Double-Blind, Placebo-Controlled Study of Bezlotoxumab in Children Receiving Antibacterial Treatment for Clostridioides difficile Infection (MODIFY III)
Thomas J Sferra, Tomas Merta, Michael Neely, Claudia Murta de Oliveira, Alvaro Lassaletta, Claudia Fortuny Guasch, Mary Beth Dorr, Gregory Winchell, Feng-Hsiu Su, Sarah Perko, Doreen Fernsler, Hetty Waskin, Stephen R Holden, Thomas J Sferra, Tomas Merta, Michael Neely, Claudia Murta de Oliveira, Alvaro Lassaletta, Claudia Fortuny Guasch, Mary Beth Dorr, Gregory Winchell, Feng-Hsiu Su, Sarah Perko, Doreen Fernsler, Hetty Waskin, Stephen R Holden
Abstract
Background: 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.
Methods: 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.
Results: 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%).
Conclusions: The results of this study support the bezlotoxumab dose of 10 mg/kg for pediatric patients.
Trial registration: NCT03182907 at ClinicalTrials.gov.
Keywords: Clostridioides difficile infection; adolescents; bezlotoxumab; children; recurrence.
© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.
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Source: PubMed