The safety profile of Haemophilus influenzae type b–Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine (HibMenCY)

Abstract

The safety profile of HibMenCY was compared with licensed Hib conjugate vaccines in a pooled analysis that included more than 8,500 subjects who were administered a four-dose series of HibMenCY or commercially available Hib vaccines at 2, 4, 6 and 12–15 mo of age in two primary vaccination and two fourth dose phase 3 studies. In all studies, HibMenCY or Hib vaccine was co-administered with age-appropriate, routinely recommended vaccines. In one primary and one fourth dose study (n = 4180), local and general symptoms were solicited using diary cards for 4 d after each dose. Serious adverse events (SAEs) and the occurrence of adverse events (AEs) indicating new onset of chronic disease (NOCD), rash, and conditions prompting Emergency Room (ER) visits were reported from dose 1 until 6 mo after dose 4. The incidences of solicited local and general symptoms were similar following HibMenCY and commercially available Hib vaccines. For some solicited symptoms (pain at the injection site and irritability), rates were lower in the HibMenCY group compared with the Hib control group (p value < 0.05). There were no statistically significant differences between groups in the incidences of SAEs, NOCDs, rash, or AEs leading to ER visits, with the exceptions of anemia and viral gastroenteritis, which occurred significantly less frequently in those receiving HibMenCY than those receiving commercially available Hib vaccines. In this pooled safety analysis, the safety profile of HibMenCY was similar to the safety profile of licensed monovalent Hib vaccines, despite the addition of meningococcal antigens.

 

These studies are registered at www.clinicaltrials.gov NCT00345579 (primary vaccination study), NCT00345683 (fourth dose vaccination study) and NCT00289783 (primary and fourth dose vaccination studies)

Keywords: :

• Neisseria meningitidis
• Haemophilus influenzae type b
• adverse drug event
• vaccine

Disclosure of Potential Conflicts of Interest

S.R. is a principal investigator in studies funded by GSK and has received travel support from GSK for attendance at investigator meetings.

K.B. is a principal investigator in studies funded by GSK, Pfizer, Novartis and MedImmune. She has also received honoraria from sanofi pasteur for lectures and consulting services, and from GSK for consulting services.

T.N. is a principal investigator in studies funded by GSK, has received travel support from GSK to scientific meetings for presentation of scientific data and an honorarium for membership of an independent DSMB for an unrelated vaccine.

N.P.R. is a principal investigator on clinical trials funded by GSK, Pfizer and Bristol, and has received honoraria for board membership on Tibotec.

C.A.D. is a principal investigator on clinical trials funded by GSK.

M.A.R.W. declares no conflict of interest.

C.C., E.A., N.M. and J.M.M. are employees of GSK Biologicals. C.C., N.M. and J.M.M. report ownership of stock options.

Acknowledgments

The authors thank co-investigators and study co-ordinators:

In Australia: Doctors Helen Marshall, Peter Richmond, Michael Nissen, Jodie McVernon, and study coordinators Marita Kefford, Susan Lee and Jennifer Kent.

In Mexico: Doctors Tania Espinosa Sierra, Renatta Pacheco Garcia and Norma Dominguez Valois.

In the US for study A/B: Doctors Gerald Bader, Mark Blatter, Dean A Blumberg, Joseph Elser, Earl Ruffin Franklin, Fernando Guerra, James Hedrick, Michael Husseman, Farha Khan, Michael Leonardi, Steven Manson, Gary S. Marshall, Sharon Nachman, Zack Sanders, Julie Shepard, Lawrence D. Sher, Hernani Soberano, Alawia Suliman, Christine Turley, Lisa Turner, Meera Varman, Emmanuel Walter, and Leonard Weiner.

In the US for study C/D: Doctors Blaise L. Congeni, Matthew Cox, John Fling, Stephen Fries, Michael Green, Edward Goldblatt, Dan Henry, Richard Hines, William Hitchcock, Michael Husseman, William Johnston, Karen Kamachi, Michael Leonardi, Joseph Ley, Keith Ramsey, Zack Sanders, Michael Simon, Hernani Soberano, Malcolm Sperling, Bradley J. Sullivan, Steven Thompson, Lisa Turner, Ellen Wald, Leonard Weiner, and study coordinators Jodie Devers and Theresa Lane.

The authors specially thank the volunteers and their parents/guardians who participated in the study, the study nurses and other staff members without whom this study would not have been possible. The authors are also grateful to collaborators from GSK: Dr Dominique Boutriau and Dr Leonard Friedland for critical evaluation of the studies; Dr Pascal Lestrate for Lab testing, Karine Muller and Anne Sumbul for performing the statistical analyses, GSK study managers Valérie Sengers, Heather Santiago, and Catherine Streeton; GSK Australia Clinical Operations Team for coordination and contacts with investigators: Maja Galic, Jacob Ryan, Audra Wilson and Felicity King. The authors also thank Dr Joanne Wolter (independent medical writer) for assistance in writing the initial manuscript draft and Dr Tatjana Mijatovic and Wouter Houthoofd (both XPE Pharma and Science) for editorial assistance and manuscript coordination on behalf of GSK.