A Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of a Single Infusion of Bezlotoxumab (MK-6072, Human Monoclonal Antibody to C. Difficile Toxin B) in Children Aged 1 to <18 Years Receiving Antibacterial Drug Treatment for C. Difficile Infection (MODIFY III)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 148
- 试验地点
- 75
- 主要终点
- Area Under the Concentration-Time Curve of Bezlotoxumab From Time 0 to Infinity (AUC0-inf)
研究概览
简要总结
The primary objectives of this study are to evaluate the pharmacokinetics (PK), safety, and tolerability of bezlotoxumab (MK-6072) in children aged 1 to <18 years of age with a confirmed diagnosis of Clostridium difficile infection (CDI) who are receiving antibacterial drug treatment. The primary hypothesis is that the area under the concentration-time curve from 0 to infinity (AUC0-inf) of bezlotoxumab after treatment of pediatric participants with bezlotoxumab is similar when compared to the AUC0-inf of bezlotoxumab after treatment of adults with bezlotoxumab.
详细描述
Historical adult pharmacokinetic data is from NCT01241552 and NCT01513239.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 1 Year 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At screening has suspected or confirmed Clostridium difficile infection (CDI), and is receiving or is planning to receive a 10- to 21-day course of antibacterial drug treatment for CDI
- •At study infusion has a diagnosis of CDI confirmed by a diagnostic assay which detects the presence of C. difficile toxin in stool, and is still receiving antibacterial drug treatment for CDI
- •Female is not pregnant, and not breastfeeding; but if of childbearing potential agrees to follow contraceptive guidance during the treatment period and for at least 12 weeks after the last dose of study treatment
- •Participant and/or parent or caregiver must be able to read, understand, and complete the daily diary
排除标准
- •Has an uncontrolled chronic diarrheal illness
- •Has a known hypersensitivity to bezlotoxumab, its active substance and/or any of its excipients
- •At randomization, their planned course of antibacterial drug treatment for CDI is longer than 21 days
- •At screening has received any listed prohibited prior and concomitant treatments and procedures
- •Has previously participated in this study, has previously received bezlotoxumab, has received an experimental monoclonal antibody against C. difficile toxin B, or has received a vaccine directed against C. difficile or its toxins.
- •Has received an investigational study agent within the previous 30 days, or is currently participating in or scheduled to participate in any other clinical study with an investigational agent during the 12-week study period
研究组 & 干预措施
Bezlotoxumab
Participants receive 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) intravenous (IV) infusion on Day 1. Additionally, participants receive background antibacterial drug treatment (ABD) for 10-21 days per institutional guidelines, at the investigator's discretion. Dose may then be changed based on results from initial 12 participants.
干预措施: Bezlotoxumab (Biological)
Bezlotoxumab
Participants receive 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) intravenous (IV) infusion on Day 1. Additionally, participants receive background antibacterial drug treatment (ABD) for 10-21 days per institutional guidelines, at the investigator's discretion. Dose may then be changed based on results from initial 12 participants.
干预措施: Antibacterial drug treatment (ABD) (Drug)
Placebo
Participants receive placebo for bezlotoxumab consisting of either 0.9% sodium chloride or 5% dextrose via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants receive background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.
干预措施: Placebo (Drug)
Placebo
Participants receive placebo for bezlotoxumab consisting of either 0.9% sodium chloride or 5% dextrose via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants receive background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.
干预措施: Antibacterial drug treatment (ABD) (Drug)
结局指标
主要结局
Area Under the Concentration-Time Curve of Bezlotoxumab From Time 0 to Infinity (AUC0-inf)
时间窗: Day 1 (2 hours postdose), Days 10, 29, 57, and 85
Blood samples were collected at specified intervals for the determination of AUC0-inf. AUC0-inf was defined as the area under the concentration-time curve of bezlotoxumab from time zero to infinity. Per protocol, AUC0-inf of bezlotoxumab was determined for each age cohort.
Percentage of Participants Who Experienced an Adverse Event (AE)
时间窗: Up to approximately 12 weeks
An AE was defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product and does not imply any judgment about causality. Per protocol, percentage of participants with AEs in the bezlotoxumab and placebo groups were presented.
Percentage of Participants Who Discontinued Study Due to an AE
时间窗: Up to approximately 12 weeks
An AE was defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product and does not imply any judgment about causality. Per protocol, percentage of participants who discontinued study due to AEs in the bezlotoxumab and placebo groups were presented.
次要结局
- Percentage of High-Risk Participants Who Experienced a SCR(Up to approximately 12 Weeks)
- Percentage of Participants Who Had Positive Antibodies to Bezlotoxumab(Up to approximately 12 Weeks)
- Percentage of Participants Who Had a Clostridium Difficile Infection (CDI) Recurrence(Up to approximately 12 Weeks)
- Percentage of Participants Who Had a Sustained Clinical Response (SCR)(Up to approximately 12 Weeks)
- Percentage of High-Risk Participants Who Experienced a CDI Recurrence(Up to approximately 12 Weeks)
- Percentage of Participants Who Experienced One or More Infusion Related Reaction(Up to approximately 24 hours after infusion on Day 1)