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

Phase 2

Completed

Conditions: Clostridium Difficile Infection
Diarrhea

Interventions: Biological: Clostridium difficile toxoids A and B (Low-dose without adjuvant)
Biological: Clostridium difficile toxoids A and B (high-dose with adjuvant)
Biological: Clostridium difficile toxoids A and B (Low-dose with adjuvant)
Biological: Clostridium difficile toxoids A and B (high-dose without adjuvant)

Registration Number: NCT01230957

Lead Sponsor: Sanofi Pasteur, a Sanofi Company

Brief Summary: 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.

Detailed 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 650

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 2	Clostridium difficile toxoids A and B (Low-dose without adjuvant)	Participants will receive a dose Low-dose ACAM-CDIFF™ vaccine without adjuvant on Day 0, 7, and 30, respectively.
Group 3	Clostridium difficile toxoids A and B (high-dose with adjuvant)	Participants will receive a dose High-dose ACAM-CDIFF™ vaccine with adjuvant on Day 0, 7, and 30, respectively.
Group 7	Clostridium difficile toxoids A and B (high-dose with adjuvant)	Participants will receive a dose of High-dose ACAM-CDIFF™ vaccine with adjuvant on Day 0, 30, and 180, respectively.
Group 6	Clostridium difficile toxoids A and B (high-dose with adjuvant)	Participants will receive a dose of High-dose ACAM-CDIFF™ vaccine with adjuvant on Day 0, 7, and 180, respectively.
Group 1	Clostridium difficile toxoids A and B (Low-dose with adjuvant)	Participants will receive a dose Low-dose ACAM-CDIFF™ vaccine with adjuvant on Day 0, 7, and 30, respectively.
Group 4	Clostridium difficile toxoids A and B (high-dose without adjuvant)	Participants will receive a dose High-dose ACAM-CDIFF™ vaccine without adjuvant on Day 0, 7, and 30, respectively.

Primary Outcome Measures

Name	Time	Method
Information concerning the safety profile in terms of solicited and unsolicited reactions in participants following vaccination with ACAM-CDIFF™ Vaccine.	6 days after each vaccination and up to 6 months post-vaccination 3
Serum antitoxin IgG concentrations to Clostridium difficile toxins A and B in participants vaccinated with ACAM-CDIFF™.	Up to 6 months post-vaccination 3

Secondary Outcome Measures