A Clinical Study to Test the Safety, Exposure, and Pharmacodynamic Markers of CSL311 in Subjects With Mild-to-moderate Asthma and in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- CSL Behring
- 入组人数
- 78
- 试验地点
- 3
- 主要终点
- Percentage of subjects with treatment-emergent adverse events (TEAEs) in SC single dose, single ascending doses (SAD) and multiple ascending doses (MAD - SC and IV)
研究概览
简要总结
This is a phase 1, first-in-human (FIH), multi-center, randomized, double-blind, placebo-controlled study of CSL311 in patients with mild-to-moderate asthma. The primary objective of this study is to assess the safety and tolerability of single ascending doses (SAD) and multiple ascending doses (MAD) of CSL311.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female subjects 18 to 65 years of age with diagnosis of mild-to-moderate asthma for Parts A and B. For part C healthy, male or female subjects 18 to 50 years
排除标准
- •Oral/parenteral corticosteroids or anti-interleukin-6 therapy within 6 months prior to screening, or any prohibited therapies prior to screening.
- •History or presence of clinically significant hypertension or other significant cardiovascular abnormality.
- •Any clinically significant abnormality on electrocardiogram at screening.
- •Parasitic infestation within 6 months before screening, or travel or intention to travel to a country with a high prevalence of such infections within 1 year before screening or within 85 days after the last dose of CSL
- •Occurrence of asthma exacerbation and/or upper/lower respiratory tract infection, or any acute infection or disease within the last 6 weeks before screening.
研究组 & 干预措施
CSL311 Cohort A4 (SAD Dose 4)
Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
干预措施: Human beta common receptor antagonist monoclonal antibody (Biological)
CSL311 Cohort A1 (SAD Dose 1)
Human beta common receptor antagonist monoclonal antibody administered intravenously at a Single Ascending Dose (SAD)
干预措施: Human beta common receptor antagonist monoclonal antibody (Biological)
CSL311 Cohort A2 (SAD Dose 2)
Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
干预措施: Human beta common receptor antagonist monoclonal antibody (Biological)
CSL311 Cohort A3 (SAD Dose 3)
Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
干预措施: Human beta common receptor antagonist monoclonal antibody (Biological)
CSL311 Cohort A5 (SAD Dose 5)
Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
干预措施: Human beta common receptor antagonist monoclonal antibody (Biological)
CSL311 Cohort A6 (SAD Dose 6)
Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
干预措施: Human beta common receptor antagonist monoclonal antibody (Biological)
CSL311 Cohort A7 (SAD Dose 7)
Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
干预措施: Human beta common receptor antagonist monoclonal antibody (Biological)
CSL311 Cohort A8 (SAD Dose 8)
Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
干预措施: Human beta common receptor antagonist monoclonal antibody (Biological)
CSL311 Cohort B1 (MAD Dose 1)
Human beta common receptor antagonist monoclonal antibody administered intravenously at a MAD
干预措施: Human beta common receptor antagonist monoclonal antibody (Biological)
Placebo
0.9% sodium chloride solution administered intravenously
干预措施: Placebo (Drug)
Placebo (2)
0.9% sodium chloride solution administered subcutaneously
干预措施: Placebo (Drug)
CSL311 Cohort C1 (MAD Dose 1)
Human beta common receptor antagonist monoclonal antibody administered subcutaneously (SC)
干预措施: Human beta common receptor antagonist monoclonal antibody (Biological)
CSL311 Cohort C2 (MAD Dose 2)
Human beta common receptor antagonist monoclonal antibody administered subcutaneously
干预措施: Human beta common receptor antagonist monoclonal antibody (Biological)
CSL311 Cohort C3 (MAD Dose 3)
Human beta common receptor antagonist monoclonal antibody administered subcutaneously
干预措施: Human beta common receptor antagonist monoclonal antibody (Biological)
结局指标
主要结局
Percentage of subjects with treatment-emergent adverse events (TEAEs) in SC single dose, single ascending doses (SAD) and multiple ascending doses (MAD - SC and IV)
时间窗: After infusion or injection, up to Day 85 for Cohorts A1 to A7, Day 57 for Cohort A8, Day 114 for Cohort B1 and Day 85 for Cohorts C1 to C3
Percentage of subjects with related TEAEs in SC single dose, SAD and MAD (SC and IV)
时间窗: After infusion or injection, up to Day 85 for Cohorts A1 to A7, Day 57 for Cohort A8, Day 114 for Cohort B1 and Day 85 for Cohorts C1 to C3
Percentage of subjects with TEAEs by severity in SC single dose, SAD and MAD (SC and IV)
时间窗: After infusion or injection, up to Day 85 for Cohorts A1 to A7, Day 57 for Cohort A8, Day 114 for Cohort B1 and Day 85 for Cohorts C1 to C3
Severity of TEAEs defined as mild, moderate, or severe
次要结局
- Half-life (t½) of CSL311 in SAD(Up to 85 days after infusion)
- Volume of distribution (Vd) of CSL311 in SAD(Up to 85 days after infusion)
- Maximum plasma concentration (Cmax) of CSL311 in SAD(Up to 85 days after infusion)
- Time to reach Cmax (tmax) of CSL311 in SAD(Up to 85 days after infusion)
- Area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-last) of CSL311 in SAD(Up to 85 days after infusion)
- Area under the concentration-time curve from time 0 extrapolated to infinite time (AUC0-inf) of CSL311 in SAD(Up to 85 days after infusion)
- Clearance (CL) of CSL311 in SAD(Up to 85 days after infusion)
- Cmax/dose of CSL311 in SAD(Up to 85 days after infusion)
- Area under the concentration-time curve from time 0 to the last measurable concentration per dose of CSL311 (AUC0-last/dose) in SAD(Up to 85 days after infusion)
- AUCtau/dose for CSL311 in MAD (SC and IV) after last dose(Up to 85 days (SC) and 114 days (IV) after infusion or injection)
- Percentage of subjects with severe or life-threatening Neutropenia in SAD and MAD (SC and IV) by treatment (CSL311 or placebo), by causality, and by CSL311 dose level(After infusion or injection, up to 85 days for SAD, and up to 85 days for MAD (SC) and 114 days for MAD (IV))
- Percentage of subjects with TEAEs of Worsening Asthma in SAD and MAD (SC and IV) by treatment (CSL311 or placebo), by causality, and by CSL311 dose level(After infusion or injection, up to 85 days for SAD, and up to 85 days for MAD (SC) and 114 days for MAD (IV))
- AUCtau for CSL311 in MAD (SC and IV) after first dose(Up to 15 days after infusion or injection)
- Cmax/dose of CSL311 in MAD (SC and IV) after first dose(Up to 15 days after infusion or injection)
- Cmax/dose of CSL311 in MAD (SC and IV) after last dose(Up to 85 days (SC) and 114 days (IV) after infusion or injection)
- Half-life (t½) of CSL311 in MAD (SC and IV) after last dose(Up to 85 days (SC) and 114 days (IV) after infusion or injection)
- Apparent Clearance (CL/F) of CSL311 in MAD (SC) after last dose(Up to 85 days after injection)
- Volume of distribution (Vd) of CSL311 in MAD (IV) after last dose(Up to 114 days after infusion)
- Number of subjects with detectable anti-CSL311 antibodies in SAD and MAD (SC and IV)(After infusion or injection, up to 85 days for SAD, and up to 85 days for MAD (SC) and 114 days for MAD (IV))
- Percentage of subjects with TEAEs of Infections and Infestations in SAD and MAD (SC and IV) by treatment (CSL311 or placebo), by causality, and by CSL311 dose level(After infusion or injection, up to 85 days for SAD, and up to 85 days for MAD (SC) and 114 days for MAD (IV))
- AUCtau/dose for CSL311 in MAD (SC and IV) after first dose(Up to 15 days after infusion or injection)
- Cmax of CSL311 in MAD (SC and IV) after first dose(Up to 15 days after infusion or injection)
- tmax of CSL311 in MAD (SC and IV) after first dose(Up to 15 days after infusion or injection)
- Cmax of CSL311 in MAD (SC and IV) after last dose(Up to 85 days (SC) and 114 days (IV) after infusion or injection)
- AUCtau for CSL311 in MAD (SC and IV) after last dose(Up to 85 days (SC) and 114 days (IV) after infusion or injection)
- tmax of CSL311 in MAD (SC and IV) after last dose(Up to 85 days (SC) and 114 days (IV) after infusion or injection)
- Clearance (CL) of CSL311 in MAD (IV) after last dose(Up to 114 days after infusion)
- Apparent volume of distribution during terminal phase (Vz/F) of CSL311 in MAD (SC) after last dose(Up to 85 days after injection)