Enrollment in the Phase 2 clinical trial of setanaxib (GKT831), an oral investigational treatment for idiopathic pulmonary fibrosis (IPF), will start in the coming weeks, Genkyotex announced in a progress report.
Following approval by the U.S. Food and Drug Administration (FDA) in July, the study protocol now has been cleared by the Institutional Review Boards (IRB). The trial will evaluate the safety and effectiveness of setanaxib in 60 IPF patients receiving standard care, versus placebo.
This trial is funded by the National Institutes of Health (NIH), which awarded an $8.9 million grant to Victor Thannickal, MD, a professor at the University of Alabama at Birmingham, to support a research program tackling the role of NOX enzymes — the therapeutic targets of setanaxib — in IPF.
Setanaxib, formerly known as GKT831, is an orally available inhibitor of the NOX1 and NOX4 enzymes, which have been implicated in various important aspects of IPF. NOX enzymes are important sources of reactive oxygen species (ROS), which are natural substances that become harmful to tissues when their levels become too high. ROS can trigger a so-called oxidative stress mechanism, an insult to cells and tissues associated with many human fibrotic diseases, including IPF.
Earlier, Thannickal and his team found that NOX4 was a key driver of lung fibrosis in mice, triggering the conversion of fibroblasts into myofibroblasts, and the production of extracellular matrix — a mesh of sugars and proteins that supports cells and accumulates in the lungs of IPF patients.
By targeting NOX enzymes, setanaxib is believed to protect against fibrosis in not only the lungs, but also in other organs.
Setanaxib showed promising anti-fibrotic activity and safety in a Phase 2 clinical study (NCT03226067) completed in April in patients with a type of liver fibrosis called primary biliary cholangitis (PBC). The therapy also is being evaluated in a trial for treating people with type 1 diabetes associated with kidney fibrosis (diabetic kidney disease, DKD).
Preclinical studies in mouse models of pulmonary fibrosis showed that setanaxib reversed lung fibrosis by deactivating and clearing myofibroblasts (cells involved in wound healing and fibrosis).
Those positive results prompted Genkyotex to launch a Phase 2 clinical trial to determine setanaxib’s safety and effectiveness in 60 IPF patients on standard care with Esbriet (pirfenidone) or Ofev (nintedanib), compared to placebo.
Participants will be assigned randomly to receive placebo or setanaxib 400 mg, twice a day for 24 weeks. This dose showed anti-fibrotic and anti-inflammatory activity and a favorable safety profile in the clinical trial for PBC.
The trial will assess markers of pulmonary oxidative stress, and setanaxib’s effects on exercise capacity and lung function.
“We are very pleased to report positive developments in both the DKD and IPF clinical trials,” Philippe Wiesel, MD, chief medical officer of Genkyotex, said in a press release.
“We are also excited to report that, following FDA approval, the IPF trial has now also received IRB clearance. Our recent results in PBC provided important dose response and safety information, which is being utilized to optimize these Phase 2 trials. We thank our academic collaborators for their continued commitment to the evaluation setanaxib in these diseases with high unmet needs,” Wiesel said.