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: Non-Alcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: TVB-2640; Other: Placebo

• 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
• Genders Eligible for Study: All

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
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TVB-2640; 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; Oral dose, tablet, daily dosing
PLACEBO_COMPARATOR: Placebo; Subjects randomly assigned to placebo will receive placebo tablets orally once a day under the same conditions and frequency as described for TVB-2640.	Other: Placebo; Oral dose, tablet, daily dosing
EXPERIMENTAL: Cross over to TVB-2640; At Catalina Research Institute, a subset of subjects who received placebo in the single-blind Cohorts 1 and 2 at that site will be recruited to an open label cross over Cohort 3 where they will receive the study drug (TVB-2640 tablet) orally every day for 12-week treatment period. Additional patients from outside the pool of previous placebo subjects may be needed to meet the enrollment target.	Drug: TVB-2640; Oral dose, tablet, daily dosing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
The safety of TVB-2640 versus placebo in subjects with NASH, including changes in liver enzymes by monitoring adverse events.		12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effect of TVB-2640 versus placebo on the change in triglycerides from baseline in subjects with NASH.		12 weeks
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
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
The effect of TVB-2640 versus placebo on the change in total cholesterol from baseline in subjects with NASH.		12 weeks
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
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
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
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

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): October 29, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

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