Clinical Trials

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;
• NOTE: Vitamin E should not have been initiated after the date the biopsy was performed and subjects should have a stable weight since the liver biopsy was performed defined by no more than a 5% change of initial body weight.

OR

• Phenotypic diagnosis of NASH based on elevated ALT and diagnosis of T2DM or pre-diabetes;
• NOTE: Elevated ALT must be ≥50 IU/L and ≤200 IU/L; Known T2DM or pre-diabetes with one of the following criteria: : random plasma glucose concentration >200 mg/dL (11.1 mmol/L) OR fasting plasma glucose >126 mg/dL (7.0 mmol/L) OR 2-hour post-load glucose >200 mg/dL (11.1 mmol/L) during a 75 g oral glucose tolerance test (OGTT) OR HbA1c of at least 6% with or without concomitant treatment with metformin.

AND

• Screening MRI-PDFF with >8% steatosis;
• Body mass index (BMI) >25 kg/m2. NOTE: for Asian-Americans, BMI >23 kg/m2;
• Subjects must have Screening laboratory values for Hepatitis B surface antigen (HBsAg), anti-HCV antibodies and HCV RNA, and Human Immunodeficiency Virus (HIV) 1 and 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.  Effective methods of contraception are defined as:
  • a condom for the male partner and at least one of the following for the female participant:
    • Intrauterine device;
    • Oral, injectable, implantable, transdermal, or intravaginal hormonal contraceptive.
  • Note: The above does not apply to female subjects of nonchildbearing potential (ie, physiologically incapable of becoming pregnant) defined as:
    • has had a complete hysterectomy greater than or equal to 3 months prior to dosing; or
    • has had a bilateral oophorectomy (ovariectomy); or
    • has had a bilateral tubal ligation or fallopian tube inserts; or
    • is post-menopausal (a demonstration of a total cessation of menses for ≥1 year with a follicle stimulating hormone (FSH) level of >35 mIU/mL).
• 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. Effective contraception is defined as a condom and spermicide for the male, or condom and at least one of the following for a female partner:
  • Intrauterine device;
  • Oral, injectable, implantable, transdermal, or intravaginal hormonal contraceptive;
  • Be of non-childbearing potential.
• Male subjects must agree to refrain from sperm donation from the date of Screening until 90 days after their last dose of study drug.
• 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);
• NOTE: Patients with Gilbert’s syndrome will be allowed if they have a known history of Gilbert’s syndrome with a normal direct bilirubin value and normal reticulocyte count, and upon review by the medical monitor.
  •  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 clearance creatinine <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.
• Prior use and/or concurrent treatment with obeticholic acid (OCA).
• 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 >2 × ULN.
• 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).
• History of regular alcohol consumption exceeding 14 drinks/week for females and 21 drinks/week for males within 6 months of Screening. One drink is defined as 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor .
• 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.
• Clinically significant electrocardiogram (ECG) abnormalities or QTcF greater than 450 ms for males and 470 ms for females at either Screening or Baseline, or any prior history of QT abnormality.
• Use of cytochrome P450 (CYP)3A4 and P-glycoprotein (P-gp) inducers and inhibitors within 14 days prior to the first dose of study medication and throughout study duration.
• 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.
• Use of a new antidiabetic regimen from Screening and throughout study duration, including metformin, GLP-1 agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, sulfonylureas, or dipeptidyl peptidase-4 (DPP4) inhibitors, insulin or peroxisome proliferator-activated receptor (PPAR)γ agonists (pioglitazone or rosiglitazone). For pre-existing antidiabetic treatment, subjects should be on a stable dose of antidiabetic drugs: (1) for at least 2 months (for metformin and/or sulfonylureas), (2) 3 months (for SGLT2 or DPP4 inhibitors), or (3) 6 months (for GLP-1 receptor agonists and thiazolidinediones) prior to Screening.
  • NOTE: Sulfonylureas and insulin are only permitted if glycemia is self-monitored by the subject; subjects treated with insulin are eligible if clinically stable on insulin treatment (ie, no recurrent acute hypo- or hyperglycemic episodes diagnosed clinically with serum glucose levels of <50 mg/dL or >200 mg/dL) for at least two months prior to Screening.
• Subjects with contraindications to MRI imaging, or not being able to have the MRI performed.