Study of TVB-2640 in Subjects With Non-Alcoholic Steatohepatitis (NASH)

Phase 2

Completed

• Conditions: MASLD/MASH (Metabolic Dysfunction-Associated Steatotic Liver Disease / Metabolic Dysfunction-Associated Steatohepatitis)
• Interventions: Drug: TVB-2640 25 mg (US); Drug: TVB-2640 50 mg (US); Drug: Placebo (US); Drug: TVB-2640 50 mg (China); Drug: Placebo (China); Drug: TVB-2640 75 mg (US)

• Registration Number: NCT03938246
• Lead Sponsor: Sagimet Biosciences Inc.

Brief Summary

This is a Phase 2 multi-center, randomized, single-blind, placebo-controlled study to evaluate the safety and efficacy of TVB-2640 in subjects with non-alcoholic steatohepatitis (NASH), a type of fatty liver disease. Subjects will be randomly assigned to 1 of 2 treatment groups (TVB-2640 at one of three doses or placebo). Following randomization, subjects will begin the 12-week treatment period and will receive once daily TVB-2640 or placebo.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-03-22
• Study First Submitted: 2019-04-24
• Study First Submitted QC: 2019-05-02
• Study First Posted: 2019-05-06
• Primary Completion: 2021-10-02
• Study Completion: 2021-10-02
• Results First Submitted: 2024-11-21
• Status Verified: 2024-12
• Results First Submitted QC: 2024-12-17
• Last Update Submitted: 2024-12-17
• Results First Posted: 2025-03-25
• Last Update Posted: 2025-03-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 142

Inclusion Criteria

1. Aged ≥ 18 years with a body mass index (BMI) ≤40 kg/m2.

2. Prior liver biopsy within 24 months of randomization with fibrosis Stage 1 to 3 and a non-alcoholic fatty liver disease (NAFLD) activity score (NAS) of ≥ 4 with at least a score of 1 in each of the following NAS components:

   • Steatosis
   • Ballooning degeneration
   • Lobular inflammation

AND

• Confirmation of ≥ 8% liver fat content on MRI-PDFF.

OR, if prior biopsy is not available:

• Either overweight or obese or diabetic or ALT ≥ 30 U/L or fatty liver on ultrasound and at least one more feature of metabolic syndrome by Adult Treatment Panel III (ATP III) criteria.

AND

• Magnetic resonance elastography (MRE) ≥ 2.5 kPa and MRI-PDFF ≥ 8% during screening.

Exclusion Criteria

Subjects meeting any of the following criteria are not eligible for enrollment in the study.

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

   Note: Significant alcohol consumption is defined as average of > 20 g/day in female subjects and > 30 g/day in male subjects.

2. Type 1 diabetes.

3. Uncontrolled Type 2 diabetes defined as:

   • HbA1c ≥ 9.5% during screening. (Subjects with HbA1c ≥ 9.5% may be rescreened).
   • Basal insulin dose adjustment > 10% within 60 days prior to enrollment.
   • Requirement for glucagon-like peptide analogue or a complex oral anti-diabetic (OAD) regimen (3 or more OADs) within 6 months of screening.
   • History of severe hypoglycemia (symptomatic hypoglycemia requiring outside assistance to regain normal neurologic status) within the previous year.

   Note: Individual diabetes regimens will be reviewed by Investigator and may be adjusted based on American Diabetes Association guidelines.

4. Presence of cirrhosis on liver biopsy (Stage 4 fibrosis) or imaging.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TVB-2640 25 mg (US)	TVB-2640 25 mg (US)	Subjects randomly assigned to receive the study drug will take TVB-2640 tablet orally every day for 12 week treatment period. The dose is to be taken at the same time of the day, with each dose separated by 24 hours (±4 hours).
TVB-2640 50 mg (US)	TVB-2640 50 mg (US)	Subjects randomly assigned to receive the study drug will take TVB-2640 tablet orally every day for 12 week treatment period. The dose is to be taken at the same time of the day, with each dose separated by 24 hours (±4 hours).
Placebo (US)	Placebo (US)	Subjects randomly assigned to placebo will receive placebo tablets orally once a day under the same conditions and frequency as described for TVB-2640.
TVB-2640 50 mg (China)	TVB-2640 50 mg (China)	Subjects randomly assigned to receive the study drug will take TVB-2640 tablet orally every day for 12 week treatment period. The dose is to be taken at the same time of the day, with each dose separated by 24 hours (±4 hours).
Placebo (China)	Placebo (China)	Subjects randomly assigned to placebo will receive placebo tablets orally once a day under the same conditions and frequency as described for TVB-2640.
TVB-2640 75 mg (US)	TVB-2640 75 mg (US)	After completion of Cohorts 1 and 2, and if no stopping criteria are met upon review by the Independent SRC, an additional TVB-2640 75 mg open-label Cohort 3 will open in the US

Primary Outcome Measures

Name	Time	Method
Percent Change in Hepatic Fat Fraction by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) From Baseline	12 weeks	As determined by MRI-PDFF

Secondary Outcome Measures

Name	Time	Method
Percentage of Subjects With at Least a 30% Reduction in Liver Fat at Week 12.	12 weeks	As determined by MRI-PDFF
Percentage of Change From Baseline in Alanine Aminotransferase (ALT)	12 weeks

Trial Locations

Locations (23)

ProSciento; 🇺🇸 Chula Vista, California, United States

Catalina Research Institute; 🇺🇸 Montclair, California, United States

Clinical Trials Research; 🇺🇸 Sacramento, California, United States

University of California San Diego (UCSD); 🇺🇸 San Diego, California, United States

Panax; 🇺🇸 Miami Lakes, Florida, United States

Lucas Research; 🇺🇸 Morehead City, North Carolina, United States

Texas Diabetes and Endocrinology - Austin; 🇺🇸 Austin, Texas, United States

Texas Digestive Disease Consultants - Cedar Park; 🇺🇸 Cedar Park, Texas, United States

Texas Digestive Disease Consultants - Dallas; 🇺🇸 Dallas, Texas, United States

Texas Digestive Disease Consultant - Ft Worth; 🇺🇸 Fort Worth, Texas, United States

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