Phase 2 Trial of Oral Setanaxib in IPF Patients Expected to Open Soon

Despite the COVID-19 outbreak, patient enrollment in the Phase 2 trial of setanaxib, an investigational oral treatment for idiopathic pulmonary fibrosis (IPF), is still expected to start by mid-year, Genkyotex, the therapy’s developer, announced in a press release.

The single-site study (NCT03865927), whose protocol has been cleared by the U.S. Food and Drug Administration (FDA) and the site’s Institutional Review Board (IRB), aims to assess the safety and efficacy of setanaxib in 60 IPF patients.

Setanaxib, formerly known as GKT831, works by blocking the activity of two enzymes — NOX1 and NOX4 — thought to be involved in IPF, and to contribute to the production of reactive oxygen species (ROS). High levels of these harmful oxidant molecules can trigger oxidative stress, and damage cells and tissues.

By blocking the activity of NOX enzymes, setanaxib is expected to protect cells and tissues in the lungs and other organs against fibrosis (tissue scarring).

Taking place at the University of Alabama at Birmingham (UAB), enrolled adults currently under standard of care for IPF — treatment with Esbriet (pirfenidone) or Ofev (nintedanib) — will be randomly assigned to either 400 mg tablets of setanaxib or a placebo twice a day for 24 weeks (six months).

Main trial goals include assessing changes in the levels of pulmonary oxidative stress biomarkers (namely o,o’-dityrosine), as well as in patients’ lung function and exercise capacity over the course of the trial.

Lung function will be evaluated based on forced vital capacity (FVC; measures the total amount of air a patient is able to exhale after taking a deep breath), and the exercise capacity based on the six-minute walk test (6MWT; measures the distance a patient is able to walk in six minutes).

Additional goals include measures of collagen fragment levels in plasma (portion of the blood obtained after removing blood cells), and evaluating the treatment’s safety and tolerability.

If the trial succeeds in demonstrating that setanaxib’s use eases lung fibrosis, it can set the foundation for a future Phase 3 trial in IPF patients.

The Phase 2 study is funded by a $8.9 million grant awarded by the U.S. National Institutes of Health (NIH), and is being led by Victor Thannickal, MD, a UAB professor with a specialty in respiratory diseases. The trial is also being supported by a consortium of five investigational centers of excellence across the U.S.

In addition to IPF, setanaxib has been tested as a treatment for patients with primary biliary cholangitis (PBC), a form of liver disease, in a completed Phase 2 trial (NCT03226067).

Data from this trial showed the medication had strong anti-inflammatory and anti-fibrotic properties, along with an excellent safety profile, when administered at a dose of 400 mg twice daily.

A planned meeting with FDA officials on a potential Phase 3 trial in PBC patients is taking place as scheduled but via conference call, and the company is moving ahead with submitting documents to the European Medicine Agency (EMA).

Another Phase 2 trial is currently testing setanaxib in patients with diabetes and kidney disease, amended to use the 400 mg dose. According to the company, 28 patients have already finished 48 weeks of treatment, but further enrollment in this trial, mainly taking place in Australia, may have delays due to the COVID-19 pandemic.

A Phase 1 trial (NCT04327089) of setanaxib at higher doses (up to 1,600 mg)  in healthy volunteers is planned to open this year. It will evaluate the treatment’s pharmacokinetic properties (therapy absorption, distribution, and elimination), possible drug interactions, and safety at those doses.