Phase II and III Clinical Studies of Diphtheria-Tetanus-Acellular Pertussis Vaccine Containing Inactivated Polio Vaccine Derived from Sabin Strains (DTaP-sIPV)

Abstract

JapicCTI-121902 for Phase II study, JapicCTI-101075 for Phase III study (http://www.clinicaltrials.jp/user/cte_main.jsp).

Development and introduction of inactivated poliovirus vaccines derived from Sabin strains in Japan

“…GMT was considerably high even for the type 1 Mahoney strain in the three groups after the booster immunization of DTaP-sIPV. The incidence of adverse events (erythema and pyrexia) was higher in Group H than that in Groups M and L, but was not statistically significant [58]. Accordingly, Kaketsuken selected formulation M (1.5, 50, and 50 sDU/0.5 mL/dose, for type 1, 2, and 3, respectively) as optimum doses for the Phase III study.…”

“…Clinical studies of the DTaP-sIPV products (1.5, 50, and 50 sDU, for type 1, 2, and 3, respectively) indicate that sufficiently high serum neutralizing antibodies against three poliovirus serotypes were induced after a booster (fourth) immunization with DTaP-sIPV [58]. In general, serum neutralizing antibodies against polioviruses are well maintained at least until preschool age after a proper series of cIPV immunizations in infants [62].…”

“…Two manufacturers, Chemo-SeroTherapeutic Research Institute (Kaketsuken) and Biken completed preclinical and clinical studies of DTaP-sIPV, and then submitted the application for manufacturing approval to the PMDA in late 2011-early 2012 [57][58][59][60][61]. Both of the companies used a sIPV bulk stock, manufactured by JPRI, and combined it with their own licensed DTaP with aluminum adjuvants, to prepare the final DTaPsIPV products.…”

“…A recent report by Okada et al [58] revealed the safety and efficacy profiles of DTaP-sIPV of Kaketsuken for the first time in humans during Phase II and III clinical studies. In a dose-finding Phase II study, three different sIPV antigen contents (3, 100, and 100 sDU/0.5 mL/dose for formulation H; 1.5, 50, and 50 sDU/0.5 mL/dose for formulation M; and 0.75, 25, and 25 sDU/0.5 mL/dose for formulation L) were incorporated in the DTaP-sIPV preparations.…”

“…After the primary DTaP immunization, the Control Group was immunized with two doses of OPV and then received a DTaP booster. Formulation M induced a 100% seropositivity rate and elevated GMT for all three serotypes of the Sabin strains, and also induced proper immunity to all components of DTaP, comparable to that of the original DTaP product, after the booster immunization [58,60]. Phase II and III clinical studies showed that formulation M was well tolerant.…”