Clinical trial NCT01230957: Study of Different Formulations of a Clostridium Difficile Toxoid Vaccine Given at Three Different Schedules in Adults
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Clostridium Difficile Infection
Diarrhea
Keywords: Clostridium difficile infection
Diarrhea
Pseudomembranous colitis
Clostridium Difficile Toxoid Vaccine
ACAM-CDIFF™ vaccine
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2010-10-29
Enrollment: 650
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Information concerning the safety profile in terms of solicited and unsolicited reactions in participants following vaccination with ACAM-CDIFF™ Vaccine.
timeFrame: 6 days after each vaccination and up to 6 months post-vaccination 3
measure: Serum antitoxin IgG concentrations to Clostridium difficile toxins A and B in participants vaccinated with ACAM-CDIFF™.
timeFrame: Up to 6 months post-vaccination 3
Secondary outcomes:
Other outcomes:
Locations:
city: Redding
country: United States
state: California
city: Bristol
country: United States
state: Connecticut
city: Stamford
country: United States
state: Connecticut
city: Clearwater
country: United States
state: Florida
city: Coral Gables
country: United States
state: Florida
city: Port Orange
country: United States
state: Florida
city: Saint Petersburg
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Idaho Falls
country: United States
state: Idaho
city: Newton
country: United States
state: Kansas
city: Brockton
country: United States
state: Massachusetts
city: Troy
country: United States
state: Michigan
city: Neptune
country: United States
state: New Jersey
city: Binghamton
country: United States
state: New York
city: Endwell
country: United States
state: New York
city: Cary
country: United States
state: North Carolina
city: Hickory
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Centerville
country: United States
state: Ohio
city: Pittsburgh
country: United States
state: Pennsylvania
city: Uniontown
country: United States
state: Pennsylvania
city: Mount Pleasant
country: United States
state: South Carolina
city: Bristol
country: United States
state: Tennessee
city: Salt Lake City
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: Richmond
country: United States
state: Virginia
city: Williamsburg
country: United States
state: Virginia
city: Marshfield
country: United States
state: Wisconsin
Study officials:
affiliation: Sanofi Pasteur Inc.
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.