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

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

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.

Study Overview

• Status: Completed
• Conditions: MASLD/MASH (Metabolic Dysfunction-Associated Steatotic Liver Disease / Metabolic Dysfunction-Associated Steatohepatitis)
• Intervention / Treatment: 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)

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100069
      • Beijing Youan Hospital, Capital Medical University
    • Beijing, Beijing, China, 100069
      • Beijing Friendship Hospital, Capital Medical University
  • Guangdong
    • Foshan, Guangdong, China, 528000
      • Foshan First People's Hospital
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital, Sun Yat-Sen University
    • Guangzhou, Guangdong, China, 510080
      • Nanfang Hospital
    • Guangzhou, Guangdong, China, 510080
      • The Third Affiliated Hospital, Sun Yat-sen University
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • The Second Hospital of Nanjing
  • Shanghai
    • Shanghai, Shanghai, China, 200336
      • Ruijin Hospital, Shanghai JiaoTong University School of Medicine
    • Shanghai, Shanghai, China, 200336
      • Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine
    • Shanghai, Shanghai, China, 200336
      • Shanghai Tongren Hospital, Shanghai JiaoTong University School of Medicine
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310015
      • The Affiliated Hospital of Hangzhou Normal University
• United States
  • California
    • Chula Vista, California, United States, 91911
      • ProSciento
    • Montclair, California, United States, 91763
      • Catalina Research Institute
    • Sacramento, California, United States, 95821
      • Clinical Trials Research
    • San Diego, California, United States, 92037
      • University of California San Diego (UCSD)
  • Florida
    • Miami Lakes, Florida, United States, 33014
      • PANAX
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Lucas Research
  • Texas
    • Austin, Texas, United States, 78749
      • Texas Diabetes and Endocrinology - Austin
    • Cedar Park, Texas, United States, 78613
      • Texas Digestive Disease Consultants - Cedar Park
    • Dallas, Texas, United States, 75246
      • Texas Digestive Disease Consultants - Dallas
    • Fort Worth, Texas, United States, 76104
      • Texas Digestive Disease Consultant - Ft Worth
    • San Antonio, Texas, United States, 78229
      • Pinnacle Clinical Research - San Antonio
    • Webster, Texas, United States, 77598
      • Texas Digestive Disease Consultants - Webster

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: TVB-2640 25 mg (US); Oral dose, tablet, daily dosing
Experimental: 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).	Drug: TVB-2640 50 mg (US); Oral dose, tablet, daily dosing
Placebo Comparator: 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.	Drug: Placebo (US); Oral dose, tablet, daily dosing
Experimental: 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).	Drug: TVB-2640 50 mg (China); Oral dose, tablet, daily dosing
Placebo Comparator: 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.	Drug: Placebo (China); Oral dose, tablet, daily dosing
Experimental: 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	Drug: TVB-2640 75 mg (US); Oral dose, tablet, daily dosing

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sagimet Biosciences Inc.
• Investigators: Principal Investigator: Rohit Loomba, MD, UCSD

Publications and helpful links

General Publications

• Loomba R, Mohseni R, Lucas KJ, Gutierrez JA, Perry RG, Trotter JF, Rahimi RS, Harrison SA, Ajmera V, Wayne JD, O'Farrell M, McCulloch W, Grimmer K, Rinella M, Wai-Sun Wong V, Ratziu V, Gores GJ, Neuschwander-Tetri BA, Kemble G. TVB-2640 (FASN Inhibitor) for the Treatment of Nonalcoholic Steatohepatitis: FASCINATE-1, a Randomized, Placebo-Controlled Phase 2a Trial. Gastroenterology. 2021 Nov;161(5):1475-1486. doi: 10.1053/j.gastro.2021.07.025. Epub 2021 Jul 23.

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2019
• Primary Completion (Actual): October 2, 2021
• Study Completion (Actual): October 2, 2021

Study Registration Dates

• First Submitted: April 24, 2019
• First Submitted That Met QC Criteria: May 2, 2019
• First Posted (Actual): May 6, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: NASH; Liver Diseases; Fatty Liver; Non-Alcoholic Steatohepatitis; Fatty Liver Disease; FASN; Fatty Acid Synthase Inhibitor
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 3V2640-CLIN-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No