A second dose of a measles-mumps-rubella vaccine administered to healthy four-to-six-year-old children: a phase III, observer-blind, randomized, safety and immunogenicity study comparing GSK MMR and MMR II with and without DTaP-IPV and varicella vaccines co-administration

Abstract

In many countries, a second dose of a combined measles, mumps, and rubella (MMR) vaccine is recommended at 4-6 years of age - similarly to the booster of diphtheria, tetanus, acellular pertussis, and inactivated polio vaccine (DTaP-IPV) and the second dose of varicella vaccine (VV). Vaccine co-administration is generally encouraged if no interferences exist among the vaccines. This phase IIIa, randomized, controlled trial (NCT01621802) evaluated the immunogenicity and safety of MMR-RIT (Priorix, GSK) when given as a second dose with or without co-administration of DTaP-IPV and VV, using MMR II (M-M-R II, Merck & Co Inc.) as comparator. Antibody geometric mean concentrations or titers (GMCs/GMTs) and response rates to the components of all the administered vaccines were assessed. Solicited, unsolicited, and serious adverse events were recorded. Four thousand eleven children aged 4-6 years were enrolled. MMR-RIT elicited immune responses that were not inferior to those of MMR II in terms of GMCs and seroresponse rates when administered alone or when co-administered with DTaP-IPV and VV. The immune responses to the co-administered vaccines in MMR-RIT recipients were non-inferior to those in MMR II recipients. MMR-RIT and MMR II demonstrated similar reactogenicity profiles; the most frequent solicited adverse events across vaccine groups and sub-cohorts were local pain and fever. In conclusion, the immunogenicity and safety profiles of MMR-RIT administered with or without DTaP-IPV and VV were similar to those of MMR II.

Keywords: DTaP-IPV; Measles-mumps-rubella vaccine; co-administration; immunogenicity; safety; varicella vaccine.

Figures

Figure 1.

Focus on the patient section.

Figure 2.

Flow diagram of the study participants in each sub-cohort. Footnote: ATP, according-to-protocol; DTaP-IPV, diphtheria, tetanus, acellular pertussis, and inactivated polio vaccine; N, number of participants; n, number of participants within the category; VV, varicella vaccine.

Figure 3.

Incidence, in each sub-cohort, of solicited injection site adverse events (Day 0–3), fever (Day 0–42), and drowsiness and loss of appetite (Day 0–3; only assessed in sub-cohort 1) (total vaccinated cohort). Footnote: N, number of participants with at least 1 vaccine administration documented.*Except for fever, drowsiness, and loss of appetite in sub-cohort 1 (MMR-RIT, N = 731 and MMR II, N = 268); fever in sub-cohort 2 (MMR-RIT, N = 767 and MMR II, N = 291); and fever in sub-cohort 3 (MMR-RIT, N = 1291 and MMR II, N = 481). Children in sub-cohort 1 received either MMR-RIT or MMR II together with DTaP-IPV and VV; children in sub-cohorts 2 and 3 received either MMR-RIT or MMR II alone.The injection site adverse events (i.e., pain, redness, and swelling) refer to the site of MMR vaccine injection. Fever: temperature ≥38.0°C. Grade 3 was defined as: limb spontaneously painful or child cried when limb was moved (pain); diameter >50 mm (redness, swelling); temperature >39.5°C (fever); adverse event preventing normal, everyday activities (drowsiness); not eating at all (loss of appetite). The error bars represent the upper and lower limits of the exact two-sided 95% confidence intervals.

Figure 4.

Study design. Footnote: , blood sampling; , vaccine administration (includes administration of DTaP-IPV and VV in sub-cohort 1); AEs, adverse events; DTaP-IPV, diphtheria, tetanus, acellular pertussis, and inactivated polio vaccine; NOCDs, new onset chronic diseases; SAEs, serious adverse events; VV, varicella vaccine.*Drowsiness and loss of appetite were recorded as solicited general AE from Day 0 to Day 3 in sub-cohort 1 only.