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 ≥ 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 PBCspecific
antinuclear antibodies (ANA)
c. Liver biopsy consistent with PBC
4) ALP ≥ 1.67x upper limit of normal (ULN) (based on two values – see section 3.5.1)
5) 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)
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 ≥ 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 b e o n a stable dose f or ≥ 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: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
