Jiri Beran1, Geert Leroux-Roels2, Pierre Van Damme3, Jan de Hoon4, Corinne Vandermeulen5, Mohamed Al-Ibrahim6, Casey Johnson7, James Peterson8, Sherryl Baker9, Claudia Seidl10, Annette Dreisbach11, Annette Karsten12, Bartholomew Corsaro13, Ouzama Henry14, Maria Lattanzi15, Zourab Bebia16. 1. Vaccination and Travel Medicine Center, Hradec Králové, Czech Republic. Electronic address: jiri.beran@vakcinace.cz. 2. Center for Vaccinology Ghent University and Ghent University Hospital, Ghent, Belgium. Electronic address: geert.lerouxroels@ugent.be. 3. Center for the Evaluation of Vaccination, University Antwerp, Antwerp, Belgium. Electronic address: pierre.vandamme@uantwerpen.be. 4. Center for Clinical Pharmacology, UZ Leuven, Leuven, Belgium. Electronic address: jan.dehoon@uzleuven.be. 5. Center for Clinical Pharmacology, UZ Leuven, Leuven, Belgium. Electronic address: corinne.vandermeulen@kuleuven.be. 6. SNBL Clinical Pharmacology Center, Baltimore, MD, United States. Electronic address: mohamed.al-ibrahim@pharmaron-us.com. 7. Johnson County Clin-Trials, Lenexa, KS, United States. Electronic address: cjohnson@jcct.com. 8. Foothill Family Clinic, Salt Lake City, UT, United States. Electronic address: jpeterson@foothillfamilyclinic.com. 9. GSK, Cambridge, MA, United States. Electronic address: sb@rscstatconsulting.com. 10. GSK, Siena, Italy. Electronic address: claudia.x.seidl@gsk.com. 11. GSK, Marburg, Germany. Electronic address: annette.x.dreisbach@gsk.com. 12. GSK, Marburg, Germany. Electronic address: annette.x.karsten@gsk.com. 13. GSK, Rockville, MD, United States. Electronic address: bart.x.corsaro@gsk.com. 14. GSK, Rockville, MD, United States. Electronic address: ouzama.n.henry@gsk.com. 15. GSK, Siena, Italy. Electronic address: maria.x.lattanzi@gsk.com. 16. GSK, Rockville, MD, United States. Electronic address: zourab.x.bebia@gsk.com.
Abstract
BACKGROUND: We evaluated the safety and immunogenicity of liquid and lyophilized formulations of an investigational trivalent group B streptococcus (GBS) vaccine in non-pregnant women and assessed the formulations' equivalence in terms of serotype-specific immune response. METHODS: This phase II, randomized, comparative, observer-blind trial enrolled healthy non-pregnant women 18-40 years of age. Women received a single dose of fully liquid (n = 529) or lyophilized (n = 521) trivalent GBS vaccine on day 1. Safety assessments were performed up to day 181 (study termination). Serotype Ia/Ib/III-specific immunoglobulin G (IgG) antibodies were measured in sera from women on day 1 (pre-vaccination) and day 31. Equivalence between the two formulations was demonstrated if the two-sided 95% confidence interval (CI) for the ratio (liquid/lyophilized) of the geometric mean concentrations (GMCs) on day 31 was contained in a (0.5, 2.0) interval for each serotype. RESULTS: Solicited and unsolicited adverse events were reported at similar rates for both formulations. Serious adverse events were reported for six (1.1%) liquid GBS and nine (1.7%) lyophilized GBS vaccinated women, none of which were considered related to vaccination or fatal. On day 31, serotype-specific IgG concentrations were 8-16-fold higher than on day 1 in both groups. Equivalence of the liquid to the lyophilized formulation 30 days post-vaccination was demonstrated as the 95% CIs of the GMC ratios were within the pre-specified interval for the three serotypes: GMC ratios were 1.02 (95% CI: 0.79, 1.32) for serotype Ia, 0.93 (0.71, 1.21) for serotype Ib and 0.99 (0.76, 1.30) for serotype III. CONCLUSIONS: Both formulations of the investigational trivalent GBS vaccine had favorable safety profiles and induced similar GBS serotype-specific antibody concentrations. This study demonstrated that the fully liquid formulation was equivalent to the lyophilized formulation in healthy non-pregnant women in terms of immunogenicity for all three serotypes. CLINICAL TRIALS REGISTRATION: NCT02270944.
BACKGROUND: We evaluated the safety and immunogenicity of liquid and lyophilized formulations of an investigational trivalent group B streptococcus (GBS) vaccine in non-pregnant women and assessed the formulations' equivalence in terms of serotype-specific immune response. METHODS: This phase II, randomized, comparative, observer-blind trial enrolled healthy non-pregnant women 18-40 years of age. Women received a single dose of fully liquid (n = 529) or lyophilized (n = 521) trivalent GBS vaccine on day 1. Safety assessments were performed up to day 181 (study termination). Serotype Ia/Ib/III-specific immunoglobulin G (IgG) antibodies were measured in sera from women on day 1 (pre-vaccination) and day 31. Equivalence between the two formulations was demonstrated if the two-sided 95% confidence interval (CI) for the ratio (liquid/lyophilized) of the geometric mean concentrations (GMCs) on day 31 was contained in a (0.5, 2.0) interval for each serotype. RESULTS: Solicited and unsolicited adverse events were reported at similar rates for both formulations. Serious adverse events were reported for six (1.1%) liquid GBS and nine (1.7%) lyophilized GBS vaccinated women, none of which were considered related to vaccination or fatal. On day 31, serotype-specific IgG concentrations were 8-16-fold higher than on day 1 in both groups. Equivalence of the liquid to the lyophilized formulation 30 days post-vaccination was demonstrated as the 95% CIs of the GMC ratios were within the pre-specified interval for the three serotypes: GMC ratios were 1.02 (95% CI: 0.79, 1.32) for serotype Ia, 0.93 (0.71, 1.21) for serotype Ib and 0.99 (0.76, 1.30) for serotype III. CONCLUSIONS: Both formulations of the investigational trivalent GBS vaccine had favorable safety profiles and induced similar GBS serotype-specific antibody concentrations. This study demonstrated that the fully liquid formulation was equivalent to the lyophilized formulation in healthy non-pregnant women in terms of immunogenicity for all three serotypes. CLINICAL TRIALS REGISTRATION: NCT02270944.