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.
Historical adult pharmacokinetic data is from NCT01241552 and NCT01513239.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
148
A single intravenous (IV) infusion of 10 mg of bezlotoxumab per kg body weight. Dose may then be changed based on results from initial 12 participants.
A single IV infusion of placebo for bezlotoxumab consisting of either 0.9% sodium chloride or 5% dextrose.
ABD will be administered for 10-21 days including the duration of ABD prior to the screening visit, during the screening period, and after the infusion of study treatment, per institutional guidelines, at the investigator's discretion. ABD is defined as the receipt of oral metronidazole, oral vancomycin, intravenous (IV) metronidazole concurrent with oral vancomycin, oral fidaxomicin, or oral fidaxomicin concurrent with IV metronidazole.
Children's Hospital - Los Angeles ( Site 0021)
Los Angeles, California, United States
UCSF Medical Center ( Site 0049)
San Francisco, California, United States
Children's Hospital - Colorado ( Site 0013)
Aurora, Colorado, United States
Children's Center for Digestive Healthcare ( Site 0052)
Atlanta, Georgia, United States
University of Chicago ( Site 0019)
Chicago, Illinois, United States
Area Under the Concentration-Time Curve of Bezlotoxumab From Time 0 to Infinity (AUC0-inf)
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.
Time frame: Day 1 (2 hours postdose), Days 10, 29, 57, and 85
Percentage of Participants Who Experienced an Adverse Event (AE)
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.
Time frame: Up to approximately 12 weeks
Percentage of Participants Who Discontinued Study Due to an AE
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.
Time frame: Up to approximately 12 weeks
Percentage of Participants Who Had a Clostridium Difficile Infection (CDI) Recurrence
CDI recurrence was defined as diarrhea recurrence (new episode of diarrhea after initial clinical response \[ICR\] as defined by a change in normal bowel habits for ≥2 days with either watery diarrhea or at least 6 unformed bowel movements \[UBMs\] within 48-hours) associated with a positive stool test for C. difficile toxin, and for which the participant, in the investigator's opinion, requires and receives ABD treatment for CDI. Per protocol, percentage of participants who had a CDI recurrence in the bezlotoxumab and placebo groups were reported.
Time frame: Up to approximately 12 Weeks
Percentage of Participants Who Had a Sustained Clinical Response (SCR)
SCR was defined as the ICR of baseline CDI episode (improvement in number and character of bowel movements and doesn't require further CDI therapy within 2 days after completion of up to 21 days of ABD treatment for CDI) and no CDI recurrence (diarrhea recurrence associated with a positive stool test for C. difficile toxin, and for which the participant, in investigator's opinion, requires and receives ABD for CDI). Per protocol, percentage of participants who had a SCR in bezlotoxumab and placebo groups were presented.
Time frame: Up to approximately 12 Weeks
Percentage of High-Risk Participants Who Experienced a CDI Recurrence
CDI recurrence was defined as diarrhea recurrence (new diarrhea episode after ICR defined by change in normal bowel habits for ≥2 days with watery diarrhea or at least 6 UBMs within 48-hours) with positive stool test for C. difficile toxin for which participant, in investigator's opinion, requires and receives ABD for CDI. High-risk was meeting ≥1 criteria at/before randomization: a) was immunocompromised b) had ≥1 CDI episode prior to baseline episode c) had severe CDI baseline episode d) had C. difficile ribotype027 in stool at baseline CDI episode e) received ≥1 systemic ABD known to increase CDI risk. Per protocol, percentage of high-risk participants who experienced a CDI recurrence in the bezlotoxumab and placebo groups were presented.
Time frame: Up to approximately 12 Weeks
Percentage of High-Risk Participants Who Experienced a SCR
SCR was ICR of baseline CDI episode (improvement in number and character of bowel movements and doesn't require further CDI therapy within 2 days after completion of up to 21 days of ABD for CDI) and no CDI recurrence (diarrhea recurrence with positive stool test for C. difficile toxin, for which participant, in investigator's opinion, requires and receives ABD for CDI). High-risk was meeting ≥1 criteria: a) was immunocompromised b) had ≥1 episodes of CDI prior to baseline episode c) had severe CDI baseline episode d) had C. difficile ribotype027 in stool at baseline CDI episode e) received ≥1 systemic ABD known to increase CDI risk. Per protocol, percentage of high-risk participants who had SCR in bezlotoxumab and placebo groups were presented.
Time frame: Up to approximately 12 Weeks
Percentage of Participants Who Experienced One or More Infusion Related Reaction
Infusion related reaction included events meeting any of the 3 criteria: 1) acute onset of an illness involving skin, mucosal tissue, or both and at least 1 of the following: respiratory compromise, reduced blood pressure (BP) or associated symptoms of end-organ dysfunction 2) two or more of the following after onset of study infusion: involving skin-mucosal tissue, respiratory compromise, reduced BP or associated symptoms, or persistent gastrointestinal symptoms 3) reduced BP after onset of infusion or \>30% decrease in systolic BP from baseline. Per protocol, percentage of participants experiencing 1 or more infusion-related reactions within 24 hours following the start of study medication infusion were reported.
Time frame: Up to approximately 24 hours after infusion on Day 1
Percentage of Participants Who Had Positive Antibodies to Bezlotoxumab
Blood samples were collected to determine antibodies to bezlotoxumab. Per protocol, percentage of participants with treatment-emergent positive antibodies to bezlotoxumab following single infusion of bezlotoxumab were reported for each age cohort.
Time frame: Up to approximately 12 Weeks
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Our Lady of the Lake Hospital ( Site 0007)
Baton Rouge, Louisiana, United States
The Johns Hopkins Rubenstein Child Health Building ( Site 0034)
Baltimore, Maryland, United States
Tufts Medical Center-Floating Hospital for Children ( Site 0046)
Boston, Massachusetts, United States
Mayo Clinic - Rochester ( Site 0004)
Rochester, Minnesota, United States
Washington University ( Site 0037)
St Louis, Missouri, United States
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