Study of Different Formulations of a Clostridium Difficile Toxoid Vaccine Given at Three Different Schedules in Adults
Study of Different Formulations of a Clostridium Difficile Toxoid Vaccine Given at Three Different Schedules in Adults
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.
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.