A Phase 3 Study Evaluating the Safety and Efficacy of Denifanstat in Patients With MASH and F2/F3 Fibrosis

NCT06594523 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: SB2640-CLIN-010
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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 in fibrosis regression without the worsening of steatohepatitis.

Conditions

MASH; NASH; Metabolic Dysfunction-associated Steatohepatitis; Noncirrhotic Metabolic Dysfunction-associated Steatohepatitis; Nonalcoholic Steatohepatitis; Nonalcoholic Fatty Liver

Keywords

fibrosis; fatty liver; steatohepatitis

Outcome Measures

Primary Outcomes (3)

• Dual Primary Efficacy Endpoint 1: Interim Analysis: MASH Resolution (denifanstat 50 mg compared to placebo)

  Proportion of patients who achieve MASH resolution (defined as NAS\* of 0 for ballooning, and 0 or 1 for inflammation) without worsening of fibrosis stage at Week 52. \*NAS: nonalcoholic fatty liver disease activity score

  52 weeks

• Dual Primary Efficacy Endpoint 2: Interim Analysis: Improvement in Fibrosis (denifanstat 50 mg compared to placebo)

  Proportion of patients who achieve at least a 1-point improvement in fibrosis stage and without worsening of steatohepatitis (defined as no increase in NAS\* for ballooning, inflammation, or steatosis) at Week 52.

  52 weeks

• Primary Endpoint: End of Study Analysis: Liver-related Composite Clinical Outcome (denifanstat 50 mg compared to placebo)

  Time to first occurrence of any event from the following composite clinical outcome: death from any cause; histopathologic progression to cirrhosis; liver transplant; Model for End-Stage Liver Disease (MELD) score ≥15; Liver decompensation event defined by: Ascites requiring chronic diuretic treatment, Hepatic encephalopathy grade 2 or above requiring at least a 24-hour hospitalization, Variceal hemorrhage requiring hospitalization and transfusion of blood.

  234 weeks

Study Arms (3)

Denifanstat 50 mg

EXPERIMENTAL

Denifanstat tablet, orally, once daily

Drug: Denifanstat

Denifanstat 25 mg

EXPERIMENTAL

Denifanstat tablet, orally, once daily

Drug: Denifanstat

Placebo

PLACEBO COMPARATOR

Placebo tablet, orally, once daily

Drug: Placebo

Interventions

Denifanstat DRUG

Tablet

Also known as: TVB-2640

Denifanstat 25 mg; Denifanstat 50 mg

Placebo DRUG

Matching Tablet

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• Previous intake of an approved MASH medication.
• 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.

Sponsors & Collaborators

• Sagimet Biosciences Inc.: lead

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Fibrosis; Fatty Liver

Interventions

TVB-2640

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2024
• First Posted: September 19, 2024
• Study Start: March 1, 2025
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: May 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share