Safety, Tolerability, Pharmacokinetics and Immunogenicity of MEDI3506 Administered as Single Ascending Doses in Healthy Adult Subjects, as Multiple Ascending Doses in COPD Subjects and Single Dose in Healthy Japanese Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 88
- 试验地点
- 1
- 主要终点
- Changes From Baseline in Blood Pressure at Day 169 in Part 1, Part 2, and Part 3
研究概览
简要总结
This is a Phase 1, randomised, blinded, placebo controlled, study designed to evaluate the safety, tolerability, pharmacokinetics, and immunogenicity response to single and multiple doses of MEDI3506.
详细描述
This is a Phase 1, randomised, blinded, placebo controlled, study designed to evaluate the safety, tolerability, pharmacokinetics, and immunogenicity response to single and multiple doses of MEDI3506 administered by either subcutaneous (SC) or intravenous (IV) routes.
Part I: Single Ascending Doses in Healthy Participants with a History of Mild Atopy
Part II: Multiple Ascending Doses in Participants with Global Initiative for Chronic Obstructive Lung Disease (GOLD) I-II Chronic Obstructive Pulmonary Disease (COPD)
Part III: Single Dose in Healthy Japanese Participants
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Part 1: Placebo
Healthy participants with a history of mild atopy and proven sensitivity to house dust mite (HDM) will receive a single dose of placebo matched to MEDI3506 subcutaneously or intravenously.
干预措施: MEDI3506 (Drug)
Part 1: Placebo
Healthy participants with a history of mild atopy and proven sensitivity to house dust mite (HDM) will receive a single dose of placebo matched to MEDI3506 subcutaneously or intravenously.
干预措施: Placebo (Drug)
Part 1: MEDI3506 SC Dose 1
Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 1 subcutaneously.
干预措施: MEDI3506 (Drug)
Part 1: MEDI3506 SC Dose 2
Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 2 subcutaneously.
干预措施: MEDI3506 (Drug)
Part 1: MEDI3506 SC Dose 3
Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 3 subcutaneously.
干预措施: MEDI3506 (Drug)
Part 1: MEDI3506 SC Dose 4
Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 4 subcutaneously.
干预措施: MEDI3506 (Drug)
Part 1: MEDI3506 SC Dose 5
Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 5 subcutaneously.
干预措施: MEDI3506 (Drug)
Part 1: MEDI3506 SC Dose 6
Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 6 subcutaneously.
干预措施: MEDI3506 (Drug)
Part 1: MEDI3506 IV Dose 6
Healthy participants with a history of mild atopy and proven sensitivity to HDM will receive a single MEDI3506 Dose 6 intravenously.
干预措施: MEDI3506 (Drug)
Part 2: Placebo
Participants with COPD will receive 3 administration of placebo matched to MEDI3506 subcutaneously two weeks apart over a 4-week dosing period (doses on Days 1, 15, and 29).
干预措施: MEDI3506 (Drug)
Part 2: Placebo
Participants with COPD will receive 3 administration of placebo matched to MEDI3506 subcutaneously two weeks apart over a 4-week dosing period (doses on Days 1, 15, and 29).
干预措施: Placebo (Drug)
Part 2: MEDI3506 SC Dose 4
Participants with COPD will receive 3 administration of MEDI3506 Dose 4 subcutaneously two weeks apart over a 4-week dosing period (doses on Days 1, 15, and 29).
干预措施: MEDI3506 (Drug)
Part 2: MEDI3506 SC Dose 5
Participants with COPD will receive 3 administration of MEDI3506 Dose 5 subcutaneously two weeks apart over a 4-week dosing period (doses on Days 1, 15, and 29).
干预措施: MEDI3506 (Drug)
Part 2: MEDI3506 SC Dose 6
Participants with COPD will receive 3 administration of MEDI3506 Dose 6 subcutaneously two weeks apart over a 4-week dosing period (doses on Days 1, 15, and 29).
干预措施: MEDI3506 (Drug)
Part 3: Placebo
Healthy Japanese participants will receive a single dose of placebo matched to MEDI3506 intravenously.
干预措施: MEDI3506 (Drug)
Part 3: Placebo
Healthy Japanese participants will receive a single dose of placebo matched to MEDI3506 intravenously.
干预措施: Placebo (Drug)
Part 3: MEDI3506 IV Dose 6
Healthy Japanese participants will receive a single MEDI3506 Dose 6 intravenously.
干预措施: MEDI3506 (Drug)
结局指标
主要结局
Changes From Baseline in Blood Pressure at Day 169 in Part 1, Part 2, and Part 3
时间窗: Day 169
Change from baseline in blood pressure at Day 169 in Part 1, Part 2, and Part 3 are reported.
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESI) in Part 1, Part 2, and Part 3
时间窗: From Day 1 through Day 169
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. An adverse event of special interest (AESI) was defined as any serious or nonserious event of scientific and medical interest specific to understand the study drug.
Number of Participants With Grade 2 or More Toxicity Grades Reported in Laboratory Parameters at Day 169 for Part 1, Part 2, and Part 3
时间窗: Day 169
Number of participants with Grade 2 or more toxicity grades reported in laboratory parameters are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of hematology and serum chemistry.
Changes From Baseline in Pulse Rate at Day 169 in Part 1, Part 2, and Part 3
时间窗: Baseline (Day 1) and Day 169
Change from baseline in pulse rate at Day 169 in Part 1, Part 2, and Part 3 is reported.
Changes From Baseline in Respiratory Rate at Day 169 in Part 1, Part 2, and Part 3
时间窗: Baseline (Day 1) and Day 169
Change from baseline in respiratory rate at Day 169 in Part 1, Part 2, and Part 3 are reported.
Changes From Baseline in Body Temperature Rate at Day 169 in Part 1, Part 2, and Part 3
时间窗: Baseline (Day 1) and Day 169
Change from baseline in body temperature at Day 169 in Part 1, Part 2, and Part 3 are reported.
Number of Participants With Change From Baseline in QTcF in Part 1, Part 2, and Part 3
时间窗: Baseline (Day 1) and Day 169
Number of participants with change from basleine in QTcF in Part 1, Part 2, and Part 3 are reported. The change from baseline in QTcF at Day 169 data are reported in 3 categories as: \<= 30 msec, \> 30 to \<= 60 msec, and \> 60 msec.
次要结局
- Terminal Elimination Half-life (t1/2) of MEDI3506 After Single Dose for Part 1 and Part 3(Day 1 (predose for all arms; except predose and end of infusion for MEDI3506 IV Dose 6 arms), Day 2, Day 3, Day 4, Day 5, Day 8, Day 15, Day 29, Day 43, Day 57, Day 85, Day 113, Day 141, and Day 169)
- Trough Serum Concentration (Ctrough) of MEDI3506 After 3rd Dose in Part 2(Day 29 (predose), Day 36, and Day 43)
- Terminal Elimination Half-life (t1/2) of MEDI3506 in Part 2(Day 36, Day 43, Day 57, Day 85, Day 113, Day 141, and Day 169)
- Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI3506 After Single Dose for Part 1 and Part 3(Day 1 (predose for all arms; except predose and end of infusion for MEDI3506 IV Dose 6 arms), Day 2, Day 3, Day 4, Day 5, Day 8, Day 15, Day 29, Day 43, Day 57, Day 85, Day 113, Day 141, and Day 169)
- Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI3506 treatment in Part 1, Part 2, and Part 3(Part 1 and Part 3: Day 1 (predose), Day 29, Day 57, Day 85, Day 113, Day 141, and Day 169; Part 2: Day 1 (predose), Day 29, Day 85, and Day 169)
- Apparent Clearance (CL/F) of MEDI3506 From Body After Single Dose for Part 1 and Part 3(Day 1 (predose for all arms; except predose and end of infusion for MEDI3506 IV Dose 6 arms), Day 2, Day 3, Day 4, Day 5, Day 8, Day 15, Day 29, Day 43, Day 57, Day 85, Day 113, Day 141, and Day 169)
- Maximum Observed Concentration (Cmax) of MEDI3506 After Single Dose for Part 1 and Part 3(Day 1 (predose for all arms; except predose and end of infusion for MEDI3506 IV Dose 6 arms), Day 2, Day 3, Day 4, Day 5, Day 8, Day 15, Day 29, Day 43, Day 57, Day 85, Day 113, Day 141, and Day 169)
- Time to Maximum Concentration (Tmax) of MEDI3506 After Single Dose for Part 1 and Part 3(Day 1 (predose for all arms; except predose and end of infusion for MEDI3506 IV Dose 6 arms), Day 2, Day 3, Day 4, Day 5, Day 8, Day 15, Day 29, Day 43, Day 57, Day 85, Day 113, Day 141, and Day 169)
- Trough Serum Concentration (Ctrough) of MEDI3506 After 1st Dose in Part 2(Day 1 (predose), Day 3, Day 8, Day 15 (predose))