MASLD/MASH (Metabolic Dysfunction-Associated Steatotic Liver Disease / Metabolic Dysfunction-Associated Steatohepatitis)
Conditions
Keywords
NASH, Non-Alcoholic Steatohepatitis, Fatty Liver Disease, Fatty Liver, Liver Diseases, FASN, Fatty Acid Synthase Inhibitor
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.
Interventions
DRUGTVB-2640 25 mg (US)
Oral dose, tablet, daily dosing
DRUGTVB-2640 50 mg (US)
Oral dose, tablet, daily dosing
DRUGPlacebo (US)
Oral dose, tablet, daily dosing
DRUGTVB-2640 50 mg (China)
Oral dose, tablet, daily dosing
DRUGPlacebo (China)
Oral dose, tablet, daily dosing
DRUGTVB-2640 75 mg (US)
Oral dose, tablet, daily dosing
Sponsors
Sagimet Biosciences Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Intervention model description
Subjects will be randomly assigned to experimental or placebo arms.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Hepatic Fat Fraction by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) From Baseline | 12 weeks | As determined by MRI-PDFF |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With at Least a 30% Reduction in Liver Fat at Week 12. | 12 weeks | As determined by MRI-PDFF |
| Percentage of Change From Baseline in Alanine Aminotransferase (ALT) | 12 weeks | — |
Countries
China, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TVB-2640 25 mg (US) TVB-2640 tablet orally every day for 12 weeks | 33 |
| TVB-2640 50 mg (US) TVB-2640 tablet orally every day for 12 weeks | 35 |
| Placebo (US) Placebo tablet orally every day for 12 weeks | 31 |
| TVB-2640 50 mg (China) TVB-2640 tablet orally every day for 12 weeks | 21 |
| Placebo (China) Placebo tablet orally every day for 12 weeks | 9 |
| TVB-2640 75 mg (US) TVB-2640 tablet orally every day for 12 weeks | 13 |
| Total | 142 |
Baseline characteristics
| Characteristic | TVB-2640 25 mg (US) | TVB-2640 50 mg (US) | Placebo (US) | TVB-2640 50 mg (China) | Placebo (China) | TVB-2640 75 mg (US) | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 6 Participants | 4 Participants | 2 Participants | 1 Participants | 1 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 29 Participants | 27 Participants | 19 Participants | 8 Participants | 12 Participants | 122 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants | 24 Participants | 25 Participants | 0 Participants | 0 Participants | 13 Participants | 84 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 11 Participants | 6 Participants | 21 Participants | 9 Participants | 0 Participants | 58 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 0 participants | 0 participants | 0 participants | 21 participants | 9 participants | 0 participants | 30 participants |
| Region of Enrollment United States | 33 participants | 35 participants | 31 participants | 0 participants | 0 participants | 13 participants | 112 participants |
| Sex: Female, Male Female | 15 Participants | 13 Participants | 17 Participants | 4 Participants | 3 Participants | 5 Participants | 57 Participants |
| Sex: Female, Male Male | 18 Participants | 22 Participants | 14 Participants | 17 Participants | 6 Participants | 8 Participants | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 35 | 0 / 31 | 0 / 21 | 0 / 9 | 0 / 13 |
| other Total, other adverse events | 25 / 33 | 14 / 35 | 12 / 31 | 17 / 21 | 5 / 9 | 9 / 13 |
| serious Total, serious adverse events | 0 / 33 | 0 / 35 | 0 / 31 | 0 / 21 | 0 / 9 | 0 / 13 |
Outcome results
Primary
Percent Change in Hepatic Fat Fraction by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) From Baseline
As determined by MRI-PDFF
Time frame: 12 weeks
Population: Analyses using only subjects in the mITT Population who had data at Baseline and Week 12 for observed relative change values from Baseline to Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TVB-2640 25 mg (US) | Percent Change in Hepatic Fat Fraction by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) From Baseline | -11.31 percent change from baseline | Standard Deviation 29.837 |
| TVB-2640 50 mg (US) | Percent Change in Hepatic Fat Fraction by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) From Baseline | -27.59 percent change from baseline | Standard Deviation 28.354 |
| Placebo (US) | Percent Change in Hepatic Fat Fraction by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) From Baseline | 2.52 percent change from baseline | Standard Deviation 33.03 |
| TVB-2640 50 mg (China) | Percent Change in Hepatic Fat Fraction by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) From Baseline | -28.68 percent change from baseline | Standard Deviation 22.265 |
| Placebo (China) | Percent Change in Hepatic Fat Fraction by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) From Baseline | -15.63 percent change from baseline | Standard Deviation 30.789 |
| TVB-2640 75 mg (US) | Percent Change in Hepatic Fat Fraction by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) From Baseline | -35.77 percent change from baseline | Standard Deviation 23.736 |
Secondary
Percentage of Change From Baseline in Alanine Aminotransferase (ALT)
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TVB-2640 25 mg (US) | Percentage of Change From Baseline in Alanine Aminotransferase (ALT) | -2.98 percentage of change | Standard Deviation 38.443 |
| TVB-2640 50 mg (US) | Percentage of Change From Baseline in Alanine Aminotransferase (ALT) | -20.46 percentage of change | Standard Deviation 25.935 |
| Placebo (US) | Percentage of Change From Baseline in Alanine Aminotransferase (ALT) | 6.82 percentage of change | Standard Deviation 37.258 |
| TVB-2640 50 mg (China) | Percentage of Change From Baseline in Alanine Aminotransferase (ALT) | -28.29 percentage of change | Standard Deviation 34.495 |
| Placebo (China) | Percentage of Change From Baseline in Alanine Aminotransferase (ALT) | 14.06 percentage of change | Standard Deviation 79.621 |
| TVB-2640 75 mg (US) | Percentage of Change From Baseline in Alanine Aminotransferase (ALT) | -3.296 percentage of change | Standard Deviation 42.5397 |
Secondary
Percentage of Subjects With at Least a 30% Reduction in Liver Fat at Week 12.
As determined by MRI-PDFF
Time frame: 12 weeks
Population: Analyses using only subjects in the mITT Population who had data at Baseline and Week 12 for observed relative change values from Baseline to Week 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TVB-2640 25 mg (US) | Percentage of Subjects With at Least a 30% Reduction in Liver Fat at Week 12. | 7 Participants |
| TVB-2640 50 mg (US) | Percentage of Subjects With at Least a 30% Reduction in Liver Fat at Week 12. | 16 Participants |
| Placebo (US) | Percentage of Subjects With at Least a 30% Reduction in Liver Fat at Week 12. | 3 Participants |
| TVB-2640 50 mg (China) | Percentage of Subjects With at Least a 30% Reduction in Liver Fat at Week 12. | 10 Participants |
| Placebo (China) | Percentage of Subjects With at Least a 30% Reduction in Liver Fat at Week 12. | 2 Participants |
| TVB-2640 75 mg (US) | Percentage of Subjects With at Least a 30% Reduction in Liver Fat at Week 12. | 4 Participants |