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RTA 408 Capsules in Patients With Mitochondrial Myopathy - MOTOR

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02255422
Recruitment Status : Completed
First Posted : October 2, 2014
Last Update Posted : July 19, 2018
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Reata Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE September 30, 2014
First Posted Date  ICMJE October 2, 2014
Last Update Posted Date July 19, 2018
Study Start Date  ICMJE April 2015
Actual Primary Completion Date November 2, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 30, 2014)
Measure the change of peak workload (in watts/kg) during exercise testing [ Time Frame: 12 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 30, 2014)
Measure the change in distance walked during a 6-minute walk test [ Time Frame: 12 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE RTA 408 Capsules in Patients With Mitochondrial Myopathy - MOTOR
Official Title  ICMJE A Phase 2 Study of the Safety, Efficacy, and Pharmacodynamics of RTA 408 in the Treatment of Mitochondrial Myopathy (MOTOR)
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.

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE MItochondrial Myopathies
Intervention  ICMJE
  • 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
  • Drug: omaveloxolone capsules, 10 mg
    Other Name: RTA 408, 10 mg
  • Drug: Placebo capsules
  • Drug: omaveloxolone capsules, 20 mg
    Other Name: RTA 408 capsules, 20 mg
  • Drug: omaveloxolone capsules, TBD mg
    Other Name: RTA 408 capsules, TBD mg
  • Drug: omaveloxolone capsules, 40 mg
    Other Name: RTA 408 capsules, 40 mg
  • Drug: omaveloxolone capsules, 80 mg
    Other Name: RTA 408 capsules, 80 mg
  • Drug: omaveloxolone capsules, 160 mg
    Other Name: RTA 408 capsules, 160 mg
Study Arms  ICMJE
  • 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
    Interventions:
    • Drug: Omaveloxolone capsules, 2.5 mg
    • Drug: omaveloxolone capsules, 5 mg
  • Experimental: omaveloxolone Capsules 10 mg
    omaveloxolone (RTA 408) capsules, 10 mg taken orally once daily for 12 weeks
    Intervention: Drug: omaveloxolone capsules, 10 mg
  • Placebo Comparator: Placebo Capsules
    Placebo capsules taken orally once daily for 12 weeks
    Intervention: Drug: Placebo capsules
  • Experimental: omaveloxolone Capsules 20 mg
    omaveloxolone (RTA 408) Capsules, 20 mg taken orally once daily for 12 weeks.
    Intervention: Drug: omaveloxolone capsules, 20 mg
  • Experimental: omaveloxolone Capsules TBD mg
    omaveloxolone (RTA 408) Capsules, TBD mg taken orally once daily for 12 weeks.
    Intervention: Drug: omaveloxolone capsules, TBD mg
  • Experimental: omaveloxolone Capsules 40 mg
    omaveloxolone (RTA 408) Capsules, 40 mg taken orally once daily for 12 weeks.
    Intervention: Drug: omaveloxolone capsules, 40 mg
  • Experimental: omaveloxone Capsules 80 mg
    omaveloxolone (RTA 408) Capsules, 80 mg taken orally once daily for 12 weeks.
    Intervention: Drug: omaveloxolone capsules, 80 mg
  • Experimental: omaveloxone Capsules 160 mg
    omaveloxolone (RTA 408) Capsules, 160 mg taken orally once daily for 12 weeks.
    Intervention: Drug: omaveloxolone capsules, 160 mg
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 2, 2018)
53
Original Estimated Enrollment  ICMJE
 (submitted: September 30, 2014)
52
Actual Study Completion Date  ICMJE November 30, 2017
Actual Primary Completion Date November 2, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02255422
Other Study ID Numbers  ICMJE RTA 408-C-1403
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Reata Pharmaceuticals, Inc.
Study Sponsor  ICMJE Reata Pharmaceuticals, Inc.
Collaborators  ICMJE AbbVie
Investigators  ICMJE Not Provided
PRS Account Reata Pharmaceuticals, Inc.
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP