Omaveloxolone for Healthy Subjects

Overseen By Global Biogen Clinical Trial Center

Age: 18 - 65

Sex: Female

Trial Phase: Phase 1

Sponsor: Reata, a wholly owned subsidiary of Biogen

Disqualifiers: Cardiovascular, Endocrine, Gastrointestinal, 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: 11

Duration: 6 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how the drug omaveloxolone transfers from a breastfeeding mother's blood into her breastmilk. Omaveloxolone is already used to treat Friedrich's Ataxia, but it has not been tested on breastfeeding women. The study will determine how much of the drug a baby might receive through breastmilk and check for any possible side effects. Women who gave birth at least six weeks ago, are currently breastfeeding, and have never taken this drug before might be suitable for this trial. Participants will spend time at a research center and have follow-ups to ensure their safety and gather necessary data. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the study involves taking a new drug, it's best to discuss your current medications with the study team to ensure safety.

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

Research has shown that omaveloxolone has been tested for safety in people with Friedreich's ataxia, a rare disease. Studies indicate that the drug is generally well-tolerated. For example, in one study where participants used omaveloxolone for 48 weeks, many did not experience serious side effects. Some common side effects included headaches and nausea, but these were mild for most people.

Another study tested a lotion form of omaveloxolone and also found it to be safe in healthy volunteers. This suggests the drug is safe in different forms and for different groups of people.

Omaveloxolone is already approved for treating Friedreich's ataxia, meaning it has passed strict safety checks. However, this study will examine how the drug enters breastmilk, which is a new area of research. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Omaveloxolone is unique because it targets oxidative stress and inflammation at the cellular level, which is not typically addressed by standard treatments. Unlike conventional therapies that might focus on managing symptoms, omaveloxolone works by activating the Nrf2 pathway, a critical regulator of cellular defense mechanisms. This novel approach offers the potential for more effective protection against cell damage, which has researchers excited about its possibilities.

What evidence suggests that omaveloxolone is effective for Friedrich's Ataxia?

Research has shown that omaveloxolone effectively treats Friedreich's ataxia, a rare inherited disease that damages the nervous system. Studies have found that omaveloxolone activates Nrf2, reducing cell damage and inflammation. These effects have been linked to symptom improvements in people with this condition. The drug is approved for use in patients with Friedreich's ataxia due to its proven benefits. While this study focuses on how the drug is processed in healthy subjects, omaveloxolone's effectiveness for its approved use is well-documented. ^{1 2 3 4 5}

Who Is on the Research Team?

Medical Director

Principal Investigator

Biogen

Are You a Good Fit for This Trial?

This trial is for healthy breastfeeding women aged 18-45, who have given birth to a full-term infant and are at least 6 weeks postpartum. They must not have used omaveloxolone before, have a BMI between 18.0-35.0 kg/m^2, and agree to stop breastfeeding from the start of the study until 19 days after taking the drug.

Inclusion Criteria

Is at least 6 weeks postpartum by Day 1

Body mass index at screening between 18.0 and < 35.0 kilograms per meter square (kg/m^2), inclusive

Is willing to discontinue breastfeeding their infant from check-in (Day -1) through 19 days after dosing

Exclusion Criteria

History of, or positive test result at Screening for, human immunodeficiency virus

I have or had low or high blood pressure.

I don't have any major health issues as decided by my doctor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive a single oral dose of BIIB141 and remain at the study center for 6 days for sample collection

6 days

In-patient stay for 6 days

Post-Treatment Monitoring

Participants return every 2 days for 10 days for additional tests and checkups

10 days

5 visits (in-person)

Follow-up

Follow-up with a lactation consultant up to 30 days after the last study visit

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Omaveloxolone

Trial Overview Researchers are testing how BIIB141 (omaveloxolone) transfers into breastmilk when taken orally by lactating women. The study involves taking a single dose of the medication and monitoring its levels in both blood and milk over several days with follow-up support from a lactation consultant.

How Is the Trial Designed?

Group I: Omaveloxolone Experimental Treatment 1 Intervention

Participants will receive a single oral dose of omaveloxolone on Day 1.

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, a wholly owned subsidiary of Biogen

Lead Sponsor

Trials

52

Recruited

7,400+

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, a drug that activates the Nrf2 pathway for antioxidant function, was found to be well-tolerated in a Phase I trial with 28 days of treatment in patients with advanced melanoma or lung cancer, showing no dose-limiting toxicities and only mild adverse effects.

While the drug did not show confirmed tumor responses, it demonstrated a trend towards activating antioxidant genes and resulted in stable disease in one patient for over a year, suggesting potential for further investigation in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and pharmacodynamics of oral omaveloxolone (RTA 408), a synthetic triterpenoid, in a first-in-human trial of patients with advanced solid tumors. Creelan, BC., Gabrilovich, DI., Gray, JE., et al.[2022]

Omaveloxolone demonstrated significant antioxidative and anti-inflammatory effects in an in vitro model of osteoarthritis, suggesting it can help protect chondrocytes from damage and degradation.

In a rat model of osteoarthritis, omaveloxolone was effective in slowing disease progression, indicating its potential as a therapeutic agent for treating osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omaveloxolone inhibits IL-1&#946;-induced chondrocyte apoptosis through the Nrf2/ARE and NF-&#954;B signalling pathways in vitro and attenuates osteoarthritis in vivo. Jiang, Z., Qi, G., Lu, W., et al.[2022]

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]

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]

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 ... Omaveloxolone (Omav) is an Nrf2 activator and has been reported to have antioxidative potential in various disease conditions.

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

216718Orig1s000 CLINICAL REVIEW(S) - accessdata.fda.gov of effectiveness of omaveloxolone in FA patients, followed by results of Part 1 and the extension phase. The primary objectives of Part 2 of ...

4. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/Omaveloxolone-Cognitive-Vitality-For-Researchers.pdf

Omaveloxolone (RTA-408) A lotion containing 3% omaveloxolone has shown a good safety profile in healthy volunteers [4], but the results of the Phase 2 RCT (PRIMROSE NCT02142959) ...

5. 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 Through these actions, omaveloxolone is expected to protect cells and reduce inflammation, thus reducing the symptoms of FA. If licensed,.