A Phase 2, Multi-Center, Single-Blind, Randomized, Placebo-Controlled Study of TVB-2640 in Subjects With Non-Alcoholic Steatohepatitis (FASCINATE-1)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 142
- 试验地点
- 23
- 主要终点
- Percent Change in Hepatic Fat Fraction by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) From Baseline
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged ≥ 18 years with a body mass index (BMI) ≤40 kg/m
- •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
- •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.
排除标准
- •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.
研究组 & 干预措施
TVB-2640 25 mg (US)
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).
干预措施: TVB-2640 25 mg (US) (Drug)
TVB-2640 50 mg (US)
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).
干预措施: TVB-2640 50 mg (US) (Drug)
Placebo (US)
Subjects randomly assigned to placebo will receive placebo tablets orally once a day under the same conditions and frequency as described for TVB-2640.
干预措施: Placebo (US) (Drug)
TVB-2640 50 mg (China)
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).
干预措施: TVB-2640 50 mg (China) (Drug)
Placebo (China)
Subjects randomly assigned to placebo will receive placebo tablets orally once a day under the same conditions and frequency as described for TVB-2640.
干预措施: Placebo (China) (Drug)
TVB-2640 75 mg (US)
After completion of Cohorts 1 and 2, and if no stopping criteria are met upon review by the Independent SRC, an additional TVB-2640 75 mg open-label Cohort 3 will open in the US
干预措施: TVB-2640 75 mg (US) (Drug)
结局指标
主要结局
Percent Change in Hepatic Fat Fraction by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) From Baseline
时间窗: 12 weeks
As determined by MRI-PDFF
次要结局
- Percentage of Subjects With at Least a 30% Reduction in Liver Fat at Week 12.(12 weeks)
- Percentage of Change From Baseline in Alanine Aminotransferase (ALT)(12 weeks)