A Phase 2, Multicenter, Placebo-Controlled, Randomized, Double-Blind, 48-Week Study to Evaluate the Efficacy and Safety of Combination Therapy of K-877-ER and CSG452 in Patients with Noncirrhotic Nonalcoholic Steatohepatitis (NASH) with Liver Fibrosis

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 300

Inclusion Criteria

Able to understand and comply with study procedures and give written informed consent, Age =18 years, NAS =4 with a score of at least 1 in each component of the NAS (steatosis, lobular inflammation, and ballooning) at the baseline biopsy, or a historical liver biopsy performed within 24 weeks of randomization, Fibrosis stage of 1 or greater and below 4 on NASH CRN fibrosis staging system at the baseline biopsy, or a historical liver biopsy performed within 24 weeks of randomization, Subject can be with or without T2DM, but T2DM subjects must be well controlled on a stable dose of antidiabetic medication for at least 8 weeks prior to Visit 1. Subjects without T2DM must have fasting plasma glucose =90 mg/dL at Visit 1. A single repeat measurement is permitted, excluding those caused by invalid measurements such as, but not limited to, hemolysis, lost samples, sample contamination, or non-fasting blood draw, which are deemed outside of the single repeat., Female subjects must not be breastfeeding and must have a negative serum pregnancy test at Visit 1 if they are women of childbearing potential.

Exclusion Criteria

Participation in another clinical trial involving an investigational agent within 30 days prior to signing the ICF for this study., Initiation of, or change in, current TG-lowering therapy within 8 weeks before Visit 1, or if a historical liver biopsy performed more than 8 weeks before Visit 1 is used, from the date of the liver biopsy until Visit 1. TG-lowering therapy is defined as niacin >100 mg/day, or dietary supplements or prescription of omega-3 fatty acids >1000 mg/day, Initiation of, or change in, current doses of orlistat, lorcaserin, phentermine, topiramate, naltrexone, or bupropion or any other medication that could promote weight loss in the opinion of the investigator within 8 weeks before Visit 1, or if a historical liver biopsy performed more than 8 weeks before Visit 1 is used, from the date of the liver biopsy until Visit 1, Subjects with severe infections, during a perioperative period, or with serious injuries, Subjects with urinary tract infection or genital infection, Subjects with active current symptomatic gallstone disease, Subjects with severe renal impairment at Visit 1, who are receiving dialysis at Visit 1, or who have had a kidney transplant, regardless of level of renal function, Subjects with weight change of 5% or more between Visit 2 and randomization, Subjects who performed significant attempt to change diet and exercise, at the investigator’s opinion, within 26 weeks of Screening, Model for End-stage Liver Disease (MELD) score >12 at Visit 1, Presence of clinical or histological evidence of compensated cirrhosis, or biochemical evidence of compensated cirrhosis, Ongoing or recent consumption of greater than moderate amounts of alcohol, or Alcohol Use Disorders Identification Test – Concise (AUDIT-C) score =3 in females or =4 in males during the Screening Period. Greater than moderate alcohol consumption is defined as on average >1 standard drink per day in women and on average >2 standard drinks per day in men over a 2-year period prior randomization. A standard alcoholic drink is any drink that contains about 14 g of pure alcohol., Inability to safely obtain a liver biopsy, History or evidence of major and clinically significant, cardiovascular, pulmonary, renal, hematologic, gastrointestinal (including clinically significant malabsorption), endocrine (other than T2DM), immunologic, dermatologic, neurologic, psychiatric, oncologic, or allergic (including drug allergies but excluding untreated or treated seasonal allergies at the time of dosing) disease that would interfere with the conduct of the study or interpretation of the data, History of malignancy within the past 5 years, except for basal or squamous cell skin carcinoma that has undergone curative therapy, Any past history of HCC and/or HCC treatment, History of bariatric surgery within 5 years of Screening, Uncontrolled hypertension at Visit 1 (systolic blood pressure =160 mm Hg and/or diastolic blood pressure =100 mm Hg after 5 minutes of sitting), Subjects with evidence of portal hypertension (e.g., low platelet counts, esophageal varices, ascites, history of hepatic encephalopathy, splenomegaly), Known infection with human immunodeficiency virus (HIV) 1 or HIV 2, Known hypersensitivity or intolerance to fibrates, PPARa agonists, or SGLT2 inhibitors, Anticipation of major surgery during the study, Evidence of other forms of chronic liver disease as follows: a. Hepatitis B as defined by presence of hepatitis B surface antigen (HBsAg) b. Hist

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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