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

Nonalcoholic Fatty Liver Disease Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04906421
• Other study ID #: SB2640-CLIN-007
• Status: Completed
• Phase: Phase 2
• Start date: August 12, 2021
• Est. completion date: October 2, 2023

Study information

• Verified date: December 2023
• Source: Sagimet Biosciences Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 162
• Est. completion date: October 2, 2023
• Est. primary completion date: October 2, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 [ß-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.

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Fatty Liver Disease

Intervention

Drug:
• TVB-2640
Oral dose, tablet

Other:
• Placebo
Oral dose, tablet

Locations

Country	Name	City	State
Canada	University of Calgary Liver Unit	Calgary	Alberta
Canada	McGill University Health Centre	Montréal	Quebec
Canada	Office of Dr. Gauthier	North Bay	Ontario
Canada	Office of Dr. Gauthier	Toronto	Ontario
Canada	Toronto Liver Centre	Toronto	Ontario
Canada	GI Research Institute	Vancouver	British Columbia
Poland	Centrum Medyczne Pratia	Katowice
Poland	Krakowskie Centrum Medyczne sp z o.o.	Kraków
Poland	Hepatology Outpatient Clinic	Slaskie
Poland	ID Clinic Arkadiusz Pisula	Slaskie
Poland	Warsaw IBD Point Profesor Kierkus	Warsaw
Poland	Centrum Medyczne K2J2	Wolomin
Poland	FutureMeds	Wroclaw
Puerto Rico	FDI Clinical Research	San Juan
United States	Texas Clinical Research Institute, LLC	Arlington	Texas
United States	Summit Clinical Research	Athens	Georgia
United States	Pinnacle Clinical Research	Austin	Texas
United States	Apex Mobile Clinical Research, LLC	Bellaire	Texas
United States	Greater Boston Gastroenterology	Boston	Massachusetts
United States	Texas Digestive Disease Consultants - Cedar Park	Cedar Park	Texas
United States	University of North Carolina at Chapel Hill. UNC Liver Center	Chapel Hill	North Carolina
United States	Ralph H. Johnson Veterans Affairs Medical Center	Charleston	South Carolina
United States	Gastro Florida	Clearwater	Florida
United States	Tampa Bay Medical Research, Inc.	Clearwater	Florida
United States	Columbia Digestive Health Research, LLC	Columbia	South Carolina
United States	GI Associates Research, LLC	Columbia	Missouri
United States	Ohio State University	Columbus	Ohio
United States	Northeast GI Research Division	Concord	North Carolina
United States	ARcare Center for Clinical Research, LLC - Conway	Conway	Arkansas
United States	Citrus Valley Gastroenterology	Covina	California
United States	American Research Institute, Inc	Cutler Bay	Florida
United States	Top Medical Research, Inc	Cutler Bay	Florida
United States	GI Alliance -Texas Digestive Disease Consultants	Dallas	Texas
United States	The Liver Institute at Methodist Health System	Dallas	Texas
United States	Southeast Clinical Research Center	Dalton	Georgia
United States	DSI Research, LLC - Northridge	Dayton	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	South Texas Research Institute	Edinburg	Texas
United States	Care Access Research	Fairview Heights	Illinois
United States	Covenant Metabolic Specialists, LLC	Fort Myers	Florida
United States	Texas Digestive Disease Consultants - Fort Worth	Fort Worth	Texas
United States	Gastro One	Germantown	Tennessee
United States	Woodholme Gastroenterology Associates	Glen Burnie	Maryland
United States	Digestive Disease Research Center LLC	Greenwood	South Carolina
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	Baylor College of Medicine - Advanced Liver Therapies	Houston	Texas
United States	Pioneer Research Solutions	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	UCSD, NAFLD Research Center / Altman Clinical and Translational Research Institute	La Jolla	California
United States	Ocala GI Research dba Lake Center for Clinical Research, LLC	Lady Lake	Florida
United States	Om Research LLC	Lancaster	California
United States	Jubilee Clinical Research, Inc.	Las Vegas	Nevada
United States	Sierra Clinical Research	Las Vegas	Nevada
United States	Digestive Health Research	Lebanon	Tennessee
United States	Clinical Trials Research	Lincoln	California
United States	Arkansas Diagnostic Center	Little Rock	Arkansas
United States	Liver Wellness Center	Little Rock	Arkansas
United States	Digestive Health Research of Southern California LLC	Long Beach	California
United States	GI Alliance / Texas Digestive Disease Consultants	Lubbock	Texas
United States	Care Access Research	Lumberton	North Carolina
United States	North Alabama GI Research Center	Madison	Alabama
United States	Accel Research Site - Maitland	Maitland	Florida
United States	Tandem Clinical Research	Marrero	Louisiana
United States	Centex Studies	McAllen	Texas
United States	CPMI	Miami	Florida
United States	Genoma Research Group, Inc	Miami	Florida
United States	Sanchez Clinical Research, Inc	Miami	Florida
United States	University of Miami	Miami	Florida
United States	Panax Clinical Research	Miami Lakes	Florida
United States	San Marcus Research Clinc, Inc.	Miami Lakes	Florida
United States	Professional Medical Research	Miramar	Florida
United States	Catalina Research Institute,LLC	Montclair	California
United States	Lucas Research, Inc.	Morehead City	North Carolina
United States	United Medical Doctors	Murrieta	California
United States	Gastroenterology Health Partners, PLLC	New Albany	Indiana
United States	Ocala GI Research, LLC	Ocala	Florida
United States	Care Access	Ogden	Utah
United States	DDSI Clinical Trials	Oklahoma City	Oklahoma
United States	Palmtree Clinical Research, INC	Palm Springs	California
United States	Innovation Medical Research Center, Inc	Palmetto Bay	Florida
United States	Pensacola GI Research Center, LLC	Pensacola	Florida
United States	ClinRx Research LLC	Plano	Texas
United States	Care Access Research	Poland	Ohio
United States	University of Gastroenterology	Providence	Rhode Island
United States	Rapid City Medical Center, LLP	Rapid City	South Dakota
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	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	Covenant Metabolic Specialists, LLC	Sarasota	Florida
United States	Headlands Research Sarasota	Sarasota	Florida
United States	Sherman Clinical Research	Sherman	Texas
United States	Louisiana Research Center LLC	Shreveport	Louisiana
United States	Digestive Research Alliance of Michiana	South Bend	Indiana
United States	FC Research LLC	South Dartmouth	Massachusetts
United States	GI Alliance Arizona Digestive Health-Sun City	Sun City	Arizona
United States	Kansas Medical Clinic, PA	Topeka	Kansas
United States	IVGI	Ventura	California
United States	Impact Research Institute	Waco	Texas
United States	Care Access Research	Warwick	Rhode Island
United States	Digestive Health Research of North Texas	Wichita Falls	Texas
United States	Trial Management Associates, LLC	Wilmington	North Carolina
United States	Conquest Research	Winter Park	Florida
United States	Care Access	Yonkers	New York

Sponsors (1)

Lead Sponsor	Collaborator
Sagimet Biosciences Inc.

Countries where clinical trial is conducted

United States,  Canada,  Poland,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Histological improvement in nonalcoholic fatty liver disease (NAFLD) activity score (NAS) without worsening of fibrosis (by NASH Clinical Research Network [CRN] fibrosis score) at Week 52	Histological improvement is defined as =2 points improvement in NAS with =1 point improvement in ballooning or inflammation	12 months
Primary	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	12 months
Primary	Safety and tolerability of PO QD doses of TVB-2640 in subjects with confirmed NASH and liver fibrosis evaluated by incidence of treatment emergent adverse events (TEAEs)		12 months