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

Non-Alcoholic Fatty Liver Disease Clinical Trial

Official title:

A Phase 2, Multi-Center, Single-Blind, Randomized, Placebo-Controlled Study of TVB 2640 in Subjects With Non-Alcoholic Steatohepatitis (FASCINATE-1)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03938246
• Other study ID #: 3V2640-CLIN-005
• Status: Completed
• Phase: Phase 2
• Start date: March 22, 2019
• Est. completion date: October 2, 2021

Study information

• Verified date: October 2021
• Source: Sagimet Biosciences Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 142
• Est. completion date: October 2, 2021
• Est. primary completion date: October 2, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-Alcoholic Fatty Liver Disease

Intervention

Drug:
• TVB-2640
Oral dose, tablet, daily dosing

Other:
• Placebo
Oral dose, tablet, daily dosing

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Sagimet Biosciences Inc.

Countries where clinical trial is conducted

United States,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The effect of TVB-2640 versus placebo on the change in hepatic fat fraction from baseline in subjects with NASH by proton-density fat fraction by magnetic resonance imaging.	Proton-density Fat Fraction by Magnetic Resonance Imaging	12 weeks
Primary	The safety of TVB-2640 versus placebo in subjects with NASH, including changes in liver enzymes by monitoring adverse events.		12 weeks
Secondary	The effect of TVB-2640 versus placebo on the change in triglycerides from baseline in subjects with NASH.		12 weeks
Secondary	The effect of TVB-2640 versus placebo on the change in low-density lipoprotein cholesterol (LDL-C) from baseline in subjects with NASH.		12 weeks
Secondary	The effect of TVB-2640 versus placebo on the change in high-density lipoprotein cholesterol (HDL-C) from baseline in subjects with NASH.		12 weeks
Secondary	The effect of TVB-2640 versus placebo on the change in total cholesterol from baseline in subjects with NASH.		12 weeks
Secondary	The effect of TVB-2640 versus placebo on the change in NASH and cytokeratin-18 (CK-18) from baseline in subjects with NASH.		12 weeks
Secondary	The effect of TVB-2640 versus placebo on the change in NASH and fibrosis-4 (FIB-4) from baseline in subjects with NASH.		12 weeks
Secondary	The effect of TVB-2640 versus placebo on the change in NASH and enhanced liver fibrosis score (ELF) from baseline in subjects with NASH.	The Enhanced Liver Fibrosis (ELF) score is a marker set consisting of tissue inhibitor of metalloproteinases 1 (TIMP-1), amino-terminal propeptide of type III procollagen (PIIINP) and hyaluronic acid (HA) showing good correlations with fibrosis stages in chronic liver disease. There are three typical cut-off values: < 7.7 for exclusion of fibrosis, 9.8 for a high specificity identification of fibrosis and 11.3 to discriminate cirrhosis.	12 weeks
Secondary	The effect of TVB-2640 versus placebo on the change in levels of eicosanoids from baseline in subjects with NASH.	Eicosanoids are lipid-derived signaling molecules including 5-LOX-derived leukotriene B4 (LTB4), COX-derived prostaglandin E2 (PGE2), and 15-LOX-derived 15-hydroxyeicosatetraenoic acid (15-HETE) and lipoxin A4 (LXA4).	12 weeks