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

• Sponsor: Sagimet Biosciences Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03938246
• Collaborator: (none)
• Enrollment: 142
• Locations: 23
• Arms: 3
• Actual Duration (Months): 30.4
• Patients Per Site: 6.2
• Patients Per Site Per Month: 0.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Alcoholic Fatty Liver Disease	Drug: TVB-2640; Other: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 142 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Subjects will be randomly assigned to experimental or placebo arms.Subjects will be randomly assigned to experimental or placebo arms.
• Masking: Single (Participant)
• Primary Purpose: Treatment
• 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: Mar 22, 2019
• Actual Primary Completion Date: Oct 2, 2021
• Actual Study Completion Date: Oct 2, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TVB-2640 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; 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.	Other: Placebo; 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.	Drug: TVB-2640; Oral dose, tablet, daily dosing

Outcome Measures

Primary Outcome Measures

1. 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. [12 weeks]

   Proton-density Fat Fraction by Magnetic Resonance Imaging

2. The safety of TVB-2640 versus placebo in subjects with NASH, including changes in liver enzymes by monitoring adverse events. [12 weeks]

Secondary Outcome Measures

1. The effect of TVB-2640 versus placebo on the change in triglycerides from baseline in subjects with NASH. [12 weeks]

2. The effect of TVB-2640 versus placebo on the change in low-density lipoprotein cholesterol (LDL-C) from baseline in subjects with NASH. [12 weeks]

3. The effect of TVB-2640 versus placebo on the change in high-density lipoprotein cholesterol (HDL-C) from baseline in subjects with NASH. [12 weeks]

4. The effect of TVB-2640 versus placebo on the change in total cholesterol from baseline in subjects with NASH. [12 weeks]

5. The effect of TVB-2640 versus placebo on the change in NASH and cytokeratin-18 (CK-18) from baseline in subjects with NASH. [12 weeks]

6. The effect of TVB-2640 versus placebo on the change in NASH and fibrosis-4 (FIB-4) from baseline in subjects with NASH. [12 weeks]

7. The effect of TVB-2640 versus placebo on the change in NASH and enhanced liver fibrosis score (ELF) from baseline in subjects with NASH. [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.

8. The effect of TVB-2640 versus placebo on the change in levels of eicosanoids from baseline in subjects with NASH. [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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. 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.

1. Type 1 diabetes.

2. 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.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ProSciento	Chula Vista	California	United States	91911
2	Catalina Research Institute	Montclair	California	United States	91763
3	Clinical Trials Research	Sacramento	California	United States	95821
4	University of California San Diego (UCSD)	San Diego	California	United States	92037
5	Panax	Miami Lakes	Florida	United States	33014
6	Lucas Research	Morehead City	North Carolina	United States	28557
7	Texas Diabetes and Endocrinology - Austin	Austin	Texas	United States	78749
8	Texas Digestive Disease Consultants - Cedar Park	Cedar Park	Texas	United States	78613
9	Texas Digestive Disease Consultants - Dallas	Dallas	Texas	United States	75246
10	Texas Digestive Disease Consultant - Ft Worth	Fort Worth	Texas	United States	76104
11	Pinnacle Clinical Research - San Antonio	San Antonio	Texas	United States	78229
12	Texas Digestive Disease Consultants - Webster	Webster	Texas	United States	77598
13	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing	China	100069
14	Beijing YouAn Hospital, Capital Medical University	Beijing	Beijing	China	100069
15	Foshan First People's Hospital	Foshan	Guangdong	China	528000
16	Nanfang Hospital	Guangzhou	Guangdong	China	510080
17	The First Affiliated Hospital, Sun Yat-Sen University	Guangzhou	Guangdong	China	510080
18	The Third Affiliated Hospital, Sun Yat-Sen University	Guangzhou	Guangdong	China	510080
19	The Second Hospital of Nanjing	Nanjing	Jiangsu	China	210000
20	Ruijin Hospital, Shanghai JiaoTong University School of Medicine	Shanghai	Shanghai	China	200336
21	Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine	Shanghai	Shanghai	China	200336
22	Shanghai Tongren Hospital, Shanghai JiaoTong University School of Medicine	Shanghai	Shanghai	China	200336
23	The Affiliated Hospital of Hangzhou Normal University	Hangzhou	Zhejiang	China	310015

Sponsors and Collaborators

• Sagimet Biosciences Inc.

Investigators

• Principal Investigator: Rohit Loomba, MD, UCSD

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sagimet Biosciences Inc.
• ClinicalTrials.gov Identifier: NCT03938246
• Other Study ID Numbers: 3V2640-CLIN-005
• First Posted: May 6, 2019
• Last Update Posted: Oct 29, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Sagimet Biosciences Inc.: NASH; Non-Alcoholic Steatohepatitis; Fatty Liver Disease; Fatty Liver; Liver Diseases; FASN; Fatty Acid Synthase Inhibitor
• Additional relevant MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease

Study Results

No Results Posted as of Oct 29, 2021