A Phase 1b/2a, Randomized, Double-Blinded, Placebo-Controlled, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-936559 in Subjects With Severe Sepsis
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 35
- 试验地点
- 25
- 主要终点
- Part 2: All-cause mortality within 90 days of study drug administration
研究概览
简要总结
The purpose of this study is to determine whether BMS-936559 is safe and has the desired pharmacologic activity in patients who have severe sepsis.
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
- •Severe sepsis or septic shock for at least 24 hours
- •Documented or suspected infection
- •Sepsis-induced immunosuppression
- •Men and women ≥ 18 years old
排除标准
- •Autoimmune disease
- •Organ transplant or bone marrow transplant
- •Cancer treated in the past 6 months
- •Hepatitis B virus (HBV) Infection
- •Human Immunodeficiency Virus (HIV) infection and not on therapy prior to this episode of sepsis
- •Hepatitis C virus (HCV) infection and still has virus (not cured)
研究组 & 干预措施
BMS-936559
BMS-936559 Intravenous infusion on specified days
干预措施: BMS-936559 (Biological)
Placebo
Placebo on specified days
干预措施: Placebo (Other)
结局指标
主要结局
Part 2: All-cause mortality within 90 days of study drug administration
时间窗: Approximately 3 months
Part 1: Safety of BMS-936559 in subjects with severe sepsis - measured by the incidence rates of death, AEs, SAEs, AEs leading to discontinuation, AEs of special interest and laboratory abnormalities
时间窗: Approximately 3 months
Safety will be measured by the incidence rates of death, Adverse event (AEs), Serious adverse event (SAEs), AEs leading to discontinuation, AEs of special interest (identified from PD-L1 oncology trial), and laboratory abnormalities
Part 1: Tolerability of BMS-936559 in subjects with severe sepsis
时间窗: Approximately 3 months
Tolerability will be measured by the incidence rates of death, AEs, SAEs, AEs leading to discontinuation, AEs of special interest (identified from PD-L1 oncology trial), and laboratory abnormalities
次要结局
- Area under the serum concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T)) of BMS-936559(Approximately 3 months)
- Terminal serum half-life (T-HALF) of BMS-936559(Approximately 3 months)
- Incidence of secondary infections (as adjudicated by a clinical committee) up to 90 days post administration of BMS-936559(Approximately 3 months)
- Volume of distribution at steady state (Vss) of BMS-936559(Approximately 3 months)
- Receptor occupancy based on PD-L1 receptor occupancy levels(Approximately 3 months)
- Duration of mechanical ventilation, vasopressor use, and/or dialysis use separately during the index hospitalization(Approximately 3 months)
- Immune system function based on absolute lymphocyte counts at planned sampling timepoints(Approximately 3 months)
- Immune system function based on lipopolysaccharide (LPS)-induced whole blood TNFalpha production levels at planned sampling timepoints(Approximately 3 months)
- Organ dysfunction measured by organ support-free days (OSFDs)(Approximately 3 months)
- Immunogenicity measured by percentage of subjects having detectable anti-drug antibodies (ADA) at baseline and following administration of BMS-936559.(Approximately 3 months)
- Maximum observed serum concentration (Cmax) of BMS-936559(Approximately 3 months)
- Time of maximum observed serum concentration (Tmax) of BMS-936559(Approximately 3 months)
- All-cause mortality at 28 days, 90 days, and 1 year after study drug administration(Approximately 3 months)
- Immunogenicity measured by number of subjects having detectable anti-drug antibodies (ADA) at baseline and following administration of BMS-936559.(Approximately 3 months)
- Area under the serum concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) of BMS-936559(Approximately 3 months)
- Total Body Clearance (CLT) of BMS-936559(Approximately 3 months)
- Immune system function based on baseline and post-dosing assessments of mHLA-DR expression on monocytes at planned sampling timepoints(Approximately 3 months)
- Organ dysfunction measured by proportion of OSFDs during index hospitalization(Approximately 3 months)