A Phase II randomized, placebo-controlled, double-blind, dose ranging study of a Clostridium difficile toxoid vaccine (ACAM-CDIFF) in subjects with Clostridium difficile-associated infection(CDI) - N/A
- Conditions
- MedDRA version: 12.0Level: LLTClassification code 10006835Term: C.difficile diarrhoeaMedDRA version: 12.0Level: LLTClassification code 10012748Term: Diarrhoea, Clostridium difficileRecurrence of Clostridium difficile Infection (CDI)MedDRA version: 12.0Level: LLTClassification code 10022661Term: Intestinal infection due to clostridium difficileMedDRA version: 12.0Level: LLTClassification code 10054236Term: Clostridium difficile infectionMedDRA version: 12.0Level: LLTClassification code 10006834Term: C.difficile diarrheaMedDRA version: 12.0Level: LLTClassification code 10012734Term: Diarrhea, Clostridium difficile
- Registration Number
- EUCTR2008-004907-69-GB
- Lead Sponsor
- Sanofi Pasteur Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 612
1. Adult subjects aged =18 years.
2. Subjects who have been diagnosed with primary CDI within the last 12 days. Primary CDI is defined as a documented, laboratory-confirmed CDI event that is either the first in the subject’s history or is occurring more than 90 days after a prior event.
A CDI event is defined as follows:
• a change in bowel habit with passage of 3 or more loose stools within a 24 hour period (that conforms to the shape of the container it is placed into)
AND:
• a positive result is obtained via stool toxin test for C. difficile using either ELISA/EIA or PCR. The ELISA/EIA assay can be used to test for both toxin A and toxin B, while PCR can be used to test only for toxin B and for toxin regulator genes.
AND also:
• absence of another identified cause for diarrhoea
In addition, a stool cytotoxicity assay will be done in order to confirm the ELISA/EIA or PCR results. Vaccination may proceed before the results of this assay are known. However, if the results are available before a subject has received all 3 doses of ACAM-CDIFF vaccine and are found to be negative, vaccination will be halted, and the subject will be followed only for safety (until 6 months after the last vaccination).
A positive result for the stool cytotoxicity assay means that the sample is either positive for cytotoxin or has a toxin-producing C. difficile by culture.
3. Subjects who are judged by the investigator to be medically stable and have a White Cell Count (WCC) < 20,000 per µL and stable serum creatinine levels.
4. Subjects who understand the risks and benefits of participation, are willing and able to comply with the study procedures and visit schedules outlined, and who have provided written informed consent for the study.
5. All female subjects of child-bearing potential must not be pregnant or lactating, and must have a negative serum pregnancy test at screening. For females of child-bearing potential, one of the following methods of contraception must have been established at least 30 days prior to baseline examination and continue for 30 days post third vaccination:
• Combined oral contraceptive pills (subjects should be consulted on the potential ineffectiveness of the oral contraceptive pill in the presence of diarrhoea and/or treatment with antibiotics, and barrier methods mandated as appropriate additional protection)
• Combined contraceptive (as distinct from hormonal replacement) patch
• Vaginal combined hormonal contraceptive ring
• Injectable (combined and single) hormonal contraception (within effective time since injection)
• Hormonal contraceptive (as distinct from hormonal replacement) implants
• IUD (within appropriate time of insertion)
6. Female subjects unable to bear children must have this documented in the case report form (e.g., tubal ligation, hysterectomy, or post-menopausal [defined as a minimum of 1 year since the last menstrual period]). Pregnancy testing of pre-menopausal women with tubal ligation without hysterectomy will be required at screening and during the study treatment period;
7. Male subjects: If his partner might become pregnant the male subject’s partner must use a reliable form of contraception during the study, (one of the following methods of contraception must be used and continue for 30 days post third vaccination: e.g. oral contraception (for the partner) and condom, intra-uterine device (for the partner) and condom, or diaphragm with spermicide (for the partner) and a condom). Hormonal
1. Subjects who are currently on treatment for a CDI recurrence, or who have had a documented, laboratory-confirmed CDI event, with or without treatment, within the past 90 days.
2. Subjects who are currently or have recently (within one month prior to enrolment in trial) been treated with immunoglobulin therapy.
3. Female subjects who are pregnant or breast feeding.
4. Subjects with WCC > 20,000 per µL and acute rising serum creatinine levels (an acute increase of >50% increase as assessed by investigator).
5. Concurrent, acutely life-threatening diseases.
6. Predicted survival < 91 days as determined by the investigator
7. Subjects with a platelet count of less than 70,000 cells/mm3 or other severe coagulation disorder that may increase risk of bleeding associated with vaccination.
8. Subjects who are significantly immunocompromised or immunodeficient due to medications (current or expected during study course) or disease, including:
• Subjects who are taking immunosuppressive therapy including systemic steroid therapy (e.g.; equivalent of prednisone =10 mg daily for more than 14 days) or who are expected to need to take such medication during the course of the study.
• Subjects who are known to be HIV+
9. Subjects who have received chemotherapy or radiation therapy within the past 6 months.
10. Subjects with lymphoproliferative disorders.
11. Subjects with a history of severe allergic reaction associated with respiratory distress, hypotension or other life-threatening condition to any medication or excipient including but not limited to alum and metronidazole or vancomycin.
12. Subjects who are unable to receive antibiotic standard of care for CDI.
13. Subjects with a body mass index (BMI) less than 14.0 kg/m2 or greater than 35 kg/ m2.
14. Subjects who have chronic or persistent intermittent diarrhoea or abdominal pain due to active Crohn’s disease, Ulcerative Colitis, Celiac disease, or other non-C. difficile causes.
15. Subjects who, in the opinion of the investigator, have any personal situation, medical condition, or illness (including mental illnesses) that could limit their ability to complete through Day 91 of the study including planned travel or surgery.
16. Organ donation within 30 days of vaccination.
17. Individuals who have previously received C. difficile toxoid vaccine.
18. Receipt of any vaccine in the 30 days preceding the first trial vaccination, with the exception of influenza vaccine and pneumococcal vaccine
19. Planned receipt of any vaccine in the 30 days following any trial vaccination, with the exception of influenza vaccine and pneumococcal vaccine
20. Subjects who are receiving other non-standard of care therapy for CDI.
21. Subjects who have any history of intestinal diverticular bleeding
22. Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 30 days preceding the (first) trial vaccination.
23. Planned participation in another clinical trial during the present trial period.
24. Subjects who have had surgery within the past three months for GI malignancy.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method