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Randomized Controlled Trial
. 2024 Apr 2;42(9):2290-2298.
doi: 10.1016/j.vaccine.2024.02.077. Epub 2024 Mar 1.

Safety and immunogenicity of Innovax bivalent human papillomavirus vaccine in girls 9-14 years of age: Interim analysis from a phase 3 clinical trial

Khalequ Zaman  1 , Anne E Schuind  2 , Samuel Adjei  3 , Kalpana Antony  4 , John J Aponte  4 , Patrick By Buabeng  3 , Firdausi Qadri  1 , Troy J Kemp  5 , Lokman Hossain  1 , Ligia A Pinto  5 , Kristen Sukraw  4 , Niranjan Bhat  4 , Tsiri Agbenyega  3
Affiliations
Randomized Controlled Trial

Safety and immunogenicity of Innovax bivalent human papillomavirus vaccine in girls 9-14 years of age: Interim analysis from a phase 3 clinical trial

Khalequ Zaman et al. Vaccine. .

Abstract

Background: World Health Organization human papillomavirus (HPV) vaccination recommendations include a single- or two-dose schedule in individuals 9-20 years old and advice for generating data on single-dose efficacy or immunobridging. The ongoing Phase 3 trial of Innovax's bivalent (types 16 and 18) HPV vaccine (Cecolin®) assesses in low- and middle-income countries alternative dosing schedules and generates data following one dose in girls 9-14 years old. Interim data for the 6-month dosing groups are presented.

Methods: In Bangladesh and Ghana, 1,025 girls were randomized to receive either two doses of Cecolin at 6-, 12-, or 24-month intervals; one dose of Gardasil® followed by one dose of Cecolin at month 24; or two doses of Gardasil 6 months apart (referent). Serology was measured by enzyme-linked immunosorbent assay (ELISA) and, in a subset, by neutralization assays. Primary objectives include immunological non-inferiority of the Cecolin schedules to referent one month after the second dose. Safety endpoints include reactogenicity and unsolicited adverse events for 7 and 30 days post-vaccination, respectively, as well as serious adverse events throughout the study.

Results: Interim analyses included data from the two groups on a 0, 6-month schedule with 205 participants per group. One month after Dose 2, 100% of participants were seropositive by ELISA and had seroconverted for both antigens. Non-inferiority of Cecolin to Gardasil was demonstrated. Six months following one dose, over 96% of participants were seropositive by ELISA for both HPV antigens, with a trend for higher geometric mean concentration following Cecolin administration. Reactogenicity and safety were comparable between both vaccines.

Conclusions: Cecolin in a 0, 6-month schedule elicits robust immunogenicity. Non-inferiority to Gardasil was demonstrated one month after a 0, 6-month schedule. Immunogenicity following one dose was comparable to Gardasil up to six months. Both vaccines were safe and well tolerated (ClinicalTrials.gov No. 04508309).

Trial registration: ClinicalTrials.gov NCT04508309.

Keywords: HPV vaccine; Human papillomavirus (HPV); Immunization; Immunobridging; One-dose immunogenicity.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Financial support for this study was provided by the Bill & Melinda Gates Foundation in Seattle, Washington, United States, and the Federal Ministry of Education and Research in Frankfurt, Germany. The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Bill & Melinda Gates Foundation. Financial support to icddr,b is provided by the governments of Bangladesh and Canada. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government. Aside from the funding provided for this study as described above, the authors do not have any other conflict of interest to declare.

Figures

Fig. 1
Fig. 1
Consort diagram * Reasons for screening failure: One subject withdrew consent during the screening process; one subject was pregnant; one subject had history of a physical, mental, or developmental disorder that may hinder ability to comply with the study requirements; two subjects received an investigational product within 30 days prior to randomization or were planning to participate in another research study involving investigational product during the conduct of this study; and one subject had a condition that in the opinion of the investigator would jeopardize the safety or rights of the participant or would render the participant unable to comply with the protocol. ** Groups not included in this interim analysis. *** Lost to follow-up at interim analysis data lock.
Fig. 2
Fig. 2
Non-inferiority evaluation of Cecolin 0–6 months 1 month post–Dose 2. HPV-16 and HPV-18 geometric mean concentration (GMC) ratio one month post–Dose 2 between Cecolin 0–6 months and Gardasil 0–6 months with 98.3 % confidence intervals. Non-inferiority is demonstrated as both lower limits of the confidence intervals are above the predefined non-inferior limit.
Fig. 3
Fig. 3
Geometric mean concentration ratios at 6 months after Dose 1 HPV-16 and HPV-18 geometric mean concentration (GMC) ratios 6 months after Dose 1 between Cecolin 0, 6-month schedule and Gardasil 0, 6-month schedule with 95 % confidence intervals.
Fig. 4
Fig. 4
Reverse cumulative distribution of immunoglobulin G HPV-16 and HPV-18 antibody concentrations by type-specific ELISA Distribution of HPV-16 and HPV-18 enzyme-linked immunosorbent assay (ELISA) antibody concentrations 6 months post–Dose 1 and one month post–Dose 2 in the per protocol population. The percentage represents the proportion of the population with antibody levels equal to or above the concentration in x-axis.
See this image and copyright information in PMC

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