Purpose

The participants of this study will have confirmed Primary Biliary Cholangitis (PBC) with inadequate response or intolerance to ursodeoxycholic acid (which is a medication used in the management and treatment of cholestatic liver disease). PBC is a slowly progressive disease characterized by damage of the bile ducts in the liver, leading to a buildup of bile acids which causes further damage. The liver damage in PBC may lead to scarring (cirrhosis). PBC may also be associated with multiple symptoms. Many patients with PBC may require liver transplant or may die if the disease progresses and a liver transplant is not done. This study has two main parts; the first part will compare a daily dose of elafibranor (the study drug) to a daily dose of placebo (a dummy treatment), and will last between a minimum of one year and a maximum of two years. In the second part, all participants will receive elafibranor, for a period between 4-5 years. The main aim of this study is to determine if elafibranor is better than placebo at decreasing the levels of a specific blood test (alkaline phosphatase) that provides information about participant's disease. This study will also study the safety of long-term treatment with elafibranor, as well as the impact on symptoms such as pruritus and fatigue.

Condition

Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Males or females age of 18 to 75 years (inclusive) - Definite or probable PBC diagnosis - ALP ≥ 1.67x upper limit of normal (ULN) - Total bilirubin (TB) ≤ 2x ULN - 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) - Must have PBC Worst Itch NRS collected prior to randomization - Females participating in this study must be of non-child bearing potential or must be using highly efficient contraception for the full duration of the study and for 1 month after the last drug intake

Exclusion Criteria

  • History or presence of other concomitant liver disease - Clinically significant hepatic decompensation, including patients with complications of cirrhosis/portal hypertension - Medical conditions that may cause non-hepatic increases in ALP (e.g., Paget's disease) or which may diminish life expectancy to < 2 years, including known cancers - Patient has a positive test for HIV Type 1 or 2 at screening, or patient is known to have tested positive for HIV - Evidence of any other unstable or untreated clinically significant disease - History of alcohol abuse - For female patients: known pregnancy or lactating - Use of fibrates and glitazones within 2 months prior to screening - Use of OCA, azathioprine, cyclosporine, methotrexate, mycophenolate, pentoxifylline, budesonide and other systemic corticosteroids (parenteral and oral chronic administration only); potentially hepatotoxic drugs - (including α-methyl-dopa, sodium valproic acid isoniazid, or nitrofurantoin) within 3 months prior to screening - Use of antibodies or immunotherapy directed against interleukins (ILs) or other cytokines or chemokines within 12 months prior to screening - For patients with previous exposure to obeticholic acid (OCA), OCA should be discontinued 3 months prior to screening - Patients 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 five half-lives, whichever is longer, prior to screening; for patients with previous exposure to seladelpar, seladelpar should be discontinued 3 months prior to screening - ALT and/or AST values > 5 x ULN - For patients with AT or TB>ULN at SV1, variability of AT or TB > 40% (see section 3.5.1) - Albumin<3.0 g/dl - Severely advanced patients according to Rotterdam criteria (TB > ULN and albumin <LLN) - INR > 1.3 due to altered hepatic function - CPK > 2 x ULN - Screening serum creatinine > 1.5 mg/dl - Significant renal disease, including nephritic syndrome, chronic kidney disease (defined as patients with markers of kidney failure damage or eGFR < 60 mL/min/1,73 m2) calculated by MDRD - Platelet count < 150 x 103/μL - AFP > 20 ng/mL with 4-phase liver CT or MRI imaging suggesting presence of liver cancer - Known hypersensitivity to the investigational product or to any of the formulation excipients of the elafibranor or placebo tablet Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
This is a double-blind (DB), randomized, placebo-controlled study followed by an open-label long term extension (LTE)
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Elafibranor 80mg
Study subjects will take 1 tablet per day orally before breakfast with a glass of water each morning
  • Drug: Elafibranor 80mg
    Elafibranor 80mg daily
Placebo Comparator
Placebo
Study subjects will take 1 tablet per day orally before breakfast with a glass of water each morning
  • Drug: Placebo
    Placebo daily for double blind period and elafibranor 80 mg daily fo the open label period.

More Details

Status
Active, not recruiting
Sponsor
Ipsen

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.