Prevention of recurrent Clostridium difficile infection (CDI) MedDRA version: 20.0 Level: LLT Classification code 10012748 Term: Diarrhoea, Clostridium difficile System Organ Class: 100000004862
Conditions
Interventions
Trade Name: ZINPLAVA (Bezlotoxumab)
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: BEZLOTOXUMAB
Current Sponsor code: MK-6072
Other descriptive name: BEZLOTOXUMAB
Conc
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. At the time of screening, participant A) has suspected or confirmed CDI, as evidenced by the following: 1. had a change in normal bowel habits for 2 or more calendar days with either watery diarrhea (for participants using diapers or other type of fecal collection device, Bristol Stool Scale types 6 or 7) or at least 6 UBMs (eg, takes shape of container, or Bristol Stool Scale types 5, 6, or 7) within a 48-hour period, and 2.produced a stool sample that has tested positive for toxigenic C. difficile according to local diagnostic criteria. B) is receiving or is planning to receive a 10- to 21-day course of antibacterial drug treatment for CDI, which is defined as oral vancomycin, oral metronidazole, or oral fidaxomicin. Additionally, IV metronidazole may be given concurrently with oral vancomycin or oral fidaxomicin 2. At the time of randomization/study infusion, participant: a)has a diagnosis of CDI confirmed by a diagnostic assay which detects the presence of C. difficile toxin in stool and b)is still receiving antibacterial drug treatment for CDI 3.Participant is of either sex and of any race, and =1 year to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Participant has an uncontrolled chronic diarrheal illness such as, but not limited to, Crohn’s disease, ulcerative colitis, or with a condition such that their normal 24-hour bowel movement habit is 3 or more UBMs. Participants with a history of IBD who are controlled (ie, had no recent active diarrhea/UBMs prior to current CDI episode) may be enrolled if in the opinion of the investigator, the symptoms are more likely due to CDI than a flare of the IBD 2. Has a known hypersensitivity to bezlotoxumab, its active substance and/or any of its excipients 3. Participant for whom, at the time of randomization, the planned course of antibacterial drug treatment for CDI is longer than 21 days 4. Participant has received any treatment or procedure listed in the protocol within the indicated exclusion window 5. Participant has previously participated in this trial, has previously received bezlotoxumab, has received an experimental mAb against C. difficile toxin B, or has received a vaccine directed against C. difficile or its toxins 6. Participant has received an investigational trial agent within the previous 30 days, or is currently participating in or scheduled to participate in any other clinical trial with an investigational agent during the 12-week trial period 7. Participant is not expected to survive for 72 hours 8. Participant has any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of the participant, would make it unlikely for the participant to complete the trial, or would confound the results of the trial 9. Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To characterize bezlotoxumab PK in 2 age cohorts (Age Cohort 1: 12 to <18 years; Age Cohort 2: 1 to <12 years) of pediatric participants to support dose selection in this population. 2.To evaluate the safety and tolerability of a single infusion of bezlotoxumab as compared with a single infusion of placebo through 12 weeks following infusion.;Secondary Objective: 1. To estimate the proportion of participants who have a CDI recurrence within 12 weeks following administration of a single infusion of bezlotoxumab or placebo. 2. To estimate the proportion of participants with sustained clinical response over a period of 12 weeks in participants who received a single infusion of bezlotoxumab or placebo. 3. To estimate efficacy (CDI recurrence and sustained clinical response) in the subset of participants at high risk of CDI recurrence within 12 weeks following administration of a single infusion of bezlotoxumab or placebo. 4. To assess the incidence of infusion-related reactions in participants who received a single infusion of bezlotoxumab or placebo. 5. To assess the potential for bezlotoxumab to induce immunogenicity within 12 weeks following administration of a single infusion of bezlotoxumab.;Primary end point(s): 1. Pharmacokinetic: The AUC0-inf will be determined for each age cohort from bezlotoxumab serum concentration data. 2. Safety: Proportion of participants with any AE and proportion of participants with a discontinuation due to an AE through 12 weeks following infusion.;Timepoint(s) of evaluation of this end point: Any endpoint assessment would need data analysis 12 weeks following a single infusion of bezlotoxumab or placebo 1. PK/PD endpoint will be assessed at following time points:a) End of Panel A Age Cohort 1 (12 subjects completed 12 wk F/UP) b) end of Panel A Age Cohort 2 (12 subjects completed 12 wk F/UP) c) At the conclusion of this trial, PK data from all participants who received the trial medication and who have sufficient d | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: 1. Proportion of participants who have a CDI recurrence within 12 weeks of study medication infusion 2. Proportion of participants with sustained clinical response over a period of 12 weeks 3.Proportion of participants who have a CDI recurrence and proportion of participants who achieve sustained clinical response within 12 weeks of study medication infusion in the subset of participants at high risk for CDI recurrence Safety: 4. Proportion of participants experiencing 1 or more infusion-related reactions within 24 hours following the start of the infusion Immunogenicity: 5. Proportion of participants with treatment-emergent positive antibodies to bezlotoxumab in serum through 12 weeks following a single dose of bezlotoxumab;Timepoint(s) of evaluation of this end point: Any endpoint assessment would need data analysis 12 weeks following administration of a single infusion of bezlotoxumab or placebo. All secondary endpoints will be assessed at following time points a) End of Panel A Age Cohort 1 (12 subjects completed 12 wk F/UP); B)end of Panel A Age Cohort 2 (12 subjects completed 12 wk F/UP) and c) end of study for aggregate data | — |
Countries
Argentina, Brazil, Colombia, Czechia, Czech Republic, Germany, Hungary, Malaysia, Mexico, Norway, Poland, Portugal, Romania, South Africa, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactStephen Richard Holden
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Outcome results
None listed