Single Ascending Dose and Repeat Dose Study to Evaluate Pharmacokinetics, Pharmacodynamics, and Safety of Sargramostim Administered Subcutaneously, by Intravenous Infusion, or by Inhalation in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 2
- 主要终点
- maximum concentration
研究概览
简要总结
This single center, single ascending dose (SAD) and repeat dose study in healthy adults comprises 2 parts. Part 1 will consist of 6 SAD cohorts, in which different dose levels of sargramostim will be given by intravenous (IV) infusion, subcutaneous (SC) injection, or inhalation (IH) administration. Part 2 will consist of 1 repeat dose cohort in which sargramostim will begiven by SC administration.
Blood samples for PK assessment will be collected before and over 24 hours after each study drug administration. Blood samples for PD assessment will be collected before and up to 14 days after drug administration in Part 1, as well as before the first and up to 14 days after the second drug administration in Part 2. Safety and tolerability will be assessed throughout the study. For Cohort 5 of Part 1 only, 3 subjects will provide a CSF sample for PK assessmen tonce after SC drug administration.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adult male and female participants
- •Nonsmoker or ex-smoker
- •Able to provide informed consent and comply with all study procedures
- •Body Mass Index within 18.5-30.0 kilograms/meter squared, inclusive
- •Females of childbearing potential willing to use highly-effective method of birth control.
排除标准
- •Females who are pregnant or breastfeeding
- •History of allergic to sargramostim or its excipients, other human GM-CSFs, or other yeast-derived products.
- •History of severe allergic reactions to other drugs.
- •History of or any current medical condition or laboratory finding that may jeopardize completion of the study, present an increased risk to the subject, or compromise interpretation of the study. .
- •Immunization with COVID-19 vaccine within 14 days of the study.
- •Scheduled immunization with COVID-19 vaccine during the study
- •Use of prescription drugs within 28 days of the study or requirement for maintenance drugs during the study.
- •Participation in another investigational drug study within 28 days
结局指标
主要结局
maximum concentration
时间窗: Blood samples collected up to 24 hours post dose
Area under the concentration-time curve (AUC) from time 0 to 24 hours
时间窗: Blood samples collected up to 24 hours post dose
Steady state volume of distribution (IV administration only)
时间窗: Blood samples collected up to 24 hours post dose
time to maximum
时间窗: Blood samples collected up to 24 hours post dose
AUC from time 0 to infinity
时间窗: Blood samples collected up to 24 hours post dose
Elimination half-life
时间窗: Blood samples collected up to 24 hours post dose
Clearance
时间窗: Blood samples collected up to 24 hours post dose
AUC from time 0 to 24 hours/infinity
时间窗: Blood samples collected up to 24 hours post dose
次要结局
- CD14/CD16/human leukocyte antigen-DR isotype (HLA-DR) absolute cell count(Up to Day 15 in Part 1, up to Day 22 in Part 2)
- Number of subjects with adverse events in Part 2(Up to Day 22 in Part 2)
- Number of subjects with adverse events in Part 1(Up to Day 15 in Part 1)
- Ratio of T-regulatory cells to T-effector cells in the blood.(Up to Day 15 in Part 1, up to Day 22 in Part 2)