Ensayos clínicos

Inclusion Criteria:

• Male or female participants between the ages of 18 (or the minimum country-specific age of consent if > 18) and 75 years, inclusive, at PreQ and SCR1.
• Biopsy proven NASH with either F2 or F3 fibrosis, per NASH CRN definition.
• At PreQ and SCR1, meet ≥ 2 of the following criteria [for laboratory parameters, results must be as assessed by the sponsor-identified central laboratory, with a single repeat permitted to assess eligibility, at each of these 2 visits, if needed]:
  • FPG ≥ 100 mg/dL (5.6 mmol/L), or on pharmacological agents with explicit purpose of improving glycemic control;
  • Fasting serum HDL-C < 40 mg/dL (1 mmol/L) for males and < 50 mg/dL (1.3 mmol/L) for females, or on pharmacological agents with explicit purpose to increase HDL-C;
  • Fasting serum TG ≥ 150 mg/dL (1.7 mmol/L), or on pharmacological agents with explicit purpose to decrease TG;
  • Seated BP ≥ 130 / 85 mm Hg, or on pharmacological agents with explicit purpose for BP control;
  • Waist circumference ≥ 40 inches (102 cm) for males and ≥ 35 inches (89 cm) for females.
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures:
  • Including following completion of screening/baseline liver biopsy, participants must confirm willingness to undergo the 2nd biopsy, while in study.
• BMI ≥ 25.0 kg/m^2 (for sites in Africa, Europe, North/South America) or ≥ 22.5 kg/m^2 (for sites in Asia) with upper limit of 45 kg/m^2 (including rounding to a maximum of 45.1 kg/m^2 , calculated using sponsor-provided NASH tool) at PreQ and SCR1 with a single repeat assessment of body weight and/or BMI permitted on a different day to assess eligibility, if needed, at each of these 2 visits.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICDs and in this protocol at PreQ and SCR1:
  • For participants who qualify based on PreQ procedures, at SCR1, evidence of a separate personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the main study, is required;
  • Plus, an additional provision/flexibility for those participating in Imaging Substudy to offer dedicated consent for this procedure closer (but prior) to Baseline MRI-PDFF or at the time of consent obtained at SCR1.

Exclusion Criteria:

• Evidence of other causes of liver disease such as alcoholic steatohepatitis, (de)compensated cirrhosis, active viral hepatitis.
• History of pancreatitis, at PreQ.
• Any condition possibly affecting drug absorption (e.g., prior bariatric surgery, gastrectomy, ileal resection) at PreQ:
  • Participants who have undergone cholecystectomy and/or appendectomy are eligible for this study so long as the surgery occurred > months prior to PreQ.
• Diagnosis of T2DM which requires management with > 3 medications within 12 weeks prior to SCR1 or management with excluded agents for glycemic control.
• Dyslipidemia which requires management with > 3 lipid-modifying agents within 12 weeks prior to SCR1 or use of excluded agents for lipid management:
  • In addition, specific restrictions need to be satisfied at SCR1 in order to progress;
  • Those on gemfibrozil or lovastatin will need to agree to be switched to another agent once deemed eligible (i.e., at initiation of Run-In) and for duration of study;
  • Those on statins will be permitted based on review of the total daily dose.
• Cardiovascular event within 12 months prior to PreQ:
  • A history of myocardial infarction, stroke, transient ischemic attack or revascularization procedure to prevent any of these events;
  • Recent history of congestive heart failure (NYHA class III or IV) or unstable angina.
• Recent (within 5 years of PreQ) systemically administered treatments for malignancy including (but not limited to):
  • the use of chemotherapy, radiotherapy, or immunotherapy; or
  • any other active malignancy (within 3 years of PreQ), except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.
• Recent (within 5 years of PreQ) systemically administered treatments for malignancy including (but not limited to):
  • the use of chemotherapy, radiotherapy, or immunotherapy; or
  • any other active malignancy (within 3 years of PreQ), except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.
• Results as reported by sponsor-identified central laboratory, at either PreQ or SCR1, as below with a single repeat assessment permitted using sponsor-identified central laboratory, to assess eligibility, if needed, at each of these 2 visits:
  • ALT 5 x ULN;
  • AST > 5 x ULN;
  • ALP > 2 x ULN;
  • Direct bilirubin >ULN;
  • Total bilirubin > ULN except when participants has a history of Gilbert syndrome where total bilirubin > ULN would be eligible for this study provided direct bilirubin level is ≤ ULN, and hemoglobin and reticulocyte count are within the reference range of the sponsor-identified central laboratory.
  • NOTE: If there is a > 50% variability between the PreQ and SCR1 results for ALT, AST, or alkaline phosphatase or total bilirubin is > ULN, these LFTs must be repeated 1 additional time, ≥ 2 weeks after SCR1, with the variability between the PreQ and the 1 additional measurement confirmed to be ≤ 50% for ALT, AST, and alkaline phosphatase, and total bilirubin ≤ ULN, and within the parameters above to confirm eligibility prior to progressing to conduct of liver biopsy at SCR2.
• HbA1C > % (75 mmol/mol), as assessed using NGSP certified method and standardized to DCCT assay.
• Fasting Plasma Glucose > 270 mg/dL (15 mmol/L).
• Fasting serum triglycerides > 400 mg/dL (4.5 mmol/L).
• Platelet count < LLN.
• INR ≥ 1.3.
• Albumin < LLN.
• eGFR (using CKD-EPI-Cystatin-C) of < 30 ml/min/1.73 m^2.
• A positive urine drug test for illicit drugs (with this 1 assessment not permitted to be repeated at each visit to confirm eligibility).

Eligibility last updated 11/18/21. Questions regarding updates should be directed to the study team contact.