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

Sanofi

Status and phase: Completed; Phase 2

Conditions: Diarrhea; Clostridium Difficile Infection

Treatments: Biological: Clostridium difficile toxoids A and B (high-dose without adjuvant); 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: Placebo: 0.9% normal saline

Study type: Interventional

Funder types: Industry

Identifiers

NCT01230957

H-030-012

UTN: U1111-1114-3917 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 650 patients

Sex: All

Ages: 40 to 75 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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650 participants in 7 patient groups, including a placebo group

Group 1

Experimental group

Description:

Participants will receive a dose Low-dose ACAM-CDIFF™ vaccine with adjuvant on Day 0, 7, and 30, respectively.

Treatment:

Biological: Clostridium difficile toxoids A and B (Low-dose with adjuvant)

Group 2

Experimental group

Description:

Participants will receive a dose Low-dose ACAM-CDIFF™ vaccine without adjuvant on Day 0, 7, and 30, respectively.

Treatment:

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

Group 3

Experimental group

Description:

Participants will receive a dose High-dose ACAM-CDIFF™ vaccine with adjuvant on Day 0, 7, and 30, respectively.

Treatment:

Biological: Clostridium difficile toxoids A and B (high-dose with adjuvant)

Biological: Clostridium difficile toxoids A and B (high-dose with adjuvant)

Biological: Clostridium difficile toxoids A and B (high-dose with adjuvant)

Group 4

Experimental group

Description:

Participants will receive a dose High-dose ACAM-CDIFF™ vaccine without adjuvant on Day 0, 7, and 30, respectively.

Treatment:

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

Group 5

Placebo Comparator group

Description:

Participants will receive a dose Placebo (0.9% normal saline) on Day 0, 7, and 30, respectively.

Treatment:

Biological: Placebo: 0.9% normal saline

Group 6

Experimental group

Description:

Participants will receive a dose of High-dose ACAM-CDIFF™ vaccine with adjuvant on Day 0, 7, and 180, respectively.

Treatment:

Biological: Clostridium difficile toxoids A and B (high-dose with adjuvant)

Biological: Clostridium difficile toxoids A and B (high-dose with adjuvant)

Biological: Clostridium difficile toxoids A and B (high-dose with adjuvant)

Group 7

Experimental group

Description:

Participants will receive a dose of High-dose ACAM-CDIFF™ vaccine with adjuvant on Day 0, 30, and 180, respectively.

Treatment:

Biological: Clostridium difficile toxoids A and B (high-dose with adjuvant)

Biological: Clostridium difficile toxoids A and B (high-dose with adjuvant)

Biological: Clostridium difficile toxoids A and B (high-dose with adjuvant)