Three ongoing clinical trials are recruiting additional participants to allow for more robust assessments of Reata Pharmaceuticals’ bardoxolone methyl therapy as a potential treatment for various forms of pulmonary hypertension.
Two of the trials — the Phase 3 CATALYST (NCT02657356) trial, which examines the drug in connective tissue disease-associated pulmonary arterial hypertension (PAH), as well as the Phase 2 LARIAT (NCT02036970) trial in pulmonary hypertension (PH) — are expected to be completed in 2018.
To assess the long-term safety of the treatment, which is intended for chronically ill patients, the ongoing RANGER (NCT03068130) Extended Access program is recruiting bardoxolone methyl-treated patients to follow for up to five years, keeping an eye on any potential negative effects that might emerge in the long run.
Bardoxolone methyl is a compound that acts on basic molecular pathways involved in inflammation and oxidation. It activates a factor called Nrf2 — which controls the activity of a gene involved in the proper function of mitochondria, the cellular power plants that convert nutrients to energy.
In doing so, it not only makes energy production more efficient, but also lowers damaging oxidative processes that emerge when mitochondria are working poorly.
In addition, the drug suppresses the activity of another factor that controls gene activity. This factor, called NF-κB, is involved in inflammatory processes.
The combined effects of bardoxolone methyl — promoting antioxidant processes, harnessing inflammation, and boosting energy production — lowers fibrosis formation, early pre-clinical studies suggest.
Data from clinical trials so far have also supported the therapy’s potential benefits. In October 2015, Reata showed that bardoxolone methyl-treated patients in the LARIAT trial significantly improved their exercise capacity, measured by the 6-minute walk distance (6MWD) test.
“The initial data from LARIAT are very encouraging and indicate that bardoxolone methyl’s novel mechanism of action may provide a new approach to PAH therapy,” Colin Meyer, MD, Reata’s Chief Medical Officer, said at the time, while adding that the acute changes might, over time, translate to better muscle function and a slowed heart and blood vessel remodeling.
LARIAT, which is expected to enroll 208 PH patients at sites across the U.S. and in Germany, Spain and the U.K., tests a range of doses of the treatment, and compares it to a placebo.
The study includes patients who developed PH for various reasons. The trial welcomes patients with PH associated with connective tissue disease, interstitial lung disease, and idiopathic PH, including subsets of patients with PH caused by lung disease (WHO Group III) or those with blood or other rare diseases that cause PH (WHO Group V).
Reata expects the study to be completed by June 2018. Patients wishing to participate can visit the trial registration website, where they can find study locations and contact details.
CATALYST is a more specific study, focusing on patients with connective tissue disease-associated PAH. Patients will receive either bardoxolone methyl or a placebo in addition to their earlier therapy.
Participants are treated once daily for six months, after which researchers will assess changes in 6MWD between treated and control patients. Exercise capacity will also be compared between the start and end of the study.
Researchers will also focus on how quickly patients improve, and assess markers of muscle injury and inflammation as an indicator of treatment effect.
According to a Reata press release, researchers will assess how much outcomes vary after the first 100 patients to determine how many patients they need to enroll at sites in the U.S. and numerous other countries. But they estimate that around 130 to 200 patients will be needed for a robust analysis of the data.
The company expects to complete the study in the second half of 2018.
Patients who wish to participate in the CATALYST study can visit the trial registration website, where they can find study site locations and contact details.
Patients enrolled in the LARIAT and CATALYST trials can opt to be transferred to the RANGER extension study once they complete the trial. More information about the RANGER study, also with test sites worldwide, can be found on the trial website.
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