Safety, Reactogenicity and Immunogenicity of the Human Rotavirus Vaccine in Preterm European Infants: A Randomized Phase IIIb Study

Background: Rotavirus disease is more severe in preterm infants than in full-term infants. This study assessed the safety, reactogenicity and immunogenicity of a human rotavirus vaccine, RIX4414, in European preterm infants. Methods: A total of 1009 preterm infants were randomized (2:1, vaccine:placebo) and stratified into 2 groups: 20% of early (27–30 weeks, group 1) and 80% of late (31–36 weeks, group 2) gestational age preterm infants in each group. Two doses of RIX4414/placebo were administered to these preterm infants according to the recommended chronologic age for full-term infants with an interval of 30–83 days between doses. Serious adverse events were recorded throughout the study period. Solicited and unsolicited adverse events were recorded for 15 and 31 days post-each dose. Antirotavirus IgA concentrations (enzyme-linked immunosorbent assay cutoff  20 U/mL) and geometric mean concentration were determined pre-dose 1 and 30–83 days post-dose 2 in a subset of 300 infants. This study is registered with ClinicalTrials.gov, number NCT00420745 (eTrack106481). Results: Serious adverse events were reported at a similar frequency in both groups (P  0.266). Fifty-seven infants reported at least 1 serious adverse event (5.1% [3.5–7.0] in the RIX4414 group and 6.8% [4.3–10.0] in the placebo group). During the 15-day postvaccination follow-up period, diarrhea, vomiting and fever occurred at a similar frequency in both groups; fever could have been due to concomitant vaccines. Five cases (RIX4414  3, Placebo  2) of rotavirus gastroenteritis were reported. The onset of rotavirus gastroenteritis in the RIX4414 group was 1–5 days after vaccination (vaccine strain identified in all cases) and in the placebo group it was 3–4 days after receiving placebo (wild-type rotavirus identified from both cases). Antirotavirus IgA seroconversion rates at 30–83 days post-dose 2 were 85.7% (79.0–90.9) in the RIX4414 group and 16.0% (8.8–25.9) in the placebo group. Geometric mean concentrations were 202.2 U/mL (153.1–267.1) in the RIX4414 group and 20 U/mL in the placebo group. Seroconversion rate in groups 1 and 2 in RIX4414 recipients were 75.9% (95% confidence interval [CI]: 56.5–89.7%) and