A Phase 1, Open-label Study to Evaluate the Pharmacokinetics of MEDI9929 (AMG 157) in Adolescents With Mild to Moderate Asthma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Area Under the Concentration-time Curve From Zero to Infinity (AUC [0-infinity])
研究概览
简要总结
To evaluate the PK profile of a single-dose of 140 mg subcutaneous (SC) administration of MEDI9929 (AMG 157) in adolescent subjects with mild to moderate asthma.
详细描述
The primary objective is to evaluate the PK profile of a single-dose of 140 mg subcutaneous (SC) administration of MEDI9929 (AMG 157) in adolescent subjects with mild to moderate asthma. The secondary objective is to evaluate the safety and tolerability of MEDI9929 and to evaluate the immunogenicity of MEDI9929 (AMG 157). The exploratory objective is to evaluate the effect of MEDI9929 (AMG 157) on pulmonary function
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •History of a deterioration in asthma that required a burst of systemic corticosteroids within 3 months of screening, up to and including Day
- •Clinical characteristics at either screening or Day 1 that are consistent with uncontrolled asthma as described in GINA guideline.
- •History of hospitalization (overnight admission) for asthma during the 6 months prior to screening.
- •History of intubation for the management of a deterioration in asthma.
- •History of systemic corticosteroid use for the maintenance treatment of asthma within 3 months prior to screening.
- •History of allergy or reaction to any component of the investigational product formulation or history of anaphylaxis following any biologic therapy.
- •Any active medical condition other than asthma, that in the opinion of the investigator and/or medical monitor, may compromise the safety of the subject in the study or interfere with evaluation of the investigational product or reduce the subject's ability to participate in the study (subjects with atopic skin conditions and allergic rhinitis are permitted).
- •Pregnant or breastfeeding females.
- •Current tobacco smoking or cessation of smoking for ≤ 6months prior to screening.
- •Any clinically relevant abnormal findings which in the opinion of the investigator or medical monitor, may compromise the safety of the subject in the study or interfere with evaluation of the investigational product or reduce the subject's ability to participate in the study.
- •Evidence of active liver disease,
- •Positive hepatitis B or hepatitis C virus
- •A positive human immunodeficiency virus (HIV) test at screening or subject taking antiretroviral medications
- •Major surgery within 8 weeks prior to Visit 1, or planned in-patient surgery or hospitalization during the study period.
- •History of any known primary immunodeficiency disorder
- •History of a clinically significant infection
- •A helminth parasitic infection within 24 weeks of Visit 1 that has not been treated or has not responded to standard of care therapy.
- •History of cancer.
研究组 & 干预措施
MEDI9929, 140 mg, Cohort 1 (12 to 14 years)
On Day 1, one MEDI9929 subcutaneous injection of 70 mg was given into the anterior aspect of one thigh immediately followed by the second injection of 70 mg into the anterior aspect of the contralateral thigh to make the required dose of 140 mg in participants with 12 to 14 years of age.
干预措施: MEDI9929, 140 mg (Drug)
MEDI9929, 140 mg, Cohort 2 (15 to 17 years)
On Day 1, one MEDI9929 subcutaneous injection of 70 mg was given into the anterior aspect of one thigh immediately followed by the second injection of 70 mg into the anterior aspect of the contralateral thigh to make the required dose of 140 mg in participants with 15 to 17 years of age.
干预措施: MEDI9929, 140 mg (Drug)
结局指标
主要结局
Area Under the Concentration-time Curve From Zero to Infinity (AUC [0-infinity])
时间窗: Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose.
The pharmacokinetic (PK) parameter AUC (0 to infinity) was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay.
Dose-normalized Cmax (Cmax/D)
时间窗: Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose.
The Cmax/D is the maximum observed concentration post dose normalized by MEDI9929 dose. The PK parameter was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay.
Time to Reach Cmax (Tmax)
时间窗: Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose.
The Tmax is the time to maximum observed serum concentration of MEDI9929. The PK parameter was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay.
Dose-normalized AUC (0-infinity) (AUC [0 Infinity]/D)
时间窗: Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose.
The AUC (0-infinity)/D is the area under concentration-time curve extrapolated to infinity postdose normalized by MEDI9929 dose. The PK parameter was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay.
Maximum Observed Serum Concentration (Cmax)
时间窗: Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose.
The PK parameter Cmax was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay.
Area Under the Concentration-Time Curve From Zero to Last Observation (AUC [0-t])
时间窗: Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose.
The PK parameter AUC (0-t) was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay.
Apparent Clearance (CL/F)
时间窗: Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose.
The PK parameter CL/F was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay.
Terminal Phase Elimination Half Life (t1/2,z)
时间窗: Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose.
The t½,z is the time measured for the serum drug concentration of MEDI9929 to decrease by one half. The PK parameter was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay.
Apparent Steady-state Volume of Distribution (Vss/F)
时间窗: Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose.
The PK parameter Vss/F was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay.
次要结局
- Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events(From the start of study drug administration up to end of follow-up period, assessed up to Day 85)
- Treatment-emergent Adverse Events Related to Vital Sign Parameters and Physical Findings(From the start of study drug administration up to end of follow-up period, assessed up to Day 85)
- Treatment-emergent Adverse Events Related to Laboratory Parameters(From the start of study drug administration up to end of follow-up period, assessed up to Day 85)
- Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations(From the start of study drug administration up to end of follow-up period, assessed up to Day 85)
- Number of Participants Positive for Anti-drug Antibodies and With Neutralizing Antibodies for MEDI9929 at Any Visit(Days 1 (predose), 29, 57 and 85)