A Study of Elafibranor in Adults With Primary Biliary Cholangitis and Inadequate Response or Intolerance to Ursodeoxycholic Acid.

Korábbi kezelés

• History or presence of other concomitant liver diseases.
• Administration of the following medications is prohibited during the study, and prior to the study as per the timelines specified below:
  • i. Systemic (oral or parenteral) use within 3 months prior to SV1 of: fibrates, seladelpar, glitazones, obeticholic acid, azathioprine, cyclosporine, methotrexate, mycophenolate, or long-term systemic corticosteroids (parenteral and oral chronic administration only); potentially hepatotoxic drugs (including α-methyl-dopa, valproic acid, isoniazid or nitrofurantoin)
• Participants with previous exposure to elafibranor.
• 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.
• International normalised ratio >1.3 in the absence of anticoagulant therapy.
• History of alcohol abuse, or other substance abuse within 1 year prior.
• Known hypersensitivity to the investigational product or to any of the excipients of elafibranor.

Más betegség

• History of liver transplantation.
• Known history of human immunodeficiency virus (HIV) infection.
• Medical conditions that may cause non-hepatic increases in ALP (e.g. Paget's disease).
• Evidence of any other unstable or untreated clinically significant conditions that are not well controlled.
• Known malignancy or history of malignancy within the last 2 years, except for successfully treated localised basal cell carcinoma or squamous cell carcinoma of the skin; or in-situ carcinoma of the uterine cervix.
• History of hepatocellular carcinoma.
• Alpha-foetoprotein (AFP) >20 ng/mL with 4-phase liver computed tomography (CT) or magnetic resonance imaging (MRI) scans suggesting presence of liver cancer.
• Significant renal disease, including nephritic syndrome, chronic kidney disease (defined as participants with evidence of significantly impaired kidney function or underlying kidney injury).
  • Other exclusions
• Any other condition that, in the opinion of the investigator, would interfere with study participation or completion, or would put the participant at risk, including a potential participant assessed as being at high risk of noncompliance with the study.

Laborértékek

• Total bilirubin (TB) >2 × ULN. Participants with Gilbert's syndrome are eligible with a TB above 2 × ULN if direct bilirubin is <30% of TB.
• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >5 × ULN.
• Creatine phosphokinase (CPK) >2 × ULN.
• Platelet count <75,000/µL.
• Estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m2.
• For female participants: known pregnancy, or has a positive serum pregnancy test, or is breastfeeding.

Életkor

• Medical condition with a life expectancy <2 years.

Egyéb

• Participants with known cirrhosis who have a Child-Pugh B or C score. Participants with cirrhosis with Child-Pugh A score are allowed.
• History or presence of clinically significant hepatic decompensation.
• 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.
• Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain.

• Male or female participants age ≥18 years of age.
• Participants with a historical diagnosis of PBC as demonstrated by the presence of ≥2 of the following three historical diagnostic criteria:
  • i. History of elevated ALP levels for ≥6 months prior to the first screening visit (SV1).
  • ii. Positive Antimitochondrial antibody (AMA) titres (≥1/40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay) or positive PBC-specific antinuclear antibodies.
  • iii. Liver biopsy consistent with PBC.
• ALP >1 × ULN and <1.67 × ULN.
• Participants taking UDCA should have been on this medication for at least 6 months and at a stable dose for ≥3 months. Participants who are intolerant to UDCA should have taken the last dose of UDCA ≥3 months prior.
• Participants taking medications for management of pruritus must be on a stable dose for ≥3 months.
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
  • (a) Male participants must agree that, if their partner is at risk of becoming pregnant, they will use an effective method of contraception. The participant must agree to use contraception during the whole period of the study and for 30 days after the last dose of study intervention.
• Capable of giving signed informed consent