Objectives: JVC-001 is a new live attenuated measles-mumps-rubella vaccine (measles AIK-C, mumps RIT4385, and rubella Takahashi strains). Two phase 3 studies were conducted, one to verify the non-inferior immunogenicity of JVC-001 versus the approved mumps and measles-rubella vaccines (J301 study) and another to compare the immunogenicity and safety of different titers (J302 study). Methods: Both studies were multicenter, randomized, observer-blinded, phase 3 studies. J301 compared the immunogenicity elicited with a single dose of JVC-001 or control vaccines (measles-rubella vaccine + mumps vaccine [Hoshino strain]). J302 was a titer-confirmation study of a single dose of a low- or high-titer formulation of JVC-001. Both studies enrolled healthy Japanese children (aged 1 year) and had a primary efficacy endpoint of seropositive rate on Day 43. Results: Overall, 861 participants completed J301 (JVC-001, n = 429; control, n = 432) and 100 participants completed J302 (low-titer, n = 48; high-titer, n = 52). For measles and rubella virus antibody titer, non- inferiority of JVC-001 was demonstrated: seropositive rates were >= 99.5 %. For mumps virus genotype D antibody titer, seropositive rates were 80.6 % (95 % confidence interval 76.5 % to 84.4 %) with JVC-001 and 88.1 % (84.6% to 91.0%) with control vaccination. Thus, non-inferiority for mumps virus genotype D antibody titer was not confirmed. Seropositive rates were similar in the low- and high-titer groups. There were no events leading to discontinuation, or cases of aseptic meningitis in either study. Conclusions: Although the non-inferiority of JVC-001 to currently approved vaccines was not demonstrated for the mumps component, clinical significance and consistent efficacy were indicated. Vaccine titer did not affect immunogenicity. JVC-001 is expected to have a lower risk of aseptic meningitis to currently approved vaccines and raised no new safety signals emerged.
