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RTA 408 Capsules in Patients With Mitochondrial Myopathy - MOTOR

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ClinicalTrials.gov Identifier: NCT02255422
Recruitment Status : Completed
First Posted : October 2, 2014
Results First Posted : September 17, 2020
Last Update Posted : September 20, 2021
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Reata Pharmaceuticals, Inc.

Study Description
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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.


Condition or disease Intervention/treatment Phase
MItochondrial Myopathies Drug: Omaveloxolone capsules, 2.5 mg Drug: omaveloxolone capsules, 5 mg Drug: omaveloxolone capsules, 10 mg Drug: Placebo capsules Drug: omaveloxolone capsules, 20 mg Drug: omaveloxolone capsules, 40 mg Drug: omaveloxolone capsules, 80 mg Drug: omaveloxolone capsules, 160 mg Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 53 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of the Safety, Efficacy, and Pharmacodynamics of RTA 408 in the Treatment of Mitochondrial Myopathy (MOTOR)
Actual Study Start Date : May 5, 2015
Actual Primary Completion Date : November 2, 2017
Actual Study Completion Date : November 30, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Muscle Disorders

Arms and Interventions
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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 Name: RTA 408 Capsules 2.5 mg

Drug: omaveloxolone capsules, 5 mg
Other Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: RTA 408 capsules, 160 mg


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02255422


Locations
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United States, California
UCLA
Los Angeles, California, United States, 90095
United States, Massachusetts
Mass General Hospital
Boston, Massachusetts, United States, 02114
United States, Ohio
Akron Children's Hospital
Akron, Ohio, United States, 44308
United States, Pennsylvania
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15224
United States, Texas
Insitute for Exercise & Environmental Medicine
Dallas, Texas, United States, 75231
Baylor College of Medicine
Houston, Texas, United States, 77030
University of Texas Medical School at Houston
Houston, Texas, United States, 77030
Denmark
Neuromuscular Clinic, Rigshospitalet, University of Copenhagen
Copenhagen, Denmark, DK-2100
Sponsors and Collaborators
Reata Pharmaceuticals, Inc.
AbbVie
  Study Documents (Full-Text)

Documents provided by Reata Pharmaceuticals, Inc.:
Study Protocol  [PDF] October 29, 2015
Statistical Analysis Plan  [PDF] March 12, 2018

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Reata Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02255422    
Other Study ID Numbers: RTA 408-C-1403
First Posted: October 2, 2014    Key Record Dates
Results First Posted: September 17, 2020
Last Update Posted: September 20, 2021
Last Verified: September 2021
Keywords provided by Reata Pharmaceuticals, Inc.:
omaveloxolone
RTA 408 capsules
mitochondrial myopathies
Additional relevant MeSH terms:
Layout table for MeSH terms
Muscular Diseases
Mitochondrial Myopathies
Musculoskeletal Diseases
Neuromuscular Diseases
 Nervous System Diseases
Mitochondrial Diseases
Metabolic Diseases