Efficacy and safety of pentavalent rotavirus vaccine in Japan: a randomized, double-blind, placebo-controlled, multicenter trial

Abstract

Rotavirus is the most common cause of severe gastroenteritis in children under 5 y of age. Estimates of disease burden in Japan suggest that between 26,500 and 78,000 children in this age group need hospitalization each year, resulting in a direct medical cost of 10 to 24 billion Yen. Since being introduced in routine infant immunization schedules in the United States in 2006, the oral live pentavalent rotavirus vaccine RV5 (RotaTeq™) has contributed to dramatic reductions in the incidence of rotavirus gastroenteritis (RVGE) and in health care resource utilization. This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of a 3-dose regimen of RV5 in healthy infants, age 6 to 12 weeks, at 32 sites across Japan. The results indicate that RV5 was significantly efficacious in preventing any severity [74.5% (95% confidence interval [CI]: 39.9%, 90.6%; p<0.001)], moderate-to-severe [80.2% (95% CI: 47.4%, 94.1%)], and severe [100% (95% CI: 55.4%, 100%)] RVGE caused by viruses with serotypes contained in the vaccine. The observed cases of RVGE included rotavirus types G1 (n=19), G3 (n=9), G9 (n=5) and one unspecified G serotype with P1A[8]. No G2 or G4 RVGE cases were observed, and this study was not powered to evaluate efficacy against individual serotypes. RV5 was generally safe and well tolerated in Japanese infants. These results are comparable to those observed in clinical studies conducted in other developed countries. Introduction of the vaccine in Japan may reduce disease burden and associated health care costs.

Keywords: RV5; RVGE; pentavalent rotavirus vaccine; rotavirus gastroenteritis; vaccine.

Figure 1. Study disposition. Data are represented as n (%) unless otherwise noted. ^aIncludes 1 subject who was randomized but did not receive the study vaccine by the investigator’s decision. ^bCompleted: the number of subjects who continued follow-up until the last study visit (visit 5) regardless of the number of vaccinations received. ^cSubjects who had <3 vaccinations or <28 d between vaccinations, who received oral poliovirus vaccine or Bacille Calmette-Guérin within 27 d of any dose. ^dSubjects were classified as unevaluable owing to wild-type rotavirus-positive test results prior to 14 d post dose 3, incomplete clinical and/or laboratory results or stool samples collected out of the day range (e.g., within 7 d after the onset of symptoms).