NASH EXploratory Single and COmbination Treatment (NEXSCOT): An Open Label, Multicenter, Platform Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Various Single and Combination Treatments in Patients With Non-alcoholic Fatty Liver Disease (NAFLD) Who Manifest a Non-alcoholic Steatohepatitis (NASH)-Like Biomarker Phenotype
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
This clinical study was designed to evaluate the safety, tolerability, pharmacokinetics and efficacy of various single and combination treatments in adult patients with non-alcoholic fatty liver disease (NAFLD) who manifest a non-alcoholic steatohepatitis (NASH)-like biomarker phenotype.
详细描述
This was a Phase II, non-confirmatory, multicenter, open label, platform study in NAFLD participants with a NASH-like biomarker phenotype to examine the effects of single and combination therapies over 12 weeks of treatment. The study consisted of four distinct study periods:
- Screening Period (Day -60 to -28): Lasted up to a maximum of 33 days where participants were assessed for inclusion and exclusion criteria prior the baseline assessments.
- Baseline Period (Day -27 to -1): Lasted up to a maximum of 27 days and comprised baseline assessments and randomization.
- Treatment Period (Day 1 to 85): Participants were randomized in a 1:1 ratio to LYS006 20 mg (twice a day) arm or to LYS006 20 mg (twice a day) and tropifexor 200ug (once a day). Participants were treated daily during 12 weeks.
- Follow-up Period (Day 85 to 113): After completion of the treatment period, participants were observed until the End Of Study (EOS) visit at Day 113.
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
- None
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
- •Phenotypic diagnosis of NASH based on the presence of all of the following:
- •ALT ≥ 43 IU/L (males) or ≥ 28 IU/L (females)
- •BMI ≥ 27 kg/m2 (race other than Asian) or ≥ 23 kg/m2 (Asian race)
- •History of type 2 diabetes mellitus with HbA1c ≤ 9%
- •ELF test score ≥ 8.5 and ≤ 10.5
- •Liver fat ≥ 8%
- •Patients must weigh between 40 kg (88 lbs.) and 150 kg (330 lbs.)
排除标准
- •Use of other investigational drugs within 5 half-lives of randomization or within 3 months, whichever is longer
- •Use of obeticholic acid (OCA) or pharmacologically-active weight loss drugs within 1 month of randomization
- •Use of strong CYP3A4/5 inhibitors or strong CYP3A4 inducers within 5 half-lives or 7 days of randomization, whichever is longer
- •History or presence of other concomitant liver diseases
- •History or current diagnosis of ECG abnormalities
- •Patients with contraindications to MRI imaging
- •Current or history of significant alcohol consumption
- •Clinical evidence of hepatic decompensation or severe liver impairment
- •Women of child bearing potential (unless on highly effective methods of contraception)
- •Presence of liver cirrhosis
- •Use of OAT3 inhibitors within 5 half-lives or 7 days of randomization, whichever is longer
研究组 & 干预措施
LYS006
LYS006 20 mg was administered orally twice per day (b.i.d) for 12 weeks
干预措施: LYS006 (Drug)
LYS006 + LJN452
LYS006 20 mg was administered orally twice per day (b.i.d) in addition to LJN452 200ug administered orally once daily for 12 weeks
干预措施: Tropifexor (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From the start of treatment to 28 days after end of treatment, assessed up to maximum duration of 113 Days
Number of participants with AEs and SAEs including significant changes from baseline in vital signs, electrocardiograms and laboratory parameters qualifying and reported as AEs. The number of participants in each category is reported in the table.
次要结局
- Change From Baseline in Cholesterol: Fasting Lipid Profile Endpoint(Baseline and Days 15, 29, 43, 57, 85 and EOS (Day 113))
- Change From Baseline in Total Body Weight(Baseline and Days 15, 29, 43, 57, 85 and EOS (Day 113))
- Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score(Baseline and Days 57, 85 and EOS (Day 113))
- Change From Baseline in Percent Liver Fat at Day 85(Baseline and Day 85)
- Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at Day 85(Baseline and Day 85)
- Change From Baseline in Fasting Glucose(Baseline and Days 15, 29, 43, 57, 85 and EOS (Day 113))
- Change From Baseline in Fasting Insulin at Day 85(Baseline and Day 85)
- Change From Baseline in Hemoglobin A1c (HbA1c)(Baseline and Days 15, 29, 43, 57, 85 and EOS (Day 113))
- Change From Baseline in Alanine Aminotransferase (ALT)(Baseline and days 15, 29, 43, 57, 85 and EOS (Day 113))
- Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)(Baseline and Days 57, 85 and EOS (Day 113))
- LYS006 Plasma Concentration(pre-dose at Days 1, 29, 57 and 85 and post-dose (1, 2, 3 and 4 hours) at Days 29 and 57)
- Maximum Observed Plasma Concentration (Cmax) of LYS006(pre-dose and post-dose (1, 2, 3 and 4 hours) at Days 29 and 57)