Study of a Candidate Clostridium Difficile Toxoid Vaccine in Subjects at Risk for C. Difficile Infection
Condition: Clostridium Difficile Infection
MeSH terms: Infections; Communicable Diseases; Clostridium Infections
Intervention: C. difficile Toxoid Vaccine; Placebo: 0.9% normal saline
Intervention description: 0.5 mL, Intramuscular; 0.5 mL, Intramuscular
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This study was observer-blind. The vaccine preparer and administrator may have been unblinded to treatment assignment due to the steps necessary for vaccine preparation. However, the participant, the Investigator, and study staff members who collected the safety data and laboratory personnel who analyzed the blood and stool samples were all blinded to the group assignment.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 9302.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Clostridium difficile Toxoid Vaccine; Clostridium difficile infection; Cdiffense

Summary:

      The aim of this study was to evaluate the efficacy of the Clostridium difficile vaccine to
      prevent primary symptomatic C. difficile infection (CDI) in participants at risk for CDI
      where there is a substantial unmet medical need.

      Primary objective:

        -  To assess the efficacy of the C. difficile vaccine in preventing the onset of
           symptomatic primary CDI confirmed by polymerase chain reaction (PCR) in adult
           participants aged >= 50 years who are at risk for CDI and have received at least 1
           injection.

      Secondary Objectives:

      Efficacy:

        -  To assess prevention of symptomatic PCR-confirmed primary CDI cases after 3 injections
           administered at 0, 7, and 30 days.

        -  To assess prevention of symptomatic PCR-confirmed primary CDI cases after completion of
           at least 2 injections.

      Immunogenicity:

        -  To describe the immunogenicity to toxin A and toxin B at specific time points in a
           subset of participant and in participants with CDI at Day 0 and Day 60.

      Safety:

        -  To describe the safety profile of all participants who received at least 1 injection.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Aged >= 50 years on the day of inclusion

          -  Informed consent form had been signed and dated.

          -  Attended all scheduled visits and complied with all trial procedures.

          -  Covered by health insurance (if required).

          -  Must fulfill at least 1 of the following criteria

        Risk Stratum 1:

          -  Had at least 2 hospital stays, each lasting at least >= 24 hours, in the 12 months
             before enrollment, and

          -  Had received systemic (not topical) antibiotics in the 12 months before enrollment, or

        Risk Stratum 2:

          -  Was anticipated to have an in-patient hospitalization for a planned surgical procedure
             within 60 days of enrollment. The impending hospital stay was 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:

          -  Participant was 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 degree Celsius [>=
             100.4°Fahrenheit]). A prospective participant 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.