Status:
WITHDRAWN
A Phase 3 Study Evaluating the Safety and Efficacy of Denifanstat in Patients With MASH and F2/F3 Fibrosis
Lead Sponsor:
Sagimet Biosciences Inc.
Conditions:
MASH
NASH
Eligibility:
All Genders
18-75 years
Phase:
PHASE3
Brief Summary
A randomized, double-blind, placebo-controlled Phase 3 study to determine if denifanstat 50 mg or 25 mg is effective, as compared to placebo, in resolving MASH without the worsening of fibrosis and/or...
Detailed Description
Approximately 1260 patients (including at least 60% of F3 patients) will be enrolled to receive either denifanstat 50 mg (580 patients), placebo (580 patients), or denifanstat 25 mg (100 patients).
Eligibility Criteria
Inclusion
- 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 of other 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 for hypertriglyceridemia.
- 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-glucose transport protein-2 inhibitors (SGLT2-Is), and alpha-glucosidase inhibitors (α-GIs): stable dose for at least 12 weeks prior to qualifying liver biopsy and screening.
- Sulfonylureas (SUs) and glinides: stable dose with no history of relevant hypoglycemia for at least 12 weeks prior to qualifying liver biopsy and screening.
- 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 liver biopsy must be performed during the screening period. Patients should be deemed likely to have MASH F2/F3 fibrosis prior to proceeding to a liver biopsy, as indicated 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
- 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 months within 1 year prior to screening.
- Presence of cirrhosis on liver histology according to the assessment of the central reader.
- 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 6 months 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 opinion would exclude the patient from participating in the study.
- Previous intake of an approved MASH medication, unless there is at least a 6-month wash-out period between the last date of intake of the approved MASH medication and date of screening.
- Use of a nonpermitted concomitant medication within 30 days or 5 half-lives prior to the qualifying liver biopsy and screening.
Key Trial Info
Start Date :
March 1 2025
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
December 1 2030
Estimated Enrollment :
Patients enrolled
Trial Details
Trial ID
NCT06594523
Start Date
March 1 2025
End Date
December 1 2030
Last Update
May 15 2025
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