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

• ClinicalTrials.gov Identifier: NCT00127803
• Recruitment Status: Completed
• First Posted: August 9, 2005
• Results First Posted: May 21, 2012
• Last Update Posted: September 14, 2012
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Clostridium Infections	Biological: Placebo (vaccine diluent); Biological: Clostridium difficile vaccine	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, 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)
• Study Start Date: July 2005
• Actual Primary Completion Date: January 2006
• Actual Study Completion Date: March 2006

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

1. 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 ]
2. 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 ]

Secondary Outcome Measures :

1. 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 ]

   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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• 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

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:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT00127803
• Other Study ID Numbers: H-030-008
• First Posted: August 9, 2005
• Results First Posted: May 21, 2012
• Last Update Posted: September 14, 2012
• Last Verified: September 2012

Keywords provided by Sanofi:

Clostridium difficile

Additional relevant MeSH terms:

Clostridium Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs