Methods: H-030-012 was a phase II trial that evaluated the safety and immunogenicity of different formulations and schedules of the Sanofi Pasteur candidate Clostridium difficile toxoid vaccine. Participants eligible for the extension phase were those who had been randomized to receive the final vaccine formulation (high dose adjuvanted) selected for Phase III and who agreed to participate in the extension. Participants described here received doses on days 0, 7, and 30, which is the schedule under evaluation in Phase III. Serious adverse events (SAEs) were monitored throughout the extension period. Immune responses were assessed every six months up to three years after the last dose in the schedule. Toxin neutralization assay (TNA) as well as toxin A and B specific IgG ELISAs were performed. The predicted durability of measured responses was examined using statistical models.
Results: 70 volunteers were enrolled and 62 completed follow up. No SAEs judged by the investigator to be related to the vaccine or vaccination were reported throughout the extension period. Comparing three year values to baseline, the geometric mean fold rise (GMFR) for toxin A and B by ELISA was 2.3 and 4.0, respectively. TNA GMFRs to Toxin A or B were higher than the corresponding ELISA value: GMFR for TNA to Toxin A was 6.5 and for Toxin B was 4.5.
Conclusion: A candidate C.difficile toxoid vaccine induced circulating antibodies to Toxins A and B as measured in both ELISA and functional assays. Mean titers were sustained above baseline for up to three years after the last dose of the primary series.
G. De Bruyn,
T. L. Poling, Sanofi Pasteur: Investigator , Research grant and Research support
X. Sheng, Sanofi Pasteur: Employee , Salary
D. Patel, Sanofi Pasteur: Employee , Salary
P. Pietrobon, Sanofi Pasteur: Employee , Salary
R. Gesser, Sanofi Pasteur: Employee , Salary