A Phase 1b/2a Randomized, Double-Blind, Placebo-controlled, Dose-escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI8897, a Monoclonal Antibody With an Extended Half-life Against Respiratory Syncytial Virus, in Healthy Preterm Infants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 151
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of an extended half-life anti-respiratory syncytial virus (RSV) monoclonal antibody compared to placebo when administered to healthy preterm infants.
详细描述
This Phase 1b/2a study will be a dose-escalation design to begin data collection on PK and safety in children. The population to be enrolled is healthy preterm infants born between 32 weeks 0 days and 34 weeks 6 days gestation who would not receive RSV prophylaxis based on the American Academy of Pediatrics (AAP) or other local guidelines. These subjects will not be receiving palivizumab, allowing for a placebo comparator group to begin collecting data on incidence rates of RSV medically attended lower respiratory illness (MA-LRI) and efficacy. Enrollment is planned at approximately 20 sites in the USA, Chile, and South Africa.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- — 至 12 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy infants born between 32 weeks 0 days and 34 weeks 6 days gestational age
- •Infants who are entering their first RSV season at the time of screening
排除标准
- •Gestational age < 32 weeks 0 days and >34 weeks 6 days
- •Meets AAP or other local criteria to receive commercial palivizumab
- •Any fever (≥ 100.4°F [≥ 38.0°C], regardless of route) or lower respiratory illness within 7 days prior to randomization
- •Acute illness (defined as the presence of moderate or severe signs and symptoms) at the time of randomization
- •Active RSV infection (a child with signs/symptoms of respiratory infection must have negative RSV testing) or known prior history of RSV infection
- •Receipt of palivizumab or any RSV vaccine, including maternal RSV vaccination
研究组 & 干预措施
Placebo
Participants will receive placebo intramuscularly.
干预措施: Placebo (Drug)
MEDI8897 10 mg
Participants will receive a single dose of MEDI8897 10 milligram (mg) intramuscularly.
干预措施: MEDI8897 10 mg (Drug)
MEDI8897 25 mg
Participants will receive a single dose of MEDI8897 25 mg intramuscularly.
干预措施: MEDI8897 25 mg (Drug)
MEDI8897 50 mg
Participants will receive a single dose of MEDI8897 50 mg intramuscularly.
干预措施: MEDI8897 50 mg (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
时间窗: From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. 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 situation (immediate risk of dying); persistent or significant disability/incapacity of a participant who received MEDI8897. TEAEs and TESAEs were the events that occurred between administration of study drug (Day 1) and Day 361 that were absent before treatment or that worsened relative to pre-treatment state.
Number of Participants With Treatment-Emergent Adverse Events of Special Interest
时间窗: From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
An AESI was one of scientific and medical interest specific to understanding of study product and may have required close monitoring and rapid communication by investigator (that is, within 24 hrs of knowledge of the event) to the sponsor. The AESIs for this study were hepatic function abnormality meeting the definition of Hy's law, hypersensitivity reactions including anaphylaxis, immune complex disease, and thrombocytopenia. Treatment-emergent AESIs were collected from the time of dosing until Day 361 post-dose.
Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events
时间窗: From Study Drug Administration (Day 1) Through the Follow-up Period (Day 151)
Laboratory abnormalities determined by the investigator to be clinically significant that occurred after study drug dosing through 151 days post-dose that were absent before treatment or that worsened relative to pre-treatment state were reported as TEAEs. Laboratory evaluations (haematology and serum chemistry) of blood samples were performed.
次要结局
- Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI8897(Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose)
- Maximum Observed Serum Concentration (Cmax) of MEDI8897(Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose)
- Area Under the Concentration-Time Curve From Day 1 to Day 151 (AUC [1-151]) of MEDI8897(Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), and 150 (± 7) Post-dose)
- Area Under the Concentration-Time Curve From Zero to Infinity (AUC [0-infinity]) of MEDI8897(Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose)
- Terminal Elimination Half Life (t1/2) of MEDI8897(Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose)
- Extravascular Clearance (CL/F) of MEDI8897(Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose)
- Extravascular Volume of Distribution (Vz/F) of MEDI8897(Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose)
- Number of Participants Positive for Anti-Drug Antibodies to MEDI8897(Pre-dose at Baseline (Days -7 to -1) and on Days 31, 151, and 361 Post-dose)