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

NCT ID: NCT04906421

Last Updated: 2025-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 168 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-12
• Study Completion Date: 2023-10-02

Brief Summary

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.

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.

Conditions

Metabolic Dysfunction-assocated Steatohepatitis/ Nonalcoholic Fatty Liver Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

TVB-2640 50 mg

Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.

Group Type: EXPERIMENTAL

TVB-2640

Intervention Type: DRUG

Oral dose, tablet

Placebo

Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Oral dose, tablet

Interventions

TVB-2640

Oral dose, tablet

Intervention Type: DRUG

Placebo

Oral dose, tablet

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sagimet Biosciences Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

North Alabama Health Research

Huntsville, Alabama, United States

North Alabama GI Research Center

Madison, Alabama, United States

GI Alliance Arizona Digestive Health-Sun City

Sun City, Arizona, United States

ARcare Center for Clinical Research, LLC - Conway

Conway, Arkansas, United States

Arkansas Diagnostic Center

Little Rock, Arkansas, United States

Liver Wellness Center

Little Rock, Arkansas, United States

Citrus Valley Gastroenterology

Covina, California, United States

UCSD, NAFLD Research Center / Altman Clinical and Translational Research Institute

La Jolla, California, United States

Om Research LLC

Lancaster, California, United States

Clinical Trials Research

Lincoln, California, United States

Digestive Health Research of Southern California LLC

Long Beach, California, United States

Digestive Health Research of Southern California

Long Beach, California, United States

Catalina Research Institute, LLC

Montclair, California, United States

United Medical Doctors

Murrieta, California, United States

Palmtree Clinical Research, INC

Palm Springs, California, United States

IVGI

Ventura, California, United States

Gastro Florida

Clearwater, Florida, United States

Tampa Bay Medical Research, Inc.

Clearwater, Florida, United States

American Research Institute, Inc

Cutler Bay, Florida, United States

Top Medical Research, Inc

Cutler Bay, Florida, United States

Covenant Metabolic Specialists, LLC

Fort Myers, Florida, United States

Direct Helpers Research Center

Hialeah, Florida, United States

Miguel A Rebollar, MD PA

Hialeah, Florida, United States

Global Research Associates

Homestead, Florida, United States

Ocala GI Research dba Lake Center for Clinical Research, LLC

Lady Lake, Florida, United States

Accel Research Site - Maitland

Maitland, Florida, United States

CPMI

Miami, Florida, United States

University of Miami

Miami, Florida, United States

Sanchez Clinical Research, Inc

Miami, Florida, United States

Genoma Research Group, Inc

Miami, Florida, United States

Panax Clinical Research

Miami Lakes, Florida, United States

San Marcus Research Clinic, Inc.

Miami Lakes, Florida, United States

Professional Medical Research

Miramar, Florida, United States

Ocala GI Research, LLC

Ocala, Florida, United States

Innovation Medical Research Center, Inc

Palmetto Bay, Florida, United States

Pensacola GI Research Center, LLC

Pensacola, Florida, United States

Covenant Metabolic Specialists, LLC

Sarasota, Florida, United States

Headlands Research Sarasota

Sarasota, Florida, United States

Conquest Research

Winter Park, Florida, United States

Summit Clinical Research

Athens, Georgia, United States

Southeast Clinical Research Center

Dalton, Georgia, United States

Care Access Research

Fairview Heights, Illinois, United States

Gastroenterology Health Partners, PLLC

New Albany, Indiana, United States

Digestive Research Alliance of Michiana

South Bend, Indiana, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Kansas Medical Clinic, PA

Topeka, Kansas, United States

Tandem Clinical Research

Marrero, Louisiana, United States

Louisiana Research Center LLC

Shreveport, Louisiana, United States

Woodholme Gastroenterology Associates

Glen Burnie, Maryland, United States

Greater Boston Gastroenterology

Boston, Massachusetts, United States

Greater Boston Gastroenterology

Framingham, Massachusetts, United States

FC Research LLC

South Dartmouth, Massachusetts, United States

Henry Ford Hospital

Detroit, Michigan, United States

GI Associates Research, LLC

Columbia, Missouri, United States

Sierra Clinical Research

Las Vegas, Nevada, United States

Jubilee Clinical Research, Inc.

Las Vegas, Nevada, United States

Care Access

Yonkers, New York, United States

University of North Carolina at Chapel Hill. UNC Liver Center

Chapel Hill, North Carolina, United States

Northeast GI Research Division

Concord, North Carolina, United States

ACME Medical Specialties PLCC

Lumberton, North Carolina, United States

Care Access Research

Lumberton, North Carolina, United States

Lucas Research, Inc.

Morehead City, North Carolina, United States

Trial Management Associates, LLC

Wilmington, North Carolina, United States

Ohio State University

Columbus, Ohio, United States

DSI Research, LLC - Northridge

Dayton, Ohio, United States

Care Access Research

Poland, Ohio, United States

DDSI Clinical Trials

Oklahoma City, Oklahoma, United States

University of Gastroenterology

Providence, Rhode Island, United States

Care Access Research

Warwick, Rhode Island, United States

Ralph H. Johnson Veterans Affairs Medical Center

Charleston, South Carolina, United States

Columbia Digestive Health Research, LLC

Columbia, South Carolina, United States

Digestive Disease Research Center LLC

Greenwood, South Carolina, United States

Rapid City Medical Center, LLP

Rapid City, South Dakota, United States

WR-ClinSearch, LLC

Chattanooga, Tennessee, United States

Gastro One

Cordova, Tennessee, United States

Gastro One

Germantown, Tennessee, United States

Digestive Health Research

Lebanon, Tennessee, United States

Texas Clinical Research Institute, LLC

Arlington, Texas, United States

Pinnacle Clinical Research

Austin, Texas, United States

Apex Mobile Clinical Research, LLC

Bellaire, Texas, United States

Texas Digestive Disease Consultants - Cedar Park

Cedar Park, Texas, United States

The Liver Institute at Methodist Health System

Dallas, Texas, United States

GI Alliance -Texas Digestive Disease Consultants

Dallas, Texas, United States

South Texas Research Institute

Edinburg, Texas, United States

Texas Digestive Disease Consultants - Fort Worth

Fort Worth, Texas, United States

Baylor College of Medicine - Advanced Liver Therapies

Houston, Texas, United States

Pioneer Research Solutions

Houston, Texas, United States

GI Alliance / Texas Digestive Disease Consultants

Lubbock, Texas, United States

Centex Studies

McAllen, Texas, United States

ClinRx Research LLC

Plano, Texas, United States

American Research Corporation

San Antonio, Texas, United States

Clinical Trials of Texas Inc.

San Antonio, Texas, United States

Diabetes and Glandular Disease Clinic, P.A.

San Antonio, Texas, United States

Endeavor Clinical Trials, LLC

San Antonio, Texas, United States

Pinnacle Clinical Research

San Antonio, Texas, United States

Sherman Clinical Research

Sherman, Texas, United States

Impact Research Institute

Waco, Texas, United States

Digestive Health Research of North Texas

Wichita Falls, Texas, United States

Care Access

Ogden, Utah, United States

Bon Secours Richmond Community Hospital LLC d/b/a Bon Secours Liver Institute of Richmond

Richmond, Virginia, United States

GI Select Health Research, LLC

Richmond, Virginia, United States

McGuire VA Medical Center

Richmond, Virginia, United States

Gastroenterology Consultants of SW Virginia

Roanoke, Virginia, United States

University of Calgary Liver Unit

Calgary, Alberta, Canada

GI Research Institute

Vancouver, British Columbia, Canada

Office of Dr. Gauthier

North Bay, Ontario, Canada

Toronto Liver Centre

Toronto, Ontario, Canada

Office of Dr. Gauthier

Toronto, Ontario, Canada

McGill University Health Centre

Montreal, Quebec, Canada

Centrum Medyczne Pratia

Katowice, , Poland

Krakowskie Centrum Medyczne sp z o.o.

Krakow, , Poland

Hepatology Outpatient Clinic

Śląskie, , Poland

ID Clinic Arkadiusz Pisula

Śląskie, , Poland

Warsaw IBD Point Profesor Kierkus

Warsaw, , Poland

Centrum Medyczne K2J2

Wołomin, , Poland

FutureMeds

Wroclaw, , Poland

FDI Clinical Research

San Juan, , Puerto Rico

Countries

United States; Canada; Poland; Puerto Rico

References

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.

Reference Type: BACKGROUND

PMID: 39396529 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://pubmed.ncbi.nlm.nih.gov/39396529/

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

Other Identifiers

SB2640-CLIN-007

Identifier Type: -

Identifier Source: org_study_id