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

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)

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.

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.

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