A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial to Evaluate the Efficacy and Safety of VSA006 Injection in Chinese Adult Patients With Nonalcoholic Steatohepatitis (NASH)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Percentage of Participants Achieving ≥ 1 Stage Improvement in Histological Fibrosis with no Worsening of NASH
研究概览
简要总结
Human genetic studies have shown that loss of function (LOF) mutations in HSD17β13 gene have a protective effect on the progression of alcohol-related and non-alcohol-related liver diseases, such as NASH, without significant adverse phenotypes.
VSA006 is a siRNA drug targeting HSD17β13 mRNA in the liver and reduce the protein level of HSD17β13. Based on phase 1 study results in healthy volunteers and NASH/suspected NASH patients, this phase 2 study is designed to evaluate the efficacy, safety, PK profiles and immunogenicity of VSA006 in Chinese NASH patients.
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
- •body mass index (BMI) of 24-35 kg/m2 ;
- •NASH patients confirmed by liver histopathology: NAS score is ≥ 4 and CRN fibrosis is F2 or F3 ;
- •At screening, ALT is > ULN;
- •At screening, the liver fat content measured by MRI-PDFF is ≥ 8%;
- •Weight change < 5% at least 3 months prior to screening;
- •For patient with T2DM, the hypoglycemic agents and HbA1c is stable
排除标准
- •Pregnant or lactating women;
- •Previous diagnosis of alcoholic liver disease or hepatitis/liver disease due to other causes;
- •Previous or current diagnosis of cirrhosis or decompensated cirrhosis;
- •Previous or current diagnosis of hyperthyroidism, hypothyroidism, or other diseases that can lead to fatty degeneration of liver;
- •Participants diagnosed with type 1 diabetes, or with unstable type 2 diabetes
- •Participants who cannot receive an MRI examination;
研究组 & 干预措施
VSA006 low dose
干预措施: VSA006 (Drug)
VSA006 low dose comparator
干预措施: Placebo (Drug)
VSA006 high dose
干预措施: VSA006 (Drug)
VSA006 high dose comparator
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants Achieving ≥ 1 Stage Improvement in Histological Fibrosis with no Worsening of NASH
时间窗: At week 52
No Worsening of NASH is defined as no increase in inflammation, ballooning, or steatosis scores in the NAS score.
Percentage of Participants Achieving NASH Improvement with no Worsening of Fibrosis
时间窗: At week 52
NASH Improvement indicates a reduction by at least 2 points in the NAS score, with at least one-point reduction in ballooning without increase in steatosis score.
次要结局
- Compared with placebo, the percentage change in serum alanine aminotransferase (ALT)(At week 24, week 52 and week 82)
- Compared with placebo, the change in liver fat fraction from baseline and liver fat percentage change from baseline(At week 24 and week 52)
- Compared with placebo, the percentage of participants with a > 30% decrease in liver fat fraction from baseline(At week 24 and week 52)
- Compared with placebo, the change and percentage change in noninvasive markers of fibrosis from baseline: FIB-4, NAFLD fibrosis score, and AST/PLT ratio index (APRI)(At week 24, week 52 and week 82)
- Percentage of Participants Achieving NASH Resolution with no Worsening of Fibrosis(At week 52)
- Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and their correlation with VSA006(Up to week 82)
- Maximum observed concentration (Cmax) of VSA006(Pre-dose, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose)
- Area under the concentration-time curve from time zero (pre-dose) to the last quantifiable concentration (AUC0-t) of VSA006(Pre-dose, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose)
- Time of maximum concentration of VSA006 (Tmax)(Pre-dose, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose)
- anti-drug antibodies (ADAs) of VSA006(up to week 82)