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

• ClinicalTrials.gov Identifier: NCT01230957
• Recruitment Status: Completed
• First Posted: October 29, 2010
• Last Update Posted: July 18, 2018
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Clostridium Difficile Infection; Diarrhea	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	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 650 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• 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
• Study Start Date: October 2010
• Actual Primary Completion Date: November 2012
• Actual Study Completion Date: March 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group 1; 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); 0.5 mL, Intramuscular on Days 0, 7, and 30; Other Name: ACAM-CDIFF™ vaccine
Experimental: Group 2; 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); 0.5 mL, Intramuscular on Days 0, 7, and 30; Other Name: ACAM-CDIFF™ vaccine
Experimental: Group 3; 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); 0.5 mL, Intramuscular on Days 0, 7, and 30; Other Name: ACAM-CDIFF™ vaccine
Experimental: Group 4; 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); 0.5 mL, Intramuscular on Days 0, 7, and 30; Other Name: ACAM-CDIFF™ vaccine
Placebo Comparator: Group 5; Participants will receive a dose Placebo (0.9% normal saline) on Day 0, 7, and 30, respectively.	Biological: Placebo: 0.9% normal saline; 0.5 mL, Intramuscular on Days 0, 7, and 30; Other Name: 0.9% normal saline
Experimental: Group 6; 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); 0.5 mL, Intramuscular on Days 0, 7, and 180; Other Name: ACAM-CDIFF™ vaccine
Experimental: Group 7; 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); 0.5 mL, Intramuscular on Days 0, 30, and 180; Other Name: ACAM-CDIFF™ vaccine

Outcome Measures

Primary Outcome Measures :

1. 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 ]
2. 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 ]

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

  Show 30 Study Locations

Sponsors and Collaborators

Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Director; Sanofi Pasteur Inc.

More Information

Publications of Results:

de Bruyn G, Saleh J, Workman D, Pollak R, Elinoff V, Fraser NJ, Lefebvre G, Martens M, Mills RE, Nathan R, Trevino M, van Cleeff M, Foglia G, Ozol-Godfrey A, Patel DM, Pietrobon PJ, Gesser R; H-030-012 Clinical Investigator Study Team. Defining the optimal formulation and schedule of a candidate toxoid vaccine against Clostridium difficile infection: A randomized Phase 2 clinical trial. Vaccine. 2016 Apr 27;34(19):2170-8. doi: 10.1016/j.vaccine.2016.03.028. Epub 2016 Mar 21.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Small RD, Ozol-Godfrey A, Yan L. On the use of nonparametric tests for comparing immunological Reverse Cumulative distribution curves (RCDCs). Vaccine. 2019 Sep 16. pii: S0264-410X(19)31195-8. doi: 10.1016/j.vaccine.2019.09.007. [Epub ahead of print]

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT01230957 History of Changes
• Other Study ID Numbers: H-030-012; UTN: U1111-1114-3917 ( Other Identifier: WHO )
• First Posted: October 29, 2010
• Last Update Posted: July 18, 2018
• Last Verified: July 2018

Keywords provided by Sanofi ( Sanofi Pasteur, a Sanofi Company ):

Clostridium difficile infection; Diarrhea; Pseudomembranous colitis; Clostridium Difficile Toxoid Vaccine; ACAM-CDIFF™ vaccine

Additional relevant MeSH terms:

Infection; Clostridium Infections; Diarrhea; Signs and Symptoms, Digestive; Signs and Symptoms; Gram-Positive Bacterial Infections; Bacterial Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs