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

A Phase 2B, Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study of the Safety and Efficacy of TVB-2640 in Subjects With Nonalcoholic Steatohepatitis (FASCINATE-2)

This is a Phase 2, multi-center, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy on TVB-2640 in subjects with non-alcoholic steatohepatitis (NASH). Subjects will be randomly assigned toTVB-2640 or matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.

Study Overview

• Status: Completed
• Conditions: Metabolic Dysfunction-assocated Steatohepatitis/ Nonalcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: TVB-2640; Other: Placebo

Detailed Description

The indication nonalcoholic steatohepatitis [NASH]) is now referred to as metabolic dysfunction-associated steatohepatitis (MASH) and is characterized by hepatocyte necrosis, chronic inflammation, and resultant fibrosis formation.

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary Liver Unit
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • GI Research Institute
  • Ontario
    • North Bay, Ontario, Canada, P1B 2H3
      • Office of Dr. Gauthier
    • Toronto, Ontario, Canada, M6H 3M1
      • Toronto Liver Centre
    • Toronto, Ontario, Canada, M6H-3M1
      • Office of Dr. Gauthier
  • Quebec
    • Montréal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre
• Poland
  • Katowice, Poland, 40-081
    • Centrum Medyczne Pratia
  • Kraków, Poland, 31-501
    • Krakowskie Centrum Medyczne sp z o.o.
  • Warsaw, Poland, 00-728
    • Warsaw IBD Point Profesor Kierkus
  • Wołomin, Poland, 05-200
    • Centrum Medyczne K2J2
  • Wrocław, Poland, 50-088
    • FutureMeds
  • Śląskie, Poland, 41-400
    • Hepatology Outpatient Clinic
  • Śląskie, Poland, 41-400
    • ID Clinic Arkadiusz Pisula
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • FDI Clinical Research
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • North Alabama Health Research
    • Madison, Alabama, United States, 35758
      • North Alabama GI Research Center
  • Arizona
    • Sun City, Arizona, United States, 85351
      • GI Alliance Arizona Digestive Health-Sun City
  • Arkansas
    • Conway, Arkansas, United States, 72032
      • ARcare Center for Clinical Research, LLC - Conway
    • Little Rock, Arkansas, United States, 72205
      • Liver Wellness Center
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Diagnostic Center
  • California
    • Covina, California, United States, 91723
      • Citrus Valley Gastroenterology
    • La Jolla, California, United States, 92093
      • UCSD, NAFLD Research Center / Altman Clinical and Translational Research Institute
    • Lancaster, California, United States, 93534
      • Om Research LLC
    • Lincoln, California, United States, 95648
      • Clinical Trials Research
    • Long Beach, California, United States, 90808
      • Digestive Health Research of Southern California LLC
    • Long Beach, California, United States, 90808
      • Digestive Health Research of Southern California
    • Montclair, California, United States, 91763
      • Catalina Research Institute, LLC
    • Murrieta, California, United States, 92563
      • United Medical Doctors
    • Palm Springs, California, United States, 92262
      • Palmtree Clinical Research, INC
    • Ventura, California, United States, 93003
      • IVGI
  • Florida
    • Clearwater, Florida, United States, 33761
      • Gastro Florida
    • Clearwater, Florida, United States, 33761
      • Tampa Bay Medical Research, Inc.
    • Cutler Bay, Florida, United States, 33157
      • American Research Institute, INC
    • Cutler Bay, Florida, United States, 33189
      • Top Medical Research, Inc
    • Fort Myers, Florida, United States, 33912
      • Covenant Metabolic Specialists, LLC
    • Hialeah, Florida, United States, 33012
      • Direct Helpers Research Center
    • Hialeah, Florida, United States, 33012
      • Miguel A Rebollar, MD PA
    • Homestead, Florida, United States, 33030
      • Global Research Associates
    • Lady Lake, Florida, United States, 32159
      • Ocala GI Research dba Lake Center for Clinical Research, LLC
    • Maitland, Florida, United States, 32751
      • Accel Research Site - Maitland
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33157
      • Sanchez Clinical Research, Inc
    • Miami, Florida, United States, 33014
      • CPMI
    • Miami, Florida, United States, 33173
      • Genoma Research Group, Inc
    • Miami Lakes, Florida, United States, 33014
      • San Marcus Research Clinic, Inc.
    • Miami Lakes, Florida, United States, 33014
      • Panax Clinical Research
    • Miramar, Florida, United States, 33025
      • Professional Medical Research
    • Ocala, Florida, United States, 34471
      • Ocala GI Research, LLC
    • Palmetto Bay, Florida, United States, 33157
      • Innovation Medical Research Center, Inc
    • Pensacola, Florida, United States, 32503
      • Pensacola GI Research Center, LLC
    • Sarasota, Florida, United States, 34243
      • Headlands Research Sarasota
    • Sarasota, Florida, United States, 34240
      • Covenant Metabolic Specialists, LLC
    • Winter Park, Florida, United States, 32789
      • Conquest Research
  • Georgia
    • Athens, Georgia, United States, 30607
      • Summit Clinical Research
    • Dalton, Georgia, United States, 30720
      • Southeast Clinical Research Center
  • Illinois
    • Fairview Heights, Illinois, United States, 62208
      • Care Access Research
  • Indiana
    • New Albany, Indiana, United States, 47150
      • Gastroenterology Health Partners, PLLC
    • South Bend, Indiana, United States, 46635
      • Digestive Research Alliance of Michiana
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Kansas Medical Clinic, PA
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research
    • Shreveport, Louisiana, United States, 71105
      • Louisiana Research Center LLC
  • Maryland
    • Glen Burnie, Maryland, United States, 21061
      • Woodholme Gastroenterology Associates
  • Massachusetts
    • Boston, Massachusetts, United States, 01702
      • Greater Boston Gastroenterology
    • Framingham, Massachusetts, United States, 01702
      • Greater Boston Gastroenterology
    • South Dartmouth, Massachusetts, United States, 02747
      • FC Research LLC
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Missouri
    • Columbia, Missouri, United States, 65201
      • GI Associates Research, LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Sierra Clinical Research
    • Las Vegas, Nevada, United States, 899106
      • Jubilee Clinical Research, Inc.
  • New York
    • Yonkers, New York, United States, 10701
      • Care Access
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill. UNC Liver Center
    • Concord, North Carolina, United States, 28027
      • Northeast GI Research Division
    • Lumberton, North Carolina, United States, 28358
      • Care Access Research
    • Lumberton, North Carolina, United States, 28358
      • ACME Medical Specialties PLCC
    • Morehead City, North Carolina, United States, 28557
      • Lucas Research, Inc.
    • Wilmington, North Carolina, United States, 28403
      • Trial Management Associates, LLC
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
    • Dayton, Ohio, United States, 45414
      • DSI Research, LLC - Northridge
    • Poland, Ohio, United States, 44514
      • Care Access Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • DDSI Clinical Trials
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • University of Gastroenterology
    • Warwick, Rhode Island, United States, 02886
      • Care Access Research
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Ralph H. Johnson Veterans Affairs Medical Center
    • Columbia, South Carolina, United States, 29204
      • Columbia Digestive Health Research, LLC
    • Greenwood, South Carolina, United States, 29646
      • Digestive Disease Research Center LLC
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Medical Center, LLP
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • WR-Clinsearch, LLC
    • Cordova, Tennessee, United States, 38018
      • Gastro One
    • Germantown, Tennessee, United States, 38138
      • Gastro One
    • Lebanon, Tennessee, United States, 37090
      • Digestive Health Research
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Clinical Research Institute, LLC
    • Austin, Texas, United States, 78557
      • Pinnacle Clinical Research
    • Bellaire, Texas, United States, 77401
      • Apex Mobile Clinical Research, LLC
    • Cedar Park, Texas, United States, 78613
      • Texas Digestive Disease Consultants - Cedar Park
    • Dallas, Texas, United States, 75203
      • The Liver Institute at Methodist Health System
    • Dallas, Texas, United States, 75246
      • GI Alliance -Texas Digestive Disease Consultants
    • Edinburg, Texas, United States, 78539
      • South Texas Research Institute
    • Fort Worth, Texas, United States, 76104
      • Texas Digestive Disease Consultants - Fort Worth
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine - Advanced Liver Therapies
    • Houston, Texas, United States, 77099
      • Pioneer Research Solutions
    • Lubbock, Texas, United States, 79410
      • GI Alliance / Texas Digestive Disease Consultants
    • McAllen, Texas, United States, 78504
      • Centex Studies
    • Plano, Texas, United States, 75023
      • ClinRx Research LLC
    • San Antonio, Texas, United States, 78229
      • Endeavor Clinical Trials, LLC
    • San Antonio, Texas, United States, 78229
      • Diabetes and Glandular Disease Clinic, P.A.
    • San Antonio, Texas, United States, 78215
      • American Research Corporation
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas Inc.
    • San Antonio, Texas, United States, 78240
      • Pinnacle Clinical Research
    • Sherman, Texas, United States, 75092
      • Sherman Clinical Research
    • Waco, Texas, United States, 76710
      • Impact Research Institute
    • Wichita Falls, Texas, United States, 76301
      • Digestive Health Research of North Texas
  • Utah
    • Ogden, Utah, United States, 84403
      • Care Access
  • Virginia
    • Richmond, Virginia, United States, 23249
      • McGuire VA Medical Center
    • Richmond, Virginia, United States, 23226
      • Bon Secours Richmond Community Hospital LLC d/b/a Bon Secours Liver Institute of Richmond
    • Richmond, Virginia, United States, 23236
      • GI Select Health Research, LLC
    • Roanoke, Virginia, United States, 24014
      • Gastroenterology Consultants of SW Virginia

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Must be willing and able to participate in the study and provide written informed consent.
• Male and female adults ≥18 years of age on the date that written informed consent to take part in the study is provided.
• Body mass index (BMI) ≥23 kg/m2 for Asians and ≥25 kg/m2 for other races.

• Female subjects must be either:

  • Not of childbearing potential OR
  • Women of childbearing potential (WOCBP) must have a negative serum pregnancy (beta-human chorionic gonadotropin [β-HCG]) test during Screening, a negative urine pregnancy test within 24 hours before the first dose of study drug on Day 1, and must agree to perform urine home pregnancy tests monthly between study visits. WOCBP must not be breastfeeding, not plan to become pregnant during the study, and must use birth control.
• Must have liver stiffness measurement ≥8.5 kPa measured by FibroScan and CAP score measured by FibroScan ≥280 dB/m during the Screening period.
• Histologic confirmation of NASH: must have had prior liver biopsy within 180 days before randomization (randomization is within 24 hours of Baseline [Day1]) with fibrosis stage F2-F3 and a NAS of ≥4 with at least a score of 1 in each of the following NAS components: steatosis, ballooning degeneration, and lobular inflammation.

Exclusion Criteria:

• History of harmful alcohol intake for a period of more than 3 consecutive months within 1 year prior to Screening in the judgement of the Investigator.
• Active substance abuse.
• Gain or loss of >5% of body weight in the 6 months prior to Baseline (Day 1) or >10% of body weight in the 12 months prior to Screening.
• Type 1 diabetes mellitus by history.
• Positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) polymerase chain reaction (PCR) test within 30 days before Baseline, history of hospitalization for coronavirus disease-2019 (COVID-19) ), or history of use of oxygen due to COVID-19) <6 months prior to the Screening visit date. Note that previous COVID-19 infection alone is not exclusionary and vaccination against SARS-CoV-2 is allowed. Infection and/or vaccination must be documented.
• Uncontrolled T2DM, defined as HbA1c ≥9.5% at Screening.
• Presence of cirrhosis on liver histology (stage 4 fibrosis), according to the judgement of the central reader, and/or cross sectional imaging evidence consistent with cirrhosis and/or portal hypertension.
• Use of glucagon-like peptide-1 (GLP-1) agonists or a sodium-glucose co-transporter-2 (SGLT2) inhibitor, unless on a stable daily dose for at least 6 months prior to the Screening visit date, or on a complex oral anti-diabetic (OAD) regimen (3 or more OADs [except for a GLP-1 agonist or an SGLT2 inhibitor]), unless on a stable dose for at least 3 months prior to the Screening visit date.
• Subjects with active or quiescent chronic liver disease of etiologies other than NASH (eg, viral or autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, and 'autoimmune hepatitis-overlap' syndromes, hemochromatosis, Wilson's disease, alpha 1 antitrypsin deficiency, alcohol-related liver disease, drug-induced liver disease, and/or infiltrative conditions [eg, sarcoidosis]).
• Current or historic clinically evident hepatic decompensation event (eg, ascites formation, variceal hemorrhage, hepatic encephalopathy).
• Any subject who has sustained a clinically evident cardiovascular, cerebrovascular, and/or peripheral vascular event during the 12 months prior to anticipated Baseline (Day 1) visit date is not eligible for study participation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TVB-2640 50 mg; Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.	Drug: TVB-2640; Oral dose, tablet
Placebo Comparator: Placebo; Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.	Other: Placebo; Oral dose, tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Histological Improvement in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) Without Worsening of Fibrosis (by NASH Clinical Research Network [CRN] Fibrosis Score).	Histological improvement is defined as ≥2 points improvement in NAS with ≥1 point improvement in ballooning or inflammation	52 Weeks
Subjects With Resolution of Steatohepatitis and No Worsening of Liver Fibrosis by NASH CRN Fibrosis Score and Histological Improvement in NAS.	NASH resolution defined as absence of fatty liver disease or isolated or simple steatosis without steatohepatitis and a score of either 0 or 1 for inflammation, 0 for ballooning and any value for steatosis and no worsening of liver fibrosis (by NASH CRN fibrosis score). Histological improvement defined as ≥2 point improvement in NAS (with ≥1 point improvement in ballooning or inflammation).	52 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Experiencing Fibrosis Improvement of ≥1 Stage by NASH CRN Score Without Worsening of Steatohepatitis	Proportion of subjects experiencing fibrosis improvement of ≥1 stage by NASH CRN score Without worsening of steatohepatitis (defined as no increase in NAS for ballooning, inflammation, or steatosis) at 52 weeks.	52 Weeks
Proportion of Subjects Experiencing Resolution of Steatohepatitis and no Worsening of Liver Fibrosis (by NASH CRN Fibrosis Score)	Resolution of steatohepatitis is defined as absence of fatty liver disease or isolated or simple steatosis without steatohepatitis and a NAS of 0 or 1 for inflammation, 0 for ballooning, and any value for steatosis.	52 Weeks
Proportion of Subjects With Improvement in Liver Fibrosis >=1 Stage by NASH CRN Fibrosis Score Without Worsening of Steatohepatitis at 52 Weeks OR Resolution of Steatohepatitis and No Worsening of Liver Fibrosis by NASH CRN Fibrosis Score	No increase in NAS for ballooning, inflammation or steatosis.	52 Weeks
Proportion of MRI-PDFF ≥30% Responders.	MRI PDFF ≥30% responder is defined as a subject with ≥8% liver fat content at Baseline who achieves a relative reduction from Baseline in MRI-PDFF ≥30%.	52 Weeks

Collaborators and Investigators

• Sponsor: Sagimet Biosciences Inc.

Publications and helpful links

General Publications

• Loomba R, Bedossa P, Grimmer K, Kemble G, Bruno Martins E, McCulloch W, O'Farrell M, Tsai WW, Cobiella J, Lawitz E, Rudraraju M, Harrison SA. Denifanstat for the treatment of metabolic dysfunction-associated steatohepatitis: a multicentre, double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Gastroenterol Hepatol. 2024 Dec;9(12):1090-1100. doi: 10.1016/S2468-1253(24)00246-2. Epub 2024 Oct 11.

Helpful Links

• Denifanstat for the treatment of metabolic dysfunctionassociated steatohepatitis: a multicentre, double-blind, randomised, placebo-controlled, phase 2b trial

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2021
• Primary Completion (Actual): October 2, 2023
• Study Completion (Actual): October 2, 2023

Study Registration Dates

• First Submitted: May 20, 2021
• First Submitted That Met QC Criteria: May 24, 2021
• First Posted (Actual): May 28, 2021

Study Record Updates

• Last Update Posted (Actual): May 9, 2025
• Last Update Submitted That Met QC Criteria: April 28, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Digestive System Diseases; Nonalcoholic Steatohepatitis; NASH; Liver Disease; Fatty Liver; Fatty Liver Disease; Biopsy Confirmed; FASN; MASH; Metabolic dysfunction-associated steatohepatitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: SB2640-CLIN-007

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