Evaluation of Immunogenicity and Safety of Two 2-dose Human Papillomavirus (HPV) Vaccine Schedules in 9-14 Year Old Girls

NCT01381575 | Completed Phase 3 Results

• 2 other identifiers: 1147002011-000757-22
• Study Type: interventional
• Target: 1,447
• Locations: 5 countries
• Sites: 33

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.

Conditions

Infections, Papillomavirus

Keywords

HPV infection; Human Papillomavirus; Cervical cancer; HPV-16; HPV-18; vaccine

Outcome Measures

Primary Outcomes (2)

• 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

  Seroconversion was defined as the appearance of antibodies (anti-HPV-16 concentrations greater than or equal to (≥) 8 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL) and anti-HPV-18 concentrations ≥ 7 EL.U/mL) in the serum of subjects seronegative before vaccination. A seronegative subject was a subject with anti-HPV-16/18 antibody concentration lower than (\<) 8/7 EL.U/mL, respectively.

  At Month 7 (i.e. one month after the last dose of study vaccine)

• Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations (by ELISA) in Cervarix 1 Group and Cervarix 2 Group at Month 7

  Antibody concentrations were assessed by ELISA and expressed as geometric mean concentrations (GMCs) in EL.U/mL.

  At Month 7 (i.e. one month after the last dose of study vaccine)

Secondary Outcomes (22)

• 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

  At Day 0 and at Months 7, 12, 18, 24 and 36

• 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

  At Day 0 and at Months 7, 12, 18, 24 and 36

• Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies in Cervarix 3 Group

  At Day 0 and at Months 13, 18, 24 and 36

• Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations (by ELISA) in Cervarix 3 Group

  At Day 0 and at Months 13, 18, 24 and 36

• Anti-HPV-16 and Anti-HPV-18 Antibody Titers [by Pseudovirion-Based Neutralisation Assay (PBNA)] in a Subset of Subjects From Cervarix 3 Group

  At Day 0 and at Months 13, 18, 24 and 36

Study Arms (3)

Cervarix 1 Group

EXPERIMENTAL

Female subjects aged 9 to 14 years at the time of the first vaccination, who received 2 doses of the Cervarix vaccine at Day 0 and at Month 6, respectively. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.

Biological: GSK Biologicals' HPV vaccine 580299

Cervarix 2 Group

ACTIVE COMPARATOR

Female subjects aged 15 to 25 years at the time of the first vaccination, who received 3 doses of the Cervarix vaccine at Day 0, at Month 1 and at Month 6, respectively. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.

Biological: GSK Biologicals' HPV vaccine 580299

Cervarix 3 Group

EXPERIMENTAL

Female subjects aged 9 to 14 years at the time of the first vaccination, who received 2 doses of the Cervarix vaccine at Day 0 and at Month 12, respectively. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.

Biological: GSK Biologicals' HPV vaccine 580299

Interventions

GSK Biologicals' HPV vaccine 580299 BIOLOGICAL

Subjects received 2 or 3 doses of HPV vaccine administered intramuscularly.

Also known as: Cervarix

Cervarix 1 Group; Cervarix 2 Group; Cervarix 3 Group

Eligibility Criteria

• Age: 9 Years - 25 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (33)

GSK Investigational Site

Coquitlam, British Columbia, V3K 3P4, Canada

Location

GSK Investigational Site

Halifax, Nova Scotia, B3K 6R8, Canada

Location

GSK Investigational Site

Greater Sudbury, Ontario, P3E 1H5, Canada

Location

GSK Investigational Site

Toronto, Ontario, M9W 4L6, Canada

Location

GSK Investigational Site

Woodstock, Ontario, N4S 5P5, Canada

Location

GSK Investigational Site

Sherbrooke, Quebec, J1H 2G2, Canada

Location

GSK Investigational Site

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

GSK Investigational Site

Kehl, Baden-Wurttemberg, 77694, Germany

Location

GSK Investigational Site

Schönau am Königssee, Bavaria, 83471, Germany

Location

GSK Investigational Site

Würzburg, Bavaria, 97070, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30657, Germany

Location

GSK Investigational Site

Wolfenbüttel, Lower Saxony, 38302, Germany

Location

GSK Investigational Site

Wolfsburg, Lower Saxony, 38440, Germany

Location

GSK Investigational Site

Kleve-Materborn, North Rhine-Westphalia, 47533, Germany

Location

GSK Investigational Site

Mainz, Rhineland-Palatinate, 55116, Germany

Location

GSK Investigational Site

Mainz, Rhineland-Palatinate, 55131, Germany

Location

GSK Investigational Site

Trier, Rhineland-Palatinate, 54290, Germany

Location

GSK Investigational Site

Flensburg, Schleswig-Holstein, 24937, Germany

Location

GSK Investigational Site

Weimar, Thuringia, 99423, Germany

Location

GSK Investigational Site

Berlin, 13055, Germany

Location

GSK Investigational Site

Hamburg, 22159, Germany

Location

GSK Investigational Site

Genoa, Liguria, 16132, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20122, Italy

Location

GSK Investigational Site

Cuneo, Piedmont, 12100, Italy

Location

GSK Investigational Site

Cagliari, Sardinia, 09127, Italy

Location

GSK Investigational Site

Ragusa, Sicily, 97100, Italy

Location

GSK Investigational Site

Padua, Veneto, 35128, Italy

Location

GSK Investigational Site

Taipei, 100, Taiwan

Location

GSK Investigational Site

Taipei, Taiwan

Location

GSK Investigational Site

Taoyuan District, 333, Taiwan

Location

GSK Investigational Site

Bangkok, 10330, Thailand

Location

GSK Investigational Site

Chiang Mai, 50200, Thailand

Location

Related Publications (4)

• 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.

  PMID: 28591778 BACKGROUND

• 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.

  PMID: 26908726 BACKGROUND

• 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.

  PMID: 28934440 BACKGROUND

• 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.

  PMID: 30715452 BACKGROUND

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Papillomavirus Infections; Uterine Cervical Neoplasms

Interventions

human papillomavirus vaccine, L1 type 16, 18

Condition Hierarchy (Ancestors)

Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2011
• First Posted: June 27, 2011
• Study Start: June 29, 2011
• Primary Completion: June 28, 2012
• Study Completion: November 13, 2014
• Last Updated: June 9, 2020
• Results First Posted: December 5, 2013

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

TW (3); TH (2); IT (6); CA (6); DE (16)