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

August 6, 2018 updated by: Merck Sharp & Dohme LLC

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 Clostridium Difficile Toxin B), and MK-3415A (Human Monoclonal Antibodies to Clostridium Difficile Toxin A and B) in Patients Receiving Antibiotic Therapy for Clostridium Difficile Infection (MODIFY II)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Interventional

Enrollment (Actual)

1203

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MK-6072 + SOC
Single intravenous (IV) infusion of 10 mg/kg MK-6072 + Standard of Care (SOC) for CDI
Biological: MK-6072
Single IV infusion of MK-6072 (10 mg/kg of monoclonal antibody to C. difficile Toxin B)
Drug: SOC
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 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 + SOC for CDI
Drug: SOC
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 metronidazole, oral vancomycin, IV metronidazole concurrent with oral vancomycin, oral fidaxomicin, or oral fidaxomicin concurrent with IV metronidazole.
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)
Placebo Comparator: Placebo + SOC
Normal saline IV infusion (0.9% sodium chloride) + SOC for CDI
Drug: SOC
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 metronidazole, oral vancomycin, IV metronidazole concurrent with oral vancomycin, oral fidaxomicin, or oral fidaxomicin concurrent with IV metronidazole.
Biological: Placebo
Single IV infusion of normal saline (0.9% sodium chloride)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With CDI Recurrence
Time Frame: 12 weeks
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 (local or central) for toxigenic C. difficile after clinical cure of the initial CDI episode. 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 =< 14 day regimen.
12 weeks
Percentage of Participants With One or More Adverse Events During 4 Weeks Following Infusion Treatment
Time Frame: Up to 4 weeks
An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the medicinal product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the medicinal product, is also an adverse event.
Up to 4 weeks
Percentage of Participants With One or More Drug-related Adverse Events During 4 Weeks Following Infusion Treatment
Time Frame: Up to 4 weeks
An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the medicinal product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the medicinal product, is also an adverse event. A drug-related adverse event is determined by the investigator to be related to the drug.
Up to 4 weeks
Percentage of Participants With One or More Serious Drug-related Adverse Events During 4 Weeks Following Infusion Treatment
Time Frame: Up to 4 weeks
A serious adverse event (SAE) is any AE occurring at any dose or during any use of the medicinal 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 other important medical events. A serious drug-related adverse event is determined by the investigator to be related to the drug.
Up to 4 weeks
Percentage of Participants Who Discontinued Study Medication Due to an Adverse Event During 4 Weeks Following Infusion Treatment
Time Frame: Up to 4 weeks
An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the medicinal product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the medicinal product, is also an adverse event.
Up to 4 weeks
Percentage of Participants With One or More Infusion-specific Adverse Events on the Day of Infusion or the Day After Infusion
Time Frame: Up to 24 hours
An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the medicinal product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the medicinal product, is also an adverse event.
Up to 24 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Global Cure
Time Frame: 12 weeks
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 =< 14 day regimen.
12 weeks
Percentage of Participants With CDI Recurrence in Those With Clinical Cure of the Initial CDI Episode
Time Frame: 12 weeks
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 (local or central) for toxigenic C. difficile. 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 =< 14 day regimen.
12 weeks
Percentage of Participants With CDI Recurrence in Those With a History of CDI in the 6 Months Prior to Enrollment
Time Frame: 12 weeks
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 (local or central) for toxigenic C. difficile. 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 =< 14 day regimen.
12 weeks
Percentage of Participants With CDI Recurrence in Those With the 027 Ribotype
Time Frame: 12 weeks
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 (local or central) for toxigenic C. difficile. 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 =< 14 day regimen. The 027 ribotype is a more virulent, epidemic strain responsible for several outbreaks of disease associated with an increased risk of severity and mortality.
12 weeks
Percentage of Participants With CDI Recurrence in Those With an Epidemic Strain
Time Frame: 12 weeks
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 (local or central) for toxigenic C. difficile. 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 =< 14 day regimen. An epidemic strain includes ribotypes 027, 014, 002, 001, 106 or 020.
12 weeks
Percentage of Participants With CDI Recurrence in Those With Clinically Severe CDI
Time Frame: 12 weeks
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 (local or central) for toxigenic C. difficile. 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 =< 14 day regimen. Participants with clinically severe CDI have a Zar Score greater than or equal to 2 points 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).
12 weeks
Percentage of Participants With CDI Recurrence in Those 65 Years and Older
Time Frame: 12 weeks
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 (local or central) for toxigenic C. difficile. 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 =< 14 day regimen.
12 weeks
Percentage of Participants With CDI Recurrence in Those With Compromised Immunity
Time Frame: 12 weeks
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 (local or central) for toxigenic C. difficile. 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 =< 14 day regimen. Compromised immunity is 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.
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2012

Primary Completion (Actual)

May 22, 2015

Study Completion (Actual)

May 22, 2015

Study Registration Dates

First Submitted

January 16, 2012

First Submitted That Met QC Criteria

January 19, 2012

First Posted (Estimate)

January 20, 2012

Study Record Updates

Last Update Posted (Actual)

September 5, 2018

Last Update Submitted That Met QC Criteria

August 6, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3415A-002
  • 132231 (Registry Identifier: JAPIC-CTI)
  • 2011-004994-94 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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