IPF Therapy PLN-74809 Showing Favorable Safety in Phase 2a Trial
No modifications needed for INTEGRIS-IPF trial, monitoring board says
Patients receiving a higher dose of PLN-74809 in the Phase 2a INTEGRIS-IPF clinical trial, which is testing the oral treatment candidate for idiopathic pulmonary fibrosis (IPF), are showing positive safety outcomes.
That’s according to data from a safety review analysis conducted by the study’s data safety monitoring board (DSMB) — an independent group of specialists who monitor patient safety and treatment effectiveness during a trial — of all doses tested.
Based on these observations, the DSMB concluded that INTEGRIS-IPF (NCT04396756), launched in March 2020 by therapy developer Pliant Therapeutics, may continue without any modifications.
“This positive safety review marks an important milestone in the development of PLN-74809,” Éric Lefebvre, MD, Pliant’s chief medical officer, said in a company press release.
“Given 320 mg is the highest dose planned to be tested in the PLN-74809 program, the positive DSMB review significantly builds on the favorable safety profile seen to date,” Lefebvre said.
Testing PLN-74809 in trial
This analysis was conducted after patient enrollment was completed in the trial’s higher dose group, where patients are being given 320 mg of PLN-74809 daily. The DSMB examined safety data from all enrolled participants, nearly half of whom had completed at least 12 weeks, or about three months, of treatment.
According to Pliant, interim results from the higher-dose patient group are expected early next year.
“In addition to the accumulating patient safety database, we have completed all necessary sub-chronic and chronic GLP [good laboratory practices] toxicology studies of PLN-74809, with no on-target or off-target safety concerns noted to date across all doses tested,” Lefebvre said.
PLN-74809 is a small molecule designed to block the activity of two integrins: alpha v beta 6 and alpha v beta 1. Integrins are proteins that mediate cell adhesion and are also thought to be involved in fibrosis, or tissue scarring. By blocking these integrins, PLN-74809 is expected to help prevent the growth of fibrotic tissues in the lungs.
To date, PLN-74809 has been given to more than 450 people, including healthy volunteers and IPF patients, according to the company. Pliant noted that no serious treatment-related side effects have been reported so far.
INTEGRIS-IPF is a Phase 2a study that is testing the safety, tolerability, and pharmacokinetics — a therapy’s movement into, through, and out of the body — of PLN-74809 versus a placebo.
The trial initially enrolled 90 people with IPF, ages 40 and older. Most of the patients were on standard-of-care IPF treatment such as Esbriet (pirfenidone) or Ofev (nintedanib).
PLN-74809 first was tested across multiple doses — 40, 80, or 160 mg — taken daily for 12 weeks, or about three months. The higher dose of 320 mg is now being given daily over at least six months, and up to 48 weeks (about 11 months), to approximately 28 patients.
The trial was designed to assess patients’ lung function using both forced vital capacity (FVC) — which indicates the total amount of air a person can forcibly exhale after taking a deep breath — and the Quantitative Lung Fibrosis score (QLF), a measure evaluating the stage of lung fibrosis via imaging tests.
Top-line data from the trial was recently announced, and indicates that PLN-74809 was well-tolerated when given up to a dose of 160 mg. No deaths nor treatment-related serious side effects were reported at the doses tested.
Results also showed that the treatment candidate was able of slowing lung function decline when given with or without current IPF standard-of-care therapies.
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