E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
recurrence of Clostridium difficile infection (CDI) |
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E.1.1.1 | Medical condition in easily understood language |
recurrence of Clostridium difficile infection (CDI) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10054236 |
E.1.2 | Term | Clostridium difficile infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participant must be 18 years of age or older.
2. 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 stool test for toxigenic C. difficile. from a stool samples collected no more than 7 days before the study infusion
3. Participant must be receiving or planning to receive 10-14 day course of 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.
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E.4 | Principal exclusion criteria |
1. Patient with an uncontrolled chronic diarrheal illness such as, but not limited to, uncontrolled ulcerative colitis or Crohn's disease or with a condition such that their normal 24–hour bowel movement habit is 3 or more loose stools as defined by the Bristol Stool Chart Types 5, 6, and/or 7. Patients with with a history of inflammatory bowel disease who are controlled may be enrolled if in the opinion of the investigator the symptoms are more likely due to CDI than a flare of the inflammatory bowel disease.
2. Patient with a planned surgery for CDI within 24 hours.
3. Patient 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. Patient is breast-feeding or plans to breastfeed prior to the completion of the 12-week study period.
5. A female patient who plans to donate ova prior to the completion of the 12-week study period, or a male patient who is planning to impregnate or provide sperm donation prior to the completion of the 12-Week study period.
6. Patient has previously participated in this study or, has previously received MK-3415 or MK-6072 (either alone or in combination).), has received a C. difficile vaccine, or has received any other experimental monoclonal antibody against C. difficile toxin A or B.
7. Patient plans to donate blood and/or blood products within 6 months following the infusion.
8. Patient 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. Patient has received more than 24 hour regimen of cholestyramine, cholestimide, 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. Patient plans to take medications to control diarrhea or which 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.
12. Patient 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.
13. Patient 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.
14. Patient is not expected to survive for 72 hours.
15. Patient has any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of the patient participating in the study, would make it unlikely for the patient to complete the study, or would confound the results of the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients with CDI recurrence. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Proportion of patients with global cure. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
adaptive design allows for discontinuation of suboptimal treatment arm(s) |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 52 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
Denmark |
Italy |
Austria |
New Zealand |
Portugal |
Australia |
Brazil |
Chile |
Colombia |
Czech Republic |
Finland |
Germany |
India |
Spain |
Israel |
Mexico |
South Africa |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |