A Study of MK-3415, MK-6072, and MK-3415A in Participants Receiving Antibiotic Therapy for Clostridium Difficile Infection (MK-3415A-001) (MODIFY I)

This study is currently recruiting participants.
Verified April 2014 by Merck Sharp & Dohme Corp.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01241552
First received: November 12, 2010
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Clostridium Difficile Infection
Biological: MK-3415
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, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Adaptive Design Study of the Efficacy, Safety, and Tolerability of a Single Infusion of MK-3415 (Human Monoclonal Antibody to Clostridium Difficile Toxin A), MK-6072 (Human Monoclonal Antibody to Clostridium Difficile Toxin B), and MK-3415A (Human Monoclonal Antibodies to Clostridium Difficile Toxin A and Toxin B) in Patients Receiving Antibiotic Therapy for Clostridium Difficile Infection (MODIFY I)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of participants with Clostridium difficile infection (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 local or central lab stool test for toxigenic Clostridium difficile following clinical cure of the initial CDI 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 and no CDI recurrence through Week 12. Clinical cure is defined as participants received ≤ 16 days 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.

  • 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: 1600
Study Start Date: October 2011
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-3415 + SOC
Single intravenous (IV) infusion of 10 mg/kg MK-3415 + Standard of Care for CDI
Biological: MK-3415
A single IV infusion of MK-3415 (10 mg/kg of monoclonal antibody to Clostridium difficile Toxin A)
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 metranidazole, oral vancomycin, IV metronidazole concurrent with oral vancomycin, oral fidaxomicin, or oral fidaxomicin concurrent with IV metronidazole.
Experimental: MK-6072 + SOC
Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI
Biological: MK-6072
A single infusion of MK-6072 (10 mg/kg of monoclonal antibody to Clostridium 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 metranidazole, 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
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)
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 metranidazole, oral vancomycin, IV metronidazole concurrent with oral vancomycin, oral fidaxomicin, or oral fidaxomicin concurrent with IV metronidazole.
Placebo Comparator: Placebo + SOC
Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI
Biological: Placebo
A 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 metranidazole, oral vancomycin, IV metronidazole concurrent with oral vancomycin, oral fidaxomicin, or oral fidaxomicin concurrent with IV metronidazole.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01241552

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

  Show 73 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01241552     History of Changes
Other Study ID Numbers: 3415A-001
Study First Received: November 12, 2010
Last Updated: April 14, 2014
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Clostridium Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Anti-Bacterial Agents
Antibiotics, Antitubercular
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Metronidazole
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on April 16, 2014