Long-term safety follow-up of children from a randomized—controlled phase II b proof—of—concept efficacy study of the live, attenuated, tetravalent dengue vaccine (CYD—TDV) in Thailand
Kriengsak Limkittikul1, Weerawan Hattasingh1, Danaya Chansinghakul2, Arunee Sabchareon1, Wut Dulyachai3, Carina Frago4, T Anh Wartel4, Edith Langevin5, Sophia Gailhardou6, Alain Bouckenooghe4
1 Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Bangkok, 10400, Thailand
2 Sanofi Pasteur Clinical Sciences, 87/2 CRC Tower 23rd Floor, All Seasons Place, Wireless Road, Lumpini, Pathumwan, Bangkok, Thailand
3 Ratchaburi Hospital, 77/4, Kathatorn Road, Tambon Na Muang, Amphoe Muang Ratchaburi, Thailand
4 Sanofi Pasteur Clinical Sciences, 38 Beach Road #18-11 South Beach Tower, Singapore 189767, Singapore
5 Sanofi Pasteur Clinical Programs, Marcy L’Etoile, France
6 Sanofi Pasteur Global Pharmacovigilance, Lyon, France
Sanofi Pasteur Clinical Sciences, 87/2 CRC Tower 23rd Floor, All Seasons Place, Wireless Road, Lumpini, Pathumwan, Bangkok 10330
Source of Support: None, Conflict of Interest: None
Objective: To investigate the long-term safety of a tetravalent dengue vaccine (CYD-TDV) in children in a phase Π b follow-up study in Thailand.
Methods: In the phase Π b study, children aged 4-11 years were randomized (2:1) to receive three injections of CYD-TDV or serve as control at 6-month intervals, with 25 months’ active follow-up (active phase). This study was an additional four-year passive surveillance for hospitalized virologically-confirmed dengue (VCD; hospital phase). Cases of hospitalized VCD, severe hospitalized VCD, vaccine-related serious adverse events, and deaths were reported for the total population, with post-hoc analyses by enrollment age (<9 and years).
Results: Of 3 997 participants receiving injection, 80.1% were recruited to the hospital phase [2 131 (CYD-TDV); 1 072 (control)]. Eighty-five hospitalized VCD cases were reported in the CYD-TDV group and 46 in the control group during the four-year hospital phase [relative risk (RR): 0.93, 95% confidence interval (CI): 0.64-1.36]. The RR over six years of follow-up was 0.77 (95% CI: 0.57-1.05). In those aged ≥9 years, the cumulative RRs in the active phase, hospital phase, and entire six years were 0.28 (95% CI: 0.08-0.81), 0.51 (95% CI: 0.25-1.05), and 0.42 (95% CI: 0.24-0.75), respectively. In the overall population, there were ten severe hospitalized VCD cases in the CYD-TDV group and five in the control group over six years (RR: 1.00, 95% CI: 0.31-3.75).
Conclusions: Over six years of follow-up, in children aged ≥9 years, CYD-TDV administration is associated with a reduced risk of hospitalized VCD.