A study of elafibranor in adult Japanese participants with Primary Biliary Cholangitis (PBC)

JRCT ID: jRCT2011240053

Registered date:22/11/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Primary Biliary Cholangitis (PBC)
• Date of first enrollment: 22/11/2024
• Target sample size: 18
• Study type: Interventional
• Intervention(s): 80 mg of Elafibranor administered orally once a day. The participant will be treated for 52 weeks during the treatment period followed by a variable treatment extension period of 2 to 5 years (the maximum treatment duration anticipated would be 6 years). The primary endpoint will be evaluated at the end of the treatment period on week 52.

Outcome(s)

• Primary Outcome: Response to treatment at Week 52 defined as ALP <1.67xULN and TB <=ULN and ALP decrease >=15%

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 75age old
• Gender: Both

Include 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 >=1.67xULN (mean value based on samples collected at SV1 and SV2).
-TB <=2xULN 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.

Exclude 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 diminsh 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:
a. 1 month prior to screening: fibrates.
b. 2 months prior to screening: glitazones.
c. For participants with previous exposure to obeticholic acid (OCA), OCA should be discontinued 3 months prior to screening.
d. 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 alpha-methyldopa, sodium valproate/valproic acid isoniazid, or nitrofurantoin).
e. 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 >5xULN.
-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) >2xULN.
-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 <150x103/ micro L.
-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.

Related Information

• Primary Sponsor: Allan Richard