A Proof-of-Concept and Dose-Ranging Study Investigating the Efficacy and Safety of HTD1801 in Adults With NASH and T2DM
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 101
- 试验地点
- 32
- 主要终点
- Absolute Change in Liver Fat Content (LFC) as Measured by MRI-PDFF
研究概览
简要总结
Randomized, double-blind, placebo-controlled, parallel-group study comparing multiple doses of HTD1801 to placebo.
详细描述
This 18-week randomized, double-blind, parallel-group, proof of concept (POC), dose-ranging study compared multiple doses of HTD1801 to placebo in a 1:1:1 ratio. Since accumulation of hepatic fat is considered the "first hit" in the pathogenesis of NASH (Adams and Angulo 2006), change in liver fat content (LFC) by magnetic resonance imaging estimated proton density fat fraction (MRI-PDFF) is an appropriate primary endpoint and is consistent with that used in other recent Phase 2 POC studies in NASH (Harrison et al., 2018, Madrigal Pharmaceuticals 2018).
The Harrison et al., 2018, Madrigal Pharmaceuticals 2018 study showed clinically meaningful absolute and relative reductions in LFC assessed by MRI-PDFF over 12-week treatment periods thus, it was considered that an 18 week HTD1801 treatment period would therefore be adequate to assess the study's primary endpoint and to maximize collection of exposure and safety related data.
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
- 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 NASH as assessed by MRI
- •Clinically documented diagnosis of T2DM
- •Body mass index (BMI) >25 kg/m2
排除标准
- •Liver disease unrelated to NASH
- •Poorly controlled T2DM or Type 1 Diabetes Mellitus
- •History of alcohol or substance abuse or dependence
- •Inability to undergo MRI for any reason
- •History of significant cardiovascular disease
研究组 & 干预措施
500mg HTD1801, bid
干预措施: HTD1801 (Drug)
1000mg HTD1801, bid
干预措施: HTD1801 (Drug)
placebo, bid
干预措施: Placebo (Drug)
结局指标
主要结局
Absolute Change in Liver Fat Content (LFC) as Measured by MRI-PDFF
时间窗: Baseline through study Week 18
The primary endpoint was the absolute change in liver fat content (LFC) as measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) from Baseline to Week 18.
次要结局
- Number of Subjects Who Achieved ≥5% Absolute Reduction in Liver Fat Content (LFC) as Measured by MRI-PDFF(Baseline through study Week 18)
- Change in LDL-c(Baseline visit through study week 18)
- Change in AST(Baseline through study week 18)
- Changes in Hemoglobin A1c(Baseline through study week 18)
- Number of Subjects Who Normalized LFC to <5% as Measured by MRI-PDFF(Baseline through study Week 18)
- Change in Serum Triglycerides(Baseline through study week 18)
- Change in ALT(Baseline through study week 18)
- Change in TIMP-1(Baseline through study week 18)
- Change in HA(Baseline through study week 18)
- Number of Participants Reporting an Adverse Events From Baseline Through Week 18(Adverse events were collected from the time the subject signed the informed consent form through the date of the last visit for a specific subject, that is, approximately 24 weeks in total for a completed subject.)
- Change in Fasting Glucose(Baseline through study Week 18)
- Proportion of Subjects Who Achieved ≥ 30% Relative Reduction in LFC as Measured by MRI-PDFF(Baseline through study week 18)
- Change in HDL-c(Baseline through study week 18)
- Relative Change in LFC as Measured by MRI-PDFF(Baseline through study week 18)
- Change in HOMA-IR(Baseline through study week 18)
- Change in ELF Score(Baseline through study week 18)
- Change in PIIINP(Baseline through study week 18)
- Change in Total Bile Acids(Baseline through study week 18)
- Change in FGF19(Baseline through study week 18)
- Proportion of Subjects With Elevated ALT at Baseline Who Normalized ALT at Week 18(Baseline through study week 18)
- Change in Pro-Peptide of Type III Collagen (Pro-C3)(Baseline through study week 18)