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
- Conditions
- Primary Biliary CholangitisMedDRA version: 21.0Level: LLTClassification code 10034176Term: PBCSystem Organ Class: 100000004871Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2019-004941-34-IT
- Lead Sponsor
- GENFIT
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 150
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 = 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)ALP = 1.67 x ULN (based on two values - see section 3.5.1)
5)TB = 2 x ULN
To ensure adequate representation of moderately advanced disease or at risk of progression to clinical outcomes, at least 10% of randomized patients will be moderately advanced per Rotterdam Criteria (TB > ULN or Albumin < 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 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 = 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)
8)If on colchicine must be on a stable dose for = 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 = 3 months prior to screening
10)Patients taking statins or ezetimibe must be on a stable dose for = 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:
•Non-child bearing potential: Cessation of menses for at least 12 months due to ovarian failure or surgical sterilization such as bilateral
oophorectomy, or hysterectomy
•Highly effective contraception methods include:
a.Combined (estrogen and progrestogen containing) hormaonal contraception associated with inhibition of ovulation, oral, intravaginal or transdermal
b.Progestogen-only hormonal contraception associated with inhibition of ovulation, oral, injectable or implantable
c.Intrauterine device (IUD)
d.Intrauterine hormoine release system (IUS)
e.Bilateral tubal occlusion
f.Vasectomized partner
g.Sexual abstinence, if required by local IRB/IEC regulations and/or considered adequate by National laws (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)
12)For patients who consent to have liver biopsy samples collected, 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 6 months before screening is available)
b.1 liver biopsy after 52-weeks of treatment
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 110
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40
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; 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
b)3 months prior to screening: azathioprine, cyclosporine, methotrexate, mycophenolate, pentoxifylline, budesonide and other systemic corticosteroids (parenteral and oral chronic administration only);
potentially hepatotoxic drugs (including a-methyl-dopa, sodium valproic acid isoniazid, or nitrofurantoin)
c)12 months prior to screening: antibodies or immunotherapy directed against ILs or other cytokines or chemokines
d)For patients with previous exposure to OCA, OCA should be discontinued 3 months prior to screening
9)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
10)Patients with previous exposure to elafibranor
11)SV value ALT and/or AST > 5 x ULN
12)For patients with AT or TB>ULN at SV1, variability of AT or TB > 4
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main 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.;Secondary Objective: To evaluate the effect of Elafibranor (80 mg/day) on normalisation of alkaline phosphatase (ALP) over 52 weeks of the treatment compared to placebo <br>To evaluate the effect of Elafibranor (80 mg/day) on pruritus over 52 weeks of the treatment compared to placebo;Primary end point(s): Response to treatment at week 52 defined as ALP < 1.67 x ULN and TB = ULN and ALP decrease = 15%.;Timepoint(s) of evaluation of this end point: week 52
- Secondary Outcome Measures
Name Time Method