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
  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 elderly subjects aged > or = 65 years. This is the companion study to H-030-008, in which healthy younger adults have already been dosed.


Condition Intervention Phase
Clostridium Infections
Biological: Vaccine diluent buffer (Placebo)
Biological: C. difficile toxoid vaccine (2 µg)
Biological: C. difficile toxoid vaccine (10 µg)
Biological: C. difficile toxoid vaccine (50 µg)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
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 Elderly Volunteers (> or =65 Years)

Further study details as provided by Sanofi:

Primary Outcome Measures:
  • 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 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).


Enrollment: 48
Study Start Date: November 2005
Study Completion Date: February 2006
Primary Completion Date: February 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Vaccine Group
Participants will receive a dose of vaccine diluent (placebo) on Days 0, 28 and 56, respectively.
Biological: Vaccine diluent buffer (Placebo)
0.5 mL, Intramuscular on Day 0, Day 28, and Day 56, respectively.
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.
Biological: C. difficile toxoid vaccine (2 µg)
0.5 mL, Intramuscular on Day 0, Day 28, and Day 56, respectively.
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.
Biological: C. difficile toxoid vaccine (10 µg)
0.5 mL, Intramuscular on Day 0, Day 28 and Day 56, respectively.
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.
Biological: C. difficile toxoid vaccine (50 µg)
0.5 mL, Intramuscular on Day 0, Day 28, and Day 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:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  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: NCT00214461

Locations
United States, Florida
Orlando Clinical Research Center
Orlando, Florida, United States, 32809
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
Sponsors and Collaborators
Sanofi
Investigators
Principal Investigator: Thomas P Marbury, MD Orlando Clinical Research Center
Principal Investigator: Richard Greenberg, MD University of Kentucky
  More 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: NCT00214461     History of Changes
Other Study ID Numbers: H-030-009
Study First Received: September 16, 2005
Results First Received: March 13, 2012
Last Updated: April 9, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
Clostridium difficile

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

ClinicalTrials.gov processed this record on July 29, 2014