Bezlotoxumab (MK-6072) Versus Placebo in Children With Clostridium Difficile Infection (CDI) (MK-6072-001)

Phase 3

Completed

Conditions: Clostridium Difficile Infection

Interventions: Biological: Bezlotoxumab
Drug: Placebo
Drug: Antibacterial drug treatment (ABD)

Registration Number: NCT03182907

Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary: 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.

Detailed Description: Historical adult pharmacokinetic data is from NCT01241552 and NCT01513239.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 148

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bezlotoxumab	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.
Bezlotoxumab	Antibacterial drug treatment (ABD)	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.
Placebo	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.
Placebo	Antibacterial drug treatment (ABD)	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.

Primary Outcome Measures

Name	Time	Method
Area Under the Concentration-Time Curve of Bezlotoxumab From Time 0 to Infinity (AUC0-inf)	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)	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	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of High-Risk Participants Who Experienced a SCR	Up to approximately 12 Weeks	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.
Percentage of Participants Who Had Positive Antibodies to Bezlotoxumab	Up to approximately 12 Weeks	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.
Percentage of Participants Who Had a Clostridium Difficile Infection (CDI) Recurrence	Up to approximately 12 Weeks	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.
Percentage of Participants Who Had a Sustained Clinical Response (SCR)	Up to approximately 12 Weeks	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.
Percentage of High-Risk Participants Who Experienced a CDI Recurrence	Up to approximately 12 Weeks	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.
Percentage of Participants Who Experienced One or More Infusion Related Reaction	Up to approximately 24 hours after infusion on Day 1	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.

Trial Locations

Locations (75): Children's Hospital - Los Angeles ( Site 0021)
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Los Angeles, California, United States
UCSF Medical Center ( Site 0049)
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San Francisco, California, United States
Children's Hospital - Colorado ( Site 0013)
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Aurora, Colorado, United States
Children's Center for Digestive Healthcare ( Site 0052)
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Atlanta, Georgia, United States
University of Chicago ( Site 0019)
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Chicago, Illinois, United States
Our Lady of the Lake Hospital ( Site 0007)
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Baton Rouge, Louisiana, United States
The Johns Hopkins Rubenstein Child Health Building ( Site 0034)
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Baltimore, Maryland, United States
Tufts Medical Center-Floating Hospital for Children ( Site 0046)
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Boston, Massachusetts, United States
Mayo Clinic - Rochester ( Site 0004)
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Rochester, Minnesota, United States
Washington University ( Site 0037)
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Saint Louis, Missouri, United States
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Children's Hospital - Los Angeles ( Site 0021)
🇺🇸Los Angeles, California, United States