A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Primary Biliary Cholangitis
Condition: Primary Biliary Cholangitis
MeSH terms: Cholangitis; Liver Cirrhosis, Biliary
Intervention: EDP-305 1 mg; EDP-305 2.5 mg; Placebo
Intervention description: Two tablets daily for 12 weeks; Two tablets daily for 12 weeks; Two tablets daily for 12 weeks
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 68.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: PBC; Primary Biliary Cholangitis (PBC)

Summary:

      A randomized, double-blind study to assess the safety, tolerability, PK and efficacy of
      EDP-305 in subjects with primary biliary cholangitis
    

Eligibility criteria:

        Inclusion Criteria:

          -  An informed consent document signed and dated by the subject.

          -  Male and female subjects of any ethnic origin between the ages of 18 and 75 years,
             inclusive

          -  Male or female with a diagnosis of PBC by at least two of the following criteria:

               -  History of ALP above ULN for at least six months

               -  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)

          -  For subjects with no documented liver biopsy performed within 2 years, subjects must
             undergo a transient elastography (Fibroscan) showing liver stiffness < 14.0 kPA

          -  Must be on a stable dose of UDCA12-20 mg/kg/day for at least 6 months prior to
             Screening or intolerant of UDCA in the opinion of the Investigator (no UDCA for at
             least 12 weeks prior to Screening)

          -  Alkaline Phosphatase (ALP) ≥ 1.67 × ULN and/or total bilirubin >ULN but < 2×ULN (<2.4
             mg/dL)

          -  Subjects must have Screening laboratory values for Hepatitis B surface antigen
             (HBsAg), anti-HCV antibodies and HCV RNA negative and Human Immunodeficiency Virus
             (HIV) 1 and 2 antibodies (Ab) as seronegative. Note: subjects previously infected by
             chronic hepatitis C and treated with direct acting antivirals (DAAs) with sustained
             virologic response (SVR) for at least 3 years will be allowed.

          -  Female subjects of childbearing potential must agree to use two effective methods of
             contraception from the date of Screening until 90 days after the last dose of EDP-305.

          -  All male participants who have not had a vasectomy must use effective contraception
             from Day -1 to 90 days after their last dose of study drug.

          -  Male subjects must agree to refrain from sperm donation from the date of Screening
             until 90 days after their last dose of study drug

          -  Screening body mass index (BMI) of ≥18 kg/m2

          -  Subject must be willing and able to adhere to the assessments, visit schedule,
             prohibitions and restrictions, as described in this protocol

        Exclusion Criteria:

          -  Laboratory Screening Results:

               -  AST >5 x ULN

               -  ALT >5 x ULN

               -  Patients with Gilbert's syndrome will not be allowed due to interpretability of
                  bilirubin levels

               -  Total white blood cells (WBC) <3000 cells/mm3

               -  Absolute neutrophil count (ANC) <1500 cells/mm3

               -  Platelet count <140,000/mm3

               -  Prothrombin time (international normalized ratio, INR) >1.2

               -  Serum creatinine >2 mg/dL or creatinine clearance <60 mL/min (based on
                  Cockroft-Gault Method)

          -  Suspected to have relevant nonalcoholic fatty liver disease (NAFLD) as based on the
             judgment of the Investigator at Screening

          -  Use of immunosuppressants known to have an effect on the liver of patients with PBC
             (eg, colchicine, methotrexate, azathioprine, or systemic steroids) in the three months
             preceding screening

          -  Current use of fibrates, including fenofibrates. Note: Subjects who discontinued
             fibrates for at least 3 months before Screening can participate

          -  Use of an experimental treatment for PBC within the past 6 months

          -  Co-existing liver or biliary diseases, such as primary sclerosing cholangitis,
             choledocholithiasis, acute or chronic hepatitis, autoimmune hepatitis, alcoholic liver
             disease, nonalcoholic steatohepatitis (NASH), acute infection of bile duct system or
             gall bladder, history of gastrointestinal bleeding (secondary to portal hypertension),
             cirrhosis, cholangiocarcinoma diagnosed or suspected liver cancers

          -  Cirrhosis with or without complications, including history or presence of: spontaneous
             bacterial peritonitis, hepatocellular carcinoma

          -  Hepatorenal syndrome (type I or II) or Screening serum creatinine > 2 mg/dL (178
             μmol/L)

          -  Prior variceal hemorrhage, uncontrolled encephalopathy, Child-Pugh Class A, B and C,
             esophageal varices, or refractory ascites within the previous 6 months of Screening
             (defined as date informed consent signed)

          -  Medical conditions that may cause nonhepatic increases in ALP (e.g., Paget's disease)

          -  Use of a new statin regimen from Screening and throughout study duration. NOTE:
             Subjects on a stable dose of statins for at least 3 months prior to Screening are
             allowed. No dose modification during the study will be allowed.

          -  Use of immunosuppressants (eg, systemic corticosteroids) for more than 2 consecutive
             weeks in duration within 1 year prior to Screening.