Safety and Immunogenicity Study of GSK's Clostridium Difficile Vaccine 2904545A When Administered in Healthy Adults Aged 18-45 Years and 50-70 Years
Condition: Clostridium Infections
MeSH terms: Clostridium Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to generate safety, reactogenicity (assessment of any expected
      or unexpected side effect of the vaccine) and immunogenicity (ability to induce an immune
      response) data for the development of a candidate Clostridium difficile (C. difficile)
      vaccine that would protect against primary cases of Clostridium difficile infection (CDI) and
      CDI recurrence.

      Clostridium difficile infection is a major cause of gastrointestinal illness with
      approximately 500,000 infections and the leading cause of gastroenteritis associated death
      with 29,000 deaths annually in the United States of America (USA). The emergence of extremely
      infectious varieties/types of C. difficile has contributed to increase the number and
      severity of CDI cases. In recent years, some countries (United Kingdom) have implemented
      hospital hygiene and other measures which resulted in significant reductions in the number of
      cases. The burden is, however, expected to remain significant until vaccination is available.
    


Intervention name(s): C. difficile investigational vaccine based on the F2 antigen (GSK2904545A); C. difficile investigational vaccine based on the F2 antigen (GSK2904545A) adjuvanted with AS01B; Placebo
Intervention type(s): Biological; Biological; Drug
Intervention description(s): Subjects in CDIFF Ag 18 - 45 Years and CDIFF Ag 50 - 70 Years Groups will receive 2 or 3 doses (0.5 mL each) of CDIFF Ag vaccine.
The vaccine will be administered intramuscularly in the deltoid, at a 0, 1-month dose interval. The third dose will be administered approximately 15 months after the second dose.; Subjects in CDIFF Ag + AS01B 50 - 70 Years Group will receive 2 or 3 doses (0.5 mL each) of CDIFF Ag + AS01B vaccine.
The vaccine will be administered intramuscularly in the deltoid, at a 0, 1-month dose interval. The third dose will be administered approximately 15 months after the second dose.; Subjects will receive 2 doses (0.5 mL each) of Placebo, administered intramuscularly in the deltoid, at a 0, 1-month dose interval.
Other intervention name(s): CDIFF Ag; CDIFF Ag + AS01B
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: A 4-step staggered design will be used to ensure maximum safety of the participating subjects:
Step 1: Vaccination of approximately 20 subjects aged 18-45 years. Step 2: Vaccination of approximately 20 subjects aged 50-70 years. Step 3: Vaccination of approximately 30 subjects aged 50-70 years. An iSRC will review all accumulating safety data after Dose 1 and 2 in Steps 1 to 3. If considered appropriate to proceed, the next step will start.
Step 4: Vaccination of approximately 70 subjects aged 50-70 years. An iSRC will review all accumulating safety data 3 weeks after the start of vaccination in Step 4 and then about every 3 weeks until all subjects have received Dose 1. In addition, the iSRC will review all safety data after Dose 2 and after that a subcohort of subjects will receive the third dose. If there are any safety concerns observed during SRT reviews post Dose 3, an ad hoc iSRC meeting will take place to review the unblinded safety data.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention