Brief Summary

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Official Title: "Safety and Immunogenicity of Different Formulations of a Clostridium Difficile Toxoid Vaccine Administered at Three Different Schedules in Adults Aged 40 to 75 Years at Risk of C. Difficile Infection"

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.

• Study Type: Interventional
• Study Design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
• Study Primary Completion Date: September 2012

Detailed Clinical Trial Description

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.

Interventions Used in this Clinical Trial

• Biological: Clostridium difficile toxoids A and B (Low-dose with adjuvant)
  • 0.5 mL, Intramuscular on Days 0, 7, and 30
• Biological: Clostridium difficile toxoids A and B (Low-dose without adjuvant)
  • 0.5 mL, Intramuscular on Days 0, 7, and 30
• Biological: Clostridium difficile toxoids A and B (high-dose with adjuvant)
  • 0.5 mL, Intramuscular on Days 0, 7, and 30
• Biological: Clostridium difficile toxoids A and B (high-dose without adjuvant)
  • 0.5 mL, Intramuscular on Days 0, 7, and 30
• Biological: Placebo: 0.9% normal saline
  • 0.5 mL, Intramuscular on Days 0, 7, and 30

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Group 1
  • Low-dose ACAM-CDIFF™ vaccine with adjuvant
• Experimental: Group 2
  • Low-dose ACAM-CDIFF™ vaccine without adjuvant
• Experimental: Group 3
  • High-dose ACAM-CDIFF™ vaccine with adjuvant
• Experimental: Group 4
  • High-dose ACAM-CDIFF™ vaccine without adjuvant
• Placebo Comparator: Group 5
  • Placebo (0.9% normal saline)

Outcome Measures for this Clinical Trial

Primary Measures

• Information concerning the safety profile in terms of solicited and unsolicited reactions in participants following vaccination with ACAM-CDIFF™ Vaccine.
  • Time Frame: 6 days after each vaccination and up to 6 months post-vaccination 3
    Safety Issue?: Yes
• Serum antitoxin IgG concentrations to Clostridium difficile toxins A and B in participants vaccinated with ACAM-CDIFF™.
  • Time Frame: Up to 6 months post-vaccination 3
    Safety Issue?: No

Criteria for Participation in this Clinical Trial

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial: Accepts Healthy Volunteers

Clinical Trial Investigator Information

• Lead Sponsor
  • Sanofi
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • Medical Director, Study Director, Sanofi Pasteur Inc.