In a new study, a single shot of Merck's investigational combination vaccine ProQuad (Measles, Mumps, Rubella and Varicella [Oka/Merck] Virus Vaccine Live) as a second dose in young children previously vaccinated against measles, mumps, rubella and varicella (chickenpox) resulted in antibody responses similar (non inferior) to those seen in children given a second dose of M-M-R II (Measles, Mumps, and Rubella Virus Vaccine Live) and in children given concomitant second doses of M-M-R II and Varivax (Varicella Virus Vaccine Live [Oka/Merck]).

Antibody responses and tolerability data from this study, the first to explore whether ProQuad can be administered instead of a second dose of M-M-R II or a second dose of M-M-R II and Varivax in children four to six years old, was presented at the National Immunization Conference in Nashville.

"The study was designed to investigate whether one shot of the investigational combination vaccine as a second dose could help children achieve similar antibody responses to these viruses compared to the responses seen with a second dose of M-M-R II and seen with concomitant second doses of M-M-R II and Varivax given at separate vaccination sites," said Keith Reisinger, M.D., M.P.H., a pediatrician and medical director of Primary Physicians Research in Pittsburgh, who presented the data at a poster session. "The results were very encouraging; the antibody responses with ProQuad in four to six year olds were similar to the comparator vaccines and the investigational vaccine was generally well tolerated."

The current U.S. vaccination recommendation is for M-M-R II to be administered at 12 to 15 months of age and at four to six years of age and for Varivax to be administered at 12 to 18 months of age.

In the double-blind, multicenter study, 799 healthy children four to six years of age who previously received M-M-R II and Varivax at 12 months of age or older were randomized to one of three vaccination groups: ProQuad and placebo (n=399); M-M-R II and placebo (n=205); and M-M-R II and Varivax concomitantly (n=195) at separate injection sites. Antibody responses (immunogenicity) were assessed by measurement of geometric mean titers (GMTs) prior to vaccination and at six weeks following vaccination.

Blood samples were collected from the participants prior to vaccination and approximately six weeks following vaccination. Serology testing was performed to measure levels of anti-measles, mumps, rubella and varicella antibodies (GMTs). Investigators compared levels of antibodies from the three study groups to determine similarity (non inferiority). Titers for participants receiving ProQuad and placebo were compared to titers for those receiving M-M-R II and placebo and receiving M-M-R II and Varivax, respectively. Antibody titers pre- and post-vaccination were measured by ELISA. Non inferiority hypothesis testing of GMTs (less than two-fold difference) between groups was performed at the one-sided 0.05 level (ANOVA).

In the study, participants who received ProQuad with placebo as a second dose achieved antibody levels to measles, mumps and rubella that were similar (non inferior) to levels seen in the groups receiving M-M-R II and placebo and M-M-R II and Varivax concomitantly when measured at six weeks after vaccination. Antibody levels to those three viruses were also similar between the group given M-M-R II and placebo and the group given M-M-R II and Varivax. Those who received ProQuad with placebo also achieved antibody levels to varicella that were similar (non inferior) to levels achieved in the group receiving M-M-R II and Varivax at six weeks after vaccination.

Adverse events were monitored using Pediatric Vaccination Report Cards for a 42-day period following vaccination. Parents or caregivers filled out the report cards, which evaluated daily temperatures, Systemic Adverse Experiences (e.g.: measles-like, rubella-like, and varicella-like rashes, mumps-like symptoms, measles, mumps, rubella, varicella and/or zoster) and local vaccination site reactions (pain, swelling, redness and/or rash).

In the study, ProQuad was generally well tolerated; the safety profile of ProQuad with placebo was generally comparable to the safety profiles observed in the comparator groups. Specific results are in Table 2 (PDF), attached.

No serious vaccine-related adverse experiences occurred in any of the three treatment groups.

The percent of subjects with one or more overall, systemic and injection-site adverse experiences as well as the number of subjects with one or more instances of elevated temperature (temperatures > 102° F oral) was generally comparable between the group given ProQuad and placebo and the M-M-R II and placebo group, and between the group given ProQuad and placebo and the group given M-M-R II and Varivax.

Although prompted for on the Vaccination Report Card, no rubella-like rashes or mumps-like symptoms were reported in any treatment group. The incidence rates of measles-like and varicella-like rashes were very low (<1 per cent of subjects) across all three treatment groups. No differences in these adverse experiences were noted.