PLN-74809-PSC-203 (INTEGRIS-PSC)
Research type
Research Study
Full title
A randomized, double-blind, dose-ranging, placebo-controlled, Phase 2a evaluation of the safety, tolerability, and pharmacokinetics of PLN-74809 in participants with primary sclerosing cholangitis (PSC) and suspected liver fibrosis (INTEGRIS-PSC)
IRAS ID
286721
Contact name
Palak Trivedi
Contact email
Sponsor organisation
Éric
Eudract number
2020-001428-33
Clinicaltrials.gov Identifier
NCT0448084
Duration of Study in the UK
1 years, 7 months, 7 days
Research summary
Primary Sclerosing Cholangitis (PSC), a rare, long-term liver disease affecting the bile ducts (small tubes) inside and outside the liver. Bile is a liquid produced inside the liver that is used to help digest fats and remove waste products from the body. It passes out of the liver through the bile ducts. With PSC, the bile ducts become inflamed, causing scarring. The scarring can block or make the bile ducts narrower which also makes it harder for the bile to travel through. As a result, the bile builds up inside the liver and damages the liver cells. Over time, this could lead to increased scarring of the liver itself and potentially liver failure, for which a liver transplant may be needed. \n\nPatients diagnosed with large duct PSC and suspected liver fibrosis will be recruited in the clinical study.\n\nPLN-74809 is a small molecule and there is an evidence to exert anti-fibrotic benefits for the treatment of PSC. The proposed trial is a randomised, double-blind, dose-ranging, placebo-controlled Phase 2a study evaluation of the safety, tolerability and Pharmacokinetics of 12 weeks treatment with PLN-74809 40mg or placebo.\n\nTotal time taking part in this study will be 8 visits over approximately 22 weeks. This includes the following study periods:\n• Screening Period of up to 42 days\n• Treatment Period (where participant will receive assigned study medication [either PLN-74809 or placebo]) of approximately 12 weeks\n• End of Study Period (to check participant overall health) 4-weeks after the last dose of the study medication
Lay summary of study results: • INTEGRIS-PSC: A study to assess the safety and pharmacokinetics (the way our body absorbs, distributes, and gets rid of a drug) of bexotegrast (PLN-74809) in participants with primary sclerosing cholangitis (PSC) and suspected liver fibrosis.
• PSC is a rare, long-term liver disease in which the bile ducts inside and outside of the liver become inflamed and scarred, and eventually narrowed or blocked. As a result, bile builds up inside the liver and damages the liver cells. Over time, this leads to increased scarring (fibrosis) of the liver.
• This study was done to test the safety, tolerability (side effects), and pharmacokinetics (the way our body absorbs, distributes, and gets rid of a drug) of bexotegrast in participants with PSC and suspected liver fibrosis.
• The study had 3 parts (Parts 1, 2, and 3) to test different amounts of bexotegrast (40 mg, 80 mg, 160 mg, and 320 mg) compared to placebo. Placebo was a “dummy” drug that looked like bexotegrast but did not contain any active ingredients. In each study part, who was given bexotegrast or placebo was decided by chance, and neither the participants nor the study staff knew which one the participant was getting.
• All participants had PSC and suspected liver fibrosis and were between 18 and 71 years old; 69% of participants were men, and 31% were women. Participants were enrolled from 9 countries in Europe, North America, and Asia-Pacific.
• All participants took the study drug (bexotegrast or placebo) once daily: 24 participants took bexotegrast 40 mg, 20 participants took bexotegrast 80 mg, 20 participants took bexotegrast 160 mg, 27 participants took bexotegrast 320 mg, and 30 participants took placebo.
• The amount of bexotegrast in participants’ blood after dosing was proportional to the dose of bexotegrast they had received.
• Overall, 73% of participants who took bexotegrast and 70% of participants who took placebo had side effects during the study. The most common side effects in participants who received bexotegrast, that occurred more frequently than in placebo group, were common cold, nausea, and frequent bowel movements. The most common side effects in participants who received placebo, that occurred more frequently than in bexotegrast group, were tiredness, itch, headache, inflamed bile ducts, fever, indigestion, yellow eyes, and COVID-19.
• Bexotegrast, given once daily for up to about 40 weeks, was well tolerated and showed acceptable safety for further study at doses of up to 320 mg in participants with PSC and suspected liver fibrosis.REC name
Yorkshire & The Humber - Leeds West Research Ethics Committee
REC reference
20/YH/0255
Date of REC Opinion
5 Nov 2020
REC opinion
Further Information Favourable Opinion