A Study of MK-6072 and MK-3415A in Participants Receiving Antibiotic Therapy for Clostridium Difficile Infection (MK-3415A-002) (MODIFY II)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Clostridium Difficile Infection

Treatments: Biological: MK-6072; Biological: MK-3415A; Biological: Placebo; Drug: SOC

Study type: Interventional

Funder types: Industry

Identifiers

NCT01513239

2011-004994-94 (EudraCT Number)

3415A-002

132231 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

An extended 9-month follow-up to assess for CDI recurrence through Month 12 will be conducted in a subset of participants.

Enrollment: 1,203 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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1,203 participants in 3 patient groups, including a placebo group

MK-6072 + SOC

Experimental group

Description:

Single intravenous (IV) infusion of 10 mg/kg MK-6072 + Standard of Care (SOC) for CDI

Treatment:

Biological: MK-6072

Drug: SOC

MK-3415A + SOC

Experimental group

Description:

Single IV infusion of 10 mg/kg MK-3415A + SOC for CDI

Treatment:

Biological: MK-3415A

Drug: SOC

Placebo + SOC

Placebo Comparator group

Description:

Normal saline IV infusion (0.9% sodium chloride) + SOC for CDI

Treatment:

Biological: Placebo

Drug: SOC