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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

In this study, researchers will learn more about BIIB141, also known as omaveloxolone or SKYCLARYS®. This drug has been approved, or made available for doctors to prescribe, for people with Friedrich'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 is processed in the body of children and teens who are 2 to 15 years old. The main question researchers want to answer in this study is: * How does the body process BIIB141 in children and teens? * 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. This study will be done as follows: * Participants will be screened to see if they can join the study. The screening period will be up to 14 days, after which participants will check into their study research center. * There are 2 parts to this study. During Part 1, participants will take a single dose of BIIB141. Participants will be in 1 of 4 different groups based on their age: * Group 1A: 12 to 15 years old, taking 150 milligrams (mg) of BIIB141 * Group 1B: 12 to 15 years old, taking a dose of BIIB141 based on the data from Group 1A * Group 2: 6 to 11 years old, taking a dose of BIIB141 based on Group 1 data * Group 3: 2 to 5 years old, taking a dose of BIIB141 based on Group 2 data * During Part 2, participants from Part 1 will take BIIB141 once in the study research center. Their dose will be based on what they could safely take during Part 1. Participants will then take it once a day at home. * After leaving the study research center in Part 2, participants will return for tests at Week 4, Week 12, Week 24, and then every 24 weeks. Participants will also be contacted by telephone at Week 2, Week 8, and Week 18. * Participants will be in this study for up to 240 weeks.

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.

What data supports the effectiveness of the drug Omaveloxolone for Friedreich's Ataxia?

Omaveloxolone has been shown to activate the Nrf2 pathway, which helps reduce oxidative stress and improve mitochondrial function in patients with Friedreich's Ataxia. Clinical trials have demonstrated its potential to improve symptoms by restoring balance in the body's cells and reducing inflammation. ^{1 2 3 4 5}

Is omaveloxolone safe for humans?

Omaveloxolone has been studied for safety in patients with Friedreich's ataxia, showing it can improve mitochondrial function and reduce inflammation. Clinical trials have assessed its safety, and it was approved in the USA for treating Friedreich's ataxia, indicating it is generally considered safe for this condition. ^{1 2 3 4 5}

How is the drug omaveloxolone unique for treating Friedreich's ataxia?

Omaveloxolone is unique because it activates the Nrf2 pathway, which helps reduce oxidative stress and improve mitochondrial function, addressing key issues in Friedreich's ataxia. It is the first approved treatment for this condition, offering a novel approach by enhancing the body's natural antioxidant defenses. ^{1 2 3 4 5}

Research Team

Medical Director

Principal Investigator

Biogen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Cohort C will contain participants ≥2 to \<6 years of age. Participants will receive a single oral dose of omaveloxolone at a dosage level determined by a Bayesian popPK analysis using the data from cohorts A1, A2, and B 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 B Experimental Treatment 1 Intervention

Cohort B will contain participants ≥6 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 III: 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 IV: 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+

Findings from Research

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Omaveloxolone: First Approval. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of the novel Nrf2 activator omaveloxolone in primates. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study). [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Omaveloxolone: potential new agent for Friedreich ataxia. [2021]