study of different formulations of a clostridium difficile toxoid vaccine given at three different schedules in adults

Conditions: Clostridium Difficile Infection; Diarrhea

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.

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.

Eligibility criteria:
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.

Keywords: clostridium difficile infection diarrhea pseudomembranous colitis clostridium difficile toxoid vaccine acam-cdiff™ vaccine