A Randomized, Double-Blind, Placebo Controlled, Parallel-Group, Phase II Trial of JKB-121 for the Treatment of Nonalcoholic Steatohepatitis (NASH)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 8
- 主要终点
- Analysis of MRI-PDFF Change From Baseline to Week 24 (Per Protocol Population)
研究概览
简要总结
To evaluate the safety and potential efficacy of two dose levels of JKB-121 (5 mg twice daily and 10 mg twice daily) in reducing liver fat and/or liver biochemistry compared to placebo in patients with biopsy-proven nonalcoholic steatohepatitis
详细描述
JKB-121 is a long-acting small molecule that is efficacious as a weak antagonist at the TLR-4 receptor. It is a non-selective opioid antagonist which has been shown to prevent the lipopolysaccharide (LPS) induced inflammatory liver injury in a methionine/choline deficient diet fed rat model of nonalcoholic fatty liver disease. In vitro, JKB-121 neutralized or reduced the LPS-induced release of inflammatory cytokines, deactivated hepatic stellate cells, inhibited hepatic stellate cell proliferation, and collagen expression. Inhibition of the TLR4 signaling pathway may provide an effective therapy in the prevention of inflammatory hepatic injury and hepatic fibrosis in patients with nonalcoholic steatohepatitis. This study will evaluate the safety and potential efficacy of two dose levels of JKB-121 (5 mg twice daily and 10 mg twice daily) in reducing liver fat and/or liver biochemistry compared to placebo in patients with biopsy-proven nonalcoholic steatohepatitis.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Provision of written informed consent
- •Biopsy-proven NASH within 12 months or at screening
- •ALT > 40 U/L for women and > 60 U/L for men at screening and at least once in the previous 12 months.
- •HBA1C of ≤ 9.0
排除标准
- •Any chronic liver disease other than NASH
- •Cirrhosis, as assessed clinically or histologically
- •Presence of vascular liver disease
- •BMI ≤ 25 kg/m2
- •Excessive alcohol use (> 20 g/day) within the past 2 years
- •AST or ALT > 250 U/L.
- •Type 1 diabetes mellitus
- •Bariatric surgery in the past 5 years.
- •Weight gain of > 5% in past 6 months or > 10% change in past 12 months.
- •Contraindication to MRI
- •Inadequate venous access
- •HIV antibody positive, hepatitis B surface antigen positive (HBsAg), or Hepatitis C virus (HCV) RNA positive.
- •Receiving an elemental diet or parenteral nutrition
- •Chronic pancreatitis or pancreatic insufficiency
- •Any history of complications of cirrhosis
- •Concurrent conditions:
- •Inflammatory bowel disease
- •Significant cardiac disease
- •chronic infection or immune mediated disease
- •Any malignant disease
- •Prior solid organ transplant
- •Any other concurrent condition which, in the opinion of the investigator, could impact adversely on the subject participating or the interpretation of the study data.
- •Concurrent medications which may treat NASH
- •HbA1C > 9.0%
- •Pregnancy or breastfeeding.
研究组 & 干预措施
C
Identical appearing placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Analysis of MRI-PDFF Change From Baseline to Week 24 (Per Protocol Population)
时间窗: Baseline to week 24
Analysis of MRI-PDFF Change From Baseline to Week 12 (Per Protocol Population)
时间窗: Baseline to Week 12
次要结局
- Analysis of ALT Change From Baseline to Week 24 (Per Protocol Population)(Baseline to week 24)
- Analysis of ALT Change From Baseline to Week 12 (Per Protocol Population)(Baseline to week 12)
- Time to Remission (in Weeks)(24 weeks)
- Change in BMI (Body Mass Index)(Baseline, week 24)
- Change in Hemoglobin A1C(Baseline, week 24)
- Percent Change in Cholesterol(Baseline, week 24)
- Percent Change in Low Density Lipoprotein (LDL) Cholesterol(Baseline, week 24)
- Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)(Baseline, week 24)
- Percent Change in Triglycerides(Baseline, week 24)
- Percent Change in High Density Lipoprotein (HDL)(Baseline, week 24)
- Mean Serum Aspartate Aminotransferase (AST)(weeks 4, 8, 12, 16, 20, and 24)
- Mean Serum Alanine Aminotransferase (ALT)(weeks 4, 8, 12, 16, 20, and 24)
- Mean Serum Gamma-glutamyl Transpeptidase (GGT)(weeks 4, 8, 12, 16, 20, and 24)
- Number of Subjects With ALT in Normal Range at Week 24(Week 24)
- Maximum Observed Concentrations (Cmax)(pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours)
- Minimum Observed Concentration (Cmin)(pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours)
- Half-life(pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours)
- Area Under Concentration-time (AUC)(pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours)
研究者
Manal Abdelmalek
Associate Professor
Duke University