Omaveloxolone for Healthy Subjects

Overseen By Global Biogen Clinical Trial Center

Age: 18 - 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Reata, a wholly owned subsidiary of Biogen

Disqualifiers: Cardiovascular, Endocrine, Gastrointestinal, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

In this study, researchers will learn how BIIB141, also known as omaveloxolone or SKYCLARYS®, moves through the body. This is a drug available for doctors to prescribe for patients with Friedrich's Ataxia. But, this drug has not yet been tested in women who have recently given birth and are breastfeeding or pumping milk for their babies. So, researchers do not know how much of the drug could be passed on to babies through the breastmilk of mothers who may take BIIB141. The main objective of this study is to learn how a single dose of BIIB141 is processed in both the breastmilk and in the blood of healthy women who are breastfeeding. The main question researchers want to answer in this study is: * How does BIIB141 move from the blood into the breastmilk? Researchers will also learn more about: * How BIIB141 moves through the blood * What dose of BIIB141 a baby may get from the mother's breastmilk * Any medical problems the participants have during the study 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. * Participants will take a single dose of BIIB141 as a tablet by mouth on Day 1. * Participants will remain at their study research center for 6 days. During this time, the participants will be provided with an electric breast pump. This is so that the researchers can collect breastmilk samples before and after the participants take BIIB141. The researchers will also collect blood samples. * After leaving the study research center, the participants will return every 2 days for the next 10 days for more tests and checkups. * Finally, there will be a follow-up with a "lactation consultant" up to 30 days after each participant's last study visit. This is someone who can help participants with breastfeeding or pumping. * Each participant will be in the study for up to 2.5 months.

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.

What makes the drug omaveloxolone unique compared to other treatments?

Omaveloxolone is unique because it activates the Nrf2 pathway, which helps reduce oxidative stress and inflammation, and improves mitochondrial function. This mechanism is particularly beneficial for conditions like Friedreich's ataxia, where these pathways are disrupted. ^{1 2 3 4 5}

Research Team

Medical Director

Principal Investigator

Biogen

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Omaveloxolone (Nrf2 Activator)

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.

Participant Groups

Group I: Omaveloxolone Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Reata, a wholly owned subsidiary of Biogen

Lead Sponsor

Trials

52

Recruited

7,400+

Findings from Research

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, 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 (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]

References

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

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

2. New Zealand 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. [2022]

3. Switzerland 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. [2022]

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

Omaveloxolone: First Approval. [2023]

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

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