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

Locations

United States, California

Redding, California, United States, 96001

United States, Connecticut

Bristol, Connecticut, United States, 06010

Stamford, Connecticut, United States, 06905

United States, Florida

Clearwater, Florida, United States, 33756

Coral Gables, Florida, United States, 33134

Port Orange, Florida, United States, 32127

Saint Petersburg, Florida, United States, 33709

Tampa, Florida, United States, 33614

United States, Georgia

Atlanta, Georgia, United States, 30342

United States, Idaho

Idaho Falls, Idaho, United States, 83404

United States, Kansas

Newton, Kansas, United States, 67114

United States, Massachusetts

Brockton, Massachusetts, United States, 02301

United States, Michigan

Troy, Michigan, United States, 48098

United States, New Jersey

Neptune, New Jersey, United States, 07753

United States, New York

Binghamton, New York, United States, 13901

Endwell, New York, United States, 13760

United States, North Carolina

Cary, North Carolina, United States, 27518

Hickory, North Carolina, United States, 28602

Raleigh, North Carolina, United States, 27609

United States, Ohio

Centerville, Ohio, United States, 45459

United States, Pennsylvania

Pittsburgh, Pennsylvania, United States, 15241

Uniontown, Pennsylvania, United States, 15401

United States, South Carolina

Mount Pleasant, South Carolina, United States, 29464

United States, Tennessee

Bristol, Tennessee, United States, 37620

United States, Utah

Salt Lake City, Utah, United States, 84093

Salt Lake City, Utah, United States, 84109

Salt Lake City, Utah, United States, 84124

United States, Virginia

Richmond, Virginia, United States, 23294

Williamsburg, Virginia, United States, 23185

United States, Wisconsin

Marshfield, Wisconsin, United States, 54449

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 Oct 16;37(44):6737-6742. doi: 10.1016/j.vaccine.2019.09.007. Epub 2019 Sep 16.

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT01230957
• 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