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

• ClinicalTrials.gov Identifier: NCT00214461
• Recruitment Status: Completed
• First Posted: September 22, 2005
• Results First Posted: April 9, 2012
• Last Update Posted: April 11, 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 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 or disease	Intervention/treatment	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

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: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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)
• Study Start Date: November 2005
• Actual Primary Completion Date: February 2006
• Actual Study Completion Date: February 2006

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

1. 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 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 ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 65 Years and older (Older Adult)
• Sexes Eligible for Study: All
• 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

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

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: NCT00214461
• Other Study ID Numbers: H-030-009
• First Posted: September 22, 2005
• Results First Posted: April 9, 2012
• Last Update Posted: April 11, 2012
• Last Verified: April 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