Clinical trial NCT04906421: Study of TVB-2640 in Subjects With Nonalcoholic Steatohepatitis (NASH)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metabolic Dysfunction-assocated Steatohepatitis/ Nonalcoholic Fatty Liver Disease
Keywords: NASH
Nonalcoholic Steatohepatitis
Fatty Liver Disease
Biopsy Confirmed
FASN
Fatty Liver
Liver Disease
Digestive System Diseases
MASH
Metabolic dysfunction-associated steatohepatitis
Lead sponsor: Sagimet Biosciences Inc.
Sponsor class: INDUSTRY
First posted: 2021-05-28
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects with liver fibrosis stage F2-F3, will be enrolled and randomized in a 2:1 ratio to receive TVB-2640, or placebo PO QD
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Histological Improvement in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) Without Worsening of Fibrosis (by NASH Clinical Research Network [CRN] Fibrosis Score).
timeFrame: 52 Weeks
measure: Subjects With Resolution of Steatohepatitis and No Worsening of Liver Fibrosis by NASH CRN Fibrosis Score and Histological Improvement in NAS.
timeFrame: 52 Weeks
Secondary outcomes:
measure: Proportion of Subjects Experiencing Fibrosis Improvement of ≥1 Stage by NASH CRN Score Without Worsening of Steatohepatitis
timeFrame: 52 Weeks
measure: Proportion of Subjects Experiencing Resolution of Steatohepatitis and no Worsening of Liver Fibrosis (by NASH CRN Fibrosis Score)
timeFrame: 52 Weeks
measure: 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
timeFrame: 52 Weeks
measure: Proportion of MRI-PDFF ≥30% Responders.
timeFrame: 52 Weeks
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: North Alabama Health Research
state: Alabama
city: Madison
country: United States
facility: North Alabama GI Research Center
state: Alabama
city: Sun City
country: United States
facility: GI Alliance Arizona Digestive Health-Sun City
state: Arizona
city: Conway
country: United States
facility: ARcare Center for Clinical Research, LLC - Conway
state: Arkansas
city: Little Rock
country: United States
facility: Arkansas Diagnostic Center
state: Arkansas
city: Little Rock
country: United States
facility: Liver Wellness Center
state: Arkansas
city: Covina
country: United States
facility: Citrus Valley Gastroenterology
state: California
city: La Jolla
country: United States
facility: UCSD, NAFLD Research Center / Altman Clinical and Translational Research Institute
state: California
city: Lancaster
country: United States
facility: Om Research LLC
state: California
city: Lincoln
country: United States
facility: Clinical Trials Research
state: California
city: Long Beach
country: United States
facility: Digestive Health Research of Southern California LLC
state: California
city: Long Beach
country: United States
facility: Digestive Health Research of Southern California
state: California
city: Montclair
country: United States
facility: Catalina Research Institute, LLC
state: California
city: Murrieta
country: United States
facility: United Medical Doctors
state: California
city: Palm Springs
country: United States
facility: Palmtree Clinical Research, INC
state: California
city: Ventura
country: United States
facility: IVGI
state: California
city: Clearwater
country: United States
facility: Gastro Florida
state: Florida
city: Clearwater
country: United States
facility: Tampa Bay Medical Research, Inc.
state: Florida
city: Cutler Bay
country: United States
facility: American Research Institute, Inc
state: Florida
city: Cutler Bay
country: United States
facility: Top Medical Research, Inc
state: Florida
city: Fort Myers
country: United States
facility: Covenant Metabolic Specialists, LLC
state: Florida
city: Hialeah
country: United States
facility: Direct Helpers Research Center
state: Florida
city: Hialeah
country: United States
facility: Miguel A Rebollar, MD PA
state: Florida
city: Homestead
country: United States
facility: Global Research Associates
state: Florida
city: Lady Lake
country: United States
facility: Ocala GI Research dba Lake Center for Clinical Research, LLC
state: Florida
city: Maitland
country: United States
facility: Accel Research Site - Maitland
state: Florida
city: Miami Lakes
country: United States
facility: Panax Clinical Research
state: Florida
city: Miami Lakes
country: United States
facility: San Marcus Research Clinic, Inc.
state: Florida
city: Miami
country: United States
facility: CPMI
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Miami
country: United States
facility: Sanchez Clinical Research, Inc
state: Florida
city: Miami
country: United States
facility: Genoma Research Group, Inc
state: Florida
city: Miramar
country: United States
facility: Professional Medical Research
state: Florida
city: Ocala
country: United States
facility: Ocala GI Research, LLC
state: Florida
city: Palmetto Bay
country: United States
facility: Innovation Medical Research Center, Inc
state: Florida
city: Pensacola
country: United States
facility: Pensacola GI Research Center, LLC
state: Florida
city: Sarasota
country: United States
facility: Covenant Metabolic Specialists, LLC
state: Florida
city: Sarasota
country: United States
facility: Headlands Research Sarasota
state: Florida
city: Winter Park
country: United States
facility: Conquest Research
state: Florida
city: Athens
country: United States
facility: Summit Clinical Research
state: Georgia
city: Dalton
country: United States
facility: Southeast Clinical Research Center
state: Georgia
city: Fairview Heights
country: United States
facility: Care Access Research
state: Illinois
city: New Albany
country: United States
facility: Gastroenterology Health Partners, PLLC
state: Indiana
city: South Bend
country: United States
facility: Digestive Research Alliance of Michiana
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Topeka
country: United States
facility: Kansas Medical Clinic, PA
state: Kansas
city: Marrero
country: United States
facility: Tandem Clinical Research
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana Research Center LLC
state: Louisiana
city: Glen Burnie
country: United States
facility: Woodholme Gastroenterology Associates
state: Maryland
city: Boston
country: United States
facility: Greater Boston Gastroenterology
state: Massachusetts
city: Framingham
country: United States
facility: Greater Boston Gastroenterology
state: Massachusetts
city: South Dartmouth
country: United States
facility: FC Research LLC
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Columbia
country: United States
facility: GI Associates Research, LLC
state: Missouri
city: Las Vegas
country: United States
facility: Sierra Clinical Research
state: Nevada
city: Las Vegas
country: United States
facility: Jubilee Clinical Research, Inc.
state: Nevada
city: Yonkers
country: United States
facility: Care Access
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill. UNC Liver Center
state: North Carolina
city: Concord
country: United States
facility: Northeast GI Research Division
state: North Carolina
city: Lumberton
country: United States
facility: ACME Medical Specialties PLCC
state: North Carolina
city: Lumberton
country: United States
facility: Care Access Research
state: North Carolina
city: Morehead City
country: United States
facility: Lucas Research, Inc.
state: North Carolina
city: Wilmington
country: United States
facility: Trial Management Associates, LLC
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Dayton
country: United States
facility: DSI Research, LLC - Northridge
state: Ohio
city: Poland
country: United States
facility: Care Access Research
state: Ohio
city: Oklahoma City
country: United States
facility: DDSI Clinical Trials
state: Oklahoma
city: Providence
country: United States
facility: University of Gastroenterology
state: Rhode Island
city: Warwick
country: United States
facility: Care Access Research
state: Rhode Island
city: Charleston
country: United States
facility: Ralph H. Johnson Veterans Affairs Medical Center
state: South Carolina
city: Columbia
country: United States
facility: Columbia Digestive Health Research, LLC
state: South Carolina
city: Greenwood
country: United States
facility: Digestive Disease Research Center LLC
state: South Carolina
city: Rapid City
country: United States
facility: Rapid City Medical Center, LLP
state: South Dakota
city: Chattanooga
country: United States
facility: WR-ClinSearch, LLC
state: Tennessee
city: Cordova
country: United States
facility: Gastro One
state: Tennessee
city: Germantown
country: United States
facility: Gastro One
state: Tennessee
city: Lebanon
country: United States
facility: Digestive Health Research
state: Tennessee
city: Arlington
country: United States
facility: Texas Clinical Research Institute, LLC
state: Texas
city: Austin
country: United States
facility: Pinnacle Clinical Research
state: Texas
city: Bellaire
country: United States
facility: Apex Mobile Clinical Research, LLC
state: Texas
city: Cedar Park
country: United States
facility: Texas Digestive Disease Consultants - Cedar Park
state: Texas
city: Dallas
country: United States
facility: The Liver Institute at Methodist Health System
state: Texas
city: Dallas
country: United States
facility: GI Alliance -Texas Digestive Disease Consultants
state: Texas
city: Edinburg
country: United States
facility: South Texas Research Institute
state: Texas
city: Fort Worth
country: United States
facility: Texas Digestive Disease Consultants - Fort Worth
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine - Advanced Liver Therapies
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions
state: Texas
city: Lubbock
country: United States
facility: GI Alliance / Texas Digestive Disease Consultants
state: Texas
city: McAllen
country: United States
facility: Centex Studies
state: Texas
city: Plano
country: United States
facility: ClinRx Research LLC
state: Texas
city: San Antonio
country: United States
facility: American Research Corporation
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas Inc.
state: Texas
city: San Antonio
country: United States
facility: Diabetes and Glandular Disease Clinic, P.A.
state: Texas
city: San Antonio
country: United States
facility: Endeavor Clinical Trials, LLC
state: Texas
city: San Antonio
country: United States
facility: Pinnacle Clinical Research
state: Texas
city: Sherman
country: United States
facility: Sherman Clinical Research
state: Texas
city: Waco
country: United States
facility: Impact Research Institute
state: Texas
city: Wichita Falls
country: United States
facility: Digestive Health Research of North Texas
state: Texas
city: Ogden
country: United States
facility: Care Access
state: Utah
city: Richmond
country: United States
facility: Bon Secours Richmond Community Hospital LLC d/b/a Bon Secours Liver Institute of Richmond
state: Virginia
city: Richmond
country: United States
facility: GI Select Health Research, LLC
state: Virginia
city: Richmond
country: United States
facility: McGuire VA Medical Center
state: Virginia
city: Roanoke
country: United States
facility: Gastroenterology Consultants of SW Virginia
state: Virginia
city: Calgary
country: Canada
facility: University of Calgary Liver Unit
state: Alberta
city: Vancouver
country: Canada
facility: GI Research Institute
state: British Columbia
city: North Bay
country: Canada
facility: Office of Dr. Gauthier
state: Ontario
city: Toronto
country: Canada
facility: Toronto Liver Centre
state: Ontario
city: Toronto
country: Canada
facility: Office of Dr. Gauthier
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Katowice
country: Poland
facility: Centrum Medyczne Pratia
city: Kraków
country: Poland
facility: Krakowskie Centrum Medyczne sp z o.o.
city: Warsaw
country: Poland
facility: Warsaw IBD Point Profesor Kierkus
city: Wołomin
country: Poland
facility: Centrum Medyczne K2J2
city: Wrocław
country: Poland
facility: FutureMeds
city: Śląskie
country: Poland
facility: Hepatology Outpatient Clinic
city: Śląskie
country: Poland
facility: ID Clinic Arkadiusz Pisula
city: San Juan
country: Puerto Rico
facility: FDI Clinical Research
Study officials:
References:
citation: 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.