Trial Outcomes & Findings for Study of TVB-2640 in Subjects With Nonalcoholic Steatohepatitis (NASH) (NCT NCT04906421)
NCT ID: NCT04906421
Last Updated: 2025-05-09
Results Overview
Histological improvement is defined as ≥2 points improvement in NAS with ≥1 point improvement in ballooning or inflammation
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
168 participants
Primary outcome timeframe
52 Weeks
Results posted on
2025-05-09
Participant Flow
Participant milestones
| Measure |
TVB-2640 50 mg
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
Placebo
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
|---|---|---|
|
Overall Study
STARTED
|
112
|
56
|
|
Overall Study
mITT
|
81
|
45
|
|
Overall Study
COMPLETED
|
80
|
47
|
|
Overall Study
NOT COMPLETED
|
32
|
9
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of TVB-2640 in Subjects With Nonalcoholic Steatohepatitis (NASH)
Baseline characteristics by cohort
| Measure |
TVB-2640 50 mg
n=112 Participants
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
Placebo
n=56 Participants
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
Total
n=168 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
56.3 years
STANDARD_DEVIATION 10.5 • n=99 Participants
|
58.4 years
STANDARD_DEVIATION 11.9 • n=107 Participants
|
57.0 years
STANDARD_DEVIATION 11.0 • n=206 Participants
|
|
Sex: Female, Male
Female
|
66 Participants
n=99 Participants
|
34 Participants
n=107 Participants
|
100 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
46 Participants
n=99 Participants
|
22 Participants
n=107 Participants
|
68 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
34 Participants
n=99 Participants
|
21 Participants
n=107 Participants
|
55 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
78 Participants
n=99 Participants
|
35 Participants
n=107 Participants
|
113 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
100 Participants
n=99 Participants
|
50 Participants
n=107 Participants
|
150 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 52 WeeksPopulation: ITT and mITT Population
Histological improvement is defined as ≥2 points improvement in NAS with ≥1 point improvement in ballooning or inflammation
Outcome measures
| Measure |
ITT: TVB-2640 50 mg
n=112 Participants
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
ITT: Placebo
n=56 Participants
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
mITT: TVB-2640 50 mg
n=81 Participants
Comprises all subjects in the ITT population who have completed at least 42 weeks of treatment and have an evaluable post treatment histological assessment.
TVB-2640: Oral dose, tablet
|
mITT: Placebo
n=45 Participants
Comprises all subjects in the ITT population who have completed at least 42 weeks of treatment and have an evaluable post treatment histological assessment.
Placebo: Oral dose, tablet
|
Subgroup: Fibrosis Stage F3; TVB-2640
Subgroup of Fibrosis Stage F3 at Baseline
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
Subgroup: Fibrosis Stage F3; Placebo
Subgroup: Fibrosis Stage F3 at Baseline
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
Subgroup: T2DM; TVB-2640
Subgroup of Type 2 Diabetes Mellitus at Baseline
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
Subgroup: T2DM; Placebo
Subgroup: Type 2 Diabetes Mellitus at Baseline
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
|---|---|---|---|---|---|---|---|---|
|
Histological Improvement in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) Without Worsening of Fibrosis (by NASH Clinical Research Network [CRN] Fibrosis Score).
|
42 Participants
|
9 Participants
|
42 Participants
|
9 Participants
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 52 WeeksPopulation: ITT and mITT Population
NASH resolution defined as absence of fatty liver disease or isolated or simple steatosis without steatohepatitis and a score of either 0 or 1 for inflammation, 0 for ballooning and any value for steatosis and no worsening of liver fibrosis (by NASH CRN fibrosis score). Histological improvement defined as ≥2 point improvement in NAS (with ≥1 point improvement in ballooning or inflammation).
Outcome measures
| Measure |
ITT: TVB-2640 50 mg
n=112 Participants
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
ITT: Placebo
n=56 Participants
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
mITT: TVB-2640 50 mg
n=81 Participants
Comprises all subjects in the ITT population who have completed at least 42 weeks of treatment and have an evaluable post treatment histological assessment.
TVB-2640: Oral dose, tablet
|
mITT: Placebo
n=45 Participants
Comprises all subjects in the ITT population who have completed at least 42 weeks of treatment and have an evaluable post treatment histological assessment.
Placebo: Oral dose, tablet
|
Subgroup: Fibrosis Stage F3; TVB-2640
Subgroup of Fibrosis Stage F3 at Baseline
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
Subgroup: Fibrosis Stage F3; Placebo
Subgroup: Fibrosis Stage F3 at Baseline
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
Subgroup: T2DM; TVB-2640
Subgroup of Type 2 Diabetes Mellitus at Baseline
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
Subgroup: T2DM; Placebo
Subgroup: Type 2 Diabetes Mellitus at Baseline
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
|---|---|---|---|---|---|---|---|---|
|
Subjects With Resolution of Steatohepatitis and No Worsening of Liver Fibrosis by NASH CRN Fibrosis Score and Histological Improvement in NAS.
|
29 Participants
|
6 Participants
|
29 Participants
|
6 Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 52 WeeksPopulation: mITT Population and Subgroups
Proportion of subjects experiencing fibrosis improvement of ≥1 stage by NASH CRN score Without worsening of steatohepatitis (defined as no increase in NAS for ballooning, inflammation, or steatosis) at 52 weeks.
Outcome measures
| Measure |
ITT: TVB-2640 50 mg
n=81 Participants
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
ITT: Placebo
n=45 Participants
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
mITT: TVB-2640 50 mg
n=34 Participants
Comprises all subjects in the ITT population who have completed at least 42 weeks of treatment and have an evaluable post treatment histological assessment.
TVB-2640: Oral dose, tablet
|
mITT: Placebo
n=22 Participants
Comprises all subjects in the ITT population who have completed at least 42 weeks of treatment and have an evaluable post treatment histological assessment.
Placebo: Oral dose, tablet
|
Subgroup: Fibrosis Stage F3; TVB-2640
n=47 Participants
Subgroup of Fibrosis Stage F3 at Baseline
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
Subgroup: Fibrosis Stage F3; Placebo
n=23 Participants
Subgroup: Fibrosis Stage F3 at Baseline
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
Subgroup: T2DM; TVB-2640
n=55 Participants
Subgroup of Type 2 Diabetes Mellitus at Baseline
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
Subgroup: T2DM; Placebo
n=27 Participants
Subgroup: Type 2 Diabetes Mellitus at Baseline
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
|---|---|---|---|---|---|---|---|---|
|
Proportion of Subjects Experiencing Fibrosis Improvement of ≥1 Stage by NASH CRN Score Without Worsening of Steatohepatitis
|
33 Participants
|
8 Participants
|
10 Participants
|
5 Participants
|
23 Participants
|
3 Participants
|
22 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: 52 WeeksPopulation: mITT Population
Resolution of steatohepatitis is defined as absence of fatty liver disease or isolated or simple steatosis without steatohepatitis and a NAS of 0 or 1 for inflammation, 0 for ballooning, and any value for steatosis.
Outcome measures
| Measure |
ITT: TVB-2640 50 mg
n=81 Participants
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
ITT: Placebo
n=45 Participants
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
mITT: TVB-2640 50 mg
Comprises all subjects in the ITT population who have completed at least 42 weeks of treatment and have an evaluable post treatment histological assessment.
TVB-2640: Oral dose, tablet
|
mITT: Placebo
Comprises all subjects in the ITT population who have completed at least 42 weeks of treatment and have an evaluable post treatment histological assessment.
Placebo: Oral dose, tablet
|
Subgroup: Fibrosis Stage F3; TVB-2640
Subgroup of Fibrosis Stage F3 at Baseline
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
Subgroup: Fibrosis Stage F3; Placebo
Subgroup: Fibrosis Stage F3 at Baseline
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
Subgroup: T2DM; TVB-2640
Subgroup of Type 2 Diabetes Mellitus at Baseline
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
Subgroup: T2DM; Placebo
Subgroup: Type 2 Diabetes Mellitus at Baseline
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
|---|---|---|---|---|---|---|---|---|
|
Proportion of Subjects Experiencing Resolution of Steatohepatitis and no Worsening of Liver Fibrosis (by NASH CRN Fibrosis Score)
|
31 Participants
|
7 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 52 WeeksPopulation: mITT Population
No increase in NAS for ballooning, inflammation or steatosis.
Outcome measures
| Measure |
ITT: TVB-2640 50 mg
n=81 Participants
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
ITT: Placebo
n=45 Participants
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
mITT: TVB-2640 50 mg
Comprises all subjects in the ITT population who have completed at least 42 weeks of treatment and have an evaluable post treatment histological assessment.
TVB-2640: Oral dose, tablet
|
mITT: Placebo
Comprises all subjects in the ITT population who have completed at least 42 weeks of treatment and have an evaluable post treatment histological assessment.
Placebo: Oral dose, tablet
|
Subgroup: Fibrosis Stage F3; TVB-2640
Subgroup of Fibrosis Stage F3 at Baseline
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
Subgroup: Fibrosis Stage F3; Placebo
Subgroup: Fibrosis Stage F3 at Baseline
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
Subgroup: T2DM; TVB-2640
Subgroup of Type 2 Diabetes Mellitus at Baseline
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
Subgroup: T2DM; Placebo
Subgroup: Type 2 Diabetes Mellitus at Baseline
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
|---|---|---|---|---|---|---|---|---|
|
Proportion of Subjects With Improvement in Liver Fibrosis >=1 Stage by NASH CRN Fibrosis Score Without Worsening of Steatohepatitis at 52 Weeks OR Resolution of Steatohepatitis and No Worsening of Liver Fibrosis by NASH CRN Fibrosis Score
|
45 Participants
|
12 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 52 WeeksPopulation: mITT Population
MRI PDFF ≥30% responder is defined as a subject with ≥8% liver fat content at Baseline who achieves a relative reduction from Baseline in MRI-PDFF ≥30%.
Outcome measures
| Measure |
ITT: TVB-2640 50 mg
n=81 Participants
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
ITT: Placebo
n=45 Participants
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
mITT: TVB-2640 50 mg
Comprises all subjects in the ITT population who have completed at least 42 weeks of treatment and have an evaluable post treatment histological assessment.
TVB-2640: Oral dose, tablet
|
mITT: Placebo
Comprises all subjects in the ITT population who have completed at least 42 weeks of treatment and have an evaluable post treatment histological assessment.
Placebo: Oral dose, tablet
|
Subgroup: Fibrosis Stage F3; TVB-2640
Subgroup of Fibrosis Stage F3 at Baseline
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
Subgroup: Fibrosis Stage F3; Placebo
Subgroup: Fibrosis Stage F3 at Baseline
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
Subgroup: T2DM; TVB-2640
Subgroup of Type 2 Diabetes Mellitus at Baseline
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
Subgroup: T2DM; Placebo
Subgroup: Type 2 Diabetes Mellitus at Baseline
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
|---|---|---|---|---|---|---|---|---|
|
Proportion of MRI-PDFF ≥30% Responders.
|
69 Participants
|
38 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
TVB-2640 50 mg
Serious events: 13 serious events
Other events: 79 other events
Deaths: 0 deaths
Placebo
Serious events: 3 serious events
Other events: 36 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
TVB-2640 50 mg
n=112 participants at risk
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
Placebo
n=56 participants at risk
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
|---|---|---|
|
Infections and infestations
Cellulitis
|
0.89%
1/112 • 12 Months
|
0.00%
0/56 • 12 Months
|
|
Infections and infestations
Empyema
|
0.89%
1/112 • 12 Months
|
0.00%
0/56 • 12 Months
|
|
Infections and infestations
Norovirus infection
|
0.89%
1/112 • 12 Months
|
0.00%
0/56 • 12 Months
|
|
Infections and infestations
Ophthalmic herpes zoster
|
0.89%
1/112 • 12 Months
|
0.00%
0/56 • 12 Months
|
|
Infections and infestations
Pneumonia parainfluenzae viral
|
0.89%
1/112 • 12 Months
|
0.00%
0/56 • 12 Months
|
|
Infections and infestations
Urosepsis
|
0.89%
1/112 • 12 Months
|
0.00%
0/56 • 12 Months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/112 • 12 Months
|
1.8%
1/56 • 12 Months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ductal adenocarcinoma of pancreas
|
0.89%
1/112 • 12 Months
|
0.00%
0/56 • 12 Months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma
|
0.89%
1/112 • 12 Months
|
0.00%
0/56 • 12 Months
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.89%
1/112 • 12 Months
|
0.00%
0/56 • 12 Months
|
|
Metabolism and nutrition disorders
Gout
|
0.89%
1/112 • 12 Months
|
0.00%
0/56 • 12 Months
|
|
Nervous system disorders
Bell's palsy
|
0.89%
1/112 • 12 Months
|
0.00%
0/56 • 12 Months
|
|
Nervous system disorders
Presyncope
|
0.89%
1/112 • 12 Months
|
0.00%
0/56 • 12 Months
|
|
Gastrointestinal disorders
Intra-abdominal fluid collection
|
0.89%
1/112 • 12 Months
|
0.00%
0/56 • 12 Months
|
|
Hepatobiliary disorders
Subcapsular hepatic haematoma
|
0.00%
0/112 • 12 Months
|
1.8%
1/56 • 12 Months
|
|
Investigations
Bronchoscopy
|
0.00%
0/112 • 12 Months
|
1.8%
1/56 • 12 Months
|
|
Psychiatric disorders
Depression
|
0.89%
1/112 • 12 Months
|
0.00%
0/56 • 12 Months
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.89%
1/112 • 12 Months
|
0.00%
0/56 • 12 Months
|
|
Reproductive system and breast disorders
Cervical dysplasia
|
0.89%
1/112 • 12 Months
|
0.00%
0/56 • 12 Months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/112 • 12 Months
|
1.8%
1/56 • 12 Months
|
Other adverse events
| Measure |
TVB-2640 50 mg
n=112 participants at risk
Subjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640: Oral dose, tablet
|
Placebo
n=56 participants at risk
Subjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
Placebo: Oral dose, tablet
|
|---|---|---|
|
Infections and infestations
COVID-19
|
17.0%
19/112 • 12 Months
|
10.7%
6/56 • 12 Months
|
|
Infections and infestations
Urinary tract infection
|
8.0%
9/112 • 12 Months
|
5.4%
3/56 • 12 Months
|
|
Infections and infestations
Sinusitis
|
5.4%
6/112 • 12 Months
|
3.6%
2/56 • 12 Months
|
|
Eye disorders
Dry Eye
|
8.9%
10/112 • 12 Months
|
14.3%
8/56 • 12 Months
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
18.8%
21/112 • 12 Months
|
3.6%
2/56 • 12 Months
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
6.2%
7/112 • 12 Months
|
0.00%
0/56 • 12 Months
|
|
Gastrointestinal disorders
Diarrhoea
|
6.2%
7/112 • 12 Months
|
5.4%
3/56 • 12 Months
|
|
Gastrointestinal disorders
Constipation
|
4.5%
5/112 • 12 Months
|
5.4%
3/56 • 12 Months
|
|
Gastrointestinal disorders
Nausea
|
4.5%
5/112 • 12 Months
|
5.4%
3/56 • 12 Months
|
|
Nervous system disorders
Headache
|
4.5%
5/112 • 12 Months
|
5.4%
3/56 • 12 Months
|
|
Psychiatric disorders
Depression
|
2.7%
3/112 • 12 Months
|
5.4%
3/56 • 12 Months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place