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
  Purpose

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.


Condition Intervention Phase
Clostridium Infections
Biological: Placebo (vaccine diluent)
Biological: Clostridium difficile vaccine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: 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)

Further study details as provided by Sanofi:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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).



Enrollment: 50
Study Start Date: July 2005
Study Completion Date: March 2006
Primary Completion Date: January 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Participants will receive a dose of vaccine diluent (placebo) on Days 0, 28, and 56, respectively.
Biological: Placebo (vaccine diluent)
0.5 mL, intramuscular (IM) on Days 0, 28, and 56, respectively.
Experimental: Low dose vaccine
Participants will receive a 2 μg dose of C. difficile toxoid vaccine on Days 0, 28, and 56, respectively.
Biological: Clostridium difficile vaccine
0.5 mL, intramuscular on Days 0, 28, and 56, respectively.
Experimental: Medium dose vaccine
Participants will receive a 10 μg dose of C. difficile toxoid vaccine on Days 0, 28, and 56, respectively
Biological: Clostridium difficile vaccine
0.5 mL, intramuscular on Days 0, 28, and 56, respectively.
Experimental: High dose vaccine
Participants will receive a 50 μg dose of C. difficile toxoid vaccine on Days 0, 28, and 56, respectively
Biological: Clostridium difficile vaccine
0.5 mL, intramuscular on Days 0, 28, and 56, respectively.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00127803

Sponsors and Collaborators
Sanofi
Investigators
Principal Investigator: Thomas Marbury, MD Orlando Clinical Research Center
Principal Investigator: Richard Greenberg, MD University of Kentucky
  More Information

Additional Information:
No publications provided by Sanofi

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00127803     History of Changes
Other Study ID Numbers: H-030-008
Study First Received: August 5, 2005
Results First Received: March 13, 2012
Last Updated: September 7, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
Clostridium difficile

Additional relevant MeSH terms:
Clostridium Infections
Bacterial Infections
Gram-Positive Bacterial Infections

ClinicalTrials.gov processed this record on October 23, 2014