The core component of the program will be to conduct a 24-week Phase 2 trial of the Company’s lead product candidate, GKT831, in patients with IPF.
The academic consortium also includes Dr. Steven Duncan at UAB, Dr. Gerard Criner at Temple University, Dr. Hyun Kim at the University of Minnesota, Dr. Kevin Flaherty at the University of Michigan, and Dr. Joseph Lasky at Tulane University.
Professor Thannickal and his colleagues previously published a seminal study in Nature Medicine identifying NOX4 as a key driver of lung fibrosis.
In a subsequent publication in Science Translational Medicine, the researchers demonstrated that pharmacological inhibition of NOX1/4 with GKT831 achieved marked anti-fibrotic effects and prolonged survival in a stringent model of lung fibrosis in aged mice.
Separately, NOX1 has been shown to drive vascular remodeling, a critical factor contributing to disease progression in IPF, in several preclinical models of lung disease. In these preclinical models, GKT831 was shown to efficiently reduce vascular remodeling and secondary right heart disease.
The investigator-initiated Phase 2 trial will be a placebo-controlled, double-blind, randomized, parallel group study to evaluate the safety and efficacy of oral GKT831 in patients with IPF receiving standard of care therapies. A total of 60 patients will be allocated to a 24-week treatment with oral GKT831 or matching placebo.
The primary endpoint of the study will be the change in plasma levels, at the end of the 24-week treatment period, of o,o’-dityrosine, which is an oxidized covalent modification of protein tyrosine residues that has been shown to be a marker of pulmonary oxidative stress and is markedly elevated in patients with interstitial lung disease.
Key secondary endpoints include changes in 6-minute walk distance, forced vital capacity and high-resolution CT. The patient enrollment is expected to begin during the first half of 2019.
Thannickal said: “We are pleased to advance our research on NOX enzymes to the clinical stage.
“Importantly, NOX1/4 inhibition may have profound disease modifying effects by addressing the fibrotic and vascular remodeling, which drives disease progression. Based on the preclinical data generated to date, we believe GKT831 has the potential to be an effective treatment in IPF.
“GKT831 has previously shown marked anti-fibrotic activity in preclinical models, and we now look forward to further evaluating this promising candidate in a Phase 2 clinical trial.”
Genkyotex chief medical officer Philippe Wiesel said: “We are very excited about this planned investigator-initiated Phase 2 trial, which expands the clinical evaluation of GKT831 into an additional fibrotic disorder.
“There is a critical need for effective therapies that can safely delay or reverse disease progression in IPF patients and, based on its profile, we believe that GKT831 could become an important treatment option in this indication. We are thankful to the consortium for supporting and conducting this strategic research program.”
GKT831 is currently being evaluated in two separate Phase 2 clinical trials in patients with respectively liver and kidney fibrosis.
Source: Company Press Release