Clinical study with biological medicine treating infection with Clostridium Difficile

• Register: EUCTR
• Last refreshed on: 22 December 2015
• Main ID: EUCTR2011-004590-90-DK
• Date of registration: 16/12/2011
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
• Public title: Clinical study with biological medicine treating infection with Clostridium Difficile
• Scientific 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
• Date of first enrolment: 20/12/2011
• Target sample size: 1600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-004590-90
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: adaptive design allows for discontinuation of suboptimal treatment arm(s) If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4

Countries of recruitment

Australia, Austria, Belgium, Brazil, Canada, Chile, Colombia, Czech Republic, Denmark, Germany, India, Israel, Italy, Mexico, New Zealand, Portugal, Puerto Rico, South Africa, Spain, United Kingdom, United States

Contacts

• Name: Mary Beth Dorr
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

• Name: Mary Beth Dorr
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Participant must be 18 years of age or older.
2. Participant has a diagnosis of CDI as defined by:
a. Presence of diarrhea, as defined by passage of 3 or more loose stools in 24 or fewer hours, AND
b. A positive stool test for toxigenic C. difficile.
3. 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.
4. 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)
5. 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 800
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 800

Exclusion criteria:
1. participant with an active chronic diarrheal illness such as, but not limited to, ulcerative colitis or Crohn's disease or with a condition that causes routine passage of loose stool (e.g., an ostomy).
2. Participant with a planned surgery for CDI within 24 hours.
3. 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.
4. Participant is breast-feeding or plans to breastfeed prior to the completion of the 12-week study period.
5. 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.
6. Participant has previously participated in this study or has previously received MK-3415 or MK-6072 (either alone or in combination).
7. Participant plans to donate blood and/or blood products within 6 months following the infusion.
8. 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.
9. Treatment with SOC therapy is planned for longer than 14 days
10. Participant has received cholestyramine, 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.
11. Participant plans to take antiperistaltic agents, 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.
12. Participant plans to take the probiotic Saccharomyces boulardii at any time following infusion (Day 1) and through the completion of the 12-week study period.
13. 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 during the 12- week study period.
14. Participant is not expected to survive for 72 hours.
15. 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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

recurrence of Clostridium difficile infection (CDI)
MedDRA version: 16.1 Level: PT Classification code 10054236 Term: Clostridium difficile infection System Organ Class: 10021881 - Infections and infestations

Intervention(s)

Product Code: MK-3415
Pharmaceutical Form: Solution for injection
Current Sponsor code: MK-3415
Other descriptive name: Human monoclonal antibodies to Clostridium difficile Toxin A
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25.0-
Pharmaceutical form of the placebo: Injection
Route of administration of the placebo: Intravenous use

Product Name: MK-6072, MDX-1388, CDB1
Product Code: MK-6072
Pharmaceutical Form: Solution for injection
Current Sponsor code: MK-6072
Other descriptive name: Human monoclonal antibodies to Clostridium difficile Toxin B
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25.0-
Pharmaceutical form of the placebo: Injection
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 12 (Day 85±5 days)

Main Objective: assess whether MK-3415A given with the standard of care antibacterial therapy (SOC) relative to MK-3415, MK-6072, and placebo given with SOC reduces CDI recurrence over a period of 12 weeks and to evaluate the safety profile of a single infusion of monoclonal antibody therapy compared to placebo.

Primary end point(s): Proportion of patients with CDI recurrence.

Secondary Objective: determine the proportion of patients with global cure (defined as clinical cure of the initial episode and no CDI recurrence through Week 12) in the treatment group receiving MK3415A given with SOC compared to the treatment group receiving placebo and SOC.

Secondary Outcome(s)

Secondary end point(s): Proportion of patients with global cure.

Secondary ID(s)

MK-3415A-001

2011-004590-90-DE

Source(s) of Monetary Support

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.