A Randomized, Double-blind Study to Assess the Safety and Efficacy of EDP-305 in Subjects With Liver-biopsy Proven NASH

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

A randomized, double-blind study to assess the safety and efficacy of EDP-305 in subjects with liver-biopsy proven Non-Alcoholic Steatohepatitis (NASH)

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Enanta Pharmaceuticals

Criteria

Inclusion Criteria:

• Informed consent documentation signed and dated by the subject.

• Male and female subjects, of all ethnic origins, between the ages of 18 and 75 years, inclusive.

• Subjects of all ethnic origins should have a Body Mass Index (BMI) > 25 kg/m2 and ≥45 except for Asian subjects who qualify for the study with BMI > 23kg/m2.

• Histological evidence of definite NASH based on NASH Clinical Research Network (CRN) criteria obtained from assessment of a liver biopsy by the central histopathologist. The biopsy may be obtained either 1) during the Screening window or 2) within 6 months prior to the Screening visit.

• NAFLD Activity Score (NAS) of 4 or greater with a score of at least 1 in each component of the NAS (steatosis scored 0-3, lobular inflammation scored 0-3, ballooning scored 0-2).

• Fibrosis stage 2 or 3 using the NASH CRN Histologic Scoring System.

• 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 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.]

• A woman of childbearing potential who is sexually active with a male must agree to use two effective methods of contraception from the date of Screening until 30 days after the last dose of study drug.

• A male subject who has not had a vasectomy and is sexually active with a woman of childbearing potential must agree to use effective contraception from the date of Screening to 90 days after the 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 as indicated below:

• Total white blood cells (WBC) <3000 cells/mm3

• Absolute neutrophil count (ANC) <1500 cells/mm3

• Platelet count <140,000/mm3

• International Normalized Ratio, INR >1.2 (unless due to use of anticoagulants)

• Estimated glomerular filtration rate (eGFR) < 60 mL/min according to the Modification of Diet in Renal Disease (MDRD) equation

• AST ≥5× ULN

• ALT ≥5× ULN

• ALP ≥ 2x ULN

• Total bilirubin > 1.5 times ULN during Screening. [Note: Patients with Gilbert's syndrome will be allowed following review by the Medical Monitor if they have a known history of Gilbert's syndrome with a normal direct bilirubin value and normal reticulocyte count.]

• Pregnant or nursing females.

• MELD: Model for End-stage Liver Disease score >12.

• Clinical or laboratory evidence of known chronic liver disease such as alcoholic liver disease, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), autoimmune hepatitis, Wilson disease, iron overload, alpha-1-antitrypsin deficiency, drug-induced liver injury, known or suspected hepatocellular carcinoma (HCC).

• History of acute liver complications due to gallstones (e.g., acute cholecystitis or acute biliary obstruction) unless the subject has had a cholecytectomy (more than 3 months prior to screening).

• History of liver transplant, or current placement on a liver transplant list.

• Hepatorenal syndrome (type I or II).

• Prior variceal hemorrhage, uncontrolled encephalopathy, liver cirrhosis Child-Pugh Class A, B, and C, esophageal varices, or refractory ascites within the previous 6 months of Screening and/or histological presence of liver cirrhosis.

• Prior or planned ileal resection, or prior or planned bariatric surgery. [Note:

Subjects who have undergone gastric surgeries that do not affect drug absorption (e.g., gastric band or gastric sleeve procedures) will be allowed if they are stable for at least 1 year prior to Screening. Gastrectomy or Roux-en-Y bypass will be allowed if stable for at least 3 years prior to Screening.]

• Subjects with clinically or otherwise documented cardiovascular or cerebrovascular disease including clinically significant anomalies of rhythm or pattern of ECG, that in the judgement of the Principal Investigator (PI) could affect the safety of the subject or their ability to comply with the study requirements.

• HbA1c ≥ 9.5% within 60 days prior to Day 1.