Phase 2a Trial Will Test Higher Dose of Anti-fibrotic Therapy PLN-74809
The higher dose of 320 mg will be given to about 28 adults with IPF once daily for at least six months as part of a Phase 2a trial that will leverage the same sites and protocol of INTEGRIS-IPF (NCT04396756), a Phase 2a study that is testing the safety, tolerability, and pharmacokinetics of PLN-74809 versus a placebo. A therapy’s pharmacokinetics refers to its movement into, through, and out of the body.
This decision follows a positive recommendation from the Data Safety Monitoring Board (DSMB), an independent committee that reviews how safe a therapy is while a clinical trial is ongoing.
The board met earlier this month and concluded that INTEGRIS-IPF may continue without any modifications. The review focused on data from all patients enrolled in all dose groups. The company recently completed enrollment at doses of 40, 80, and 160 mg, with top-line data expected to become available midway through this year.
“We are pleased that the favorable safety and tolerability profile seen with PLN-74809 to date supports the advancement of our Phase 2a program to evaluate a higher dose at a longer treatment duration,” Bernard Coulie, MD, PhD, president and CEO of Pliant, said in a press release.
PLN-74809 is designed to block the activity of two integrins, called alpha v beta 6 and alpha v beta 1. An integrin is a type of protein found on the surface of cells that helps them adhere to, and communicate with, neighboring cells. Integrins are also thought to be involved in fibrosis, or tissue scarring, in IPF and other fibrotic diseases.
According to Pliant, PLN-74809 has been given to more than 450 people so far, including healthy volunteers and patients, with no serious side effects reported. Lower doses in INTEGRIS-IPF are being given for up to 12 weeks (about three months), while the higher 320 mg dose will be given for up to 48 weeks (almost one year).
“It is noteworthy that our sub-chronic and chronic [good laboratory practice] toxicology studies have revealed no on-target or off-target safety concerns across all doses tested. Moreover, throughout Phase 1 and Phase 2 trials, PLN-74809 has been well tolerated with no drug-related safety concerns identified to date,” Coulie said.
The company is conducting another Phase 2a trial, called INTEGRIS-PSC (NCT04480840), that is testing PLN-74809 in primary sclerosing cholangitis. The disease, which affects the bile ducts — the small tubes that carry the digestive fluid bile — is often associated with liver scarring.