A Double-blind, Randomized, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MK-1654 in Pre-Term and Full-Term Infants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 183
- 试验地点
- 34
- 主要终点
- Percentage of Participants Who Experienced At Least One Solicited Systemic Adverse Event (AE)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and incidence of anti-drug antibodies (ADAs) of single ascending doses of clesrovimab in healthy pre-term (born at 29 to 35 weeks gestational age) and full-term (born at >35 weeks gestational age) infants. Participants will be randomized into 1 of 4 dose escalation panels (Panels A to D); an additional panel (Panel E) of full-term infants will receive the same dose as Panel D. Key safety and tolerability variables will be reviewed after each dose panel prior to administering the next-highest dose.
详细描述
Participants in Dose Panels A, B, C, D1, and E1 will be followed for up to 365 days. After protocol Amendment 4 (AM4), participants in Dose Panels D2 and E2 will be followed for up to 545 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 2 Weeks 至 8 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •is healthy, based on screening safety laboratory, medical history, and physical examination results
- •is a pre-term infant (born at 29 weeks to 35 weeks gestational age [inclusive]) or a full-term infant (born at over 35 weeks gestational age), as confirmed in medical records
- •weighs ≥2 kg at screening
排除标准
- •has been recommended to receive palivizumab per local standard of care
- •has ≥1 documented out-of-range safety laboratory results (adjusted for age) at the time of screening
- •has a known hypersensitivity to any component of the respiratory syncytial virus (RSV) monoclonal antibody
- •has a history of congenital or acquired immunodeficiency (e.g., splenomegaly)
- •has documented human immunodeficiency virus (HIV) infection, hepatitis B (HBsAg positive), or hepatitis C (HCV ribonucleic acid [RNA] positive)
- •has known history of functional or anatomic asplenia
- •has a diagnosis of failure to thrive within 14 days of screening
- •has known or history of a coagulation disorder contraindicating intramuscular injection
- •has received or is expected to receive blood products (except irradiated platelets) within 3 months prior to enrollment
- •has prior known documented RSV infection
- •has hemodynamically significant congenital heart disease
- •has chronic lung disease of prematurity requiring ongoing medical therapy
- •has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that, in the opinion of the investigator, might expose the participant to undue risk by participating in the study, confound the results of the study, or interfere with the participant's participation for the full duration of the study
- •has any history of malignancy prior to randomization
- •if any of the following apply, the Day 1 visit may be rescheduled for a time when these criteria are not met:
- •has had a recent febrile illness (rectal temperature 38.1°C [100.5°F] or higher or axillary temperature 37.8°C [100.0°F] or higher) within 72 hours pre-dose
- •is not up-to-date on required vaccinations per local pediatric vaccine schedule at time of screening
- •has received inactivated or component vaccines (eg, influenza, hepatitis B) less than 14 days pre-dose
- •has received live, attenuated, non-study licensed pediatric vaccines (e.g., Bacillus Calmette-Guerin vaccine) less than 30 days pre-dose
- •has received any prior vaccine or monoclonal antibody (mAb) for the prevention of RSV
- •is currently participating in or has participated in an interventional clinical study with an investigational compound or device at any time prior to first dose administration or while participating in this current study (participants enrolled in observational studies may be included and will be reviewed on a case-by-case basis for approval by the Sponsor)
- •has enrolled previously in this study and been discontinued
- •participant's mother participated in a RSV vaccine clinical study while pregnant and participant is ≤3 months of chronological age
- •is unable to provide blood sample at screening
- •cannot be adequately followed for safety according to the protocol plan
- •has a parent/legally acceptable representative who is unlikely to adhere to study procedures, keep appointments, or is planning to relocate during the study
- •is, or has, an immediate family member (eg, spouse, parent/guardian, sibling, or child) who is directly involved with the study at the site or with the Sponsor
研究组 & 干预措施
Panel A: Pre-term clesrovimab Dose 1
Pre-term infants will receive clesrovimab Dose 1 via intramuscular (IM) injection and will be followed for up to 365 days.
干预措施: Clesrovimab (Drug)
Panel B: Pre-term clesrovimab Dose 2
Pre-term infants will receive clesrovimab Dose 2 via IM injection and will be followed for up to 365 days.
干预措施: Clesrovimab (Drug)
Panel C: Pre-term clesrovimab Dose 3
Pre-term infants will receive clesrovimab Dose 3 via IM injection and will be followed for up to 365 days.
干预措施: Clesrovimab (Drug)
Panel D1: Pre-term clesrovimab Dose 4
Pre-term infants enrolled prior to AM4 will receive clesrovimab Dose 4 via IM injection and will be followed for up to 365 days.
干预措施: Clesrovimab (Drug)
Panel D2: Pre-term clesrovimab Dose 4
Pre-term infants enrolled after AM4 will receive clesrovimab Dose 4 via IM injection and will be followed for up to 545 days.
干预措施: Clesrovimab (Drug)
Panel E1: Full-term clesrovimab Dose 4
Full-term infants enrolled prior to AM4 will receive clesrovimab Dose 4 via IM injection and will be followed for up to 365 days.
干预措施: Clesrovimab (Drug)
Panel E2: Full-term clesrovimab Dose 4
Full-term infants enrolled after AM4 will receive clesrovimab Dose 4 via IM injection and will be followed for up to 545 days.
干预措施: Clesrovimab (Drug)
Placebo
Pre-term infants will receive placebo via IM injection.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants Who Experienced At Least One Solicited Systemic Adverse Event (AE)
时间窗: Up to Day 5
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited systemic AEs were monitored from Day 1 to Day 5.
Percentage of Participants Who Experienced At Least One Solicited Injection Site Adverse Event (AE)
时间窗: Up to Day 5
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited injection site AEs were monitored from Day 1 to Day 5.
Percentage of Participants Who Experienced At Least One Serious Adverse Event (SAE)
时间窗: Up to Day 545
An SAE is any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant injury/incapacity; is a congenital anomaly/birth defect; or is an other important medical event.
次要结局
- Serum Concentration of Clesrovimab on Day 365 (C365days)(Day 365)
- Area Under the Serum-Concentration Time Curve From Zero to Infinity (AUC0-∞)(At designated time points (up to 1 year post-dose))
- Maximum Serum Concentration (Cmax) of Clesrovimab(At designated time points (up to 1 year post-dose))
- Time to Maximum Serum Concentration (Tmax) of Clesrovimab(At designated time points (up to 1 year post-dose))
- Serum Concentration of Clesrovimab on Day 7 (C7days)(Day 7)
- Apparent Terminal Half-life (t1/2) of Clesrovimab(At designated time points (up to 1 year post-dose))
- Serum Concentration of Clesrovimab on Day 90 (C90days)(Day 90)
- Serum Concentration of Clesrovimab on Day 14 (C14days)(Day 14)
- Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2(Days 14, 90, 150, 365 and 545)
- Serum Concentration of Clesrovimab on Day 150 (C150days)(Day 150)