Safety, Tolerability, and Immunogenicity Study of a Clostridium Difficile Toxoid Vaccine in Healthy Adult Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00127803
First received: August 5, 2005
Last updated: September 7, 2012
Last verified: September 2012

August 5, 2005
September 7, 2012
July 2005
January 2006   (final data collection date for primary outcome measure)
  • Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. [ Time Frame: Day 0 and up to 7 days post each vaccination ] [ Designated as safety issue: No ]
  • Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. [ Time Frame: Day 0 to up to 70 days post-first vaccination ] [ Designated as safety issue: No ]
Safety
Complete list of historical versions of study NCT00127803 on ClinicalTrials.gov Archive Site
Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. [ Time Frame: Days 28, 56, 70, and 236 Post First Vaccination ] [ Designated as safety issue: No ]

Seroconversion was defined as a ≥4-fold increase in antibody levels from Baseline. For values below the limit of quantification (LLQ) for the assay, the LLQ was used.

Serum anti-toxin IgG levels were determined by enzyme linked immunosorbent assay (ELISA).

Immunogenicity
Not Provided
Not Provided
 
Safety, Tolerability, and Immunogenicity Study of a Clostridium Difficile Toxoid Vaccine in Healthy Adult Volunteers
A Phase I Randomized, Placebo-Controlled, Double-Blind, Dose-Ranging Study of the Safety, Tolerability and Immunogenicity of a Clostridium Difficile Toxoid Vaccine, Alum Adsorbed, in Healthy Adult Volunteers (18-55 Years)

The purpose of this study is to determine the safety and tolerability of a modified C. difficile vaccine at 3 dose levels compared with a placebo control administered via intramuscular injection in healthy adults aged 18-55 years of age.

Clostridium difficile is the leading infectious cause of nosocomial diarrhea in developed countries. Hospital outbreaks of Clostridium difficile-associated diarrhea (CDAD) are associated with substantial patient morbidity and mortality. Conventional therapy with antibiotics often results in secondary infection with resistant organisms or clinical relapse after discontinuation of the antimicrobial course. New strategies are needed to limit the impact of this opportunistic pathogen. Considerable evidence exists that immunity against C. difficile toxins may be effective in controlling CDAD. 48 subjects will be enrolled to receive one of three dose levels of modified C difficile vaccine or placebo administered on a 3-dose schedule. The study consists of a 30-day screening period, a 70-day treatment period, one follow-up phone interview 2 months after the last vaccination, and one follow-up clinic visit 6 months after the last vaccination.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Clostridium Infections
  • Biological: Placebo (vaccine diluent)
    0.5 mL, intramuscular (IM) on Days 0, 28, and 56, respectively.
  • Biological: Clostridium difficile vaccine
    0.5 mL, intramuscular on Days 0, 28, and 56, respectively.
  • Placebo Comparator: Placebo
    Participants will receive a dose of vaccine diluent (placebo) on Days 0, 28, and 56, respectively.
    Intervention: Biological: Placebo (vaccine diluent)
  • Experimental: Low dose vaccine
    Participants will receive a 2 μg dose of C. difficile toxoid vaccine on Days 0, 28, and 56, respectively.
    Intervention: Biological: Clostridium difficile vaccine
  • Experimental: Medium dose vaccine
    Participants will receive a 10 μg dose of C. difficile toxoid vaccine on Days 0, 28, and 56, respectively
    Intervention: Biological: Clostridium difficile vaccine
  • Experimental: High dose vaccine
    Participants will receive a 50 μg dose of C. difficile toxoid vaccine on Days 0, 28, and 56, respectively
    Intervention: Biological: Clostridium difficile vaccine
Greenberg RN, Marbury TC, Foglia G, Warny M. Phase I dose finding studies of an adjuvanted Clostridium difficile toxoid vaccine. Vaccine. 2012 Mar 16;30(13):2245-9. doi: 10.1016/j.vaccine.2012.01.065. Epub 2012 Feb 2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
50
March 2006
January 2006   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Adult males or females, 18-55 years (inclusive)
  • In good general health
  • Clinical lab tests within normal range
  • Non-pregnant female subjects
  • Able and willing to participate for duration of study and must not participate in any other experimental study for at least 60 days after receiving the last dose of study vaccine

Exclusion Criteria:

  • Evidence of C. difficile infection
  • Evidence of any previous antibiotic-associated diarrhea
  • Active or inactive inflammatory bowel disease, irritable colon syndrome, chronic abdominal pain or other chronic diarrhea
  • History of malignancy within 5 years
  • History of anaphylaxis, asthma or severe vaccine or severe allergic drug reaction
  • Known or suspected history of immunodeficiency;
  • Active or inactive immune-mediated or inflammatory disease;
  • Pregnant or lactating female subjects;
  • History of drug or alcohol abuse disorders;
  • Serology positive for HIV, hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV)
  • Receipt of antibiotic therapy or an investigational drug within prior 30 days
  • Blood or organ donation within prior 30 days
Both
18 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00127803
H-030-008
No
Sanofi
Sanofi
Not Provided
Principal Investigator: Thomas Marbury, MD Orlando Clinical Research Center
Principal Investigator: Richard Greenberg, MD University of Kentucky
Sanofi
September 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP