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

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.