Resumen

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. The main aim of this study is to determine if elafibranor (the study drug) is better than placebo (a dummy treatment) at decreasing the levels of a specific blood test (alkaline phosphatase) that provides information about participant's disease. This study will also evaluate the safety of long-term treatment with elafibranor, as well as the impact on symptoms such as itchy skin (pruritus) and tiredness (fatigue). This study has two main parts: Part 1 will compare a daily dose of elafibranor to a daily dose of placebo and will last between a minimum of one year and a maximum of two years. Part 2, all participants will receive elafibranor for a period of up to 5 years or until the total treatment duration (part 1 and part 2) reaches 6 years, whichever occurs first.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 75 YearsSexo: ALL

Criterios de inclusión

Males or females age of 18 to 75 years (inclusive)
Definite or probable Primary biliary cholangitis (PBC) diagnosis
Alkaline phosphatase (ALP) ≥ 1.67x upper limit of normal (ULN)
Total bilirubin (TB) ≤ 2x ULN
Ursodeoxycholic acid (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 Numeric rating scale (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

Criterios de exclusión

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 Obeticholic acid (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 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
Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (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 m\^2) calculated by Modification of diet in renal disease (MDRD)
Platelet count \< 150 x 10\^3/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

Ubicaciones

Hospital Italiano de Buenos Aires

CABA, Buenos Aires, Argentina

Hospital Alemán

Caba, Buenos Aires, Argentina

Hospital Británico de Buenos Aires

CABA, Buenos Aires, Argentina

Hospital Italiano de La Plata

La Plata, Buenos Aires, Argentina

Hospital Espanol De Mendoza

Godoy Cruz, Mendoza Province, Argentina

Hospital Provincial del Centenario

Rosario, Santa Fe Province, Argentina

A Double-blind, Randomized, Placebo-Controlled Study and Open-label Long Term Extension to Evaluate the Efficacy and Safety of Elafibranor 80 mg in Patients With Primary Biliary Cholangitis With Inadequate Response or Intolerance to Ursodeoxycholic Acid