Department of Pediatrics, UH Rainbow Babies & Children's Hospital and Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Department of Pediatric Oncology, University Hospital Brno, Brno, Czech Republic.
J Pediatric Infect Dis Soc. 2023 Jun 30;12(6):334-341. doi: 10.1093/jpids/piad031.
Therapies to prevent recurrence of Clostridioides difficile infection (CDI) in pediatric patients are needed. Bezlotoxumab is a fully human monoclonal antibody approved for prevention of recurrent CDI in adults. We assessed the pharmacokinetics, safety, tolerability, and efficacy of bezlotoxumab in pediatric patients.
MODIFY III was a multicenter, double-blind, placebo-controlled study of bezlotoxumab in children (1 to <18 years) receiving antibacterial treatment for CDI. Participants were randomized 3:1 to receive a single infusion of bezlotoxumab (10 mg/kg) or placebo and were stratified by age at randomization (cohort 1: 12 to <18 years, cohort 2: 1 to <12 years). The primary objective was to characterize bezlotoxumab pharmacokinetics to support dose selection for pediatric patients; the primary endpoint was the area under the bezlotoxumab serum concentration-time curve (AUC0-inf). Safety, tolerability, and efficacy were monitored for 12 weeks post-infusion.
A total of 148 participants were randomized and 143 were treated: 107 with bezlotoxumab and 36 with placebo (cohort 1 n = 60, cohort 2 n = 83; median age 9.0 years); 52.4% of participants were male and 80.4% were white. Geometric mean ratios (90% CI) for bezlotoxumab AUC0-inf were 1.06 (0.95, 1.18) and 0.82 (0.75, 0.89) h * μg/mL for cohorts 1 and 2, respectively. Bezlotoxumab 10 mg/kg was generally well-tolerated with an adverse event profile similar to placebo, including no treatment discontinuations due to adverse events. CDI recurrence was low and comparable for bezlotoxumab (11.2%) and placebo (14.7%).
The results of this study support the bezlotoxumab dose of 10 mg/kg for pediatric patients.
NCT03182907 at ClinicalTrials.gov.
需要治疗小儿患者复发性艰难梭菌感染（CDI）的疗法。贝洛妥珠单抗是一种获批用于预防成人复发性 CDI 的全人源单克隆抗体。我们评估了贝洛妥珠单抗在儿科患者中的药代动力学、安全性、耐受性和疗效。
MODIFY III 是一项评估贝洛妥珠单抗在接受抗 CDI 治疗的儿童（1 至<18 岁）中的多中心、双盲、安慰剂对照研究。参与者按 3:1 随机接受单次输注贝洛妥珠单抗（10mg/kg）或安慰剂，并按随机分组时的年龄分层（队列 1：12 至<18 岁，队列 2：1 至<12 岁）。主要目的是描述贝洛妥珠单抗的药代动力学，以支持儿科患者的剂量选择；主要终点是贝洛妥珠单抗血清浓度-时间曲线下面积（AUC0-inf）。在输注后 12 周内监测安全性、耐受性和疗效。
共有 148 名参与者被随机分组，143 名接受了治疗：107 名接受贝洛妥珠单抗治疗，36 名接受安慰剂治疗（队列 1 n=60，队列 2 n=83；中位年龄 9.0 岁）；52.4%的参与者为男性，80.4%为白人。贝洛妥珠单抗 AUC0-inf 的几何均数比值（90%CI）分别为 1.06（0.95，1.18）和 0.82（0.75，0.89）h*μg/mL，适用于队列 1 和队列 2。贝洛妥珠单抗 10mg/kg 通常具有良好的耐受性，其不良事件谱与安慰剂相似，包括无因不良事件而停药。贝洛妥珠单抗（11.2%）和安慰剂（14.7%）的 CDI 复发率较低且相似。
本研究结果支持贝洛妥珠单抗在儿科患者中的 10mg/kg 剂量。
NCT03182907 于 ClinicalTrials.gov。
