Search

Background Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants. Methods Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 × 1010 viral particles) followed by placebo (RSV_1D); 2 high ChAd155-RSV doses (5 × 1010 viral particles) (RSV_2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years. Results Two hundred one infants were vaccinated (RSV_1D: 65; RSV_2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post–ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post–dose 2. Conclusions ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response. Clinical Trials Registration.  NCT03636906. [ABSTRACT FROM AUTHOR]

A new pediatric fixed combination of beclometasone dipropionate (BDP) 50 μg and formoterol fumarate (FF) 6 μg via pressurized metered-dose inhaler (pMDI) (CHF1535, Chiesi, Italy) was investigated. In a double-blind, randomized, placebo-controlled, cross-over study, a single CHF1535 administration using AeroChamber Plus™ spacer device (2 actuations, total dose BDP 100 μg/FF 12 μg) was compared to the same pMDI free combination in 56 asthmatic children aged ≥ 5 and < 12 years. Primary efficacy variable was forced expiratory volume during the first second (FEV1) area under the curve corrected by time over 12 h following morning dose (AUC0-12h). Further CHF1535 doses (50 μg/6 μg, 100 μg/12 μg, and 200 μg/24 μg) were also explored. Adverse events, electrocardiogram, and vital signs were monitored for safety. CHF1535 was non-inferior to free combination [adjusted mean difference (95% CI) 0.004 L (− 0.050, 0.041] with lower confidence limit greater than the limit set at 0.1 L. FEV1 AUC0-12h of each CHF1535 dose vs placebo were 0.037 L (p = 0.160), 0.119 L (p < 0.001), and 0.094 (p < 0.001) for 50/6, 100/12, and 200/24, respectively. No safety signals were found. Conclusion: CHF1535 was as effective as free combination BDP/FF, with a trend towards a dose-related response. All treatments were safe. Trial registration: ClinicalTrials.gov ID: NCT01584492 What is Known: •Inhaled pressurized metered-dose solutions (pMDI) are the preferred treatment for pediatric asthma. •Combination therapy of inhaled corticosteroids and long-acting β2- agonists is a well-established approach to control airway inflammation and airway obstruction also in pediatric patients. What is New: •A novel pediatric pMDI fixed combination of beclomethasone dipropionate 50 μg and formoterol fumarate 6 μg (CHF 1535) was non-inferior to the free combination at the same dose in pulmonary function over the 12-h post-dose period in asthmatic children, with trend towards a dose-related response. [ABSTRACT FROM AUTHOR]