zumab was eva luated in four additional studies in 4337 patients (children born at 35 weeks of gestation or less and 6 months of age or less, or 24 months of age or less with bronchopulmonary dysplasia, or with haemodynamically significant congenital heart disease were included in these studies) and was observed in 0% – 1.5% of patients at different study timepoints. There was no association observed between the presence of antibody and adverse events. Therefore, anti-drug antibody (ADA) responses appear to be of no clinical relevance.
Studies using lyophilised palivizumab
In a placebo-controlled trial of RSV disease prophylaxis in (IMpact-RSV trial) 1502 high-risk children (1002 Synagis; 500 placebo), 5 monthly doses of 15 mg/kg reduced the incidence of RSV related hospitalisation by 55% (p = < 0.001). The RSV hospitalisation rate was 10.6% in the placebo group. On this basis, the absolute risk reduction is 5.8% which means the number needed to treat is 17 to prevent one hospitalisation. The severity of RSV disease in children hospitalised despite prophylaxis with palivizumab in terms of days in ICU stay per 100 children and days of mechanical ventilation per 100 children was not affected.
A total of 222 children were enrolled in two separate studies to examine the safety of palivizumab when it is administered for a second RSV season. One hundred and three (103) children received monthly palivizumab injections for the first time, and 119 children received palivizumab for two consecutive seasons. No difference between groups regarding immunogenicity was observed in either study. However, as the efficacy of palivizumab when administered to patients as a second course of treatment during an ensuing RSV season has not been formally investigated in a study performed with this objective, the relevance of these data in terms of efficacy is unknown.
In an open label prospective trial designed to eva luate pharmacokinetics, safety, and immunogenicity after administration of 7 doses of palivizumab within a single RSV season, pharmacokinetic data indicated that adequate mean palivizumab levels were achieved in all 18 children enrolled. Transient, low levels of antipalivizumab antibody were observed in one child after the second dose of palivizumab that dropped to undetectable levels at the fifth and seventh dose.
In a placebo-controlled trial in 1,287 patients ≤ 24 months of age with haemodynamically significant congenital heart disease (639 Synagis; 648 placebo), 5 monthly doses of 15 mg/kg Synagis; reduced the incidence of RSV hospitalisations by 45% (p = 0.003) (congenital heart disease study). Groups were equally balanced between cyanotic and acyanotic patients. The RSV hospitalisation rate was 9.7% in the placebo group and 5.3% in the Synagis group. Secondary efficacy endpoints showed significant reductions in the Synagis group compared to placebo in total days of RSV hospitalisation (56% reduction, p = 0.003) and total RSV days with increased supplemental oxygen (73% reduction, p = 0.014) per 100 children.
A retrospective observational study was conducted in young children with hemodynamically significant congenital heart disease (HSCHD) comparing the occurrence of primary serious adverse events (PSAEs: infection, arrhythmia, and death) between those who did (1009) and did not receive Synagis prophylaxis (1009) matched by age, type of cardiac lesion, and prior corrective surgery. The incidence of arrhythmia and death PSAEs was similar in children who did a |
