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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

Primary Objective

Primary Objective: To evaluate the effect of Elafibranor (80 mg/day) on cholestasis as defined by the primary endpoint over 52 weeks of the treatment compared to placebo Key Secondary Objectives: To evaluate the effect of Elafibranor (80 mg/day) on normalisation of alkaline phosphatase (ALP) over 52 weeks of the treatment compared to placebo To evaluate the effect of Elafibranor (80 mg/day) on pruritus over 52 weeks of the treatment compared to placebo

Study category: Digestive Health

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Description

This is a phase 3 double-blind (DB), randomized, placebo-controlled study with an open-label long term extension (LTE) evaluating the efficacy and safety of Elafibranor 80 mg once daily versus placebo in patients with PBC and inadequate response or intolerance to ursodeoxycholic acid (UDCA). In the DB period, patients will be randomized in a 2:1 ratio to receive Elafibranor 80 mg or placebo, once daily. The DB period will last until the last completed week 52 (V6) or until a maximum of 104 weeks DB period, whichever happens first, to further collect safety and clinical outcomes data in a DB manner. After the DB period, all patients will receive Elafibranor 80 mg daily for up to 5 years during the LTE period. When applicable, patients should continue their pre-study dose of UDCA throughout the study participation.

Details
Age

Adult

Eligibility

Inclusion Criteria: 1) Must have provided written informed consent and agree to comply with the study protocol 2) Males or females age of 18 to 75 years inclusive at first Screening Visit (SV) 3) PBC diagnosis as demonstrated by the presence of &#8805; 2 of the following 3 diagnostic criteria: a. History of elevated ALP levels for &#8805; 6 months prior to randomization (V1) b. Positive anti-mitochondrial antibodies (AMA) titers (> 1:40 on immunofluorescence or M2 positive by enzyme-linked immunosorbent assay [ELISA]) or positive PBCspecific antinuclear antibodies (ANA) c. Liver biopsy consistent with PBC 4) ALP &#8805; 1.67x upper limit of normal (ULN) (based on two values &#8211; see section 3.5.1) 5) Total bilirubin (TB) &#8804; 2x ULN To ensure adequate representation of moderately advanced disease or patients at risk of progression to clinical outcomes, at least 10% of randomized patients will be moderately advanced per Rotterdam Criteria (TB > ULN or Albumin < lower limit of normal [LLN]) and at least 20% will have a TB > 0.6 x ULN (patients at risk of progression) 6) 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 randomization (V1), for a total of at least 8 values for PBC Worst Itch NRS in the last 14 days prior to randomization (V1) 7) UDCA for at least 12 months (stable dose &#8805; 3 months) prior to screening, or unable to tolerate UDCA treatment (no UDCA for &#8805; 3 months) prior to screening (per country standard-of-care dosing) 8) If on colchicine must be on a stable dose for &#8805; 3 months prior to screening 9) Medications for management of pruritus (e.g., cholestyramine, rifampin, naltrexone or sertraline) must be on a stable dose for &#8805; 3 months prior to screening 10) Patients taking statins or ezetimibe must b e o n a stable dose f or &#8805; 2 months prior to screening 11) 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:

Detailed Eligibility: Exclusion Criteria: Patients presenting any of the following exclusion criteria will not be eligible for randomization into the study: 1) History or presence of other concomitant liver disease including: a) Positive anti-hepatitis A virus (HAV) immunoglobulin M (IgM) antibodies or positive hepatitis B surface antigen (HBsAg) or positive anti-hepatitis C virus (HCV) ribonucleic acid (RNA) (tested for in case of known cured HCV infection or positive HCV Ab at screening) b) Primary sclerosing cholangitis (PSC) c) Alcoholic liver disease (ALD) d) Autoimmune hepatitis (AIH) or if treated for an overlap of PBC with AIH, or if there is suspicion and evidence of overlap AIH features, that cannot be explained alone by insufficient response to UDCA e) Nonalcoholic steatohepatitis (NASH) f) Gilbert’s Syndrome (exclusion due to interpretability of bilirubin levels) g) Known history of alpha-1 antitrypsin deficiency 2) Clinically significant hepatic decompensation, including: a) History of liver transplantation, current placement on a liver transplant list, current Model for End-Stage Liver Disease-Sodium (MELD-Na) s core ≥ 1 2 linked to hepatic impairment b) Patients with cirrhosis/portal hypertension complications, including known esophageal varices, ascites, history of variceal bleeds or related interventions (e.g., insertion of variceal bands or transjugular intrahepatic portosystemic shunts [TIPS]), and hepatic encephalopathy, history or presence of spontaneous bacterial peritonitis, hepatocellular carcinoma c) Hepatorenal syndrome (type I or II) 3) 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 4) Patient has a positive test for Human Immunodeficiency Virus (HIV) Type 1 or 2 at screening, or patient is known to have tested positive for HIV 5) Evidence of any other unstable or untreated clinically significant immunological, endocrine, hematologic, gastrointestinal, neurological, or psychiatric disease as evaluated by the investigator; other clinically significant medical conditions that are not well controlled 6) 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 screening visit (SV1) 7) For female patients: known pregnancy, or has a positive serum pregnancy test, or lactating 8) Administration of the following medications are prohibited as specified below: a) 2 months prior to screening: fibrates and glitazones

Phase

III - Research Studies that gather more information about a drug's safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. These studies typically involve more participants.

Type of Study

Treatment

Scope

National

Location

University of Colorado Hospital

Principal Investigator
Lisa Forman,  MD

Lisa Forman, MD

Study ID

Protocol Number: 20-2899

More information available at ClinicalTrials.gov: NCT04526665

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