Clinical trial NCT01381575: Evaluation of Immunogenicity and Safety of Two 2-dose Human Papillomavirus (HPV) Vaccine Schedules in 9-14 Year Old Girls
Official title: Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' HPV-16/18 L1 AS04 Vaccine When Administered According to Alternative 2-dose Schedules in 9 - 14 Year Old Females
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Papillomavirus
Keywords: HPV infection
Human Papillomavirus
Cervical cancer
HPV-16
HPV-18
vaccine
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-06-27
Enrollment: 1447
Sex: FEMALE
Minimum age (years): 9
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study has been designed to evaluate the immunogenicity and safety of GSK Biologicals' HPV-16/18 vaccine when administered according to alternative 2-dose schedules (0,6 months and 0,12 months) in healthy 9-14 year old females as compared to the standard 3-dose schedule (0,1,6 months) in 15-25 year old females.


Eligibility criteria: Inclusion Criteria:

* Subjects who the investigator believes can and will comply with the requirements of the protocol or/ and subjects who the investigator believes their parent(s)/Legally Acceptable Representative(s) \[LAR(s)\] can and will comply with the requirements of the protocol
* A female between, and including, 9 and 25 years of age at the time of the first vaccination
* Written informed consent obtained from the subject/from the parent(s)/LAR(s) of the subject prior to enrolment in the study. In addition, subjects below the legal age of consent should sign and personally date a written informed assent form
* Healthy subjects
* Female subjects of non-childbearing potential may be enrolled in the study
* Female subjects of childbearing potential may be enrolled in the study, if the subject:

  * has practiced adequate contraception for 30 days prior to vaccination, and
  * has a negative pregnancy test on the day of vaccination, and
  * has agreed to continue adequate contraception during the entire vaccination period and up to two months after the last study vaccine dose

Exclusion Criteria:

* Pregnant or breastfeeding
* A female planning to become pregnant, likely to become pregnant or planning to discontinue contraceptive precautions during the entire vaccination period and up to two months after the last study vaccine dose
* Previous vaccination against HPV or planned administration of another HPV vaccine during the study
* Child in care. A child in care is a child who has been placed under the control or protection of an agency, organisation, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation. The definition of a child in care does not include a child who is adopted or has an appointed legal guardian.
* Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period
* Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. History of allergic disease, suspected allergy or reactions likely to be exacerbated by any component of the study vaccines
* Cancer or autoimmune disease under treatment
* Planned administration/administration of a vaccine/product not foreseen by the study protocol within 30 days before each dose of vaccine. Administration of routine meningococcal, hepatitis B, hepatitis A, inactivated influenza, diphtheria/tetanus and/or diphtheria/tetanus-containing vaccine up to 8 days before each dose of study vaccine is allowed. Enrolment will be deferred until the subject is outside of specified window
* Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product
* Previous administration of MPL or AS04 adjuvant.
* Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period
* Any confirmed or suspected immunosuppressive or immunodeficient condition
* Family history of congenital or hereditary immunodeficiency
* Major congenital defects or serious chronic illness
* Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests, which in the opinion of the investigator precludes administration of the study vaccine
* Acute disease and/or fever at the time of enrolment

Primary outcomes:
measure: Number of Seroconverted Subjects for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies in Cervarix 1 Group and Cervarix 2 Group at Month 7
timeFrame: At Month 7 (i.e. one month after the last dose of study vaccine)
measure: Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations (by ELISA) in Cervarix 1 Group and Cervarix 2 Group at Month 7
timeFrame: At Month 7 (i.e. one month after the last dose of study vaccine)
Secondary outcomes:
measure: Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies in Cervarix 1 Group and Cervarix 2 Group at Day 0 and at Months 7, 12, 18, 24 and 36
timeFrame: At Day 0 and at Months 7, 12, 18, 24 and 36
measure: Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations (by ELISA) in Cervarix 1 Group and Cervarix 2 Group at Day 0 and at Months 7, 12, 18, 24 and 36
timeFrame: At Day 0 and at Months 7, 12, 18, 24 and 36
measure: Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies in Cervarix 3 Group
timeFrame: At Day 0 and at Months 13, 18, 24 and 36
measure: Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations (by ELISA) in Cervarix 3 Group
timeFrame: At Day 0 and at Months 13, 18, 24 and 36
measure: Anti-HPV-16 and Anti-HPV-18 Antibody Titers [by Pseudovirion-Based Neutralisation Assay (PBNA)] in a Subset of Subjects From Cervarix 3 Group
timeFrame: At Day 0 and at Months 13, 18, 24 and 36
measure: Anti-HPV-16 and Anti-HPV-18 Antibody Titers (by PBNA) in a Subset of Subjects From Cervarix 1 Group and Cervarix 2 Group
timeFrame: At Day 0 and at Months 7, 12, 18, 24 and 36
measure: Cell-mediated Immunogenicity Related to Anti-HPV-16 Specific T Cell-mediated Immune Response (CMI) for Cervarix 1 Group and Cervarix 2 Group in a Sub-cohort of Subjects
timeFrame: At Day 0 and at Months 7, 12, 24 and 36
measure: Cell-mediated Immunogenicity Related to Anti-HPV-18 Specific T CMI Response for Cervarix 1 Group and Cervarix 2 Group in a Sub-cohort of Subjects
timeFrame: At Day 0 and at Months 7, 12, 24 and 36
measure: Cell-mediated Immunogenicity Related to Anti-HPV-16 Specific T CMI Response for Cervarix 3 Group in a Sub-cohort of Subjects
timeFrame: At Day 0 and at Months 13, 18 and 36
measure: Cell-mediated Immunogenicity Related to Anti-HPV-18 Specific T CMI Response for Cervarix 3 Group in a Sub-cohort of Subjects
timeFrame: At Day 0 and at Months 13, 18 and 36
measure: Cell-mediated Immunogenicity Related to Anti-HPV-16 Specific B CMI Response for Cervarix 1 Group and Cervarix 2 Group in a Sub-cohort of Subjects
timeFrame: At Day 0 and at Months 7, 12, 24 and 36
measure: Cell-mediated Immunogenicity Related to Anti-HPV-18 Specific B CMI Response for Cervarix 1 Group and Cervarix 2 Group in a Sub-cohort of Subjects
timeFrame: At Day 0 and at Months 7, 12, 24 and 36
measure: Cell-mediated Immunogenicity Related to Anti-HPV-16 Specific B CMI Response for Cervarix 3 Group in a Sub-cohort of Subjects
timeFrame: At Day 0 and at Months 13, 18 and 36
measure: Cell-mediated Immunogenicity Related to Anti-HPV-18 Specific B CMI Response for Cervarix 3 Group in a Sub-cohort of Subjects
timeFrame: At Day 0 and at Months 13, 18 and 36
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 7-day period (Days 0-6) after each vaccine dose and across doses
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 7-day period (Days 0-6) after each vaccine dose and across doses
measure: Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
timeFrame: During the 30 day (Days 0-29) post-vaccination period
measure: Number of Subjects With Any Potential Immune-Mediated Diseases (pIMDs)
timeFrame: From Day 0 up to Month 13 (for Cervarix 1 Group and Cervarix 2 Group) and from Day 0 up to Month 18 (for Cervarix 3 Group)
measure: Number of Subjects With Medically Significant Conditions (MSCs)
timeFrame: From Day 0 up to Month 36 (throughout the study period)
measure: Number of Subjects With Any, Related and Fatal Serious Adverse Events (SAEs)
timeFrame: From Day 0 up to Month 36 (throughout the study period)
measure: Number of Subjects Reporting Pregnancies and Outcomes of Reported Pregnancies
timeFrame: From Day 0 up to Month 36 (throughout the study period)
measure: Number of Subjects Completing the Vaccination Course
timeFrame: From Day 0 up to Month 13
Other outcomes:
Locations:
city: Coquitlam
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Halifax
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: Sudbury
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Woodstock
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Sherbrooke
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Freiburg
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Kehl
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Schoenau Am Koenigssee
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Wuerzburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Wolfenbuettel
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Wolfsburg
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Kleve-Materborn
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Mainz
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Trier
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Flensburg
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Weimar
country: Germany
facility: GSK Investigational Site
state: Thueringen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Genova
country: Italy
facility: GSK Investigational Site
state: Liguria
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Cuneo
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Cagliari
country: Italy
facility: GSK Investigational Site
state: Sardegna
city: Ragusa
country: Italy
facility: GSK Investigational Site
state: Sicilia
city: Padova
country: Italy
facility: GSK Investigational Site
state: Veneto
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taoyuan
country: Taiwan
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Chiangmai
country: Thailand
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Huang LM, Puthanakit T, Cheng-Hsun C, Ren-Bin T, Schwarz T, Pellegrino A, Esposito S, Frenette L, McNeil S, Durando P, Rheault P, Giaquinto C, Horn M, Petry KU, Peters K, Azhar T, Hillemanns P, De Simoni S, Friel D, Pemmaraju S, Hezareh M, Thomas F, Descamps D, Folschweiller N, Struyf F. Sustained Immunogenicity of 2-dose Human Papillomavirus 16/18 AS04-adjuvanted Vaccine Schedules in Girls Aged 9-14 Years: A Randomized Trial. J Infect Dis. 2017 Jun 1;215(11):1711-1719. doi: 10.1093/infdis/jix154.
citation: Puthanakit T, Huang LM, Chiu CH, Tang RB, Schwarz TF, Esposito S, Frenette L, Giaquinto C, McNeil S, Rheault P, Durando P, Horn M, Klar M, Poncelet S, De Simoni S, Friel D, De Muynck B, Suryakiran PV, Hezareh M, Descamps D, Thomas F, Struyf F. Randomized Open Trial Comparing 2-Dose Regimens of the Human Papillomavirus 16/18 AS04-Adjuvanted Vaccine in Girls Aged 9-14 Years Versus a 3-Dose Regimen in Women Aged 15-25 Years. J Infect Dis. 2016 Aug 15;214(4):525-36. doi: 10.1093/infdis/jiw036. Epub 2016 Feb 3.
citation: Stevenson L, Huang LM, Berlaimont V, Folschweiller N. Reply to Poddighe. J Infect Dis. 2017 Sep 15;216(6):783-785. doi: 10.1093/infdis/jix365. No abstract available.
citation: Folschweiller N, Behre U, Dionne M, Durando P, Esposito S, Ferguson L, Ferguson M, Hillemanns P, McNeil SA, Peters K, Ramjattan B, Schwarz TF, Supparatpinyo K, Suryakirian PV, Janssens M, Moris P, Decreux A, Poncelet S, Struyf F. Long-term Cross-reactivity Against Nonvaccine Human Papillomavirus Types 31 and 45 After 2- or 3-Dose Schedules of the AS04-Adjuvanted Human HPV-16/18 Vaccine. J Infect Dis. 2019 May 5;219(11):1799-1803. doi: 10.1093/infdis/jiy743.