An Open- Label, Dose Escalation Study to Assess the Safety, Pharmacokinetics and Pharmacodynamic Signals of DUR-928 in Patients With Alcoholic Hepatitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Durect
- 入组人数
- 19
- 试验地点
- 7
- 主要终点
- Model for End Stage Liver Disease (MELD) Score
研究概览
简要总结
This is a research trial testing DUR-928 (an experimental medication). The purpose of this trial is to assess the dose related safety, Pharmacokinetics, and Pharmacodynamics of DUR 928 in patients with moderate and severe alcoholic hepatitis (AH).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to provide written informed consent (either from patient or patient's legally acceptable representative)
- •Male or female patients 21 years of age or older with BMI ≥ 20 to ≤ 40 kg/m2
- •Patients with alcoholic hepatitis defined as:
- •History of heavy alcohol abuse: > 40 g/day in females or > 60 g/day in males for a minimum period of 6 months, AND
- •Consumed alcohol within 12 weeks of entry into the study, AND
- •Serum bilirubin > 3 mg/dL AND AST > ALT, but less than 300 U/L AND
- •MELD score between 11-30, inclusive
- •No evidence of active infection as determined by the investigator.
- •Women of child-bearing potential must utilize appropriate birth control throughout the study duration.
- •Male patients must agree to use a medically acceptable method of contraception/birth control throughout the study duration
排除标准
- •Other or concomitant cause(s) of liver disease as a result of:
- •Autoimmune liver disease
- •Wilson disease
- •Vascular liver disease
- •Drug induced liver disease
- •Co-infection with human immunodeficiency virus (HIV) or Hepatitis B
- •Any active malignancies other than curatively treated skin cancer (basal cell or squamous cell carcinomas)
- •If female, known pregnancy, or has a positive serum pregnancy test, or lactating/breastfeeding
- •Serum creatinine > 2.5 mg/dL
- •Patients who have had organ transplantation (such as liver, kidney, lung, heart, bone marrow, or stem cell etc.), other than cornea transplant
- •Stage 3 or greater encephalopathy by West Haven criteria
研究组 & 干预措施
Part A (Moderate AH) DUR-928 30 mg
Lowest dose of 3 dose escalation arms: 30mg, 90 mg and 150 mg
干预措施: DUR-928 30 mg (Drug)
Part A (Moderate AH) DUR-928 90 mg
Middle dose of 3 dose escalation arms: 30mg, 90 mg and 150 mg
干预措施: DUR-928 90 mg (Drug)
Part A (Moderate AH) DUR-928 150 mg
Highest dose of dose escalation arms: 30mg, 90 mg and 150 mg
干预措施: DUR-928 150 mg (Drug)
Part B (Severe AH) DUR-928 30 mg
Lowest dose of dose escalation arms: 30mg, 90 mg and 150 mg
干预措施: DUR-928 30 mg (Drug)
Part B (Severe AH) DUR-928 90 mg
Middle dose of dose escalation arms: 30mg, 90 mg and 150 mg
干预措施: DUR-928 90 mg (Drug)
Part B (Severe AH) DUR-928 150 mg
Highest dose of dose escalation arms: 30mg, 90 mg and 150 mg
干预措施: DUR-928 150 mg (Drug)
结局指标
主要结局
Model for End Stage Liver Disease (MELD) Score
时间窗: Baseline (Screening or Day 1 Pre-dose), Day 7 and Day 28
The MELD score at enrollment is a good predictor for AH patient prognosis. Laboratory values for international normalized ratio (INR), serum creatinine (sCr) and bilirubin are used to calculate the MELD score. The MELD score ranges from 6.0 to 40.0 (capped) with a higher score predicting a higher risk of death. A sequentially improving MELD score is associated with a better chance of recovery. MELD score will be calculated using the original formula (pre-2016) which does not include serum sodium level. Original MELD Score = (0.957 x Ln(Serum Creatinine in mg/dL) + 0. 378 x Ln(Serum Bilirubin in mg/dL) + 1.120 x Ln (INR) + 0.643) x 10 Note: (1) If patient received two or more dialysis treatments within the prior 7 days, then the value for serum creatinine will be set to 4.0. (2) If any laboratory value is less than 1.0, the value will be set to 1.0 for the MELD score calculation, in order to avoid negative values resulting from taking the natural log of values less than 1.
Model for End Stage Liver Disease (MELD) Score - Percent Change From Baseline
时间窗: Baseline (Screening or Day 1 Pre-dose), Day 7 and Day 28
The MELD Score %change from baseline is a %change between 2 time points, baseline and value at a specific time point (Day 7 or Day 28). MELD score is a good predictor of outcome. A declining MELD score suggests disease improvement. Lab values for international normalized ratio (INR), serum creatinine (sCr) and bilirubin are used to calculate the MELD score. MELD score will be calculated using the original formula (pre-2016) which does not include serum sodium level. Original MELD Score = (0.957 x Ln(Serum Creatinine in mg/dL) + 0. 378 x Ln(Serum Bilirubin in mg/dL) + 1.120 x Ln (INR) + 0.643) x 10 Note: (1) If patient received two or more dialysis treatments within the prior 7 days, then the value for serum creatinine will be set to 4.0. (2) If any laboratory value is less than 1.0, the value will be set to 1.0 for the MELD score calculation, in order to avoid negative values resulting from taking the natural log of values less than 1.
Lille Model for Alcoholic Hepatitis Score
时间窗: Day 7
The Lille score predicts response of AH subjects to treatment with glucocorticoids, such as prednisolone. This score is based on age, serum albumin, creatinine, PT, and the difference in bilirubin between pre-treatment and Day 7 post-treatment. The Lille score ranges from 0.01 to 1.00. A score \>0.45 predicts a higher risk of death and the recommendation to stop steroid administration. Lille Score = Exp(-R)/(1 + Exp(-R)) Where: R = \[3.19 - (0.101 x Age in years)\] + (1.47 x Albumin in g/dL) + \[0.28215 x (Bilirubin initial - Bilirubin day 7 in mg/dL)\] - (0.206 x Creatinine in mg/dL) - (0.11115 x Bilirubin initial in mg/dL) - (0.0096 x PT in seconds) NOTE: When calculating Lille, use "baseline" values for ALL parameters EXCEPT bilirubin at Day 7. Baseline would be the Day 1 Pre-dose sample result, if available. If not available, then use the Screening sample result.
次要结局
- Serum Cytokeratin 18 (M30)(Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28)
- Serum Cytokeratin 18 (M65)(Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28)
- International Normalized Ratio (INR) - Percent Change From Baseline(Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28)
- Bilirubin - Percent Change From Baseline(Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28)