A Phase II, Multicentre, Randomised, Double-Blind, Placebo-Controlled, Dose Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of Intravenous Infusions of AZD9773 (CytoFab™) in Japanese Patients With Severe Sepsis and/or Septic Shock
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Safety and Tolerability of AZD9773
研究概览
简要总结
The two co-primary objectives of this study are to assess in Japanese patients with severe sepsis and/or septic shock: 1) the safety and tolerability of two different doses of intravenous AZD9773 and 2) the PK of AZD9773.
The secondary objective is to make a preliminary assessment of the pharmacodynamics of two different doses of intravenous AZD9773 in Japanese patients with severe sepsis and/or septic shock.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Japanese adults with a first episode of sepsis during this hospitalisation and objective evidence of infection that requires parenteral antibiotics.
- •At least 2 of 4 SIRS criteria in the 24 hours before organ dysfunction (must include either fever OR elevated white blood cells [WBC])
- •Cardiovascular or respiratory dysfunction.
排除标准
- •Immunocompromising comorbidities or concomitant medications:
- •Advanced human immunodeficiency virus (HIV) infection (CD4 ≤50/mm3).
- •Haemopoietic or lymphoreticular malignancies not in remission.
- •Receiving radiation therapy or chemotherapy.
- •Any organ or bone marrow transplant within the past 24 weeks.
- •Absolute neutrophil count <500 per μL.
- •High dose steroids or other immunocompromising drugs.
- •Concomitant diseases:
- •Deep-seated fungal infection or active tuberculosis.
- •Severe chronic liver disease associated with portal hypertension, cirrhosis, chronic ascites or Child-Pugh class C.
- •History of chronic hypercarbia, respiratory failure in past 6 months or use of home oxygen in the setting of severe chronic respiratory disease.
- •Neuromuscular disorders that impact breathing/spontaneous ventilation.
- •Quadriplegia.
- •Cardiac arrest in the past 30 days.
- •New York Heart Association functional Class III or IV due to heart failure or any disorder.
- •Burns over > 30% of body surface area in the past 5 days.
- •Medication and allergy disqualifications.
- •Treatment with anti-TNF agents within the last 8 weeks.
- •Previously received ovine derived products (CroFab™, DigiFab™).
- •Sheep product allergy or allergy to papain, chymopapain.
研究组 & 干预措施
1
AZD9773 250 units/kg (1 infusion) + 50 units/kg (9 infusions) (Dose Cohort 1):
AZD9773 500 units/kg (1 infusion) + 100 units/kg (9 infusions) (Dose Cohort 2)
干预措施: AZD9773 (Drug)
2
干预措施: Placebo (Drug)
结局指标
主要结局
Safety and Tolerability of AZD9773
时间窗: 28 day study period
Number of patients with treatment-emergent adverse events and number of patients who died over 28 days
Pharmacokinetics of AZD9773
时间窗: From first dose to last dose (Day 5/6 or at premature treatment discontinuation)
Maximum concentration at steady state (Cmax ss) for serum total and specific fabs
次要结局
- Pharmacodynamic Effects of AZD9773 on TNF-alpha(Levels taken at baseline, over the dosing period (up to Day 5/6))