Study of TVB 2640 in Subjects With Non-Alcoholic Steatohepatitis (NASH)
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|ClinicalTrials.gov Identifier: NCT03938246|
Recruitment Status : Completed
First Posted : May 6, 2019
Last Update Posted : October 29, 2021
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|Condition or disease||Intervention/treatment||Phase|
|Non-Alcoholic Fatty Liver Disease||Drug: TVB-2640 Other: Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||142 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Subjects will be randomly assigned to experimental or placebo arms.|
|Official Title:||A Phase 2, Multi-Center, Single-Blind, Randomized, Placebo-Controlled Study of TVB 2640 in Subjects With Non-Alcoholic Steatohepatitis (FASCINATE-1)|
|Actual Study Start Date :||March 22, 2019|
|Actual Primary Completion Date :||October 2, 2021|
|Actual Study Completion Date :||October 2, 2021|
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).
Oral dose, tablet, daily dosing
Placebo Comparator: Placebo
Subjects randomly assigned to placebo will receive placebo tablets orally once a day under the same conditions and frequency as described for TVB-2640.
Oral dose, tablet, daily dosing
Experimental: Cross over to 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.
Oral dose, tablet, daily dosing
- 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. [ Time Frame: 12 weeks ]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. [ Time Frame: 12 weeks ]
- The effect of TVB-2640 versus placebo on the change in triglycerides from baseline in subjects with NASH. [ Time Frame: 12 weeks ]
- 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 ]
- 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 ]
- The effect of TVB-2640 versus placebo on the change in total cholesterol from baseline in subjects with NASH. [ Time Frame: 12 weeks ]
- 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 ]
- 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 ]
- The effect of TVB-2640 versus placebo on the change in NASH and enhanced liver fibrosis score (ELF) from baseline in subjects with NASH. [ Time Frame: 12 weeks ]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. [ Time Frame: 12 weeks ]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).
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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:
- Ballooning degeneration
- Lobular inflammation
- 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.
- Magnetic resonance elastography (MRE) ≥ 2.5 kPa and MRI-PDFF ≥ 8% during screening.
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03938246
|Principal Investigator:||Rohit Loomba, MD||UCSD|
|Responsible Party:||Sagimet Biosciences Inc.|
|Other Study ID Numbers:||
|First Posted:||May 6, 2019 Key Record Dates|
|Last Update Posted:||October 29, 2021|
|Last Verified:||October 2021|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Fatty Liver Disease
Fatty Acid Synthase Inhibitor
Non-alcoholic Fatty Liver Disease
Digestive System Diseases