RTA 408 Capsules in Patients With Friedreich's Ataxia - MOXIe

Status:	Active, not recruiting
Conditions:	Neurology
Therapuetic Areas:	Neurology
Healthy:	No
Age Range:	16 - 40
Updated:	3/6/2019
Start Date:	January 2015
End Date:	December 2022

A Phase 2 Study of the Safety, Efficacy, and Pharmacodynamics of RTA 408 in the Treatment of Friedreich's Ataxia (MOXIe)

Friedreich's ataxia is an autosomal recessive cerebellar ataxia caused by triplet-repeat
expansions. The causative mutation is a trinucleotide (GAA) repeat expansion in the first
intron of the frataxin gene, leading to impaired transcription of frataxin. The pathological
consequences of frataxin deficiency include a severe disruption of iron-sulfur cluster
biosynthesis, mitochondrial iron overload coupled to cellular iron dysregulation, and an
increased sensitivity to oxidative stress.

A hallmark of Friedreich's ataxia is impairment of antioxidative defense mechanisms, which
play a major role in disease progression. Studies have demonstrated that nuclear factor
erythroid-derived 2-related factor 2 (Nrf2) signaling is grossly impaired in patients with
Friedreich's ataxia. Therefore, the ability of omaveloxolone (RTA 408) to activate Nrf2 and
induce antioxidant target genes is hypothesized to be therapeutic in patients with
Friedreich's ataxia.

This 2-part study will evaluate the efficacy, safety, and pharmacodynamics of omaveloxolone
(RTA 408) in the treatment of patients with Friedreich's ataxia.

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 Friedreich's ataxia.

Part 2: The second part of this study is a randomized, placebo-controlled, double-blind,
parallel-group study to evaluate the safety and efficacy of omaveloxolone (RTA 408) 150 mg in
patients with Friedreich's ataxia. Patients enrolled in Part 2 will be randomized 1:1 to
receive omaveloxolone (RTA 408) 150 mg or placebo.

Extension: The extension will assess long-term safety and tolerability of omaveloxolone (RTA
408) in qualified patients with Friedreich's ataxia following completion of Part 1 or Part 2.
Patients will not be unblinded to study treatment in Part 1 or Part 2 upon entering the
extension study. Patients will receive open-label omaveloxolone (RTA 408) at 150 mg once
daily.

Inclusion Criteria:

1. Have genetically confirmed Friedreich's ataxia

2. Have a modified FARS score ≥20 and ≤80

3. Be male or female and ≥16 years of age and ≤40 years of age

4. 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

5. Have the ability to complete maximal exercise testing

6. Be able to swallow capsules

Exclusion Criteria:

1. Have uncontrolled diabetes (HbA1c >11.0%)

2. Have B-type natriuretic peptide value >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, or alanine aminotransferase

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. Moderate or strong inhibitors or inducers of cytochrome P450 3A4 (e.g.,
carbamazepine, phenytoin, ciprofloxacin, grapefruit juice)

3. 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

11. Prior participation in a trial with omaveloxolone (RTA 408)

We found this trial at

sites

Children's Hospital of Philadelphia

South 34th Street
Philadelphia, Pennsylvania 19104

215-590-1000