A Study of MK-6072 and MK-3415A in Participants Receiving Antibiotic Therapy for Clostridium Difficile Infection (MK-3415A-002)
Condition: Clostridium Difficile Infection
MeSH terms: Infections; Communicable Diseases; Clostridium Infections
Intervention: MK-6072; MK-3415A; Placebo; SOC
Intervention description: Single IV infusion of MK-6072 (10 mg/kg of monoclonal antibody to C. difficile Toxin B); Single IV infusion of MK-3415A (10 mg/kg of monoclonal antibody to C. difficile Toxin A and 10 mg/kg of monoclonal antibody to C. difficile Toxin B); Single IV infusion of normal saline (0.9% sodium chloride); SOC for CDI will be prescribed for 10 to 14 days and can begin on the day of study drug infusion; but the first dose must have been administered prior to or within a few hours following study drug infusion. SOC is defined as the receipt of oral metronidazole, oral vancomycin, IV metronidazole concurrent with oral vancomycin, oral fidaxomicin, or oral fidaxomicin concurrent with IV metronidazole.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 1203.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Clostridium difficile; Clostridium difficile infection (CDI); recurrent Clostridium difficile; vancomycin; metronidazole; monoclonal antibody

Summary:

      MK-3415A is the combination of monoclonal antibodies to Clostridium (C.) difficile toxin A
      (MK-3415) and toxin B (MK-6072). This study will investigate whether: 1) treatment with
      MK-6072 or MK-3415A in addition to standard of care (SOC) antibiotic therapy will decrease
      Clostridium Difficile Infection (CDI) recurrence compared with placebo; and 2) MK-6072 and
      MK-3415A will be generally well tolerated in participants receiving SOC therapy for CDI
      compared with placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant has a diagnosis of CDI defined as: a) presence of diarrhea (passage of 3
             or more loose stools in 24 or fewer hours); and b) positive test for toxigenic C.
             difficile from a stool collected no more than 7 days before study infusion.

          -  Participant is receiving SOC therapy (i.e., oral metronidazole, oral vancomycin, IV
             metronidazole concurrent with oral vancomycin, oral fidaxomicin, or oral fidaxomicin
             concurrent with IV metronidazole) for CDI.

          -  Participant is highly unlikely to become pregnant or to impregnate a partner by
             meeting at least one of the following criteria: a) females not of reproductive
             potential (i.e., one who has either (1) reached natural menopause, defined as 6 months
             of spontaneous amenorrhea with serum follicle stimulating hormone [FSH] levels in the
             postmenopausal range, or 12 months of spontaneous amenorrhea not including cases with
             an underlying disease, such as anorexia nervosa, that causes amenorrhea; (2) 6 weeks
             post surgical bilateral oophorectomy with or without hysterectomy; or (3) bilateral
             tubal ligation); or b) participants of reproductive potential who agree to remain
             abstinent or use (or have their partner use) two acceptable methods of birth control
             (i.e., intrauterine device [IUD], diaphragm with spermicide; contraceptive sponge,
             condom, vasectomy and any registered and marketed hormonal contraceptives that contain
             an estrogen and/or progestational agent including oral, subcutaneous, intrauterine, or
             intramuscular agents) starting at enrollment and throughout the 12-week study.

        Exclusion Criteria:

          -  Participant with an uncontrolled chronic diarrheal illness such that their normal
             24-hour bowel movement habit is 3 or more loose stools.

          -  Participant with planned surgery for CDI within 24 hours.

          -  Female participant with a positive pregnancy test in the 48 hours before infusion and
             pre-menopausal females who are not sterilized and therefore have the potential to bear
             a child who are unwilling to undergo pregnancy testing.

          -  Female participant breast feeding or planning to breast feed before completion of the
             12-week study.

          -  Female participant planning to donate ova before completion of the 12-week study and
             male participants planning to impregnate or donate sperm before completion of the
             12-week study.

          -  Participant has previously participated in this study, has previously received MK-3415
             or MK-6072 (either alone or in combination), has received a C. difficile vaccine, or
             has received another experimental monoclonal antibody against C. difficile toxin A or
             B.

          -  Participant plans to donate blood and/or blood products within 6 months after
             infusion.

          -  Participant has received immune globulin within 6 months before infusion or is
             planning to receive immune globulin before completion of the 12-week study.

          -  Treatment with SOC therapy is planned for longer than 14 days.

          -  Participant has received more than a 24-hour regimen of cholestyramine, colestimide,
             rifaximin, or nitazoxanide within 14 days before infusion or plans to receive these
             medication before completion of the 12-week study period.

          -  Participant plans to take medications that are given to decrease gastrointestinal
             peristalsis, such as loperamide (Imodium™) or diphenoxylate hydrochloride/atropine
             sulfate (Lomotil™) any time during the 14 days after infusion. Participants receiving
             opioid medications at the onset of diarrhea may be included if they are on a stable
             dose or if there is anticipation of a dose decrease or cessation of use.

          -  Participant plans to take the probiotic Saccaromyces boulardii or plans to receive
             fecal transplantation therapy, or any other therapies that have been demonstrated to
             decrease CDI recurrence at any time after infusion (Day 1) and through completion of
             the 12-week study period.

          -  Participant has received another investigational study agent within the past 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.

          -  Participant is not expected to survive for 72 hours.

          -  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 study, or would confound the results of the study.