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

Sagimet Biosciences

Status and phase: Completed; Phase 2

Conditions: MASLD/MASH (Metabolic Dysfunction-Associated Steatotic Liver Disease / Metabolic Dysfunction-Associated Steatohepatitis)

Treatments: Drug: TVB-2640 50 mg (US); Drug: Placebo (US); Drug: TVB-2640 50 mg (China); Drug: TVB-2640 25 mg (US); Drug: Placebo (China); Drug: TVB-2640 75 mg (US)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03938246

3V2640-CLIN-005

Details and patient eligibility

About

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.

Enrollment: 142 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

142 participants in 6 patient groups, including a placebo group

TVB-2640 25 mg (US)

Experimental group

Description:

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).

Treatment:

Drug: TVB-2640 25 mg (US)

TVB-2640 50 mg (US)

Experimental group

Description:

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).

Treatment:

Drug: TVB-2640 50 mg (US)

Placebo (US)

Placebo Comparator group

Description:

Subjects randomly assigned to placebo will receive placebo tablets orally once a day under the same conditions and frequency as described for TVB-2640.

Treatment:

Drug: Placebo (US)

TVB-2640 50 mg (China)

Experimental group

Description:

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).

Treatment:

Drug: TVB-2640 50 mg (China)

Placebo (China)

Placebo Comparator group

Description:

Subjects randomly assigned to placebo will receive placebo tablets orally once a day under the same conditions and frequency as described for TVB-2640.

Treatment:

Drug: Placebo (China)

TVB-2640 75 mg (US)

Experimental group

Description:

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

Treatment:

Drug: TVB-2640 75 mg (US)