Date: 2014-09-30
Type of information: Clinical trial autorization
phase: 2
Announcement: clinical trial authorisation
Company: Reata Pharmaceuticals (USA - CA)
Product: RTA 408 ( N-((4aS,6aR,6bS,8aR,12aS,14aR,14bS)-1 1-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,12a,14,14a,14b- octadecahydropicen-4a-yl)-2,2-difluoropropanamide)
Action
mechanism: RTA 408 is a member of the synthetic oleanane triterpenoid class of compounds and an activator of nuclear factor erythroid 2 [NF-E2]-related factor 2 (Nrf2, Nfe2l2), with potential chemopreventive activity. RTA 408 activates the cytoprotective transcription factor Nrf2, a leucine zipper transcription factor that plays a key role in the maintenance of redox balance and cytoprotection against oxidative stress. In turn, Nrf2 translocates to the nucleus, dimerizes with a small Maf protein (sMaf), and binds to the antioxidant response element (ARE). This induces the expression of a number of cytoprotective genes, including NAD(P)H quinone oxidoreductase 1 (NQO1), sulfiredoxin 1 (Srxn1), heme oxygenase-1 (HO1, HMOX1), superoxide dismutase 1 (SOD1), gamma-glutamylcysteine synthetase (gamma-GCS), thioredoxin reductase-1 (TXNRD1), glutathione S-transferase (GST), glutamate-cysteine ligase catalytic subunit (Gclc) and glutamate-cysteine ligase regulatory subunit (Gclm), and increases the synthesis of the antioxidant glutathione (GSH). Check for active clinical trials or closed clinical trials using this agent.
Disease: Friedreich\'s ataxia
Therapeutic area: Rare diseases - Neurodegenerative diseases
Country: USA
Trial details:
Latest
news: * On September 30, 2014, Reata has received clearance from the Division of Neurology Products of the FDA to begin two new Phase 2 clinical programs in patients with Friedreich\'s Ataxia and Mitochondrial Myopathies. Both of these orphan diseases are associated with reduced energy production, fatigue, and impaired exercise capacity. There are no existing therapies specifically approved to treat patients with these diseases. RTA 408 works by inducing Nrf2, which regulates multiple genes that play both direct and indirect roles in the production of cellular energy (i.e., adenosine triphosphate or ATP) within the mitochondria. Directly, activation of the Nrf2 pathway increases the efficient use of fuel (fatty acids and glucose) by mitochondria and increases mitochondrial biogenesis and basal oxygen consumption. Indirectly, activation of Nrf2, through its antioxidative effects, balances reducing equivalents and maintains mitochondrial homeostasis and efficiency. In addition to its positive effects on metabolic efficiency, Nrf2 activation has been shown in preclinical studies to promote muscle repair and recovery and reduce markers of oxidative stress and muscle injury. The two initial Phase 2 trials will both be multi-center, double-blind, randomized, dose-ranging, placebo-controlled studies. The primary efficacy endpoint in both studies will be peak work as assessed during exercise testing. The studies will also explore changes in other measures of physical activity, fatigue, and biomarkers associated with mitochondrial functioning.
