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

Study Overview
=================
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.

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

Conditions
-----------------
Clostridium Difficile Infection, Diarrhea

Intervention / Treatment
-----------------
* Biological: Clostridium difficile toxoids A and B (Low-dose with adjuvant)
* 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 (high-dose without adjuvant)
* Biological: Placebo: 0.9% normal saline
* Biological: Clostridium difficile toxoids A and B (high-dose with adjuvant)
* Biological: Clostridium difficile toxoids A and B (high-dose with adjuvant)


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Participants will receive a dose Low-dose ACAM-CDIFF™ vaccine with adjuvant on Day 0, 7, and 30, respectively. | Biological: Clostridium difficile toxoids A and B (Low-dose with adjuvant)<br>* 0.5 mL, Intramuscular on Days 0, 7, and 30<br>* Other names: ACAM-CDIFF™ vaccine;|
| Experimental: Group 2<br>Participants will receive a dose Low-dose ACAM-CDIFF™ vaccine without adjuvant on Day 0, 7, and 30, respectively. | Biological: Clostridium difficile toxoids A and B (Low-dose without adjuvant)<br>* 0.5 mL, Intramuscular on Days 0, 7, and 30<br>* Other names: ACAM-CDIFF™ vaccine;|
| Experimental: Group 3<br>Participants will receive a dose High-dose ACAM-CDIFF™ vaccine with adjuvant on Day 0, 7, and 30, respectively. | Biological: Clostridium difficile toxoids A and B (high-dose with adjuvant)<br>* 0.5 mL, Intramuscular on Days 0, 7, and 30<br>* Other names: ACAM-CDIFF™ vaccine;|
| Experimental: Group 4<br>Participants will receive a dose High-dose ACAM-CDIFF™ vaccine without adjuvant on Day 0, 7, and 30, respectively. | Biological: Clostridium difficile toxoids A and B (high-dose without adjuvant)<br>* 0.5 mL, Intramuscular on Days 0, 7, and 30<br>* Other names: ACAM-CDIFF™ vaccine;|
| Placebo Comparator: Group 5<br>Participants will receive a dose Placebo (0.9% normal saline) on Day 0, 7, and 30, respectively. | Biological: Placebo: 0.9% normal saline<br>* 0.5 mL, Intramuscular on Days 0, 7, and 30<br>* Other names: 0.9% normal saline;|
| Experimental: Group 6<br>Participants will receive a dose of High-dose ACAM-CDIFF™ vaccine with adjuvant on Day 0, 7, and 180, respectively. | Biological: Clostridium difficile toxoids A and B (high-dose with adjuvant)<br>* 0.5 mL, Intramuscular on Days 0, 7, and 180<br>* Other names: ACAM-CDIFF™ vaccine;|
| Experimental: Group 7<br>Participants will receive a dose of High-dose ACAM-CDIFF™ vaccine with adjuvant on Day 0, 30, and 180, respectively. | Biological: Clostridium difficile toxoids A and B (high-dose with adjuvant)<br>* 0.5 mL, Intramuscular on Days 0, 30, and 180<br>* Other names: ACAM-CDIFF™ vaccine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Clostridium difficile infection, Diarrhea, Pseudomembranous colitis, Clostridium Difficile Toxoid Vaccine, ACAM-CDIFF™ vaccine