Double-Blind, Placebo-Controlled Study of Bezlotoxumab in Children Receiving Antibacterial Treatment for Clostridioides difficile Infection (MODIFY III).
J Pediatric Infect Dis Soc
; 12(6): 334-341, 2023 Jun 30.
Article
en En
| MEDLINE
| ID: mdl-37389891
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 31 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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Infecciones por Clostridium
/
Antibacterianos
Tipo de estudio:
Clinical_trials
Límite:
Adult
/
Child
/
Female
/
Humans
/
Male
Idioma:
En
Año:
2023
Tipo del documento:
Article