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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00214461
First received: September 16, 2005
Last updated: April 9, 2012
Last verified: April 2012

September 16, 2005
April 9, 2012
November 2005
February 2006   (final data collection date for primary outcome measure)
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 and Tolerability
Complete list of historical versions of study NCT00214461 on ClinicalTrials.gov Archive Site
Number of Participants Achieving Seroconversion of Serum Immunoglobulin G (IgG) After Vaccination With Either a Formulation of C. Difficile Toxoid Vaccine or a Placebo Vaccine. [ Time Frame: Day up to Day 236 post first vaccination ] [ Designated as safety issue: No ]
Seroconversion was defined as a ≥ 4-fold increase from baseline in a subject's specific IgG levels: Serum Levels of Anti-toxin Immunoglobulin (IgG) against toxin A and toxin B in enzyme units (EU) were assessed by enzyme linked immunosorbent assay (ELISA).
Immunogenicity
Not Provided
Not Provided
 
Safety, Tolerability, and Immunogenicity of a Clostridium Difficile Toxoid Vaccine in Healthy Elderly 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 Elderly Volunteers (> or =65 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 elderly subjects aged > or = 65 years. This is the companion study to H-030-008, in which healthy younger adults have already been dosed.

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, Outcomes Assessor)
Primary Purpose: Prevention
Clostridium Infections
  • Biological: Vaccine diluent buffer (Placebo)
    0.5 mL, Intramuscular on Day 0, Day 28, and Day 56, respectively.
  • Biological: C. difficile toxoid vaccine (2 µg)
    0.5 mL, Intramuscular on Day 0, Day 28, and Day 56, respectively.
  • Biological: C. difficile toxoid vaccine (10 µg)
    0.5 mL, Intramuscular on Day 0, Day 28 and Day 56, respectively.
  • Biological: C. difficile toxoid vaccine (50 µg)
    0.5 mL, Intramuscular on Day 0, Day 28, and Day 56, respectively.
  • Placebo Comparator: Placebo Vaccine Group
    Participants will receive a dose of vaccine diluent (placebo) on Days 0, 28 and 56, respectively.
    Intervention: Biological: Vaccine diluent buffer (Placebo)
  • Experimental: Low Dose Vaccine Group
    Participants will receive a dose of vaccine containing of 2 µg Clostridium Difficile toxoid on Days 0, 28 and 56, respectively.
    Intervention: Biological: C. difficile toxoid vaccine (2 µg)
  • Experimental: Medium dose vaccine group
    Participants will receive a dose of vaccine containing of 10 µg Clostridium Difficile toxoid on Days 0, 28 and 56, respectively.
    Intervention: Biological: C. difficile toxoid vaccine (10 µg)
  • Experimental: High dose vaccine group
    Participants will receive a dose of vaccine containing of 50 µg Clostridium Difficile toxoid on Days 0, 28 and 56, respectively.
    Intervention: Biological: C. difficile toxoid vaccine (50 µg)
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
48
February 2006
February 2006   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Adult males or females, > or = 65 years
  • In good general health
  • Clinical lab tests within normal range
  • Females must be post-menopausal
  • 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
  • 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
65 Years and older
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00214461
H-030-009
No
Sanofi
Sanofi
Not Provided
Principal Investigator: Thomas P Marbury, MD Orlando Clinical Research Center
Principal Investigator: Richard Greenberg, MD University of Kentucky
Sanofi
April 2012

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