TY - JOUR
T1 - Immunogenicity and safety of measles-mumps-rubella vaccine at two different potency levels administered to healthy children aged 12-15 months
T2 - A phase III, randomized, non-inferiority trial
AU - The MMR-161 Study Group
AU - Ahonen, Anitta
AU - Berry, Andrea
AU - Chatterjee, Archana
AU - Clifford, Robert
AU - Diaz Perez, Clemente
AU - Diez-Domingo, Javier
AU - Haney, Byron
AU - Harrison, Christopher J.
AU - Kerdpanich, Angkool Phirangkul
AU - Lee, Jimmy K.F.
AU - Leonardi, Michael
AU - Martinón-Torres, Federico
AU - Miranda, Mariano
AU - Perez Porcuna, Xavier Maria
AU - Phongsamart, Wanatpreeya
AU - Sharifah Huda, Engku Alwi
AU - Toh, Teck Hock
AU - Twiggs, Jerry
AU - Ulied Arminana, Angels
AU - Varman, Meera
AU - Zissman, Edward
AU - Caplanusi, Adrian
AU - Carryn, Stephane
AU - Povey, Michael
AU - Henry, Ouzama
N1 - Funding Information:
All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: Stephane Carryn, Ouzama Henry, and Michael Povey are employed by the GSK group of companies. Adrian Caplanusi was an employee of the GSK group of companies at the time of the study conduct. Stephane Carryn and Ouzama Henry hold shares in the GSK group of companies as part of their employee remuneration. Andrea Berry’s institution received payment from the GSK group of companies for her participation as a principal investigator in the trial. Her institution has received payment from the GSK group of companies, NIAID, Novartis, and Pfizer to conduct vaccine or epidemiological trials. Archana Chatterjee's institution received a grant from the GSK group of companies for her participation as a principal investigator in the trial. Clemente Diaz Perez’s institution (UPR Medical Sciences Campus) received payment from the GSK group of companies to support partially the execution of the study. Javier Diez-Domingo received personal fees from the GSK group of companies and MSD for participation as a board member, grant from Sanofi Pasteur MSD, and non-financial support from Sanofi-Pasteur for ESWI meeting (2017). Byron Haney received fees and non-financial support from the GSK group of companies. Christopher J Harrison’s institution received grant from the GSK group of companies for his participation as a principal investigator in the trial and for another vaccine trial and grant funding from Pfizer for his investigator role in a project. He has also received reimbursement and honorarium from Pfizer for the presentation of data. Michael Leonardi has received grant funding from the GSK group of companies for his participation as principal investigator in the study. He also received grant funding from Merck, Medimmune, and Novartis. Federico Martinón-Torres’s institution received payment from the GSK group of companies for his participation as a principal investigator in the trial. The institution also received fees from Ablynx, Janssen, the GSK group of companies, Regeneron, Medimmune, Pfizer, MSD, and Sanofi-Pasteur to conduct trials. Federico Martinón-Torres also received personal fees from Pfizer, MSD, and Sanofi-Pasteur. Xavier Maria Pérez Porcuna’s institution received grant funding from the GSK group of companies for the conduct of the study. Xavier Maria Pérez Porcuna also received personal fees from the GSK group of companies for advisory board participation and lecture. Angels Ulied Arminana received personal fees through her institution from the GSK group of companies for the study conduct. She also received grant funding from Pfizer for lecture and personal fees from MSD and Novartis for her participation as investigator in clinical trials. Meera Varman from the Creighton University received grant funding from Merck, the GSK group of companies, Medimmune, Regeneron, Novartis, Sanofi-Pasteur, and Pfizer for her participation in vaccine clinical trials; she had received honoraria for speaking on behalf of Merck and Pfizer. All other authors declare no potential conflict of interest.
Publisher Copyright:
© 2018 Published by Elsevier Ltd.
PY - 2018/9/11
Y1 - 2018/9/11
N2 - Background: The potency of live viral vaccines decreases over time. We compared the immunogenicity and safety of GSK measles-mumps-rubella vaccine (MMR-RIT) formulations at two different potencies with that of the commercially-available MMR II formulation. Methods: In this phase III observer-blind clinical study (NCT01681992), 4516 healthy children aged 12-15 months were randomized (1:1:1 ratio) to receive one dose of MMR-RIT at the minimum potency used for this study (MMR-RIT-Min) or MMR-RIT at the second lowest potency used for this study (MMRRIT-Med), or control MMR II vaccine. A second dose (MMR-RIT or MMR II) was administered 42 days after the first. The study had 10 co-primary objectives to evaluate MMR-RIT versus MMR II immunogenicity via a hierarchical procedure. Anti-measles and anti-rubella antibodies were measured by ELISA and antimumps antibodies by ELISA and unenhanced plaque reduction neutralization test (PRNT). Results: Each formulation induced immune responses to all vaccine antigens after each MMR dose. While the primary objectives for MMR-RIT-Min were not met, MMR-RIT-Med induced immune responses as measured by ELISA against the three vaccine antigens that met pre-specified non-inferiority criteria. The immune response following MMR-RIT-Med against mumps measured by PRNT failed the noninferiority criterion for seroresponse rate: the 97.5% confidence interval lower limit (-10.94%) was beyond the pre-defined limit of -10%. Immune responses were comparable among groups post-dose 2. No safety concerns were identified, and MMR-RIT and MMR II vaccines had similar reactogenicity and safety profiles. Conclusions: One dose of MMR-RIT formulation with lower potency (MMR-RIT-Med) induced a noninferior immune response compared to commercial MMR II vaccine, measured by ELISA in one-yearold children. Non-inferiority was not demonstrated in terms of immune response against mumps virus measured by unenhanced PRNT, although the difference was of uncertain clinical relevance. After the second dose, immune responses were comparable among the MMR-RIT and MMR II groups.
AB - Background: The potency of live viral vaccines decreases over time. We compared the immunogenicity and safety of GSK measles-mumps-rubella vaccine (MMR-RIT) formulations at two different potencies with that of the commercially-available MMR II formulation. Methods: In this phase III observer-blind clinical study (NCT01681992), 4516 healthy children aged 12-15 months were randomized (1:1:1 ratio) to receive one dose of MMR-RIT at the minimum potency used for this study (MMR-RIT-Min) or MMR-RIT at the second lowest potency used for this study (MMRRIT-Med), or control MMR II vaccine. A second dose (MMR-RIT or MMR II) was administered 42 days after the first. The study had 10 co-primary objectives to evaluate MMR-RIT versus MMR II immunogenicity via a hierarchical procedure. Anti-measles and anti-rubella antibodies were measured by ELISA and antimumps antibodies by ELISA and unenhanced plaque reduction neutralization test (PRNT). Results: Each formulation induced immune responses to all vaccine antigens after each MMR dose. While the primary objectives for MMR-RIT-Min were not met, MMR-RIT-Med induced immune responses as measured by ELISA against the three vaccine antigens that met pre-specified non-inferiority criteria. The immune response following MMR-RIT-Med against mumps measured by PRNT failed the noninferiority criterion for seroresponse rate: the 97.5% confidence interval lower limit (-10.94%) was beyond the pre-defined limit of -10%. Immune responses were comparable among groups post-dose 2. No safety concerns were identified, and MMR-RIT and MMR II vaccines had similar reactogenicity and safety profiles. Conclusions: One dose of MMR-RIT formulation with lower potency (MMR-RIT-Med) induced a noninferior immune response compared to commercial MMR II vaccine, measured by ELISA in one-yearold children. Non-inferiority was not demonstrated in terms of immune response against mumps virus measured by unenhanced PRNT, although the difference was of uncertain clinical relevance. After the second dose, immune responses were comparable among the MMR-RIT and MMR II groups.
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U2 - 10.1016/j.vaccine.2018.07.076
DO - 10.1016/j.vaccine.2018.07.076
M3 - Article
C2 - 30104117
AN - SCOPUS:85051383542
VL - 36
SP - 5781
EP - 5788
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 38
ER -