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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
1,452
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.
Percentage of Participants With Clostridium Difficile Infection (CDI) Recurrence
CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic Clostridium (C.) difficile following clinical cure of the initial CDI episode
Time frame: Up to 12 weeks
Percentage of Participants With One or More Adverse Events (AEs) During 4 Weeks Following Infusion
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended signs (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specific procedure, whether or not considered related to the medicinal product or protocol specific procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time frame: Up to 28 days
Percentage of Participants With Any Drug-related AE During 4 Weeks Following Infusion
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended signs (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specific procedure, whether or not considered related to the medicinal product or protocol specific procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. A drug-related AE was an AE determined by the investigator to be related to the drug.
Time frame: Up to 28 days
Percentage of Participants With Any Serious Adverse Events (SAEs) During 4 Weeks Following Infusion
A SAE is any AE occurring at any dose or during any use of Sponsor's product that: results in death; or is life threatening; or results in a persistent or significant disability/incapacity; or results in or prolongs an existing inpatient hospitalization; or is a congenital anomaly/birth defect; or is a cancer, or is associated with an overdose (whether accidental or intentional); or is other important medical events.
Time frame: Up to 28 days
Percentage of Participants With Any Serious Drug-related Adverse Events During 4 Weeks Following Infusion
A SAE is any AE occurring at any dose or during any use of Sponsor's product that: results in death; or is life threatening; or results in a persistent or significant disability/incapacity; or results in or prolongs an existing inpatient hospitalization; or is a congenital anomaly/birth defect; or is a cancer, or is associated with an overdose (whether accidental or intentional); or is other important medical events. A serious drug-related AE was a SAE determined by the investigator to be related to the drug.
Time frame: Up to 28 days
Percentage of Participants Who Discontinued Study Medication Due to an AE During 4 Weeks Following Infusion
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended signs (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specific procedure, whether or not considered related to the medicinal product or protocol-specific procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time frame: Up to 28 days
Percentage of Participants With Infusion-specific AEs
Infusion-specific AEs included local infusion site AEs; and systemic AEs which include nausea, vomiting, chills, fatigue, feeling hot, infusion site conditions (bruising, coldness, erythema, extravasation, pain, phlebitis, pruritus), pyrexia, arthralgia, musculoskeletal pain, myalgia, dizziness, headache, dysphonia, nasal congestion, pruritus, rash, pruritic rash, urticaria, flushing, hot flush, hypertension, and hypotension.
Time frame: Up to 24 hours
Percentage of Participants With Global Cure
Global Cure is defined as the clinical cure of the initial CDI episode and no CDI recurrence through Week 12. Clinical cure is defined as participants who received ≤ 14 day regimen of SOC therapy and have no diarrhea (≤2 loose stools per 24 hours) for two consecutive days following completion of SOC therapy for the initial CDI episode.
Time frame: Up to 12 weeks
Percentage of Participants With CDI Recurrence in Those With Clinical Cure of the Initial CDI Episode
CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode. Clinical cure is defined as participants who received ≤ 14 day regimen of SOC therapy and have no diarrhea (≤2 loose stools per 24 hours) for two consecutive days following completion of SOC therapy for the baseline CDI episode.
Time frame: Up to 12 weeks
Percentage of Participants ≥ 65 Years of Age at Study Entry With CDI Recurrence
CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode.
Time frame: Up to 12 weeks
Percentage of Participants With a History of CDI in the 6 Months Prior to Enrollment With CDI Recurrence
CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode.
Time frame: Up to 12 weeks
Percentage of Participants With Clinically Severe CDI at Study Entry With CDI Recurrence
CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode. Clinically severe CDI is defined as a Zar Score ≥ 2 based on the presence of 1 or more of the following: 1) age \>60 years old (1 point); 2)body temperature \>38.3°C (\>100°F) (1 point); 3) albumin level ˂2.5 mg/dL (1 point); 4) peripheral white blood cell count \>15,000 cells/mm\^3 within 48 hours (1 point); 5) endoscopic evidence of pseudomembranous colitis (2 points); and 6) treatment in Intensive Care Unit (2 points).
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Time frame: Up to 12 weeks
Percentage of Participants With the B1/NAP1/027 Strain of C. Difficile at Study Entry With CDI Recurrence
CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode.
Time frame: Up to 12 weeks
Percentage of Participants With an Epidemic Strain of C. Difficile (Ribotypes 027, 014, 002, 001, 106, and 020) at Study Entry With CDI Recurrence
CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode.
Time frame: Up to 12 weeks
Percentage of Participants With Compromised Immunity at Study Entry With CDI Recurrence
CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode. Compromised immunity is defined as follows: an active hematological malignancy (including leukemia, lymphoma, multiple myeloma), an active malignancy requiring recent cytotoxic chemotherapy, receipt of a prior hematopoietic stem cell transplant, receipt of a prior solid organ transplant, asplenia, or neutropenia/pancytopenia due to other conditions.
Time frame: Up to 12 weeks