BACKGROUND: An oral, live attenuated human rotavirus vaccine, RIX4414 has been developed to prevent rotavirus gastroenteritis. An integrated safety summary of 8 randomized, placebo-controlled, double-blind phase II and III trials of vaccine at potency licensed for use worldwide was performed. METHODS:Healthy 1- to 18-week-old infants (N = 71209) were enrolled to receive 2 doses of RIX4414/placebo according to 0, 1 or 0, 2 month schedules. Solicited (fever, fussiness/irritability, loss of appetite, vomiting, diarrhea, cough/rhinorrhea) and unsolicited adverse events (AEs) were recorded for 8 days and 31 days, respectively, after each dose. Serious adverse events (SAEs) including intussusception and death were collected throughout the entire study periods. Potential imbalances were defined as the 95% confidence interval (CI) for the relative risk (RR) stratified by trials excluding "1." RESULTS: Solicited AEs were evaluated in 3286 RIX4414 vaccinees and 2015 placebo recipients. Among solicited AEs, no imbalance was noted between groups. SAEs, including death and intussusception, were evaluated in 36755 RIX4414 and 34454 placebo recipients. Within 31 days after each dose, no imbalances were noted between the groups for all SAEs (RR = 0.9; 95% CI: 0.81, 1.01), deaths (RR = 1.64; 95% CI: 0.92, 3.02), and intussusception (RR 1.23; 95% CI: 0.41, 3.90). SAEs because of gastrointestinal diseases including diarrhea, gastroenteritis (all cause and due to rotavirus), dehydration, and intestinal ileus occurred significantly less often in RIX4414 than placebo recipients. CONCLUSIONS: Across the phase II and III clinical trials, the reactogenicity and safety profile between RIX4414 and placebo was similar, in particular with no increased risk of intussusception.
RCT Entities:
BACKGROUND: An oral, live attenuated human rotavirus vaccine, RIX4414 has been developed to prevent rotavirus gastroenteritis. An integrated safety summary of 8 randomized, placebo-controlled, double-blind phase II and III trials of vaccine at potency licensed for use worldwide was performed. METHODS: Healthy 1- to 18-week-old infants (N = 71209) were enrolled to receive 2 doses of RIX4414/placebo according to 0, 1 or 0, 2 month schedules. Solicited (fever, fussiness/irritability, loss of appetite, vomiting, diarrhea, cough/rhinorrhea) and unsolicited adverse events (AEs) were recorded for 8 days and 31 days, respectively, after each dose. Serious adverse events (SAEs) including intussusception and death were collected throughout the entire study periods. Potential imbalances were defined as the 95% confidence interval (CI) for the relative risk (RR) stratified by trials excluding "1." RESULTS: Solicited AEs were evaluated in 3286 RIX4414 vaccinees and 2015 placebo recipients. Among solicited AEs, no imbalance was noted between groups. SAEs, including death and intussusception, were evaluated in 36755 RIX4414 and 34454 placebo recipients. Within 31 days after each dose, no imbalances were noted between the groups for all SAEs (RR = 0.9; 95% CI: 0.81, 1.01), deaths (RR = 1.64; 95% CI: 0.92, 3.02), and intussusception (RR 1.23; 95% CI: 0.41, 3.90). SAEs because of gastrointestinal diseases including diarrhea, gastroenteritis (all cause and due to rotavirus), dehydration, and intestinal ileus occurred significantly less often in RIX4414 than placebo recipients. CONCLUSIONS: Across the phase II and III clinical trials, the reactogenicity and safety profile between RIX4414 and placebo was similar, in particular with no increased risk of intussusception.