RTA 408 Capsules in Patients With Friedreich's Ataxia - MOXIe
Status:
Active, not recruiting
Trial end date:
2022-12-01
Target enrollment:
Participant gender:
Summary
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.