RTA 408 Capsules in Patients With Mitochondrial Myopathy - MOTOR

May 23, 2025 updated by: Biogen

A Phase 2 Study of the Safety, Efficacy, and Pharmacodynamics of RTA 408 in the Treatment of Mitochondrial Myopathy (MOTOR)

Mitochondrial myopathies are a multisystemic group of disorders that are characterized by a wide range of biochemical and genetic mitochondrial defects and variable modes of inheritance. Currently there are no effective treatments for this disease. Despite the heterogeneous myopathy phenotypes, a unifying feature of mitochondrial myopathies is that the pathogenic mtDNA mutations and/or nuclear mutations of the electron transport chain invariably lead to dysfunctional mitochondrial respiration. This reduction in mitochondrial respiration leads to a reduced ability to produce cellular adenosine triphosphate (ATP), often resulting in muscle weakness, exercise intolerance, and fatigue in patients with mitochondrial myopathies.

RTA 408 is a potent activator of Nrf2 and inhibitor of NF κB (nuclear factor kappa-light-chain-enhancer of activated B cells), and thus induces an antioxidant and anti-inflammatory phenotype. Several lines of evidence suggest that Nrf2 activation can increase mitochondrial respiration and biogenesis. Collectively, available data suggest that the ability of RTA 408 to activate Nrf2 and induce its target genes could potentially improve muscle function, oxidative phosphorylation, antioxidant capacity, and mitochondrial biogenesis in patients with mitochondrial myopathies.

This study will be a randomized, placebo-controlled, double-blind, dose-escalation study to evaluate the safety of omaveloxolone (RTA 408) at various doses in patients with mitochondrial myopathies.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Study Sponsor, originally Reata Pharmaceuticals, Inc., is now Reata Pharmaceuticals, Inc., a wholly owned subsidiary of Biogen.

Study Type

Interventional

Enrollment (Actual)

53

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Copenhagen, Denmark, DK-2100
        • Neuromuscular Clinic, Rigshospitalet, University of Copenhagen
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Mass General Hospital
    • Ohio
      • Akron, Ohio, United States, 44308
        • Akron Children's Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • The Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15224
        • University of Pittsburgh
    • Texas
      • Dallas, Texas, United States, 75231
        • Insitute for Exercise & Environmental Medicine
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
      • Houston, Texas, United States, 77030
        • University of Texas Medical School at Houston

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Have mitochondrial myopathy as evidenced by the following 2 criteria (must meet both):

    1. Have a history of exercise intolerance with or without weakness and/or progressive exercise intolerance (in which modest exercise typically provokes heaviness, weakness, aching of active muscles, or tachycardia)
    2. Have a known primary mitochondrial DNA mutation or a nuclear DNA defect that is associated with reduced activity of at least 1 mitochondrially encoded respiratory chain complex
  2. Be male or female and ≥18 years of age and ≤75 years of age
  3. Have no changes to exercise regimen within 30 days prior to Study Day 1 and be willing to remain on the same exercise regimen during the 16-week study period
  4. Have the ability to complete maximal exercise testing
  5. Have a peak workload during maximal exercise testing of ≤ 1.5 W/kg
  6. Be able to swallow capsules

Exclusion Criteria:

  1. Have uncontrolled diabetes (HbA1c >11.0%)
  2. Have B-type natriuretic peptide level >200 pg/mL
  3. Have a history of clinically significant left-sided heart disease and/or clinically significant cardiac disease
  4. Have known active fungal, bacterial, and/or viral infection, including human immunodeficiency virus or hepatitis virus (B or C)
  5. Have known or suspected active drug or alcohol abuse
  6. Have clinically significant abnormalities of clinical hematology or biochemistry, including but not limited to elevations greater than 1.5 times the upper limit of normal of aspartate aminotransferase, alanine aminotransferase, or creatinine
  7. Have any abnormal laboratory test value or serious pre-existing medical condition that, in the opinion of the investigator, would put the patient at risk by study enrollment

  8. Have taken any of the following drugs within 7 days prior to Study Day 1 or plan to take any of these drugs during the time of study participation:

    1. Sensitive substrates for cytochrome P450 2C8 or 3A4 (e.g., repaglinide, midazolam, sildenafil)
    2. Substrates for p-glycoprotein transporter (e.g., ambrisentan, digoxin)
  9. Have participated in any other interventional clinical study within 30 days prior to Study Day 1
  10. Have a cognitive impairment that may preclude ability to comply with study procedures

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: omaveloxolone Capsules 2.5 mg and 5 mg
omaveloxolone (RTA 408) Capsules, 2.5 mg taken orally once daily for 2 weeks, then 5 mg taken orally once daily for 10 weeks
Drug: Omaveloxolone capsules, 2.5 mg
Other Names:
  • RTA 408 Capsules 2.5 mg
Drug: omaveloxolone capsules, 5 mg
Other Names:
  • RTA 408 capsules, 5 mg
Experimental: omaveloxolone Capsules 10 mg
omaveloxolone (RTA 408) capsules, 10 mg taken orally once daily for 12 weeks
Drug: omaveloxolone capsules, 10 mg
Other Names:
  • RTA 408, 10 mg
Placebo Comparator: Placebo Capsules
Placebo capsules taken orally once daily for 12 weeks
Drug: Placebo capsules
Experimental: omaveloxolone Capsules 20 mg
omaveloxolone (RTA 408) Capsules, 20 mg taken orally once daily for 12 weeks.
Drug: omaveloxolone capsules, 20 mg
Other Names:
  • RTA 408 capsules, 20 mg
Experimental: omaveloxolone Capsules 40 mg
omaveloxolone (RTA 408) Capsules, 40 mg taken orally once daily for 12 weeks.
Drug: omaveloxolone capsules, 40 mg
Other Names:
  • RTA 408 capsules, 40 mg
Experimental: omaveloxolone Capsules 80 mg
omaveloxolone (RTA 408) Capsules, 80 mg taken orally once daily for 12 weeks.
Drug: omaveloxolone capsules, 80 mg
Other Names:
  • RTA 408 capsules, 80 mg
Experimental: omaveloxolone Capsules 160 mg
omaveloxolone (RTA 408) Capsules, 160 mg taken orally once daily for 12 weeks.
Drug: omaveloxolone capsules, 160 mg
Other Names:
  • RTA 408 capsules, 160 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of Peak Workload (in Watts/kg) During Exercise Testing
Time Frame: 12 weeks
Cycle ergometry using a stationary recumbent bike was used to conduct maximal exercise testing. Peak work is defined as the workload at which patients reach maximal volition (defined as an inability to continue to exercise due to exhaustion). Change of peak workload during exercise testing was measured at baseline, Week 4, and Week 12. Change from baseline at Week 12 reported.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in 6-minute Walk Test (6MWT) Distance
Time Frame: 6MWT was assessed at Week 4, Week 8, and Week 12 and compared to baseline
Patients were instructed to walk as far as they could along a marked path for 6 minutes. Distance walked was measured. If patients used a cane or walking assist device at Screening, the same walking assist device was to be used for all 6MWT assessments.
6MWT was assessed at Week 4, Week 8, and Week 12 and compared to baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Biogen

Collaborators

AbbVie

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 5, 2015

Primary Completion (Actual)

November 2, 2017

Study Completion (Actual)

November 30, 2017

Study Registration Dates

First Submitted

September 30, 2014

First Submitted That Met QC Criteria

September 30, 2014

First Posted (Estimated)

October 2, 2014

Study Record Updates

Last Update Posted (Actual)

June 5, 2025

Last Update Submitted That Met QC Criteria

May 23, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RTA 408-C-1403

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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