A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Non-Alcoholic Steatohepatitis
Condition: Non-Alcoholic Steatohepatitis
MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease
Intervention: EDP-305 Dose 1; EDP-305 Dose 2; 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: 134.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: NASH; Non-Alcoholic Steatohepatitis (NASH)

Summary:

      A randomized, double-blind study to assess the safety, tolerability, PK and efficacy of
      EDP-305 in subjects with Non-Alcoholic Steatohepatitis
    

Eligibility criteria:

        Inclusion Criteria:

          -  An informed consent document must be 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 presence of NASH by:

               -  Histologic evidence on a historical liver biopsy within 24 months of Screening
                  consistent with NASH with fibrosis (no cirrhosis), and elevated ALT at Screening
                  AND Screening MRI PDFF with >8 % steatosis OR

               -  Phenotypic diagnosis of NASH based on elevated ALT and diagnosis of T2DM or
                  pre-diabetes AND Screening MRI PDFF with >8 % steatosis

          -  Body mass index (BMI) >25 kg/m2; for Asian-Americans, BMI >23 kg/m2

          -  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.

          -  Subject must be willing and able to adhere to the assessments, visit schedules,
             prohibitions and restrictions, as described in this protocol

        Exclusion Criteria:

          -  Laboratory Screening Results:

               -  Total bilirubin > ULN (normal range 0.2-1.2 mg/dL)

               -  Total white blood cells (WBC) <3,000 cells/mm3

               -  Absolute neutrophil count (ANC) <1,500 cells/mm3

               -  Platelet count <140,000/mm3

               -  Prothrombin time (international normalized ratio, INR) > 1.2

               -  Creatine kinase above the upper limit of normal (ULN) except when in relation
                  with intense exercise

               -  Serum creatinine >2 mg/dL or creatinine clearance <60 ml/min (based on Cockroft
                  Gault method)

          -  Known history of alpha-1-antitrypsin deficiency

          -  Use of an experimental treatment for NASH within the past 6 months

          -  Use of immunosuppressant (eg, corticosteroids) for more than 2 weeks in duration
             within 1 year prior to Screening and during the course of the study

          -  Use of experimental or unapproved drugs within a year of Screening

          -  Any other condition(s) (including cardiovascular diseases) that would compromise the
             safety of the subject or compromise the quality of the clinical study, as judged by
             the Principal Investigator (PI)

          -  Pregnant or nursing females

          -  Recipients of liver or other organ transplantation or anticipated need for orthotropic
             organ transplantation in one year as determined by a Model for End-Stage Liver Disease
             (MELD) Score ≥ 15

          -  Clinical suspicion of advanced liver disease or cirrhosis

          -  Coexisting liver or biliary diseases, such as primary sclerosing cholangitis (PSC),
             choledocholithiasis, acute or chronic hepatitis, autoimmune hepatitis, alcoholic liver
             disease, acute infection of bile duct system or gall bladder, history of
             gastrointestinal bleeding (secondary to portal hypertension), cirrhosis

          -  Suspicion of cancer (eg, liver cancer) with the exception of basal cell carcinoma that
             has been resected

          -  Cirrhosis with or without complications, including history or presence of: spontaneous
             bacterial peritonitis, hepatocellular carcinoma, bilirubin > 2xULN

          -  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)

          -  Any condition possibly affecting drug absorption (eg, gastrectomy <3 years prior to
             Screening)

          -  Subject has received an investigational agent or vaccine within 30 days, or a
             biological product within 3 months or 5 elimination half-lives (whichever is longer)
             prior to the planned intake of study drug. NOTE: Flu vaccine will be allowed upon
             Medical Monitor's approval

          -  Use of a new statin regimen from Screening and throughout study duration. NOTE:
             Subjects on a stable dose of statins for at least three months prior to Screening are
             allowed. No dose modification during the study will be allowed.

          -  Current use of fibrates. Note: Subjects who discontinued fibrates for at least 3
             months before Screening can participate

          -  Clinically significant history of drug sensitivity or allergy, as determined by the PI

          -  Uncontrolled diabetes mellitus (ie, HbA1c ≥9% or higher) 60 days prior to Day 1

          -  Subjects with contraindications to MRI imaging, or not being able to have the MRI
             performed