A prospective, single-arm, open-label, non-randomized, phase IIa trial of a nonavalent prophylactic HPV vaccine to assess immunogenicity of a prime and deferred-booster dosing schedule among 9-11 year-old girls and boys - clinical protocol

Yi Zeng, Anna-Barbara Moscicki, Vikrant V Sahasrabuddhe, Francisco Garcia, Heide Woo, Chiu-Hsieh Hsu, Eva Szabo, Eileen Dimond, Susan Vanzzini, Angelica Mondragon, Valerie Butler, Hillary DeRose, H-H Sherry Chow, Yi Zeng, Anna-Barbara Moscicki, Vikrant V Sahasrabuddhe, Francisco Garcia, Heide Woo, Chiu-Hsieh Hsu, Eva Szabo, Eileen Dimond, Susan Vanzzini, Angelica Mondragon, Valerie Butler, Hillary DeRose, H-H Sherry Chow

Abstract

Background: Human papillomavirus (HPV) vaccines are indicated for the prevention of cancers and genital warts caused by vaccine-covered HPV types. Although the standard regimen requires a two or three-dose vaccine series, there is emerging data suggesting that a single dose of the bivalent or quadrivalent HPV vaccine generates persistently positive antibody titers. No similar data is yet available for the nonavalent HPV vaccine, currently the only HPV vaccine available in the United States. The overall objective of our study is to assess the stability and kinetics of antibody titers for 24 months following a single dose of the nonavalent HPV vaccine among preteen girls and boys.

Methods: This is a prospective, single-arm, open-label, non-randomized, Phase IIa trial among 9-11 year-old girls and boys to determine the immunogenicity after a single dose of the nonavalent HPV vaccine (GARDASIL® 9) over 24 months, with a deferred booster dose at 24 months and an optional booster at 30 months after the first dose. Participants provide blood specimens at 6, 12, 18, 24, and 30 months after the first dose. Serologic geometric mean titers (GMT) of the nine vaccine types (HPV 16/18/ 6/11/31/33/45/52/58) will be measured at each time point. The primary objective is to determine the stability of type-specific serologic GMT of HPV16 and HPV18 between the 6- vs. 12-month, 12- vs. 18-month, and 18- vs. 24-month visits. Secondary objectives are to determine the stability of type-specific serologic GMT of the other HPV types (HPV 6/11/31/33/45/52/58) between the visits and to assess safety and reactogenicity after each vaccine dose.

Discussion: Single dose HPV vaccination could simplify the logistics and reduce costs of HPV vaccination in the US and across the world. This study will contribute important immunogenicity data on the stability and kinetics of type-specific antibody titers and inform feasibility of the single dose HPV vaccination paradigm.

Trial registration: ClinicalTrials.gov Identifier: NCT02568566 . Registered on October 6, 2015.

Keywords: Cervical cancer; Gardasil 9; HPV vaccine; Human papillomavirus; Nonavalent HPV vaccine; Serologic geometric mean titer.

Conflict of interest statement

Ethics approval and consent to participate

The protocol and all recruiting materials have been approved by the Central Institutional Review Board for the National Cancer Institute (protocol #UAZ 2015-05-01) and institutional IRBs. Written informed consent to participate in the study was obtained from the legal representatives (most often parents and legal guardians) of all study participants. Written assent form to participate in the study was obtained from all study participant. Participants and their legal representatives also signed the amended consent, when changes were made to the consent.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

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Fig. 1
Projected and actual participant accrual

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