Clinical trial NCT00214461: Safety, Tolerability, and Immunogenicity of a Clostridium Difficile Toxoid Vaccine in Healthy Elderly Volunteers
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Clostridium Infections
Keywords: Clostridium difficile
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2005-09-22
Enrollment: 48
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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 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.

Primary outcomes:
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.
timeFrame: Day 0 to up to 70 days post first vaccination
Secondary outcomes:
measure: 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.
timeFrame: Day up to Day 236 post first vaccination
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
Study officials:
affiliation: Orlando Clinical Research Center
name: Thomas P Marbury, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Kentucky
name: Richard Greenberg, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.