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

Primary Purpose

Non-Alcoholic Fatty Liver Disease

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
TVB-2640
Placebo
Sponsored by
Sagimet Biosciences Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Alcoholic Fatty Liver Disease focused on measuring NASH, Non-Alcoholic Steatohepatitis, Fatty Liver Disease, Fatty Liver, Liver Diseases, FASN, Fatty Acid Synthase Inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

  2. 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.

Exclusion Criteria:

Subjects meeting any of the following criteria are not eligible for enrollment in the study.

  1. 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.

  2. Type 1 diabetes.

  3. 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.

  4. Presence of cirrhosis on liver biopsy (Stage 4 fibrosis) or imaging.

Sites / Locations

  • ProSciento
  • Catalina Research Institute
  • Clinical Trials Research
  • University of California San Diego (UCSD)
  • Panax
  • Lucas Research
  • Texas Diabetes and Endocrinology - Austin
  • Texas Digestive Disease Consultants - Cedar Park
  • Texas Digestive Disease Consultants - Dallas
  • Texas Digestive Disease Consultant - Ft Worth
  • Pinnacle Clinical Research - San Antonio
  • Texas Digestive Disease Consultants - Webster
  • Beijing Friendship Hospital, Capital Medical University
  • Beijing YouAn Hospital, Capital Medical University
  • Foshan First People's Hospital
  • Nanfang Hospital
  • The First Affiliated Hospital, Sun Yat-Sen University
  • The Third Affiliated Hospital, Sun Yat-Sen University
  • The Second Hospital of Nanjing
  • Ruijin Hospital, Shanghai JiaoTong University School of Medicine
  • Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine
  • Shanghai Tongren Hospital, Shanghai JiaoTong University School of Medicine
  • The Affiliated Hospital of Hangzhou Normal University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

TVB-2640

Placebo

Cross over to TVB-2640

Arm Description

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).

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

At Catalina Research Institute, a subset of subjects who received placebo in the single-blind Cohorts 1 and 2 at that site will be recruited to an open label cross over Cohort 3 where they will receive the study drug (TVB-2640 tablet) orally every day for 12-week treatment period. Additional patients from outside the pool of previous placebo subjects may be needed to meet the enrollment target.

Outcomes

Primary Outcome Measures

The effect of TVB-2640 versus placebo on the change in hepatic fat fraction from baseline in subjects with NASH by proton-density fat fraction by magnetic resonance imaging.
Proton-density Fat Fraction by Magnetic Resonance Imaging
The safety of TVB-2640 versus placebo in subjects with NASH, including changes in liver enzymes by monitoring adverse events.

Secondary Outcome Measures

The effect of TVB-2640 versus placebo on the change in triglycerides from baseline in subjects with NASH.
The effect of TVB-2640 versus placebo on the change in low-density lipoprotein cholesterol (LDL-C) from baseline in subjects with NASH.
The effect of TVB-2640 versus placebo on the change in high-density lipoprotein cholesterol (HDL-C) from baseline in subjects with NASH.
The effect of TVB-2640 versus placebo on the change in total cholesterol from baseline in subjects with NASH.
The effect of TVB-2640 versus placebo on the change in NASH and cytokeratin-18 (CK-18) from baseline in subjects with NASH.
The effect of TVB-2640 versus placebo on the change in NASH and fibrosis-4 (FIB-4) from baseline in subjects with NASH.
The effect of TVB-2640 versus placebo on the change in NASH and enhanced liver fibrosis score (ELF) from baseline in subjects with NASH.
The Enhanced Liver Fibrosis (ELF) score is a marker set consisting of tissue inhibitor of metalloproteinases 1 (TIMP-1), amino-terminal propeptide of type III procollagen (PIIINP) and hyaluronic acid (HA) showing good correlations with fibrosis stages in chronic liver disease. There are three typical cut-off values: < 7.7 for exclusion of fibrosis, 9.8 for a high specificity identification of fibrosis and 11.3 to discriminate cirrhosis.
The effect of TVB-2640 versus placebo on the change in levels of eicosanoids from baseline in subjects with NASH.
Eicosanoids are lipid-derived signaling molecules including 5-LOX-derived leukotriene B4 (LTB4), COX-derived prostaglandin E2 (PGE2), and 15-LOX-derived 15-hydroxyeicosatetraenoic acid (15-HETE) and lipoxin A4 (LXA4).

Full Information

First Posted
April 24, 2019
Last Updated
October 27, 2021
Sponsor
Sagimet Biosciences Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03938246
Brief Title
Study of TVB 2640 in Subjects With Non-Alcoholic Steatohepatitis (NASH)
Official Title
A Phase 2, Multi-Center, Single-Blind, Randomized, Placebo-Controlled Study of TVB 2640 in Subjects With Non-Alcoholic Steatohepatitis (FASCINATE-1)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
March 22, 2019 (Actual)
Primary Completion Date
October 2, 2021 (Actual)
Study Completion Date
October 2, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sagimet Biosciences Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Alcoholic Fatty Liver Disease
Keywords
NASH, Non-Alcoholic Steatohepatitis, Fatty Liver Disease, Fatty Liver, Liver Diseases, FASN, Fatty Acid Synthase Inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Subjects will be randomly assigned to experimental or placebo arms.
Masking
Participant
Allocation
Randomized
Enrollment
142 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TVB-2640
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects randomly assigned to placebo will receive placebo tablets orally once a day under the same conditions and frequency as described for TVB-2640.
Arm Title
Cross over to TVB-2640
Arm Type
Experimental
Arm Description
At Catalina Research Institute, a subset of subjects who received placebo in the single-blind Cohorts 1 and 2 at that site will be recruited to an open label cross over Cohort 3 where they will receive the study drug (TVB-2640 tablet) orally every day for 12-week treatment period. Additional patients from outside the pool of previous placebo subjects may be needed to meet the enrollment target.
Intervention Type
Drug
Intervention Name(s)
TVB-2640
Intervention Description
Oral dose, tablet, daily dosing
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Oral dose, tablet, daily dosing
Primary Outcome Measure Information:
Title
The effect of TVB-2640 versus placebo on the change in hepatic fat fraction from baseline in subjects with NASH by proton-density fat fraction by magnetic resonance imaging.
Description
Proton-density Fat Fraction by Magnetic Resonance Imaging
Time Frame
12 weeks
Title
The safety of TVB-2640 versus placebo in subjects with NASH, including changes in liver enzymes by monitoring adverse events.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
The effect of TVB-2640 versus placebo on the change in triglycerides from baseline in subjects with NASH.
Time Frame
12 weeks
Title
The effect of TVB-2640 versus placebo on the change in low-density lipoprotein cholesterol (LDL-C) from baseline in subjects with NASH.
Time Frame
12 weeks
Title
The effect of TVB-2640 versus placebo on the change in high-density lipoprotein cholesterol (HDL-C) from baseline in subjects with NASH.
Time Frame
12 weeks
Title
The effect of TVB-2640 versus placebo on the change in total cholesterol from baseline in subjects with NASH.
Time Frame
12 weeks
Title
The effect of TVB-2640 versus placebo on the change in NASH and cytokeratin-18 (CK-18) from baseline in subjects with NASH.
Time Frame
12 weeks
Title
The effect of TVB-2640 versus placebo on the change in NASH and fibrosis-4 (FIB-4) from baseline in subjects with NASH.
Time Frame
12 weeks
Title
The effect of TVB-2640 versus placebo on the change in NASH and enhanced liver fibrosis score (ELF) from baseline in subjects with NASH.
Description
The Enhanced Liver Fibrosis (ELF) score is a marker set consisting of tissue inhibitor of metalloproteinases 1 (TIMP-1), amino-terminal propeptide of type III procollagen (PIIINP) and hyaluronic acid (HA) showing good correlations with fibrosis stages in chronic liver disease. There are three typical cut-off values: < 7.7 for exclusion of fibrosis, 9.8 for a high specificity identification of fibrosis and 11.3 to discriminate cirrhosis.
Time Frame
12 weeks
Title
The effect of TVB-2640 versus placebo on the change in levels of eicosanoids from baseline in subjects with NASH.
Description
Eicosanoids are lipid-derived signaling molecules including 5-LOX-derived leukotriene B4 (LTB4), COX-derived prostaglandin E2 (PGE2), and 15-LOX-derived 15-hydroxyeicosatetraenoic acid (15-HETE) and lipoxin A4 (LXA4).
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rohit Loomba, MD
Organizational Affiliation
UCSD
Official's Role
Principal Investigator
Facility Information:
Facility Name
ProSciento
City
Chula Vista
State/Province
California
ZIP/Postal Code
91911
Country
United States
Facility Name
Catalina Research Institute
City
Montclair
State/Province
California
ZIP/Postal Code
91763
Country
United States
Facility Name
Clinical Trials Research
City
Sacramento
State/Province
California
ZIP/Postal Code
95821
Country
United States
Facility Name
University of California San Diego (UCSD)
City
San Diego
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Panax
City
Miami Lakes
State/Province
Florida
ZIP/Postal Code
33014
Country
United States
Facility Name
Lucas Research
City
Morehead City
State/Province
North Carolina
ZIP/Postal Code
28557
Country
United States
Facility Name
Texas Diabetes and Endocrinology - Austin
City
Austin
State/Province
Texas
ZIP/Postal Code
78749
Country
United States
Facility Name
Texas Digestive Disease Consultants - Cedar Park
City
Cedar Park
State/Province
Texas
ZIP/Postal Code
78613
Country
United States
Facility Name
Texas Digestive Disease Consultants - Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Texas Digestive Disease Consultant - Ft Worth
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Pinnacle Clinical Research - San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Texas Digestive Disease Consultants - Webster
City
Webster
State/Province
Texas
ZIP/Postal Code
77598
Country
United States
Facility Name
Beijing Friendship Hospital, Capital Medical University
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100069
Country
China
Facility Name
Beijing YouAn Hospital, Capital Medical University
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100069
Country
China
Facility Name
Foshan First People's Hospital
City
Foshan
State/Province
Guangdong
ZIP/Postal Code
528000
Country
China
Facility Name
Nanfang Hospital
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China
Facility Name
The First Affiliated Hospital, Sun Yat-Sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China
Facility Name
The Third Affiliated Hospital, Sun Yat-Sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China
Facility Name
The Second Hospital of Nanjing
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210000
Country
China
Facility Name
Ruijin Hospital, Shanghai JiaoTong University School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200336
Country
China
Facility Name
Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200336
Country
China
Facility Name
Shanghai Tongren Hospital, Shanghai JiaoTong University School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200336
Country
China
Facility Name
The Affiliated Hospital of Hangzhou Normal University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310015
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34310978
Citation
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.
Results Reference
derived

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

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