Back to resultsRTA 408 Capsules in Patients With Mitochondrial Myopathy - MOTOR
Primary Purpose
MItochondrial Myopathies
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Omaveloxolone capsules, 2.5 mg
omaveloxolone capsules, 5 mg
omaveloxolone capsules, 10 mg
Placebo capsules
omaveloxolone capsules, 20 mg
omaveloxolone capsules, 40 mg
omaveloxolone capsules, 80 mg
omaveloxolone capsules, 160 mg
Sponsored by
About this trial
This is an interventional treatment trial for MItochondrial Myopathies focused on measuring omaveloxolone, RTA 408 capsules, mitochondrial myopathies
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
- 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
Sites / Locations
- UCLA
- Mass General Hospital
- Akron Children's Hospital
- The Children's Hospital of Philadelphia
- University of Pittsburgh
- Insitute for Exercise & Environmental Medicine
- Baylor College of Medicine
- University of Texas Medical School at Houston
- Neuromuscular Clinic, Rigshospitalet, University of Copenhagen
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm Type
Experimental
Experimental
Placebo Comparator
Experimental
Experimental
Experimental
Experimental
Arm Label
omaveloxolone Capsules 2.5 mg and 5 mg
omaveloxolone Capsules 10 mg
Placebo Capsules
omaveloxolone Capsules 20 mg
omaveloxolone Capsules 40 mg
omaveloxolone Capsules 80 mg
omaveloxolone Capsules 160 mg
Arm Description
omaveloxolone (RTA 408) Capsules, 2.5 mg taken orally once daily for 2 weeks, then 5 mg taken orally once daily for 10 weeks
omaveloxolone (RTA 408) capsules, 10 mg taken orally once daily for 12 weeks
Placebo capsules taken orally once daily for 12 weeks
omaveloxolone (RTA 408) Capsules, 20 mg taken orally once daily for 12 weeks.
omaveloxolone (RTA 408) Capsules, 40 mg taken orally once daily for 12 weeks.
omaveloxolone (RTA 408) Capsules, 80 mg taken orally once daily for 12 weeks.
omaveloxolone (RTA 408) Capsules, 160 mg taken orally once daily for 12 weeks.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Change in 6-minute Walk Test (6MWT) Distance
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.
Full Information
NCT ID
NCT02255422
First Posted
September 30, 2014
Last Updated
September 15, 2021
Sponsor
Reata Pharmaceuticals, Inc.
Collaborators
AbbVie
1. Study Identification
Unique Protocol Identification Number
NCT02255422
Brief Title
RTA 408 Capsules in Patients With Mitochondrial Myopathy - MOTOR
Official Title
A Phase 2 Study of the Safety, Efficacy, and Pharmacodynamics of RTA 408 in the Treatment of Mitochondrial Myopathy (MOTOR)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
May 5, 2015 (Actual)
Primary Completion Date
November 2, 2017 (Actual)
Study Completion Date
November 30, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Reata Pharmaceuticals, Inc.
Collaborators
AbbVie
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
MItochondrial Myopathies
Keywords
omaveloxolone, RTA 408 capsules, mitochondrial myopathies
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
53 (Actual)
8. Arms, Groups, and Interventions
Arm Title
omaveloxolone Capsules 2.5 mg and 5 mg
Arm Type
Experimental
Arm Description
omaveloxolone (RTA 408) Capsules, 2.5 mg taken orally once daily for 2 weeks, then 5 mg taken orally once daily for 10 weeks
Arm Title
omaveloxolone Capsules 10 mg
Arm Type
Experimental
Arm Description
omaveloxolone (RTA 408) capsules, 10 mg taken orally once daily for 12 weeks
Arm Title
Placebo Capsules
Arm Type
Placebo Comparator
Arm Description
Placebo capsules taken orally once daily for 12 weeks
Arm Title
omaveloxolone Capsules 20 mg
Arm Type
Experimental
Arm Description
omaveloxolone (RTA 408) Capsules, 20 mg taken orally once daily for 12 weeks.
Arm Title
omaveloxolone Capsules 40 mg
Arm Type
Experimental
Arm Description
omaveloxolone (RTA 408) Capsules, 40 mg taken orally once daily for 12 weeks.
Arm Title
omaveloxolone Capsules 80 mg
Arm Type
Experimental
Arm Description
omaveloxolone (RTA 408) Capsules, 80 mg taken orally once daily for 12 weeks.
Arm Title
omaveloxolone Capsules 160 mg
Arm Type
Experimental
Arm Description
omaveloxolone (RTA 408) Capsules, 160 mg taken orally once daily for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Omaveloxolone capsules, 2.5 mg
Other Intervention Name(s)
RTA 408 Capsules 2.5 mg
Intervention Type
Drug
Intervention Name(s)
omaveloxolone capsules, 5 mg
Other Intervention Name(s)
RTA 408 capsules, 5 mg
Intervention Type
Drug
Intervention Name(s)
omaveloxolone capsules, 10 mg
Other Intervention Name(s)
RTA 408, 10 mg
Intervention Type
Drug
Intervention Name(s)
Placebo capsules
Intervention Type
Drug
Intervention Name(s)
omaveloxolone capsules, 20 mg
Other Intervention Name(s)
RTA 408 capsules, 20 mg
Intervention Type
Drug
Intervention Name(s)
omaveloxolone capsules, 40 mg
Other Intervention Name(s)
RTA 408 capsules, 40 mg
Intervention Type
Drug
Intervention Name(s)
omaveloxolone capsules, 80 mg
Other Intervention Name(s)
RTA 408 capsules, 80 mg
Intervention Type
Drug
Intervention Name(s)
omaveloxolone capsules, 160 mg
Other Intervention Name(s)
RTA 408 capsules, 160 mg
Primary Outcome Measure Information:
Title
Change of Peak Workload (in Watts/kg) During Exercise Testing
Description
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.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Change in 6-minute Walk Test (6MWT) Distance
Description
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.
Time Frame
6MWT was assessed at Week 4, Week 8, and Week 12 and compared to baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Facility Information:
Facility Name
UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Mass General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Akron Children's Hospital
City
Akron
State/Province
Ohio
ZIP/Postal Code
44308
Country
United States
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Insitute for Exercise & Environmental Medicine
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Texas Medical School at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Neuromuscular Clinic, Rigshospitalet, University of Copenhagen
City
Copenhagen
ZIP/Postal Code
DK-2100
Country
Denmark
12. IPD Sharing Statement
Citations:
PubMed Identifier
31896620
Citation
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.
Results Reference
derived
Learn more about this trial
RTA 408 Capsules in Patients With Mitochondrial Myopathy - MOTOR
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