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RTA 408 Capsules in Patients With Mitochondrial Myopathy - MOTOR

This study is currently recruiting participants.
Verified November 2016 by Reata Pharmaceuticals, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02255422
First Posted: October 2, 2014
Last Update Posted: November 16, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
AbbVie
Information provided by (Responsible Party):
Reata Pharmaceuticals, Inc.
  Purpose

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.

Part 1: The first part of 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.

Part 2: The second part of this study is a randomized, placebo-controlled, double-blind, parallel study to evaluate the safety, efficacy, and pharmacodynamics of up to 2 dose levels of omaveloxolone (RTA 408) in patients with mitochondrial myopathies. Eligible patients in Part 2 will be randomized 1:1:1 to receive omaveloxolone (RTA 408) (at one of 2 doses chosen from Part 1), or placebo.


Condition Intervention 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, TBD mg Drug: omaveloxolone capsules, 40 mg Drug: omaveloxolone capsules, 80 mg Drug: omaveloxolone capsules, 160 mg Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel 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)

Resource links provided by NLM:


Further study details as provided by Reata Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Measure the change of peak workload (in watts/kg) during exercise testing [ Time Frame: 12 weeks ]

Secondary Outcome Measures:
  • Measure the change in distance walked during a 6-minute walk test [ Time Frame: 12 weeks ]

Estimated Enrollment: 100
Study Start Date: April 2015
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 TBD mg
omaveloxolone (RTA 408) Capsules, TBD mg taken orally once daily for 12 weeks.
Drug: omaveloxolone capsules, TBD mg
Other Name: RTA 408 capsules, TBD 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: omaveloxone 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: omaveloxone 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

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
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
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
United States, California
UCLA Recruiting
Los Angeles, California, United States, 90095
Contact: Michael Bonitati    310-825-3264    mbonitati@mednet.ucla.edu   
Principal Investigator: Perry Shieh, MD         
United States, Massachusetts
Mass General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Erica Kelly    617-724-7726    elkelly@mgh.harvard.edu   
Principal Investigator: Amel Karaa, MD         
United States, Ohio
Akron Children's Hospital Recruiting
Akron, Ohio, United States, 44308
Contact: Hilary Tonni    330-543-4734    HTonni@chmca.org   
Principal Investigator: Bruce Cohen, MD         
United States, Pennsylvania
The Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Lyntovia Hylton    267-426-0241    hyltonl@email.chop.edu   
Principal Investigator: Marni Falk, MD         
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Michele Graham    412-692-3476    michele.graham@chp.edu   
Principal Investigator: Gerard Vockley, MD         
United States, Texas
Insitute for Exercise & Environmental Medicine Recruiting
Dallas, Texas, United States, 75231
Contact: Marta Newby    214-345-4655    martanewby@texashealth.org   
Principal Investigator: Ron Haller, MD         
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Beverly Feldman, RN, MSN    832-822-4301    bmfeldma@texaschildrens.org   
Principal Investigator: Fernando Scaglia, MD         
University of Texas Medical School at Houston Recruiting
Houston, Texas, United States, 77030
Contact: Sreejeta Dasgupta    713-500-5757    sreejeta.dasgupta@uth.tmc.edu   
Principal Investigator: Mary Kay Koenig, MD         
Denmark
Neuromuscular Clinic, Rigshospitalet, University of Copenhagen Recruiting
Copenhagen, Denmark, DK-2100
Contact: Karen Lindhardt Madsen    +45-3545 6135    karen.Lindhardt.Madsen@regionh.dk   
Principal Investigator: Karen Madsen, MD         
Sponsors and Collaborators
Reata Pharmaceuticals, Inc.
AbbVie
  More Information

Responsible Party: Reata Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02255422     History of Changes
Other Study ID Numbers: RTA 408-C-1403
First Submitted: September 30, 2014
First Posted: October 2, 2014
Last Update Posted: November 16, 2016
Last Verified: November 2016

Keywords provided by Reata Pharmaceuticals, Inc.:
omaveloxolone
RTA 408 capsules
mitochondrial myopathies

Additional relevant MeSH terms:
Muscular Diseases
Mitochondrial Myopathies
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Mitochondrial Diseases
Metabolic Diseases