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

Phase 1

• Conditions: Primary Biliary Cholangitis; MedDRA version: 21.0Level: LLTClassification code 10034176Term: PBCSystem Organ Class: 100000004871; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2019-004941-34-FR
• Lead Sponsor: GENFIT

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-10-09
• Last Update Posted: 21 May 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 150

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)Definite or probable PBC diagnosis as demonstrated by the presence of = 2 of the following 3 diagnostic criteria:
a.History of elevated ALP levels for = 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 PBC-specific antinuclear antibodies (ANA)
c.Liver biopsy consistent with PBC
4)Patients in whom it is safe and practical to proceed with a liver biopsy, and who agree to have:
a.1 liver biopsy during the Screening Period (if no historical biopsy within 12 months before screening is available)
b.1 liver biopsy after 52-weeks of treatment
5)ALP = 1.67x upper limit of normal (ULN)
6)Total bilirubin (TB) = 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)
7)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)
8)UDCA for at least 12 months (stable dose = 3 months) prior to randomization, or unable to tolerate UDCA treatment (no UDCA for = 3 months) prior to randomization (per country standard-of-care dosing)
9)If on colchicine must be on a stable dose for = 3 months prior to randomization
10)Medications for management of pruritus (e.g., cholestyramine, rifampin, naltrexone or sertraline) must be on a stable dose for = 3 months prior to randomization
11)Patients taking statins or ezetimibe must be on a stable dose for = 2 months prior to randomization
12)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:
•Non-child bearing potential: cessation of menses for at least 12 months due to ovarian failure or surgical sterilization such as bilateral oophorectomy, hysterectomy, or medically documented ovarian failure for > 6 months prior to randomization
•If required by local Institutional Review Board (IRB) / Independent Ethics Committee (IEC) and/or national regulations, sexual abstinence may be considered adequate (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient)
•Using a highly effective non-hormonal medical contraception (bilateral tubal occlusion, vasectomized partner or intra-uterine device) for = 3 months prior to screening
•Highly effective contraception with barrier or highly effective hormonal method of contraception (oral, intravaginal or transdermal combined estrogen and progestogen hormonal contraception associated with inhibition of ovulation, oral, injectable or implantable progestogen-only hormonal contraception associated with inhibition of ovulation or intrauterine hormone-releasing system). The hormonal contraception must be started at least one month prior

Exclusion Criteria

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) score = 12 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
6)Other clinically significant medical conditions that are not well controlled or for which medication needs are anticipated to change during the study
7)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)
8)For female patients: known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating
9)Administration of the following medications are prohibited as specified below:
a)2 months prior to randomization and throughout the study (up to the last study visit): fibrates and glitazones
b)3 months prior to randomization and throughout the study (up to the last study visit): Obeticholic acid (OCA), azathioprine, cyclosporine, methotrexate, mycophenolate, pentoxifylline, budesonide and other systemic corticosteroids; potentially hepatotoxic drugs (including a-methyl-dopa, sodium valproic acid isoniazid, or nitrofurantoin)
c)12 months prior to randomization and throughout the study (up to the last study visit): antibodies or immunotherapy directed against interleukins (ILs) or other cytokines or chemokines
10)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; patients with previous exposure to seladelpar are excluded.
11)Patients with previous ex

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified