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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Merck Sharp & Dohme Corp.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01513239
First received: January 16, 2012
Last updated: October 1, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Clostridium Difficile Infection
Biological: MK-6072
Biological: MK-3415A
Biological: Placebo
Drug: SOC
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of a Single Infusion of MK-6072 (Human Monoclonal Antibody to C. Difficile Toxin B), and MK-3415A (Human Monoclonal Antibodies to C. Difficile Toxin A and B) in Patients Receiving Antibiotic Therapy for C. Difficile Infection (MODIFY II)

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of participants with CDI recurrence [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 lab stool test for toxigenic C. difficile after clinical cure of the initial episode.


Secondary Outcome Measures:
  • Number of participants with Global Cure [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Global cure is defined as the clinical cure of the initial CDI episode with no CDI recurrence through Week 12. (Clinical cure is defined as no diarrhea [2 or fewer loose stools per 24 hours] for 2 consecutive days following completion of SOC therapy for the initial CDI episode in participants who received 16 or fewer days of SOC therapy.)

  • Number of participants with CDI recurrence in those with clinical cure of the initial CDI episode [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 1200
Study Start Date: February 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-6072 + SOC
Single intravenous (IV) infusion of 10 mg/kg MK-6072 + Standard of Care for CDI
Biological: MK-6072
Single infusion of MK-6072 (10 mg/kg of monoclonal antibody to C. difficile Toxin B)
Drug: SOC
Standard of care (SOC) for CDI will be prescribed for 10 to 14 days beginning on the day of 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.
Experimental: MK-3415A + SOC
Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI
Biological: MK-3415A
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)
Drug: SOC
Standard of care (SOC) for CDI will be prescribed for 10 to 14 days beginning on the day of 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.
Placebo Comparator: Placebo + SOC
Normal saline IV infusion (0.9% sodium chloride) + Standard of Care for CDI
Biological: Placebo
Single IV infusion of normal saline (0.9% sodium chloride)
Drug: SOC
Standard of care (SOC) for CDI will be prescribed for 10 to 14 days beginning on the day of 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.

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01513239

Contacts
Contact: Toll Free Number 1-888-577-8839

  Show 53 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01513239     History of Changes
Other Study ID Numbers: 3415A-002, 132231
Study First Received: January 16, 2012
Last Updated: October 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Clostridium difficile
Clostridium difficile infection (CDI)
recurrent Clostridium difficile
vancomycin
metronidazole
monoclonal antibody

Additional relevant MeSH terms:
Communicable Diseases
Infection
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 21, 2014