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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 142

Inclusion Criteria

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

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.
Type 1 diabetes.
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.
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): Shanghai Tongren Hospital, Shanghai JiaoTong University School of Medicine
🇨🇳
Shanghai, Shanghai, China
ProSciento
🇺🇸
Chula Vista, California, United States
Catalina Research Institute
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Montclair, California, United States
Clinical Trials Research
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Sacramento, California, United States
Panax
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Miami Lakes, Florida, United States
University of California San Diego (UCSD)
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San Diego, California, United States
Lucas Research
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Morehead City, North Carolina, United States
Texas Digestive Disease Consultants - Cedar Park
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Cedar Park, Texas, United States
Texas Diabetes and Endocrinology - Austin
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Austin, Texas, United States
Texas Digestive Disease Consultants - Dallas
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Dallas, Texas, United States
Texas Digestive Disease Consultant - Ft Worth
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Fort Worth, Texas, United States
Pinnacle Clinical Research - San Antonio
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San Antonio, Texas, United States
Texas Digestive Disease Consultants - Webster
🇺🇸
Webster, Texas, United States
Foshan First People's Hospital
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Foshan, Guangdong, China
Beijing Friendship Hospital, Capital Medical University
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Beijing, Beijing, China
Nanfang Hospital
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Guangzhou, Guangdong, China
Beijing YouAn Hospital, Capital Medical University
🇨🇳
Beijing, Beijing, China
The First Affiliated Hospital, Sun Yat-Sen University
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Guangzhou, Guangdong, China
The Third Affiliated Hospital, Sun Yat-Sen University
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Guangzhou, Guangdong, China
The Second Hospital of Nanjing
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Nanjing, Jiangsu, China
The Affiliated Hospital of Hangzhou Normal University
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Hangzhou, Zhejiang, China
Ruijin Hospital, Shanghai JiaoTong University School of Medicine
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Shanghai, Shanghai, China
Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine
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Shanghai, Shanghai, China