A Phase 3 Study Evaluating the Safety and Efficacy of Denifanstat in Patients With MASLD and MASH (FASCINIT)

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Denifanstat in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease (MALSD)/Metabolic Dysfunction-Associated Steatohepatitis (MASH)

A phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and tolerability of denifanstat 50 mg compared to placebo in patients with metabolic dysfunction-associated steatotic liver disease (MALSD)/metabolic dysfunction-associated steatohepatitis (MASH) after 52 weeks of treatment.

Study Overview

• Status: Withdrawn
• Conditions: Nonalcoholic Steatohepatitis; Nonalcoholic Fatty Liver; NASH; MASLD; MASH; Metabolic Dysfunction-Associated Steatohepatitis; Metabolic Dysfunction-Associated Steatotic Liver Disease
• Intervention / Treatment: Drug: Placebo; Drug: denifanstat

Detailed Description

Up to 2000 patients will be randomized to receive either denifanstat 50 mg or placebo.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Willing and able to participate in the study and provide written informed consent.

2. Adults between 18 and 75 years of age.

3. Body mass index (BMI) ≥23 kg/m2 for Asian patients and ≥25 kg/m2 for patients of other races.

4. Presence of metabolic risk factor(s), as follows:

1. T2DM

   OR

2. At least 2 out of 4 of the following:

   • BMI ≥30 kg/m2,
   • 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.

5. For patients with T2DM:

1. HbA1c ≤9.5%
2. If treatment naive: patients must have been diagnosed for at least 12 weeks prior to screening

6. Suspected or confirmed diagnosis of MASH or MASLD or non-invasively diagnosed MASH or MASLD

7. Stable ALT and AST levels

Exclusion Criteria:

1. Previous intake of an approved MASH medication

2. Exclusionary laboratory values:

1. ALT and/or AST >5 × ULN.
2. ALP ≥2 × ULN.
3. Total serum bilirubin concentration >1.3 mg/dL.
4. Serum albumin concentration <3.5 g/dL.
5. International normalized ratio (INR) >1.3, except for patients receiving anticoagulant treatment.
6. Platelet count <140,000/μL.
7. Fasting TG level ≥500 mg/dL.
8. eGFR <45 mL/min/1.73 m2.

3. History of excessive alcohol intake for a period of more than 3 consecutive months within 1 year prior to screening.

4. Presence of cirrhosis on liver histology and/or cross-sectional imaging evidence consistent with cirrhosis and/or portal hypertension.

5. Current or historical clinically evident hepatic decompensation.

6. Evidence of another form of active liver disease.

7. Positive serologic evidence of current infectious liver disease.

8. MELD score ≥12.

9. Planned or history of liver transplantation.

10. Prior or planned bariatric surgery.

11. 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).

12. Any of the following conditions or procedures within 6 months prior to the baseline visit (V1):

1. Myocardial infarction
2. Cardiac revascularization surgery
3. Unstable angina
4. Transient ischemic attack, stroke, or cerebrovascular disease

13. Unstable or undiagnosed arrhythmias.

14. Uncontrolled high BP.

15. Malignancy with a complete remission date within 5 years prior to the baseline visit (V1).

16. Any current or history of hepatocellular carcinoma.

17. Diabetes other than T2DM

18. Uncontrolled hypothyroidism.

19. Any other known serious disease or other disease which in the Investigator's opinion would exclude the patient from participating in the study.

20. Use of a nonpermitted concomitant medication within 30 days or 5 half-lives prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Denifanstat 50 mg; Denifanstat tablet, orally, once daily	Drug: denifanstat; Tablet; Other Names: TVB-2640
Placebo Comparator: Placebo; Placebo tablet, orally, once daily	Drug: Placebo; Matching tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Safety Outcome Measure: TEAEs	Incidence of treatment-emergent adverse events (TEAEs) in patients with MASLD/MASH treated with denifanstat 50 mg compared to placebo after 52 weeks of treatment.	52 weeks

Collaborators and Investigators

• Sponsor: Sagimet Biosciences Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: September 10, 2024
• First Submitted That Met QC Criteria: November 14, 2024
• First Posted (Actual): November 18, 2024

Study Record Updates

• Last Update Posted (Actual): May 15, 2025
• Last Update Submitted That Met QC Criteria: May 12, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: fatty liver; steatohepatitis; steatotic liver
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: SB2640-CLIN-011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No