Reata Pharmaceuticals, Inc. has announced that it has enrolled the first patient in a new Friedreich’s Ataxia clinical trial in collaboration with AbbVie, and the Friedreich’s Ataxia Research Alliance. In their currently recruiting phase 2/3 clinical trial, “RTA 408 Capsules in Patients with Friedreich’s Ataxia – MOXIe,” safety and efficacy of RTA 408 are under evaluation in patients with Friedreich’s ataxia.
“Our large body of preclinical and clinical data with RTA 408 and related molecules provides strong support for the hypothesis being tested in MOXIe that RTA 408 may be beneficial in patients suffering from Friedreich’s ataxia,” said Dr. Colin Meyer, Reata’s Chief Medical Officer, in a recent press release from the company. “We have been productively collaborating with key Friedreich’s ataxia clinicians and patient advocacy, and we look forward to evaluating the results of MOXIe as they become available.”
This new treatment is based on the nuclear factor erythroid-derived 2-related factor 2 (Nrf2) signaling pathway. RTA 408 activates Nrf2, leading to antioxidant target gene expression that may help attenuate oxidative damage found in Friedreich’s ataxia. Oxidative damage can in large part be explained by mitochondrial impairment due to a frataxin deficiency resulting from a frataxin gene mutation.
Thus, it is hoped that RTA 408 can improve the health of patients treated during the two-part trial. In the first part of the trial, patients will receive escalating doses of RTA 408 or placebo in order to evaluate the maximum tolerated dose between 2.5 and 10 milligrams. In the second part of the trial, assuming all doses are well-tolerated by patients, 24 participants from the first cohort will be split among groups of 2.5 mg RTA 408, 10 mg RTA 408, or placebo.
In addition to the safety profile of RTA 408, peak workload during exercise is of primary interest. Patients will complete exercises while being monitored for workload, measured in watts/kg body weight. Secondly, clinicians will evaluate patients using the modified Friedreich’s ataxia rating scale (FARS), which monitors adeptness of patients during daily activities.
A total of 52 patients are sought for enrollment, and the final primary outcome measures are expected to be obtained in March 2016, with the study completing in June. Oral treatments will be given to patients once daily for twelve weeks, with outcomes measured at the end as change from baseline. Due to the nature of evaluations, patients must be willing to remain on the same exercise regimen for 16 weeks, and they must also be able to complete maximal exercise testing.
In addition to Friedreich’s ataxia, another mitochondrial disorder (Mitochondrial Myopathies) is the subject of a clinical trial in the works for RTA 408. Reata is further looking into using RTA 408 to treat melanoma, lung cancer, dermatological cancers such as radiation dermatitis in breast cancer, and corneal endothelial cell loss due to cataract surgery.
“Our collaborators and we have shown in preclinical studies that genetic or pharmacologic Nrf2 activation positively regulates mitochondrial function and energy production,” said Dr. Meyer in a news release when the trial was initiated. “We hope to translate this effect into improved physical functioning and reduced fatigue in patients with Friedreich’s ataxia and mitochondrial myopathies. These rare, debilitating diseases currently have no approved therapies.”