Setanaxib Phase 1 Trial Approved in France for Testing in Healthy Volunteers

The French Medicines Agency has authorized Genkyotex to launch a Phase 1 trial to evaluate the safety and pharmacological properties of high-dose setanaxib, the company’s investigational oral treatment for idiopathic pulmonary fibrosis (IPF).

Setanaxib (formerly known as GKT831) is an investigational anti-fibrotic therapy that is thought to reduce tissue scarring (fibrosis) by inhibiting the activity of two enzymes — NOX1 and NOX4 — that contribute to the production of oxidant molecules that damage cells and tissues.

The new Phase 1 trial (NCT04327089) will assess the safety, pharmacokinetics, and possible drug-drug interactions of setanaxib when administered at a dose of up to 1,600 mg per day in a group of 54 healthy adult volunteers. Of note, pharmacokinetics is the study of how a therapy is absorbed, distributed, metabolized, and eliminated from the body.

The study will be divided into two phases, starting with an initial single ascending dose phase, in which four groups of 6–8 subjects will receive a single dose of the medication, at daily doses ranging from 400 to 1,600 mg while fasting. This will be followed by a multiple ascending dose phase, in which participants will be treated with repeated doses of setanaxib (1,200 or 1,600 mg per day), administered twice a day, in the morning and evening, for a period of 14 days.

In light of the current COVID-19 outbreak, Genkyotex is anticipating the trial will be launched in the second quarter of 2020, with results from both phases expected by the third quarter of this year.

If successful in healthy volunteers, this trial may open the door to potential future studies assessing the effects of higher doses of setanaxib in patients with IPF and primary biliary cholangitis (PBC), a form of liver disease.

“Regulatory approval to evaluate setanaxib at doses up to 1,600 mg/day attests to the excellent safety profile of our lead compound,”  Philippe Wiesel, MD, executive vice president and chief medical officer of Genkyotex, said in a press release. “Successful results of this Phase 1 study will allow us to include higher doses in future setanaxib trials and reach the full efficacy potential of setanaxib.”

To date, 275 individuals have been treated with setanaxib in five Phase 1 and three Phase 2 trials, and no safety signals or dose-limiting toxicity events were reported in any of them.

A recently-completed Phase 2 trial (NCT03226067) in PBC patients has shown that setanaxib was well-tolerated when administered at a daily dose of 400 or 800 mg. In addition, the study demonstrated a dose-dependent effect on markers of liver inflammation and fibrosis, as well as in patient quality of life measures.

The company completed another Phase 1 trial (NCT03740217) in healthy volunteers that supported the transition from its original 100 mg tablet to the new 400 mg tablet formulation.

Genkyotex is currently in discussions with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency about the registration strategy for setanaxib in PBC. The end of the company’s Phase 2 meeting with the FDA took place at the end of April as planned.

“We are progressing with our regulatory agency discussions and will communicate the final outcome in the near future,” Wiesel said.