A Study of Elafibranor in Adult Japanese Participants With Primary Biliary Cholangitis (PBC)

Prior treatment

• History or presence of other concomitant liver disease
• History of alcohol abuse, defined as consumption of more than 30 g pure alcohol per day for men, and more than 20 g pure alcohol per day for women, or other substance abuse within 1 year prior to SV1.
• 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 screening; for participants with previous exposure to seladelpar, seladelpar should be discontinued 3 months prior to screening.
• Participants with previous exposure to elafibranor.
• Known hypersensitivity to the investigational product or to any of the formulation excipients of the elafibranor tablet.

Other illness

• 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.
• Participant has a positive test for human immunodeficiency virus (HIV) Type 1 or 2 at screening, or participant is known to have tested positive for HIV.
• Evidence of any other unstable or untreated clinically significant immunological, endocrine, haematologic, gastrointestinal, neurological, or psychiatric disease as evaluated by the investigator; other clinically significant medical conditions that are not well controlled.
• Alpha-fetoprotein (AFP) \>20 ng/mL with 4-phase liver computerised tomography (CT) or magnetic resonance imaging (MRI) imaging suggesting presence of liver cancer.

Lab values

• For female participants: known pregnancy, or has a positive serum pregnancy test, or breastfeeding.
• Administration of the following medications are prohibited as specified below:
  • 1 month prior to screening: fibrates.
  • 2 months prior to screening: glitazones.
  • For participants with previous exposure to obeticholic acid (OCA), OCA should be discontinued 3 months prior to screening.
  • 3 months prior to screening: azathioprine, cyclosporine (systemic), methotrexate, mycophenolate, pentoxifylline, budesonide and other systemic corticosteroids (parenteral and oral chronic administration only); potentially hepatotoxic drugs (including α-methyldopa, sodium valproate/valproic acid isoniazid, or nitrofurantoin).
  • 12 months prior to screening: antibodies or immunotherapy directed against interleukins (ILs) or other cytokines or chemokines.
• SV1 or SV2 value ALT and/or AST \>5×ULN.
• For participants with aminotransferases or TB \>ULN at SV1, variability (between SV1 and SV2) of aminotransferases or TB \>40%.
• SV1 value albumin \<3.0 g/dL.
• Severely advanced participants according to Rotterdam criteria (TB \>ULN and albumin \<LLN).
• SV1 international normalised ratio (INR) \>1.3 due to altered hepatic function.
• SV1 creatine phosphokinase (CPK) \>2×ULN.
• SV1 serum creatinine \>1.5 mg/dL.
• Significant renal disease, including nephritic syndrome, chronic kidney disease (defined as participants with markers of kidney failure damage or estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m2) calculated by modification of diet in renal disease study (MDRD).
• SV1 platelet count \<150×103/μL.

Age

• Medical conditions that may cause non-hepatic increases in ALP (for example, Paget's disease) or which may diminish life expectancy to \<2 years, including known cancers.

Other

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

• Must have provided written informed consent and agree to comply with the study protocol.
• Japanese male or female participants aged 18 to 75 years inclusive at Screening Visit 1 (SV1).
• PBC diagnosis as described in the study protocol
• ALP ≥1.67×ULN (mean value based on samples collected at SV1 and SV2).
• TB ≤2×ULN at SV1 and SV2.
• Must have at least 4 available values for PBC Worst Itch Numeric Rating Scale (NRS) during each of the 7-day intervals in the 14 days prior to visit (V)1, for a total of at least 8 values for PBC Worst Itch NRS in the last 14 days prior to V1.
• Participants taking UDCA for at least 12 months (stable dose ≥3 months) prior to screening, or unable to tolerate UDCA treatment (no UDCA for ≥3 months) prior to screening (per country standard-of-care dosing).
• If on colchicine, must be on a stable dose for ≥3 months prior to screening.
• Medications for management of pruritus (for example, cholestyramine, rifampicin, naltrexone, sertraline or nalfurafine hydrochloride) must be on a stable dose for ≥3 months prior to screening.
• Participants taking statins or ezetimibe must be on a stable dose for ≥2 months prior to screening.
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies