Clostridium Difficile Infection, Diarrhea
Conditions
Keywords
Clostridium difficile infection, Diarrhea, Pseudomembranous colitis, Clostridium Difficile Toxoid Vaccine, ACAM-CDIFF™ vaccine
Brief summary
This study will further evaluate the ACAM-CDIFF™ vaccine in a population of middle-aged to elderly individuals at risk of exposure to Clostridium difficile because of impending hospitalization or residence in a care facility. Primary Objectives: * To describe the safety profile of subjects in each of the study groups. * To describe the immune responses elicited by toxoid A and toxoid B of subjects in each of the study groups. Observational Objective: * To describe the occurrence of first-time Clostridium difficile infection (CDI) episodes.
Detailed description
Participants will receive 3 doses of either one of 4 different formulations of ACAM-CDIFF™ vaccine or placebo, on one of 3 different schedules. The trial will have 2 stages. Stage I will test 4 different formulations of ACAM-CDIFF™ vaccine. Stage II will explore different vaccination schedules using one of these formulations. Participants will be followed up for safety and immunogenicity; stool samples will also be provided in case of diarrhea.
Interventions
BIOLOGICALClostridium difficile toxoids A and B (Low-dose with adjuvant)
0.5 mL, Intramuscular on Days 0, 7, and 30
BIOLOGICALClostridium difficile toxoids A and B (Low-dose without adjuvant)
0.5 mL, Intramuscular on Days 0, 7, and 30
BIOLOGICALClostridium difficile toxoids A and B (high-dose with adjuvant)
0.5 mL, Intramuscular on Days 0, 7, and 30
BIOLOGICALClostridium difficile toxoids A and B (high-dose without adjuvant)
0.5 mL, Intramuscular on Days 0, 7, and 30
BIOLOGICALPlacebo: 0.9% normal saline
0.5 mL, Intramuscular on Days 0, 7, and 30
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Aged 40 to 75 years on the day of inclusion * Informed consent form has been signed and dated * Able to attend all scheduled visits and to comply with all trial procedures * For a woman of childbearing potential, use of an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 4 weeks after the last vaccination * At risk for developing Clostridium difficile infection during the trial because of impending elective surgery or hospitalization within 60 days of enrollment, or current or impending residence in a long-term care facility or rehabilitation facility.
Exclusion criteria
* Known pregnancy, or a positive urine pregnancy test * Currently breastfeeding a child * Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the first trial vaccination * Planned participation in another clinical trial during the present trial period * Receipt of any vaccine in the 4 weeks preceding the first trial vaccination, except for influenza (seasonal or pandemic) and pneumococcal vaccine * Planned receipt of any vaccine in the 4 weeks following any trial vaccination, except for influenza (seasonal or pandemic) and pneumococcal vaccines * Previous vaccination against Clostridium difficile with either the trial vaccine or another vaccine * Current or prior Clostridium difficile infection (CDI) episode * Receipt of blood or blood-derived products in the past 3 months, which might interfere with assessment of the immune response * Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months) * Self-reported seropositivity for Human Immunodeficiency Virus (HIV), hepatitis B, or hepatitis C * Anticipated or current receipt of kidney dialysis treatment * Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to a vaccine containing any of the same substances * Self-reported thrombocytopenia, contraindicating intramuscular (IM) vaccination * Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM vaccination * Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily * Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures * Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion * Identified as a study site employee who is involved in the protocol and may have direct access to trial-related data * Subjects who have any history of intestinal diverticular bleeding * Subjects who have had surgery within the past three months for gastrointestinal (GI) malignancy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Information concerning the safety profile in terms of solicited and unsolicited reactions in participants following vaccination with ACAM-CDIFF™ Vaccine. | 6 days after each vaccination and up to 6 months post-vaccination 3 |
| Serum antitoxin IgG concentrations to Clostridium difficile toxins A and B in participants vaccinated with ACAM-CDIFF™. | Up to 6 months post-vaccination 3 |
Countries
United States
Outcome results
None listed