Study of a Candidate Clostridium Difficile Toxoid Vaccine in Subjects at Risk for C. Difficile Infection

The study is designed as an event-driven group sequential protocol with 4 interim analyses at
defined information milestones and a final analysis when a specific number of clinical
endpoints are reached.

Subjects will be randomly assigned to receive either the candidate vaccine or a placebo that
will be administered in a 3-dose schedule.

Inclusion Criteria:

- Aged ≥ 50 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

- Covered by health insurance (if required)

- Must fulfill at least 1 of the following criteria

Risk Stratum 1:

- Has had at least 2 hospital stays, each lasting at least ≥ 24 hours, in the 12 months
before enrollment, and

- Has received systemic (not topical) antibiotics in the 12 months before enrollment, or

Risk Stratum 2:

- Is anticipated to have an in-patient hospitalization for a planned surgical procedure
within 60 days of enrollment. The impending hospital stay is planned to be ≥ 72 hours
for a surgery involving 1 of the following:

- Kidney/bladder/urinary system

- Musculoskeletal system

- Respiratory system

- Circulatory system

- Central nervous system.

Exclusion Criteria:

- Subject is pregnant, or lactating, or of childbearing potential (to be considered of
non-childbearing potential, a female must be post-menopausal for at least 1 year,
surgically sterile, or using an effective method of contraception or abstinence from
at least 4 weeks prior to the first vaccination and until at least 4 weeks after the
last vaccination)

- Participation in the 4 weeks preceding the first trial vaccination or participation
during the present trial period in another clinical trial investigating a vaccine,
drug, medical device, or medical procedure

- Receipt of any vaccine in the 4 weeks preceding the first trial vaccination except for
influenza (seasonal or pandemic) and pneumococcal vaccines. This exception includes
monovalent pandemic influenza vaccines and multivalent influenza vaccines

- Previous vaccination against C. difficile with either the trial vaccine, another
vaccine, or monoclonal antibodies

- Diarrhea on day of enrollment

- Self-reported current or prior CDI episode

- Anticipated or current receipt of kidney dialysis treatment

- History of gastrointestinal surgery for gastrointestinal malignancy (Note:
Colonoscopy, polypectomy, and appendectomy are not exclusion criteria.)

- History of inflammatory bowel disease, irritable bowel syndrome (must include diarrhea
as a symptom), colostomy, or small or large intestine bowel surgery where resection
was performed

- Receiving enteral feeding (e.g., nasogastric, gastrostomy, and jejunostomy tube
feeding)

- 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)

- Known systemic hypersensitivity to any of the vaccine components, or history of a
life-threatening reaction to the vaccine used in the trial or to a vaccine containing
any of the same substances

- Self-reported thrombocytopenia, contraindicating intramuscular 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 in the opinion of the Investigator

- Chronic illness that, in the opinion of the investigator, is at a stage where it might
interfere with trial conduct or completion

- Moderate or severe acute illness/infection (according to investigator judgment) on the
day of vaccination or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]). A
prospective subject should not be included in the study until the condition has
resolved or the febrile event has subsided

- Identified as an Investigator or employee of the Investigator or study center with
direct involvement in the proposed study, or identified as an immediate family member
(i.e., parent, spouse, natural or adopted child) of the Investigator or employee with
direct involvement in the proposed study.