A Study of MK-3415, MK-6072, and MK-3415A in Participants Receiving Antibiotic Therapy for Clostridium Difficile Infection (MK-3415A-001)
Condition: Clostridium Difficile Infection
MeSH terms: Infections; Communicable Diseases; Clostridium Infections
Intervention: MK-3415; MK-6072; MK-3415A; Placebo; SOC
Intervention description: A single IV infusion of MK-3415 (10 mg/kg of monoclonal antibody to Clostridium difficile Toxin A); A single infusion of MK-6072 (10 mg/kg of monoclonal antibody to Clostridium difficile Toxin B); A single IV infusion of MK-3415A (10 mg/kg of monoclonal antibody to Clostridium difficile Toxin A and 10mg/kg of monoclonal antibody to Clostridium difficile Toxin B); A single IV infusion of normal saline (0.9% sodium chloride); Standard of care (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 metranidazole, oral vancomycin, IV metronidazole concurrent with oral vancomycin, oral fidaxomicin, or oral fidaxomicin concurrent with IV metronidazole.
Intervention MeSH terms: Antibodies, Monoclonal
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1452.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Clostridium difficile; recurrent Clostridium difficile; vancomycin; metronidazole; monoclonal antibody; Clostridium difficile infection (CDI)

Summary:

      This study will investigate whether: 1) treatment with MK-3415A in addition to standard of
      care (SOC) antibiotic therapy will decrease Clostridium difficile infection (CDI) recurrence
      as compared to treatment with MK-6072 or MK-3415, 2) treatment with MK-3415A, MK-6072, or
      MK-3415, in addition to SOC antibiotic therapy will decrease CDI recurrence as compared to
      placebo, and 3) MK-3415A, MK-6072, and MK-3415 will be generally well tolerated in
      participants receiving SOC therapy for CDI as compared to placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  participant has a confirmed diagnosis of CDI as defined by: a. diarrhea, as defined by
             passage of 3 or more loose stools in 24 or fewer hours, AND b. A positive test for
             toxigenic C. difficile from a stool collected no more than 7 days before study
             infusion.

          -  participant must be receiving SOC therapy for CDI. SOC therapy 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.

          -  participant is highly unlikely to become pregnant or to impregnate a partner since
             they meet at least one of the following criteria: a. A female participant who is not
             of reproductive potential is eligible without requiring the use of contraception. A
             female participant who is not of reproductive potential is defined as: 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 as
             determined by the local laboratory, or 12 months of spontaneous amenorrhea); (2) 6
             weeks post surgical bilateral oophorectomy with or without hysterectomy; or (3)
             bilateral tubal ligation. Spontaneous amenorrhea does not include cases for which
             there is an underlying disease that causes amenorrhea (e.g. anorexia nervosa). b. A
             participant who is of reproductive potential agrees to remain abstinent or use (or
             have their partner use) 2 acceptable methods of birth control starting at enrollment
             and through the 12 Week study period. Acceptable methods of birth control are:
             intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom,
             vasectomy and any registered and marketed hormonal contraceptives that contain an
             estrogen and/or a progestational agent (including oral, subcutaneous, intrauterine, or
             intramuscular agents)

          -  participant or legal representative must have voluntarily agreed to participate by
             providing written informed consent after the nature of the study has been fully
             explained.

        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 a planned surgery for CDI within 24 hours.

          -  participant has a positive pregnancy test in the 48 hours before the infusion or is
             unwilling to undergo pregnancy testing if a pre-menopausal female who is not
             sterilized and therefore has the potential to bear a child.

          -  participant is breast-feeding or plans to breast-feed prior to the completion of the
             12-week study period.

          -  A female participant who plans to donate ova prior to the completion of the 12-week
             study period, or a male participant who is planning to impregnate or provide sperm
             donation prior to the completion of the 12-week study period.

          -  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 following the
             infusion.

          -  participant has received immune globulin within 6 months prior to receipt of the
             infusion or is planning to receive immune globulin prior to the completion of the
             12-week study period.

          -  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 prior to receipt of the infusion or is
             planning to receive these medications prior to the 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™), at any time during the 14 days following 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 Saccharomyces boulardii or receive fecal
             transplant therapy, or any other therapies that have been demonstrated to decrease CDI
             recurrences at any time following infusion (Day 1) and through the completion of the
             12-week study period.

          -  participant has received another investigational study 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 study period.

          -  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 participating in the study, would
             make it unlikely for the participant to complete the study, or would confound the
             results of the study.