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Immunogenicity and safety of the 4CMenB and MenACWY-CRM meningococcal vaccines administered concomitantly in infants: A phase 3b, randomized controlled trial.
Vaccine. 2018 Nov 29; 36(50):7609-7617.V

Abstract

BACKGROUND

Invasive meningococcal disease has its highest incidence in infants. Co-administration of serogroup B (4CMenB) and quadrivalent conjugate (MenACWY-CRM) vaccines could protect against 5 clinically-relevant meningococcal serogroups.

METHODS

This phase 3b, open, multicenter study (NCT02106390), conducted in Mexico and Argentina, enrolled and randomized (1:1:1) 750 healthy infants to receive either 4CMenB co-administered with MenACWY-CRM (4CMenB/MenACWY group), 4CMenB (4CMenB group), or MenACWY-CRM alone (MenACWY group) at ages 3, 5, 7 and 13 months. Non-inferiority of immune responses of co-administration to single administration of vaccines was assessed at 1 month post-booster dose (primary objective). Immunogenicity was evaluated pre- and 1 month post-primary and booster vaccinations using human serum bactericidal assay (hSBA). Safety was assessed.

RESULTS

At 1 month post-booster vaccination, between-group hSBA geometric mean titer (GMT) ratios ranged from 0.89 to 1.03 for serogroup B strains (group 4CMenB/MenACWY over 4CMenB), and from 1.05 to 2.48 for ACWY serogroups (group 4CMenB/MenACWY over MenACWY). The lower limit of the 2-sided 95% confidence intervals for all GMT ratios was >0.5; the primary objective was demonstrated. Across all groups and serogroup B strains, 68-100% and 87-100% of children had hSBA titers ≥5 at 1 month post-primary and booster vaccination, respectively. For serogroups ACWY, ≥96% (post-primary vaccination) and ≥98% (post-booster vaccination) of children in all groups had hSBA titers ≥4. Post-booster vaccination, GMTs increased ≥5.99-fold from pre-booster values for each strain/serogroup. Solicited adverse events (AEs) were more frequent in groups 4CMenB/MenACWY and 4CMenB than in MenACWY; incidence of all other AEs was similar between groups. Serious AEs were reported for 6, 13, and 11 participants in groups 4CMenB/MenACWY, 4CMenB, and MenACWY, respectively; 1 (group 4CMenB) was considered vaccine-related.

CONCLUSION

Immune responses elicited by co-administration of 4CMenB and MenACWY-CRM was non-inferior to single immunization. Co-administration of vaccines was immunogenic and well tolerated in infants. ClinicalTrials.gov: NCT02106390.

Authors+Show Affiliations

Instituto Nacional de Pediatría, Insurgentes Cuicuilco, 04530 Mexico City, Mexico. Electronic address: mermacpar@hotmail.com.Hospital de Niños "Ricardo Gutiérrez", Gallo 1330, Ciudad Autónoma de Buenos Aires, Argentina. Electronic address: angelagentile@fibertel.com.ar.Asociacion de Investigacion Pediatrica Y Adultos (AINPAD A.C.), Montaña Monarca No 31 Consultorio 209 y 2010 Col Jesús del Monte Morelia, Michoacán CP58350, Mexico. Electronic address: jorge.vazquez@ainpad.com.mx.Paideia, Investigacion Clinica en Pediatria, Salguero 2835, Ciudad Autónoma de Buenos Aires, Argentina. Electronic address: vax_ar@yahoo.com.Hospital Nuestra Señora de la Misericordia del Nuevo Siglo, Belgrano 1502, 5000 Córdoba, Argentina. Electronic address: angelminguez04@yahoo.com.ar.CAIMED Investigación en Salud S.A de C.V, Calle de Manzanillo # 100 Colonia Roma Sur, Piso 2 Delegación Cuauhtémoc, México City, Mexico. Electronic address: monica.carrascal@caimed.com.Plus100 B.V. c/o GSK, Hullenbergweg 83-85, 1101 CL Amsterdam, the Netherlands. Electronic address: arnold.x.willemsen@gsk.com.GSK, Via Fiorentina, 1, 53100 Siena, Italy. Electronic address: chiranjiwi.x.bhusal@gsk.com.GSK, Via Fiorentina, 1, 53100 Siena, Italy. Electronic address: daniela.x.toneatto@gsk.com.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30414782

Citation

Macias Parra, Mercedes, et al. "Immunogenicity and Safety of the 4CMenB and MenACWY-CRM Meningococcal Vaccines Administered Concomitantly in Infants: a Phase 3b, Randomized Controlled Trial." Vaccine, vol. 36, no. 50, 2018, pp. 7609-7617.
Macias Parra M, Gentile A, Vazquez Narvaez JA, et al. Immunogenicity and safety of the 4CMenB and MenACWY-CRM meningococcal vaccines administered concomitantly in infants: A phase 3b, randomized controlled trial. Vaccine. 2018;36(50):7609-7617.
Macias Parra, M., Gentile, A., Vazquez Narvaez, J. A., Capdevila, A., Minguez, A., Carrascal, M., Willemsen, A., Bhusal, C., & Toneatto, D. (2018). Immunogenicity and safety of the 4CMenB and MenACWY-CRM meningococcal vaccines administered concomitantly in infants: A phase 3b, randomized controlled trial. Vaccine, 36(50), 7609-7617. https://doi.org/10.1016/j.vaccine.2018.10.096
Macias Parra M, et al. Immunogenicity and Safety of the 4CMenB and MenACWY-CRM Meningococcal Vaccines Administered Concomitantly in Infants: a Phase 3b, Randomized Controlled Trial. Vaccine. 2018 Nov 29;36(50):7609-7617. PubMed PMID: 30414782.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunogenicity and safety of the 4CMenB and MenACWY-CRM meningococcal vaccines administered concomitantly in infants: A phase 3b, randomized controlled trial. AU - Macias Parra,Mercedes, AU - Gentile,Angela, AU - Vazquez Narvaez,Jorge Alejandro, AU - Capdevila,Alejandro, AU - Minguez,Angel, AU - Carrascal,Monica, AU - Willemsen,Arnold, AU - Bhusal,Chiranjiwi, AU - Toneatto,Daniela, Y1 - 2018/11/07/ PY - 2018/04/17/received PY - 2018/10/28/revised PY - 2018/10/30/accepted PY - 2018/11/12/pubmed PY - 2019/4/23/medline PY - 2018/11/12/entrez KW - 4CMenB KW - Co-administration KW - Infants KW - MenACWY-CRM KW - Meningococcal vaccination SP - 7609 EP - 7617 JF - Vaccine JO - Vaccine VL - 36 IS - 50 N2 - BACKGROUND: Invasive meningococcal disease has its highest incidence in infants. Co-administration of serogroup B (4CMenB) and quadrivalent conjugate (MenACWY-CRM) vaccines could protect against 5 clinically-relevant meningococcal serogroups. METHODS: This phase 3b, open, multicenter study (NCT02106390), conducted in Mexico and Argentina, enrolled and randomized (1:1:1) 750 healthy infants to receive either 4CMenB co-administered with MenACWY-CRM (4CMenB/MenACWY group), 4CMenB (4CMenB group), or MenACWY-CRM alone (MenACWY group) at ages 3, 5, 7 and 13 months. Non-inferiority of immune responses of co-administration to single administration of vaccines was assessed at 1 month post-booster dose (primary objective). Immunogenicity was evaluated pre- and 1 month post-primary and booster vaccinations using human serum bactericidal assay (hSBA). Safety was assessed. RESULTS: At 1 month post-booster vaccination, between-group hSBA geometric mean titer (GMT) ratios ranged from 0.89 to 1.03 for serogroup B strains (group 4CMenB/MenACWY over 4CMenB), and from 1.05 to 2.48 for ACWY serogroups (group 4CMenB/MenACWY over MenACWY). The lower limit of the 2-sided 95% confidence intervals for all GMT ratios was >0.5; the primary objective was demonstrated. Across all groups and serogroup B strains, 68-100% and 87-100% of children had hSBA titers ≥5 at 1 month post-primary and booster vaccination, respectively. For serogroups ACWY, ≥96% (post-primary vaccination) and ≥98% (post-booster vaccination) of children in all groups had hSBA titers ≥4. Post-booster vaccination, GMTs increased ≥5.99-fold from pre-booster values for each strain/serogroup. Solicited adverse events (AEs) were more frequent in groups 4CMenB/MenACWY and 4CMenB than in MenACWY; incidence of all other AEs was similar between groups. Serious AEs were reported for 6, 13, and 11 participants in groups 4CMenB/MenACWY, 4CMenB, and MenACWY, respectively; 1 (group 4CMenB) was considered vaccine-related. CONCLUSION: Immune responses elicited by co-administration of 4CMenB and MenACWY-CRM was non-inferior to single immunization. Co-administration of vaccines was immunogenic and well tolerated in infants. ClinicalTrials.gov: NCT02106390. SN - 1873-2518 UR - https://www.unboundmedicine.com/medline/citation/30414782/Immunogenicity_and_safety_of_the_4CMenB_and_MenACWY_CRM_meningococcal_vaccines_administered_concomitantly_in_infants:_A_phase_3b_randomized_controlled_trial_ DB - PRIME DP - Unbound Medicine ER -