일차성 담즙성 담관염(PBC)이 있는 일본 성인 참가자를 대상으로 한 Elafibranor에 대한 연구 (ELONSEN)

Inclusion Criteria:

• 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

Exclusion Criteria

• History or presence of other concomitant liver disease

• 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,

• 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.

• 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.

• 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.

• 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. 1 month prior to screening: fibrates.
  2. 2 months prior to screening: glitazones.
  3. For participants with previous exposure to obeticholic acid (OCA), OCA should be discontinued 3 months prior to screening.
  4. 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).
  5. 12 months prior to screening: antibodies or immunotherapy directed against interleukins (ILs) or other cytokines or chemokines.

• 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.

• 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.

• Alpha-fetoprotein (AFP) >20 ng/mL with 4-phase liver computerised tomography (CT) or magnetic resonance imaging (MRI) imaging suggesting presence of liver cancer.

• Known hypersensitivity to the investigational product or to any of the formulation excipients of the elafibranor tablet.

• Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain.