Phase
Condition
Liver Disease
Scar Tissue
Treatment
Placebo
Denifanstat
Matching Placebo
Clinical Study ID
Study Summary
Eligibility Criteria
Inclusion
Inclusion Criteria:
Willing and able to participate in the study and provide written informed consent.
Adults between 18 and 75 years of age.
Body mass index (BMI) ≥23 kg/m^2 for Asian patients and ≥25 kg/m^2 for patients ofother races.
Presence of metabolic risk factor(s), as follows:
T2DM.OR
2 out of 4 of the following:
- BMI ≥30 kg/m^2.
- Hypertension, or on active antihypertensive treatment.
- Elevated fasting serum TGs or on active treatment forhypertriglyceridemia.
- Reduced fasting serum HDL-c or on active treatment for dyslipidemia.
- For patients with T2DM:
HbA1c ≤9.5%.
Metformin, insulin, dipeptidyl peptidase-4 inhibitors (DPP4-Is), sodium-glucosetransport protein-2 inhibitors (SGLT2-Is), and alpha-glucosidase inhibitors (α-GIs): stable dose for at least 12 weeks prior to qualifying liver biopsy andscreening.
Sulfonylureas (SUs) and glinides: stable dose with no history of relevanthypoglycemia for at least 12 weeks prior to qualifying liver biopsy andscreening.
GLP-1 RA: stable dose for at least 18 weeks prior to start of screening.
Noncirrhotic, biopsy-proven MASH with:
A fibrosis stage of F2 or F3.
NAS ≥4 with at least a score of 1 in each of the following NAS components:
- Steatosis (scored 0 to 3).
- Hepatocyte ballooning (scored 0 to 2).
- Lobular inflammation (scored 0 to 3).
A qualifying historical liver biopsy within 6 months before the screening visit.Historical biopsy results will be confirmed by central reading. If there is no available historical liver biopsy within this time period, a liverbiopsy must be performed during the screening period. Patients should be deemedlikely to have MASH F2/F3 fibrosis prior to proceeding to a liver biopsy, asindicated by the following:
FibroScan.
- Liver stiffness measurement (LSM) ≥8.5 kPa.
- Controlled attenuation parameter (CAP) ≥280 dB/m.
Aspartate aminotransferase (AST) >20 U/L.
Stable ALT and AST levels.
Exclusion
Exclusion Criteria:
Previous intake of an approved MASH medication.
Exclusionary laboratory values:
ALT and/or AST >5 × ULN.
ALP ≥2 × ULN.
Total serum bilirubin concentration >1.3 mg/dL.
Serum albumin concentration <3.5 g/dL.
INR >1.3 except for patients receiving anticoagulant treatment.
Platelet count <140,000/μL.
Fasting TG level ≥500 mg/dL.
eGFR <45 mL/min/1.73 m^2.
History of excessive alcohol intake for a period of more than 3 consecutive monthswithin 1 year prior to screening.
Presence of cirrhosis on liver histology according to the assessment of the centralreader.
Current or historical clinically evident hepatic decompensation.
Evidence of another form of active liver disease.
Positive serologic evidence of current infectious liver disease.
MELD score ≥12.
Planned or history of liver transplantation.
Prior or planned bariatric surgery.
Gain or loss of >5% of body weight in the 3 months or >10% of body weight in the 6months prior to screening, qualifying liver biopsy, and the baseline visit (V1).
Any of the following within 6 months prior to the baseline visit (V1):
Myocardial infarction.
CABG/PTCA.
Unstable angina.
Transient ischemic attack, stroke, or cerebrovascular disease.
Unstable or undiagnosed arrhythmias.
Uncontrolled high BP.
Malignancy with a complete remission date within 5 years prior to the baseline visit (V1).
Any current or history of hepatocellular carcinoma.
Diabetes other than T2DM.
Uncontrolled hypothyroidism.
Any other known serious disease or other disease which in the Investigator's opinionwould exclude the patient from participating in the study.
Previous intake of an approved MASH medication, unless there is at least a 6-monthwash-out period between the last date of intake of the approved MASH medication anddate of screening.
Use of a nonpermitted concomitant medication within 30 days or 5 half-lives prior tothe qualifying liver biopsy and screening.