Pliant Reports Positive DSMB Safety Review and Begins Enrollment in Phase 2a Trial of Bexotegrast at High Dose in Primary Sclerosing Cholangitis

Rare Daily Staff

Pliant Therapeutics, a clinical-stage company focused on treatments for fibrosis, said that following a positive independent Data Safety Monitoring Board safety review, enrollment has commenced in a phase 2a trial of bexotegrast at 320 mg dosed once daily for at least 24 weeks and up to 48 weeks in patients with primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a rare, chronic, and progressive liver disorder that frequently occurs in the setting of inflammatory bowel disease. It is characterized by inflammation, and eventually scarring of the liver and its bile ducts.

Bexotegrast, is an oral, small molecule, dual-selective inhibitor of αvβ6 and αvβ1 integrins being developed for the treatment of PSC and idiopathic pulmonary fibrosis (IPF). Bexotegrast has been administered to more than 600 study participants to date, including healthy volunteers and patients, with no drug-related severe or serious adverse events reported to date.

“We recognize the high unmet medical need in PSC, as there are no FDA approved therapies for the indication and look forward to sharing 12-week interim data from our Phase 2a trial in the third quarter,” said Éric Lefebvre, chief medical officer of Pliant Therapeutics.

Following the completion of enrollment of the 40, 80 and 160 mg dose groups in the INTEGRIS-PSC phase 2a trial, a meeting of the bexotegrast independent DSMB was held earlier this month to review safety data from all patients enrolled in the trial to date. The DSMB recommended that the INTEGRIS-PSC trial continue without modification, enabling the initiation of enrollment of the 320 mg dose group.

The INTEGRIS-PSC phase 2a trial is a randomized, double-blind, dose-ranging, placebo-controlled study evaluating bexotegrast at doses ranging from 40 to 320 mg, administered daily in approximately 112 patients with PSC. The initiation of the 320 mg dose group coincides with the FDA authorization to evaluate long-term dosing of bexotegrast in PSC patients, who will therefore be treated for at least 24 weeks and up to 48 weeks. The primary endpoint is the evaluation of the safety and tolerability of bexotegrast, and the secondary endpoint is the assessment of pharmacokinetics. The trial is also evaluating exploratory pharmacodynamic endpoints including fibrosis biomarkers such as PRO-C3 and enhanced liver fibrosis (ELF) score, changes in alkaline phosphatase (ALP), and liver imaging. Interim 12-week data from the 40, 80, and 160 mg dose groups of this trial is expected in the third quarter of 2023.

Photo: Éric Lefebvre, chief medical officer of Pliant Therapeutics