RTA 408 Capsules in Patients With Mitochondrial Myopathy - MOTOR

Status:	Completed
Conditions:	Neurology
Therapuetic Areas:	Neurology
Healthy:	No
Age Range:	18 - 75
Updated:	7/21/2018
Start Date:	April 2015
End Date:	November 30, 2017

A Phase 2 Study of the Safety, Efficacy, and Pharmacodynamics of RTA 408 in the Treatment of Mitochondrial Myopathy (MOTOR)

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.

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

We found this trial at

sites

University of Texas Medical School in Houston

Houston, Texas 77030

Principal Investigator: Mary Kay Koenig, MD

Phone: 713-500-5757

from

Houston, TX