Omaveloxolone for Drug Interaction Study

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Biogen

Must not be taking: Prescription medications

Disqualifiers: Major disorders, Drug abuse, 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: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to study the interaction between a drug called omaveloxolone and another medication, efavirenz, in healthy individuals. Participants will initially take omaveloxolone alone, followed by both drugs together in a later phase. The trial seeks healthy adults without major health issues, who are not on prescription medication, and have no history of drug or alcohol abuse. As a Phase 1 trial, the 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?

Yes, you will need to stop taking any prescription medications at least 14 days before the study starts, except for hormonal contraception.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that omaveloxolone is generally safe for use. Studies have found that side effects are usually mild. For instance, in a study with 165 patients with Friedreich's ataxia, most experienced only mild side effects after taking omaveloxolone.

Omaveloxolone is already approved for treating Friedreich's ataxia, indicating its safety. However, researchers are still examining its long-term safety.

Less information exists about the safety of using omaveloxolone with efavirenz. Efavirenz, a drug commonly used to treat HIV, can cause side effects like dizziness or trouble sleeping, especially if taken with food. This study is in the early stages and aims to gather more information on the safety of using both drugs together.

In summary, omaveloxolone alone appears safe. Less is known about its interaction with efavirenz, and this trial aims to provide more insights. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Omaveloxolone is unique because it targets oxidative stress and inflammation in a novel way. Unlike standard treatments that often focus on symptom management, Omaveloxolone works by activating the Nrf2 pathway, which boosts the body's own antioxidant defenses. This mechanism not only offers a fresh approach to tackling conditions related to oxidative stress but also holds the potential for fewer side effects and broader therapeutic applications. Researchers are excited about Omaveloxolone because it could represent a significant advancement in treating conditions where current options are limited or less effective.

What evidence suggests that this trial's treatments could be effective?

Research has shown that omaveloxolone, which participants in this trial will receive, may help treat Friedreich's ataxia, a rare genetic disorder. One study found that patients experienced a 55% reduction in symptoms, as measured by the mFARS scale, suggesting omaveloxolone's effectiveness for this condition. In this trial, participants will first receive omaveloxolone alone and then in combination with efavirenz, an HIV medication. However, efavirenz may reduce omaveloxolone's effectiveness by lowering its levels in the body. Omaveloxolone is generally well tolerated, whether taken alone or with other drugs. ^{2 5 6 7 8}

Who Is on the Research Team?

Michelle Valentine, DO

Principal Investigator

Celerion

Are You a Good Fit for This Trial?

Inclusion Criteria

BMI at screening between 18.0 and 32.0 kg/m2 (inclusive)

Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception

Able to comprehend and willing to sign an ICF and to abide by the study restrictions

Exclusion Criteria

Use of any prescription medication before the first study drug administration (within 14 days before initial study drug administration or within 5 half-lives of the prescription medication, whichever is longer), and until after the last protocol-specified blood sample is prohibited, other than use of hormonal contraception

Clinically significant abnormal 12 lead ECGs

You have experienced fainting without a clear reason in the past, or someone in your family has a history of a heart condition that can cause sudden unexplained death.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment Period 1

Participants receive a single oral dose of 150 mg omaveloxolone on Day 1

2 weeks

1 visit (in-person)

Treatment Period 2

Participants receive 600 mg efavirenz daily from Days 15 to 42 and a single oral dose of 150 mg omaveloxolone on Day 29

4 weeks

Multiple visits (in-person) for blood sampling

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Efavirenz
• Omaveloxolone

How Is the Trial Designed?

Group I: Omaveloxolone only (Period 1), Then Omaveloxolone and efavirenz (Period 2) Experimental Treatment 2 Interventions

Period 1 (Day 1 - 15): Omaveloxolone Capsules, 150 mg, administered orally in a single dose on Day 1 Period 2 (Day 15 - 43): Efavirenz Tablet, 600 mg, administered orally once daily from Day 15 - Day 42 and Omaveloxolone Capsules, 150 mg, administered orally in a single dose on Day 29

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?

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 Pharmaceuticals, Inc.

Lead Sponsor

Trials

52

Recruited

6,900+

Reata, a wholly owned subsidiary of Biogen

Lead Sponsor

Trials

52

Recruited

7,400+

altasciences

Collaborator

Trials

3

Recruited

140+

Celerion

Industry Sponsor

Trials

85

Recruited

7,600+

Dr. Susan Thornton

Celerion

Chief Executive Officer since 2010

PhD in Molecular Biology from the University of Pennsylvania

Dr. Lorraine M. Rusch

Celerion

Chief Medical Officer since 2020

MD from an unspecified institution

Q2 Solutions

Industry Sponsor

Trials

15

Recruited

1,600+

Altasciences Company Inc.

Industry Sponsor

Trials

18

Recruited

860+

Published Research Related to This Trial

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]

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

Omaveloxolone (RTA-408) However, in submaximal exercise testing, treated patients demonstrated a significant lowering of heart rate (p=0.01) and blood lactate (p=0.04), which are ...

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/216718Orig1s000ClinPharmR.pdf

216718Orig1s000 CLINICAL PHARMACOLOGY REVIEW(S) Safety, pharmacokinetics, and pharmacodynamics of oral omaveloxolone (RTA 408), a synthetic triterpenoid, in a first-in-human trial of patients.

6. cdn.caymanchem.com cdn.caymanchem.com/cdn/msds/17854m.pdf

Safety Data Sheet 1474034-05-3 RTA 408. (Contd. on page 3). US. Page 3. Page 3/8. Safety Data Sheet acc. to OSHA HCS. Date of issue: 07/16/2025. Revision date 07/ ...

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 ... Omaveloxolone was well tolerated, and adverse events were generally mild. Optimal pharmacodynamic changes (noted by changes in ferritin and GGT) were observed ...