OC 06-06SUSTAINED NON-INFERIORITY OF IMMUNE RESPONSE TO 2-DOSE SCHEDULES 0,6 AND 0,12 MONTHS (M) VERSUS 3 DOSES 0,1,6 M OF HPV-16/18 AS04-ADJUVANTED VACCINE; END OF STUDY ANALYSIS OF A RANDOMIZED TRIAL

05. HPV prophylactic vaccines
L.M. Huang 1, T. Puthanakit 2, C.H. Chiu 3, R.B. Tang 4, T. Schwarz 5, A. Pellegrino 6, S. Esposito 7, L. Frenette 8, S. Mcneil 9, P. Durando 10, P. Rheault 11, C. Giaquinto 12, M. Horn 13, K.U. Petry 14, K. Peters 15, A. Toma 16, P. Hillemanns 17, S. De Simoni 18, D. Friel 18, P. Suryakiran 19, M. Hezareh 20, F. Thomas 18, D. Descamps 18, N. Folschweiller 18, F. Struyf 18.
1National Taiwan University Children's Hospital, National Taiwan University, Taipei (Taiwan, Republic of China), 2Chulalongkorn University, Bangkok (Thailand), 3Chang Gung Children's Hospital, Chang Gung University, Taoyuan (Taiwan, Republic of China), 4Cheng Hsin General Hospital, Taipei (Taiwan, Republic of China), 5Stiftung Juliusspital, Würzburg (Germany), 6Azienda Sanitaria Locale Cuneo 1, Cuneo (Italy), 7Università degli Studi di Milano, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan (Italy), 8Q&T Research Incorporated, Sherbrooke (Canada), 9Canadian Center for Vaccinology, IWK Health Centre and Nova Scotia Health Authority, Dalhousie University, Halifax (Canada), 10University of Genoa, Genoa (Italy), 11Medicor Research Inc., Sudbury (Canada), 12University of Padova, Padova (Italy), 13Pediatric Office Dr. med. Michael Horn, Schoenau a. K. (Germany), 14Klinikum Wolfsburg, Wolfsburg (Germany), 15Facharzt für Frauenheilkunde und Geburtshilfe, Hamburg (Germany), 16Manna Research, Toronto (Canada), 17Medizinische Hochschule Hannover, Hannover (Germany), 18GSK Vaccines, Wavre (Belgium), 19GSK Pharmaceuticals India Ltd., Bangalore (India), 20Chiltern International for GSK Vaccines, Wavre (Belgium)

Background / Objectives

This phase III, randomized, open-label, multi-centre trial (NCT01381575) previously demonstrated the non-inferior immunogenicity of HPV-16/18 AS04-adjuvanted vaccine when administered to girls as different 2-dose (2D) schedules versus 3-dose (3D) schedule in women, up to 24M post dose 1.1 We report the immunogenicity and safety results 36M post dose 1.


Methods

Healthy girls (9–14 years [y]) were randomized 1:1 to receive 2D of HPV-16/18 AS04-adjuvanted vaccine at M0,6 or M0,12; a third group included healthy women (15‒25y) who received 3D(M0,1,6). Anti-HPV-16/18 antibodies (by ELISA and pseudovirion-based neutralising assay [PBNA]) and T and B cell-mediated immune (CMI) responses were measured. Non-inferiority by ELISA was met if, for both HPV-16 and HPV-18, the upper limit of the 95% confidence interval for the seroconversion rate difference was <5% and for the geometric mean titre (GMT) ratio was <2.


Results

1285 subjects (506 in 2D[M0,6]; 378 in 2D[M0,12]; 401 in 3D[M0,1,6]) were included in the M36 according-to-protocol cohort for immunogenicity (ATP-I). At M36 in ATP-I initially seronegative subjects, 2D(M0,6) and 2D(M0,12) anti-HPV-16/18 responses were non-inferior to 3D(M0,1,6); 2D(M0,12) response was also non-inferior to 2D(M0,6) (Table). Anti-HPV-16/18 neutralising antibody levels at M36 appeared comparable or higher in 2D(M0,6) and 2D(M0,12) vs. 3D(M0,1,6). CMI responses at M36 were in the same range as 1M post vaccination in all groups (descriptive analyses). The vaccine safety profile remained clinically acceptable in all groups.

Table: Non-inferiority of the HPV-16/18 antibody responses (ELISA) in 2D(M0,6) and 2D(M0,12) vs 3D(M0,1,6) 36M after first vaccination
 

Anti-HPV-16

(95% CI)

Anti-HPV-18

(95% CI)

Seroconversion difference, % 

3D(M0,1,6)–2D(M0,6)		 0.00 (-1.15, 0.84) -0.06 (-1.37, 0.96)

GMT ratio

3D(M0,1,6)/2D(M0,6)		 1.10 (0.97, 1.24) 0.98 (0.85, 1.13)

Seroconversion difference, % 

3D(M0,1,6)–2D(M0,12)		 0.00 (-1.15, 1.12) -0.28 (-1.58, 0.79)

GMT ratio

3D(M0,1,6)/2D(M0,12)		 0.85 (0.74, 0.97) 0.69 (0.59, 0.80)

Seroconversion difference, % 

2D(M0,6)–2D(0,12)		 0.00 (-0.84, 1.12) -0.22 (-1.22, 0.86)

GMT ratio

2D(M0,6)/2D(0,12)		 0.78 (0.69, 0.87) 0.70 (0.62, 0.80)

                                                                        Numbers in bold signify the non-inferiority criterion was met.


Conclusion

2D schedules of the HPV-16/18 AS04-adjuvanted vaccine administered in girls at 0,6M and 0,12M elicited a sustained and non-inferior immune response when compared to 3D schedule in young women, 36M after the 1st dose.

Funding: GlaxoSmithKline Biologicals SA


References

1. Tang RB et al. Abstract O9-011, APCMV 2015, Taipei, Taiwan.