A Randomized, Patient and Investigator Blinded, Placebo Controlled, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of LMB763 in Patients With Non-alcoholic Steatohepatitis (NASH)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 122
- 试验地点
- 1
- 主要终点
- Change From Baseline in Alanine Aminotransferase (ALT) Levels
研究概览
简要总结
The purpose of the present study is to assess the effects of LMB763 with respect to safety, tolerability, and on markers of liver inflammation in patients with NASH
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
- Triple (Participant, Care Provider, Investigator)
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
- •Male/female patients, 18 years or older
- •Written informed consent
- •Presence of NASH by histologic evidence (liver biopsy) and elevated alanine aminotransferase (ALT), OR phenotypic diagnosis of NASH based on elevated ALT, BMI and diagnosis of Type 2 diabetes mellitus
排除标准
- •Current use of obeticholic acid (OCA)
- •New initiation GLP-1 agonists such as liraglutide, exenatide , lixisenatide, albiglutide or dulaglutide within 3 months of screening
- •Pregnant or nursing (lactating) women
- •Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 5 days after stopping study medication
- •Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening
- •Clinical evidence of hepatic decompensation or severe liver impairment
- •Previous diagnosis of other forms of chronic liver disease
- •Uncontrolled diabetes mellitus
- •History or current diagnosis of ECG abnormalities
- •Patients with contraindications to MRI imaging
研究组 & 干预措施
LMB763
Oral dose once daily for 12 weeks (84 days)
干预措施: LMB763 (Drug)
Placebo
Oral dose once daily for 12 weeks (84 days)
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Alanine Aminotransferase (ALT) Levels
时间窗: Baseline to Day 84 (Week 12)
ALT level assessment is one of the diagnostic parameters in Liver function test (LFT). Baseline was defined as the mean of ALT levels at baseline and pre-dose visits. Geometric Mean and Geometric Coefficient of Variation for change are based on log-transformed ratio to baseline (i.e., change from baseline in the log domain).
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From date of First Participant First Treatment until Last Patient Last Visit (up to Day 112 (End of Study (EOS))
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation as per Medical or scientific judgment. No statistical analysis was planned for this primary outcome measure.
次要结局
- Change From Baseline in Body Mass Index (BMI)(Baseline to Days 28, 42, 56, 84 and 112 (EOS))
- Time to Reach Maximum Concentration (Tmax) of LMB763(0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Days 1 and 42)
- Change From Baseline in Waist to Hip Ratio(Baseline to Days 28, 42, 56, 84 and 112 (EOS))
- Area Under Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of LMB763(0 to 96 hours post-dose on Days 1 and 42)
- Accumulation Ratio (Racc) of LMB763(Day 42)
- Change From Baseline in Weight(Baseline to Days 28, 42, 56, 84 and 112 (EOS))
- Change From Baseline in Enhanced Liver Fibrosis (ELF) Test Panel(Baseline to Days 42 and 84)
- Change From Baseline in Fibrosis Biomarker Test(Baseline to Days 42 and 84)
- Change From to Baseline in Liver Stiffness(Baseline to Day 84 (Week 12))
- Observed Maximum Plasma Concentration (Cmax) of LMB763(0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Days 1 and 42)
- Change From Baseline in Percentage of Liver Fat as Measured by Magnetic Resonance Imaging (MRI)(Baseline to Day 84 (Week 12))
- Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG)(Baseline to Days 7, 14, 28, 42, 56, 84 and 112 (EOS))
- Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol(Baseline to Days 7, 14, 28, 42, 56, 84 and 112 (EOS))
- Change From Baseline in Visual Analog Scale (VAS) for Itching of Skin(Baseline to Day 84 (Week 12))