A randomized, observer-blinded, equivalence trial comparing two variations of Euvichol®, a bivalent killed whole-cell oral cholera vaccine, in healthy adults and children in the Philippines

Paola Russo, Antonio D. Ligsay, Remigio Olveda, Seuk Keun Choi, Deok Ryun Kim, Ju Yeon Park, Ju Yeong Park, Khalid Ali Syed, Ayan Dey, Yang Hee Kim, Sung Hee Lee, Jayoung Kim, Yun Chon, Laura Digilio, Chan Wha Kim, Jean Louis Excler

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: To contribute to the global demand for oral cholera vaccine (OCV), the production of Euvichol® was scaled up with elimination of thimerosal. To demonstrate the equivalence of the variations, a study was carried out in the Philippines. Methods: Healthy male and female adults and children in Manila were randomized to receive two doses of Euvichol® two weeks apart from either the 100L (Comparator) or the 600L (Test) variation. Primary and secondary immunogenicity endpoints were respectively geometric mean titer (GMT) of vibriocidal antibodies (two weeks post second dose) and seroconversion rate (two weeks after each dose) against O1 Inaba, Ogawa, and O139 serogroups. The GMT of vibriocidal antibodies against O1 Inaba, Ogawa, and O139 two weeks post first dose was also measured. To show the equivalence of two variations of Euvichol®, the ratio of GMT and the difference of seroconversion rate between Test and Comparator vaccines were tested with equivalence margin of [0.5, 2.0] for GMT ratio and of 15% for seroconversion rate, respectively. Safety assessment included solicited reactogenicity within 6 days after each dose and unsolicited and serious adverse events. Results: A total of 442 participants were enrolled. For the overall population, equivalence between Test and Comparator was demonstrated for vibriocidal antibody response against O1 Inaba and Ogawa serotypes and O139 serogroup in both modified intention-to-treat (mITT) and per protocol analysis, since the 95% confidence intervals (CI) of GMT to any serotypes were within the lower and upper boundary [0.5, 2.0]. Seroconversion rates after two doses also showed equivalence for O1 Inaba, Ogawa, and O139. The vaccine was safe and well tolerated, similarly between the two groups. Conclusion: The study results support the equivalence of the 600L Euvichol® to the 100L formulation in healthy children and adults. The 600L Euvichol® is safe and immunogenic in adults and children. ClinicalTrials.gov registration number: NCT02502331.

Original languageEnglish
Pages (from-to)4317-4324
Number of pages8
JournalVaccine
Volume36
Issue number29
DOIs
Publication statusPublished - 2018 Jul 5

Keywords

  • Cholera
  • Equivalence
  • Euvichol
  • Oral cholera vaccine
  • The Philippines

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Fingerprint Dive into the research topics of 'A randomized, observer-blinded, equivalence trial comparing two variations of Euvichol®, a bivalent killed whole-cell oral cholera vaccine, in healthy adults and children in the Philippines'. Together they form a unique fingerprint.

  • Cite this

    Russo, P., Ligsay, A. D., Olveda, R., Choi, S. K., Kim, D. R., Park, J. Y., Park, J. Y., Syed, K. A., Dey, A., Kim, Y. H., Lee, S. H., Kim, J., Chon, Y., Digilio, L., Kim, C. W., & Excler, J. L. (2018). A randomized, observer-blinded, equivalence trial comparing two variations of Euvichol®, a bivalent killed whole-cell oral cholera vaccine, in healthy adults and children in the Philippines. Vaccine, 36(29), 4317-4324. https://doi.org/10.1016/j.vaccine.2018.05.102