Clinical trial NCT03938246: 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
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Sagimet Biosciences Inc.
Sponsor class: INDUSTRY
First posted: 2019-05-06
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be randomly assigned to experimental or placebo arms.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percent Change in Hepatic Fat Fraction by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) From Baseline
timeFrame: 12 weeks
Secondary outcomes:
measure: Percentage of Subjects With at Least a 30% Reduction in Liver Fat at Week 12.
timeFrame: 12 weeks
measure: Percentage of Change From Baseline in Alanine Aminotransferase (ALT)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: ProSciento
state: California
city: Montclair
country: United States
facility: Catalina Research Institute
state: California
city: Sacramento
country: United States
facility: Clinical Trials Research
state: California
city: San Diego
country: United States
facility: University of California San Diego (UCSD)
state: California
city: Miami Lakes
country: United States
facility: Panax
state: Florida
city: Morehead City
country: United States
facility: Lucas Research
state: North Carolina
city: Austin
country: United States
facility: Texas Diabetes and Endocrinology - Austin
state: Texas
city: Cedar Park
country: United States
facility: Texas Digestive Disease Consultants - Cedar Park
state: Texas
city: Dallas
country: United States
facility: Texas Digestive Disease Consultants - Dallas
state: Texas
city: Fort Worth
country: United States
facility: Texas Digestive Disease Consultant - Ft Worth
state: Texas
city: San Antonio
country: United States
facility: Pinnacle Clinical Research - San Antonio
state: Texas
city: Webster
country: United States
facility: Texas Digestive Disease Consultants - Webster
state: Texas
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing YouAn Hospital, Capital Medical University
state: Beijing
city: Foshan
country: China
facility: Foshan First People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: The Third Affiliated Hospital, Sun Yat-Sen University
state: Guangdong
city: Nanjing
country: China
facility: The Second Hospital of Nanjing
state: Jiangsu
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai JiaoTong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Tongren Hospital, Shanghai JiaoTong University School of Medicine
state: Shanghai
city: Hangzhou
country: China
facility: The Affiliated Hospital of Hangzhou Normal University
state: Zhejiang
Study officials:
affiliation: UCSD
name: Rohit Loomba, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.