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

NCT03938246 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 3V2640-CLIN-005
• Study Type: interventional
• Target: 142
• Locations: 2 countries
• Sites: 23

Brief Summary

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.

Conditions

MASLD/MASH (Metabolic Dysfunction-Associated Steatotic Liver Disease / Metabolic Dysfunction-Associated Steatohepatitis)

Keywords

NASH; Non-Alcoholic Steatohepatitis; Fatty Liver Disease; Fatty Liver; Liver Diseases; FASN; Fatty Acid Synthase Inhibitor

Outcome Measures

Primary Outcomes (1)

• Percent Change in Hepatic Fat Fraction by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) From Baseline

  As determined by MRI-PDFF

  12 weeks

Secondary Outcomes (2)

• Percentage of Subjects With at Least a 30% Reduction in Liver Fat at Week 12.

  12 weeks

• Percentage of Change From Baseline in Alanine Aminotransferase (ALT)

  12 weeks

Study Arms (6)

TVB-2640 25 mg (US)

EXPERIMENTAL

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 25 mg (US)

TVB-2640 50 mg (US)

EXPERIMENTAL

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 50 mg (US)

Placebo (US)

PLACEBO COMPARATOR

Subjects randomly assigned to placebo will receive placebo tablets orally once a day under the same conditions and frequency as described for TVB-2640.

Drug: Placebo (US)

TVB-2640 50 mg (China)

EXPERIMENTAL

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 50 mg (China)

Placebo (China)

PLACEBO COMPARATOR

Subjects randomly assigned to placebo will receive placebo tablets orally once a day under the same conditions and frequency as described for TVB-2640.

Drug: Placebo (China)

TVB-2640 75 mg (US)

EXPERIMENTAL

After completion of Cohorts 1 and 2, and if no stopping criteria are met upon review by the Independent SRC, an additional TVB-2640 75 mg open-label Cohort 3 will open in the US

Drug: TVB-2640 75 mg (US)

Interventions

TVB-2640 25 mg (US) DRUG

Oral dose, tablet, daily dosing

TVB-2640 25 mg (US)

TVB-2640 50 mg (US) DRUG

Oral dose, tablet, daily dosing

TVB-2640 50 mg (US)

Placebo (US) DRUG

Oral dose, tablet, daily dosing

Placebo (US)

TVB-2640 50 mg (China) DRUG

Oral dose, tablet, daily dosing

TVB-2640 50 mg (China)

Placebo (China) DRUG

Oral dose, tablet, daily dosing

Placebo (China)

TVB-2640 75 mg (US) DRUG

Oral dose, tablet, daily dosing

TVB-2640 75 mg (US)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥ 18 years with a body mass index (BMI) ≤40 kg/m2.
• 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.

You may not qualify if:

• Subjects meeting any of the following criteria are not eligible for enrollment in the study.
• 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.
• Type 1 diabetes.
• 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.
• Presence of cirrhosis on liver biopsy (Stage 4 fibrosis) or imaging.

Sponsors & Collaborators

• Sagimet Biosciences Inc.: lead

Study Sites (23)

ProSciento

Chula Vista, California, 91911, United States

Location

Catalina Research Institute

Montclair, California, 91763, United States

Location

Clinical Trials Research

Sacramento, California, 95821, United States

Location

University of California San Diego (UCSD)

San Diego, California, 92037, United States

Location

Panax

Miami Lakes, Florida, 33014, United States

Location

Lucas Research

Morehead City, North Carolina, 28557, United States

Location

Texas Diabetes and Endocrinology - Austin

Austin, Texas, 78749, United States

Location

Texas Digestive Disease Consultants - Cedar Park

Cedar Park, Texas, 78613, United States

Location

Texas Digestive Disease Consultants - Dallas

Dallas, Texas, 75246, United States

Location

Texas Digestive Disease Consultant - Ft Worth

Fort Worth, Texas, 76104, United States

Location

Pinnacle Clinical Research - San Antonio

San Antonio, Texas, 78229, United States

Location

Texas Digestive Disease Consultants - Webster

Webster, Texas, 77598, United States

Location

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, 100069, China

Location

Beijing YouAn Hospital, Capital Medical University

Beijing, Beijing Municipality, 100069, China

Location

Foshan First People's Hospital

Foshan, Guangdong, 528000, China

Location

Nanfang Hospital

Guangzhou, Guangdong, 510080, China

Location

The First Affiliated Hospital, Sun Yat-Sen University

Guangzhou, Guangdong, 510080, China

Location

The Third Affiliated Hospital, Sun Yat-Sen University

Guangzhou, Guangdong, 510080, China

Location

The Second Hospital of Nanjing

Nanjing, Jiangsu, 210000, China

Location

Ruijin Hospital, Shanghai JiaoTong University School of Medicine

Shanghai, Shanghai Municipality, 200336, China

Location

Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine

Shanghai, Shanghai Municipality, 200336, China

Location

Shanghai Tongren Hospital, Shanghai JiaoTong University School of Medicine

Shanghai, Shanghai Municipality, 200336, China

Location

The Affiliated Hospital of Hangzhou Normal University

Hangzhou, Zhejiang, 310015, China

Location

Related Publications (1)

• 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.

  PMID: 34310978 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Fatty Liver; Liver Diseases

Interventions

TVB-2640

Condition Hierarchy (Ancestors)

Digestive System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Sagimet Biosciences Inc.

sitecontact@sagimet.com

650-561-8675

Study Officials

• Rohit Loomba, MD

  UCSD

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be randomly assigned to experimental or placebo arms.

Study Record Dates

• First Submitted: April 24, 2019
• First Posted: May 6, 2019
• Study Start: March 22, 2019
• Primary Completion: October 2, 2021
• Study Completion: October 2, 2021
• Last Updated: December 19, 2024
• Results First Posted: December 19, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (12); CN (11)