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

Phase 1

Completed

Interventions: 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)

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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Placebo Vaccine Group	Vaccine diluent buffer (Placebo)	Participants will receive a dose of vaccine diluent (placebo) on Days 0, 28 and 56, respectively.
Low Dose Vaccine Group	C. difficile toxoid vaccine (2 µg)	Participants will receive a dose of vaccine containing of 2 µg Clostridium Difficile toxoid on Days 0, 28 and 56, respectively.
Medium dose vaccine group	C. difficile toxoid vaccine (10 µg)	Participants will receive a dose of vaccine containing of 10 µg Clostridium Difficile toxoid on Days 0, 28 and 56, respectively.
High dose vaccine group	C. difficile toxoid vaccine (50 µg)	Participants will receive a dose of vaccine containing of 50 µg Clostridium Difficile toxoid on Days 0, 28 and 56, respectively.

Primary Outcome Measures

Name	Time	Method
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.	Day 0 to up to 70 days post first vaccination

Secondary Outcome Measures

Name	Time	Method
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.	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).