BACKGROUND: As an evolution of its currently licensed rabies vaccine Verorab(®), Sanofi Pasteur has developed a next-generation, serum-free, highly purified Vero rabies vaccine (PVRV-NG). Through this Phase III clinical trial, we aimed to demonstrate the non-inferiority of PVRV-NG over Verorab when administered according to a post-exposure regimen and to assess its clinical safety. METHODS: A total of 816 healthy subjects aged ≥10 years were randomized according to a 2:1 ratio to receive PVRV-NG or Verorab. Half of the subjects were aged 10-17 years, the other half were aged ≥18 years. All subjects were to receive 5 injections on days 0, 3, 7, 14 and 28. Three blood samples were taken for rabies virus neutralizing antibodies (RVNA) assessment, at baseline, on day 14 and day 42. Solicited adverse reactions (between injections 1, 2 and 3, and within 7 days post-injections 4 and 5) and adverse events (up to 28 days after the last injection) were collected for clinical safety assessment; serious adverse events were reported up to 6-months after the last injection. RESULTS: The proportion of subjects with an RVNA titer ≥0.5 IU/mL after the third injection of PVRV-NG was non-inferior to the proportion of those who received Verorab. PVRV-NG was shown to be as immunogenic as Verorab in each age range in the per-protocol and full analysis sets. PVRV-NG induced a strong immune response in both age ranges, with high RVNA levels and increased geometric mean titers compared to baseline after each measured time point. PVRV-NG had a satisfactory safety profile after each injection, similar to Verorab with regards to the nature, frequency, duration and severity of adverse events. Two serious adverse events were reported, none was related to vaccination. CONCLUSIONS: This trial demonstrated the immunogenic non-inferiority of PVRV-NG over Verorab and showed that both vaccines have similar safety profiles. This trial is registered at ClinicalTrials.gov (NCT01339312). This manuscript is the first full report of the study. An abstract of the study results was previously presented at the Rabies in the Americas (RITA) conference in October 2012 in São Paulo, Brazil. FUNDING: Sanofi Pasteur.
RCT Entities:
BACKGROUND: As an evolution of its currently licensed rabies vaccine Verorab(®), Sanofi Pasteur has developed a next-generation, serum-free, highly purified Vero rabies vaccine (PVRV-NG). Through this Phase III clinical trial, we aimed to demonstrate the non-inferiority of PVRV-NG over Verorab when administered according to a post-exposure regimen and to assess its clinical safety. METHODS: A total of 816 healthy subjects aged ≥10 years were randomized according to a 2:1 ratio to receive PVRV-NG or Verorab. Half of the subjects were aged 10-17 years, the other half were aged ≥18 years. All subjects were to receive 5 injections on days 0, 3, 7, 14 and 28. Three blood samples were taken for rabies virus neutralizing antibodies (RVNA) assessment, at baseline, on day 14 and day 42. Solicited adverse reactions (between injections 1, 2 and 3, and within 7 days post-injections 4 and 5) and adverse events (up to 28 days after the last injection) were collected for clinical safety assessment; serious adverse events were reported up to 6-months after the last injection. RESULTS: The proportion of subjects with an RVNA titer ≥0.5 IU/mL after the third injection of PVRV-NG was non-inferior to the proportion of those who received Verorab. PVRV-NG was shown to be as immunogenic as Verorab in each age range in the per-protocol and full analysis sets. PVRV-NG induced a strong immune response in both age ranges, with high RVNA levels and increased geometric mean titers compared to baseline after each measured time point. PVRV-NG had a satisfactory safety profile after each injection, similar to Verorab with regards to the nature, frequency, duration and severity of adverse events. Two serious adverse events were reported, none was related to vaccination. CONCLUSIONS: This trial demonstrated the immunogenic non-inferiority of PVRV-NG over Verorab and showed that both vaccines have similar safety profiles. This trial is registered at ClinicalTrials.gov (NCT01339312). This manuscript is the first full report of the study. An abstract of the study results was previously presented at the Rabies in the Americas (RITA) conference in October 2012 in São Paulo, Brazil. FUNDING: Sanofi Pasteur.