RTA 408 Capsules in Patients With Mitochondrial Myopathy - MOTOR

NCT02255422 | Completed Phase 2 Results DMC

• 1 other identifier: RTA 408-C-1403
• Study Type: interventional
• Target: 53
• Locations: 2 countries
• Sites: 9

Brief Summary

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.

Conditions

MItochondrial Myopathies

Keywords

omaveloxolone; RTA 408 capsules; mitochondrial myopathies

Outcome Measures

Primary Outcomes (1)

• Change of Peak Workload (in Watts/kg) During Exercise Testing

  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 Outcomes (1)

• Change in 6-minute Walk Test (6MWT) Distance

  6MWT was assessed at Week 4, Week 8, and Week 12 and compared to baseline

Study Arms (7)

omaveloxolone Capsules 2.5 mg and 5 mg

EXPERIMENTAL

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; Drug: omaveloxolone capsules, 5 mg

omaveloxolone Capsules 10 mg

EXPERIMENTAL

omaveloxolone (RTA 408) capsules, 10 mg taken orally once daily for 12 weeks

Drug: omaveloxolone capsules, 10 mg

Placebo Capsules

PLACEBO COMPARATOR

Placebo capsules taken orally once daily for 12 weeks

Drug: Placebo capsules

omaveloxolone Capsules 20 mg

EXPERIMENTAL

omaveloxolone (RTA 408) Capsules, 20 mg taken orally once daily for 12 weeks.

Drug: omaveloxolone capsules, 20 mg

omaveloxolone Capsules 40 mg

EXPERIMENTAL

omaveloxolone (RTA 408) Capsules, 40 mg taken orally once daily for 12 weeks.

Drug: omaveloxolone capsules, 40 mg

omaveloxolone Capsules 80 mg

EXPERIMENTAL

omaveloxolone (RTA 408) Capsules, 80 mg taken orally once daily for 12 weeks.

Drug: omaveloxolone capsules, 80 mg

omaveloxolone Capsules 160 mg

EXPERIMENTAL

omaveloxolone (RTA 408) Capsules, 160 mg taken orally once daily for 12 weeks.

Drug: omaveloxolone capsules, 160 mg

Interventions

Omaveloxolone capsules, 2.5 mg DRUG

Also known as: RTA 408 Capsules 2.5 mg

omaveloxolone Capsules 2.5 mg and 5 mg

omaveloxolone capsules, 5 mg DRUG

Also known as: RTA 408 capsules, 5 mg

omaveloxolone Capsules 2.5 mg and 5 mg

omaveloxolone capsules, 10 mg DRUG

Also known as: RTA 408, 10 mg

omaveloxolone Capsules 10 mg

Placebo capsules DRUG

Placebo Capsules

omaveloxolone capsules, 20 mg DRUG

Also known as: RTA 408 capsules, 20 mg

omaveloxolone Capsules 20 mg

omaveloxolone capsules, 40 mg DRUG

Also known as: RTA 408 capsules, 40 mg

omaveloxolone Capsules 40 mg

omaveloxolone capsules, 80 mg DRUG

Also known as: RTA 408 capsules, 80 mg

omaveloxolone Capsules 80 mg

omaveloxolone capsules, 160 mg DRUG

Also known as: RTA 408 capsules, 160 mg

omaveloxolone Capsules 160 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have mitochondrial myopathy as evidenced by the following 2 criteria (must meet both):
• 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)
• 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
• Be male or female and ≥18 years of age and ≤75 years of age
• 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
• Have the ability to complete maximal exercise testing
• Have a peak workload during maximal exercise testing of ≤ 1.5 W/kg
• Be able to swallow capsules

You may not qualify if:

• Have uncontrolled diabetes (HbA1c \>11.0%)
• Have B-type natriuretic peptide level \>200 pg/mL
• Have a history of clinically significant left-sided heart disease and/or clinically significant cardiac disease
• Have known active fungal, bacterial, and/or viral infection, including human immunodeficiency virus or hepatitis virus (B or C)
• Have known or suspected active drug or alcohol abuse
• 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
• 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
• 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:
• Sensitive substrates for cytochrome P450 2C8 or 3A4 (e.g., repaglinide, midazolam, sildenafil)
• Substrates for p-glycoprotein transporter (e.g., ambrisentan, digoxin)
• Have participated in any other interventional clinical study within 30 days prior to Study Day 1
• Have a cognitive impairment that may preclude ability to comply with study procedures

Sponsors & Collaborators

• Biogen: lead
• AbbVie: collaborator

Study Sites (9)

UCLA

Los Angeles, California, 90095, United States

Location

Mass General Hospital

Boston, Massachusetts, 02114, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Insitute for Exercise & Environmental Medicine

Dallas, Texas, 75231, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Texas Medical School at Houston

Houston, Texas, 77030, United States

Location

Neuromuscular Clinic, Rigshospitalet, University of Copenhagen

Copenhagen, DK-2100, Denmark

Location

Related Publications (1)

• Madsen KL, Buch AE, Cohen BH, Falk MJ, Goldsberry A, Goldstein A, Karaa A, Koenig MK, Muraresku CC, Meyer C, O'Grady M, Scaglia F, Shieh PB, Vockley J, Zolkipli-Cunningham Z, Haller RG, Vissing J. Safety and efficacy of omaveloxolone in patients with mitochondrial myopathy: MOTOR trial. Neurology. 2020 Feb 18;94(7):e687-e698. doi: 10.1212/WNL.0000000000008861. Epub 2020 Jan 2.

  PMID: 31896620 DERIVED

MeSH Terms

Conditions

Mitochondrial Myopathies

Interventions

omaveloxolone; ORF 50 transactivator

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: US Biogen Clinical Trial Center
• Organization: Biogen

clinicaltrials@biogen.com

866-633-4636

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2014
• First Posted: October 2, 2014
• Study Start: May 5, 2015
• Primary Completion: November 2, 2017
• Study Completion: November 30, 2017
• Last Updated: June 5, 2025
• Results First Posted: September 17, 2020

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (8); DK (1)