Clinical Research Studies

Are you eligible to participate in this study?

You may be eligible for this study if you meet the following criteria:

• Conditions:
  Primary Sclerosing Cholangitis (psc)
• Age: Between 18 Year(s) - 75 Year(s)
• Gender: Male or Female

• Other Inclusion Criteria:
  

  1. Male or female participants must be 18 to 75 years of age inclusive, at the time of signing the informed consent.
  2. Participants taking UDCA who have:
  • Total daily dose =23 mg/kg/day.
  • Minimum of 6 months of stable treatment prior to screening period and expected to remain on stable dose through the 12-week DBP.
  • Minimum of 3 months off treatment prior to screening period if UDCA was recently discontinued.
  3. For participants with IBD:
  • Participants with Crohn’s disease must be in remission based on the investigator’s clinical assessment and should be on stable treatment prior to randomisation and during screening.
  • Participants with ulcerative colitis must be in remission or have low activity disease as per the judgement of the investigator and should be on stable treatment prior to randomisation and during screening.
  • Current treatment for IBD is permitted, if the participant has been well controlled for =3 months prior to the screening period and is anticipated to remain on a stable dose of drugs for IBD treatment, including biologics, immunosuppressants, immunomodulators, or systemic corticosteroids. This provision regarding stability of IBD treatment applies to the following, among others:
  • 5-aminosalicylic acid drugs
  • Azathioprine; 6-mercaptopurine; methotrexate.
  • Budesonide (within recommended doses for management of IBD). In addition to oral formulation, topical application of budesonide (rectal foam or enema) is allowed.
  • Other systemic corticosteroids.
  • Biologics (e.g. anti-tumour necrosis factor or anti-integrin therapies).
  • Other immunosuppressants or immunomodulators used for IBD treatment.
  • Participants with IBD should have a colonoscopy performed within one year prior to the screening period showing no evidence of dysplasia or cancer.
  4. Medications for management of pruritus (e.g. cholestyramine, rifampin, naltrexone or sertraline) must be on a stable dose for =3 months prior to the screening period.
  5. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  
  Male Participants
  • Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 1 month after the last dose of study intervention:
  • Refrain from donating sperm and either:
    • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent.
    
    OR
    
    
    • Must agree to use contraception / barrier as detailed:
      Agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak as there remains a risk to pregnant women and women of childbearing potential.
  
  Female Participants
  • A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
  • Is a woman of non-childbearing potential
  
  OR
  
  
  • Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, during the study intervention period and for at least 1 month after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (e.g. noncompliance, recently initiated) in relationship to the first dose of study intervention.
  • A woman of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum, as required by local regulations) within 24 hours before the first dose of study intervention
  • If a urine test cannot be confirmed as negative (e.g. an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
  6. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

  
  

You may not be eligible for this study if the following are true:

• 1. History or presence of other concomitant chronic liver disease including:
  • Small duct primary sclerosing cholangitis (PSC).
  • Documented history of secondary sclerosing cholangitis
  • Presence of hepatitis B surface antigen (HBsAg)
  • Hepatitis C virus (HCV) infection (Note: Participants with positive anti-HCV antibody due to previously treated HCV infection, may be enrolled if a confirmatory HCV RNA is undetectable and sustained viral response has been documented).
  • Alcoholic liver disease
  • Presence of history of PSC-PBC or PSC-AIH overlap syndrome
  • NASH
  • Known history of alpha-1 antitrypsin deficiency.
  2. Presence of percutaneous drain or bile duct stent at screening or within three months prior to screening.
  3. History of bacterial cholangitis within 60 days prior to the screening period, or participant on antibiotics for prophylaxis of recurrent cholangitis.
  4. History or any current suspicion of cholangiocarcinoma
  5. Participants with cirrhosis who are also classified as Child-Pugh B or C based on the Child-Pugh score. Participants with cirrhosis with Child-Pugh A score are allowed.
  6. History of clinically significant hepatic decompensation, including:
  • History of liver transplantation, current placement on a liver transplant list, current model for end-stage liver disease
  • Evidence of complications of cirrhosis, including hepatic decompensation or evidence of significant portal hypertension complications including presence of ascites requiring treatment; history or presence of spontaneous bacterial peritonitis; presence of hepatic encephalopathy grade 2 or higher; history of oesophageal variceal bleeding or related interventions (e.g. oesophageal variceal banding, or transjugular intrahepatic portosystemic shunt placement). Note: Participants with grade 1 varices may be eligible to enrol.
  • Hepatorenal syndrome (type I or II).
  7. Presence or history of hepatocellular carcinoma.
  8. Medical conditions that may cause non-hepatic increases in ALP (e.g. Paget’s disease)
  9. Medical conditions that may diminish life expectancy to <2 years, including known cancers.
  10. Participant has a positive test for human immunodeficiency virus (HIV) type 1 or 2, or participant is known to have tested positive for HIV.
  11. Evidence of any other unstable or untreated clinically significant immunological, endocrine, neurological, gastrointestinal, haematologic, psychiatric diseases as evaluated by the investigator; other clinically significant conditions that are not well controlled.
  12. Known malignancy or history of malignancy within the last 5 years, with the exception of local, successfully treated basal cell carcinoma or in-situ carcinoma of the uterine cervix.
  
  
  Prior/ Concomitant Therapy:
  
  
  13. Administration of the following medications are prohibited as specified below
  • 3 months prior to the screening period: fibrates and glitazones.
  • 3 months prior to the screening period: cyclosporine, mycophenolate, pentoxifylline, and chronic systemic corticosteroids (except as specified in inclusion criteria 6 as part of management of IBD at an ongoing stable dose) (NOTE: Short courses =21 days of tapered oral steroids in the previous 3 months for a non-hepatic and non-IBD related indication would not be exclusionary if tapering was completed at least 6 weeks prior to screening); potentially hepatotoxic drugs (including a-methyl-dopa, sodium valproic acid, isoniazid, or nitrofurantoin).
  • Obeticholic acid.
  • 2 months prior to the screening period: systemic antibiotics (e.g. minocycline, vancomycin, metronidazole) for prophylaxis of recurrent cholangitis or for treatment of PSC. Note: Antibiotic courses for other indications are permitted during the study if medically necessary.
  
  
  Prior/concurrent clinical study experience:
  
  
  14. Participants who are currently participating in, plan to participate in, or have participated in an investigational drug study or medical device study containing active substance within 30 days or 5 half-lives, whichever is longer, prior to the screening period. If the previous trial was for an experimental therapy being studied for potential benefit in PSC, and the potential therapeutic agent was proven to have no beneficial effect in PSC and there are no safety concerns, the participant may enroll after 30 days or 5 half-lives, whichever is longer. For therapeutic agents being studied for potential benefit in PSC for which it is still unclear if there may be a potential benefit, participant may enroll after 6 months.
  15. Participants with previous exposure to elafibranor.
  
  
  Other exclusions:
  
  
  16. Significant renal disease, including nephritic syndrome, chronic kidney disease (defined as participants with evidence of impaired kidney function or underlying kidney injury).
  17. For female participants: known pregnancy, or has a positive serum pregnancy test, or lactating.
  18. Regular alcohol intake in excess of the recommended limit of 2 standard drinks per day for men or 1 standard drink per day for women, where one standard measure corresponds to 10 gm of alcohol.
  19. History of alcohol abuse, or other substance abuse within 1 year prior to screening.
  20. A positive drug screen at screening would be exclusionary unless it can be explained by a prescribed medication.
  21. Known hypersensitivity to the investigational product or to any of the formulation excipients of the elafibranor or placebo tablet.
  22. Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain.