A Phase 2b, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of HTD1801 in Adult Subjects With Nonalcoholic Steatohepatitis (NASH) and Liver Fibrosis Who Have Type 2 Diabetes (T2DM) or Pre-Diabetes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 218
- 试验地点
- 88
- 主要终点
- Primary Endpoint
研究概览
简要总结
A phase 2b, multicenter, randomized, double-blind, placebo-controlled study of HTD1801 in adult subjects with non-alcoholic steatohepatitis and liver fibrosis who have type 2 diabetes mellitus or pre-diabetes.
详细描述
This phase 2b, double-blind, randomized, placebo-controlled, multicenter study will evaluate the effect of HTD1801, 1250 mg twice daily (BID) compared to placebo BID on histologic improvements in adult subjects with non-alcoholic steatohepatitis and liver fibrosis who have type 2 diabetes mellitus or pre-diabetes.
The study will enroll approximately 210 subjects with biopsy-confirmed non-alcoholic steatohepatitis and evidence of stage 2 or stage 3 liver fibrosis. Subjects will receive investigational product for up to 60 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of non-alcoholic steatohepatitis (NASH) upon central read of a liver biopsy obtained no more than 6 months before Day
- •Histologic evidence of fibrosis stage 2 or stage 3 as defined by the non-alcoholic steatohepatitis (NASH) clinical research network (CRN) scoring of fibrosis.
- •Clinically documented diagnosis of type 2 diabetes mellitus for at least 6 months prior to screening or prediabetes at screening.
- •BMI >25 kilograms/meters squared (>23 kilograms/meters squared if Asian).
排除标准
- •Fibrosis stage
- •History of alcohol or substance abuse or dependence.
- •Liver disease unrelated to non-alcoholic steatohepatitis.
- •History of significant cardiovascular disease.
- •History of type 1 diabetes.
- •Inability or unwillingness to undergo 2 planned liver biopsies OR 1 planned biopsy if historical liver biopsy was used to confirm eligibility at entry.
研究组 & 干预措施
placebo
placebo, BID
干预措施: Placebo (Drug)
HTD1801
HTD1801,1250 mg, BID
干预措施: HTD1801 (Drug)
结局指标
主要结局
Primary Endpoint
时间窗: Up to 60 Weeks
A decrease of ≥2-points in non-alcoholic fatty liver disease activity score (NAS) with ≥1-point decrease of either lobular inflammation or ballooning and no worsening of fibrosis; OR Resolution of non-alcoholic steatohepatitis (NASH) (defined as the overall histopathologic interpretation of 1) "no fatty liver disease" or 2) "fatty liver disease (simple or isolated steatosis) without steatohepatitis AND a non-alcoholic fatty liver disease activity score (NAS) of 0 for ballooning and 0-1 for inflammation and no worsening of fibrosis. Nonalcoholic fatty liver disease activity score (NAS) is a histological scoring system that assesses a liver biopsy and gives scores for steatosis (0-3), lobular inflammation (0-3), and hepatocyte ballooning (0-2). The higher the score the more severe the disease. The total range for non-alcoholic fatty liver disease activity score (NAS) is between 0 to 8. The lower the score the better the outcome.
次要结局
- Endpoint 16(Up to 60 Weeks)
- Endpoint 17(Up to 60 Weeks)
- Endpoint 1(Up to 60 Weeks)
- Endpoint 2(Up to 60 Weeks)
- Endpoint 4(Up to 60 Weeks)
- Endpoint 5(Up to 60 Weeks)
- Endpoint 6(Up to 60 Weeks)
- Endpoint 15(Up to 60 Weeks)
- Endpoint 14(Up to 60 Weeks)
- Endpoint 3(Up to 60 Weeks)
- Endpoint 7(Up to 60 Weeks)
- Endpoint 8(Up to 60 Weeks)
- Endpoint 9(Up to 60 Weeks)
- Endpoint 10(Up to 60 Weeks.)
- Endpoint 11(Up to 60 Weeks)
- Endpoint 12(Up to 60 Weeks)
- Endpoint 13(Up to 60 Weeks)
- Endpoint 18(Up to 60 Weeks)
- Endpoint 19(Up to 60 Weeks)
- Endpoint 20(Up to 60 Weeks)
- Endpoint 21(Up to 60 Weeks)
- Endpoint 22(Up to 60 Weeks)
- Endpoint 23(Up to 60 Weeks)
- Endpoint 24(Up to 60 Weeks)
- Endpoint 25(Up to 60 Weeks)
- Endpoint 26(Up to 60 Weeks)
- Endpoint 27(Up to 60 Weeks)
- Endpoint 28(Up to 60 Weeks)