RESUMEN
This phase IV, single blind study assessed the immunogenicity and safety of India-manufactured purified chick embryo cell rabies vaccine (PCECV), compared with a German-manufactured batch obtained by the same production process. A total of 340 participants enrolled at 2 study sites in India were randomized (1:1:1:1) in 4 groups to receive a 5-dose Essen regimen with either 1 of the 3 Indian batches (PCECV-I) or the German batch (PCECV-G), administered on Days (D) 0, 3, 7, 14 and 30. The lot-to-lot consistency of PCECV-I batches in terms of induced immune response at D14 was demonstrated. The immune response elicited by PCECV-I was shown to be non-inferior to that induced by PCECV-G, as the lower limit of the 95% confidence interval for the ratio (PCECV-I/PCECV-G) of rabies virus neutralising antibody (RVNA) geometric mean concentrations was higher than 0.5 at D14. At least 96% of participants developed adequate RVNA concentrations (≥ 0.5 IU/mL) by D14 and all achieved RVNA concentrations ≥ 0.5 IU/mL by D90. RVNA levels were comparable across all groups throughout the entire study. Solicited local and general symptoms had a similar incidence in all groups. Unsolicited adverse events (AEs) were reported by 11% of participants. Only 1 serious AE (leg fracture) was reported and was not related to vaccination. No deaths and no rabies cases were recorded during the 90 days of observation. The study showed that the 3 PCECV-I and the PCECV-G batches induced a similar immune response and had a comparable safety profile when administered according to a 5-dose schedule.
Asunto(s)
Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Vacunas Antirrábicas/efectos adversos , Vacunas Antirrábicas/inmunología , Virus de la Rabia/inmunología , Adolescente , Adulto , Anciano , Animales , Técnicas de Cultivo de Célula , Embrión de Pollo , Niño , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Alemania , Humanos , Esquemas de Inmunización , Incidencia , India , Masculino , Persona de Mediana Edad , Vacunas Antirrábicas/administración & dosificación , Vacunas Antirrábicas/aislamiento & purificación , Método Simple Ciego , Tecnología Farmacéutica , Adulto JovenRESUMEN
Zydus Cadila Health care, India developed a new purified chick embryo cell rabies vaccine (PCECV, Vaxirab-N; 1 mL) by adapting Pitman-Moore strain of virus on to the chick embryo fibroblast cell line in 2006. During 2007-10, a series of safety and immunogenicity studies were conducted as per ICH-GCP guidelines after obtaining permission from Drug Controller General of India. In the first study, Vaxirab-N was administered to 35 healthy adult volunteers by intramuscular (IM) route using pre exposure regimen. The geometric mean concentration (GMC) of rabies virus neutralizing antibody (RvnAb) of 7.5 IU/mL on day 35. In the second study, Vaxirab-N was administered to 35 healthy adult volunteers using simulated post- exposure prophylaxis regimen by IM route. A GMC of 6.3 IU/mL on day 14, 13.2 IU/mL on day 28 and 8.6 IU/mL on day 90 was obtained. In the third study, Vaxirab-N administered by intradermal (ID) route using Updated Thai Red Cross (TRC) regimen in 36 healthy adult volunteers showed GMC of 7.8 IU/mL on day 14, 11.5 IU/mL on day 28 and 6.0 IU/mL on day 90. The 4th study was multi centric and Vaxirab-N was administered to 129 animal bite cases by IM route using post-exposure Essen regimen. The GMC following this schedule was 8.2 IU/mL on day 14, 13.01 IU/mL on day 28, 7.92 IU/mL on day 90 and 3.72 IU/mL on day 180. Mild to moderate adverse events were reported to Vaxirab-N but no serious adverse events were reported in any of these studies. In conclusion, Vaxirab-N developed by Zydus Cadila was found to be safe and immunogenic by both intramuscular and intradermal route and is recommended for rabies prophylaxis (CTRI No. 2010/091/000055 and 2010/091/000509).