Research Study Summary
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 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 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 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 study to evaluate the safety, efficacy, and pharmacodynamics of up to 2 dose levels of RTA 408 in patients with Friedreich's ataxia. Eligible patients in Part 2 will be randomized 1:1:1 to receive RTA 408 (at one of 2 doses chosen from Part 1), or placebo.
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CW ID: 209281
Date Last Changed:
March 8, 2016