enhances Nrf2 activity, could be a promising novel treatment for FRDA, although it is not yet approved for use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omaveloxolone: potential new agent for Friedreich ataxia. Lynch, DR., Johnson, J.[2021]

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]

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]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT02255435

NCT02255435 | A Study to Learn About the Effects and ... This 2-part study will evaluate the efficacy, safety, and pharmacodynamics of omaveloxolone (RTA 408) in the treatment of participants with Friedreich's ataxia.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11684145/

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 ...

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/216718Orig1s000MedR.pdf

216718Orig1s000 CLINICAL REVIEW(S) - accessdata.fda.gov The evidence of effectiveness of omaveloxolone in the treatment of Friedreich's ataxia was based on a single Study 408-C-1402 Part 2 (MoXIe) ...

4. io.nihr.ac.uk io.nihr.ac.uk/wp-content/uploads/2023/08/10491-Omaveloxolone-for-Friedreichs-Ataxia-V1.0-AUG2023-NON-CONF.pdf

Omaveloxolone for the treatment of Friedreich's ataxia This briefing reflects the evidence available at the time of writing and a limited literature search. It is not intended to be a definitive.

5. cell.com cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(23)00065-2

Omaveloxolone (SkyclarysTM) for patients with ... Omaveloxolone is the first and only FDA-approved drug for patients with Friedreich's ataxia. Omaveloxolone has received Orphan Drug, Fast Track, ...

6. 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 ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/216718Orig1s000lbl.pdf

SKYCLARYS (omaveloxolone) - accessdata.fda.gov The safety of SKYCLARYS 150 mg once daily has been evaluated in 165 patients with Friedreich's ataxia, including 137 patients exposed for at ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6331199/

Safety, pharmacodynamics, and potential benefit of ... Treatment of Friedreich ataxia patients with omaveloxolone at the optimal dose level of 160 mg/day appears to improve neurological function. Therefore, ...