Immunogenicity and Safety of GlaxoSmithKline Biologicals' Huma Papillomavirus (HPV) Vaccine 580299 in Healthy Females 15 - 25 Years of Age

Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' HPV Vaccine GSK580299 Administered According to an Alternative Dosing Schedule as Compared to the Standard Dosing Schedule in Young Female Subjects Aged 15-25 Years

Infection with human papillomavirus (HPV) has been clearly established as the central cause of cervical cancer. The current phase 3b study is designed to assess the immunogenicity and safety of GlaxoSmithKline Biologicals' HPV vaccine GSK580299 administered according to an alternative dosing schedule as compared to the standard dosing schedule in young female subjects aged 15 - 25 years. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Study Overview

• Status: Completed
• Conditions: Infections, Papillomavirus
• Intervention / Treatment: Biological: Cervarix TM; Biological: Cervarix TM

• Study Type: Interventional
• Enrollment (Actual): 805
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Lombardia
    • Brescia, Lombardia, Italy, 25123
      • GSK Investigational Site
    • Lodi, Lombardia, Italy, 26900
      • GSK Investigational Site
    • Milano, Lombardia, Italy, 20122
      • GSK Investigational Site
  • Sardegna
    • Cagliari, Sardegna, Italy, 09127
      • GSK Investigational Site
    • Sassari, Sardegna, Italy, 07100
      • GSK Investigational Site
  • Sicilia
    • Palermo, Sicilia, Italy, 90127
      • GSK Investigational Site
    • Ragusa, Sicilia, Italy, 97100
      • GSK Investigational Site
• Romania
  • Bucharest, Romania, 077190
    • GSK Investigational Site
  • Bucharest, Romania, 010507
    • GSK Investigational Site
  • Bucharest, Romania, 22102
    • GSK Investigational Site
  • Cluj-Napoca, Romania, 400217
    • GSK Investigational Site
  • Sibiu, Romania, 550245
    • GSK Investigational Site
  • Sibiu, Romania
    • GSK Investigational Site
• Slovakia
  • Dolny Kubin, Slovakia, 026 01
    • GSK Investigational Site
  • Nova Dubnica, Slovakia, 018 51
    • GSK Investigational Site
  • Trencin, Slovakia, 911 01
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Subjects who the investigator believes that they and/or their parent(s)/Legally acceptable representative(s) (LAR) can and will comply with the requirements of the protocol
• A female between and including 15 and 25 years of age at the time of the first vaccination.
• Written informed consent obtained from the subject prior to enrolment. For subjects below the legal age of consent, written informed consent must be obtained from the subject's parents/legally acceptable representative (LAR), and written informed assent must be obtained from the subject.
• Healthy subjects as established by medical history and/or clinical examination before entering into the study.
• Subject must be of non-childbearing potential, or if she is of child bearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative urine pregnancy test and continue such precautions for 2 months after completion of the vaccination series.
• Subject who had no more than 6 lifetime sexual partners prior to enrolment.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) 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.
• Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before and 30 days after the first dose of vaccine. Planned administration/administration of routine vaccines up to 8 days before the first dose of study vaccine is allowed. Enrolment will be deferred until the patient 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 (pharmaceutical product or device).
• Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period.
• previous administration of components of the investigational vaccine
• Cancer or autoimmune disease under treatment.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Hypersensitivity to latex
• Acute disease at the time of enrolment.
• Administration of immunoglobulins and/or any blood products within the three months preceding blood sampling.
• Pregnant or breastfeeding female.
• Female planning to become pregnant, likely to become pregnant (as determined by the investigator) or planning to discontinue contraceptive precautions during the study period starting at visit one and up to two months after the last vaccine dose.
• Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal function abnormality as determined by physical examination or lab tests.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cervarix-12 Group; Women received 3 doses of Cervarix TM (human papillomavirus (HPV) vaccine) administered according to a 0, 1, 12-month schedule	Biological: Cervarix TM; Intramuscular administration into the deltoid region of the non-dominant arm according to a 0, 1, 12-month schedule.; Other Names: HPV vaccine (GSK580299); Biological: Cervarix TM; Intramuscular administration into the deltoid region of the non-dominant arm according to a 0, 1, 6-month schedule.
Active Comparator: Cervarix-6 Group; Women received 3 doses of Cervarix TM (HPV vaccine) administered according to a 0, 1, 6-month schedule.	Biological: Cervarix TM; Intramuscular administration into the deltoid region of the non-dominant arm according to a 0, 1, 12-month schedule.; Other Names: HPV vaccine (GSK580299); Biological: Cervarix TM; Intramuscular administration into the deltoid region of the non-dominant arm according to a 0, 1, 6-month schedule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies	Seroconversion is defined as the appearance of anti-HPV-16 and/or anti- HPV-18 antibodies (i.e. antibody titer ≥ cut-off value) in the sera of subjects seronegative before vaccination. Cut-off values were 8 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti- HPV-18 antibodies.	One month after the third vaccine dose
Titer of Anti-HPV-16 and Anti-HPV-18 Antibodies	Titer given as geometric mean titer (GMT).	One month after the third vaccine dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Seroconverted for Anti-HPV-16 and Anti-HPV-18 Antibodies	Seroconversion is defined as the appearance of anti-HPV-16 and/or anti- HPV-18 antibodies (i.e. antibody titer ≥ cut-off value) in the sera of subjects seronegative before vaccination. Cut-off values were 8 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti- HPV-18 antibodies.	One month after the second vaccine dose
Titer of Anti-HPV-16 and Anti-HPV-18 Antibodies	Titer given as GMT.	One month after the second vaccine dose
Number of Subjects Reporting Solicited Local Symptoms	Solicited local symptoms assessed include pain, redness and swelling at the injection site.	During the 7-day (Days 0-6) period following each vaccination
Number of Subjects Reporting Solicited General Symptoms	Solicited general symptoms assessed include arthralgia, fatigue, fever, gastrointestinal symptoms, headache, myalgia, rash, and urticaria.	During the 7-day (Days 0-6) period following each vaccination
Number of Subjects Reporting Unsolicited Adverse Events (AE)	An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	During the 30-day (Days 0-29) period following each vaccination
Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs), New Onset Autoimmune Diseases (NOADs), Serious Adverse Events (SAEs), and Medically Significant Conditions (MSCs)	Entire study period = up to Month 18 Cervarix-12 & Month 12 Cervarix-6. NOCDs assessed include eg. autoimmune disorders (NOADs), asthma, type I diabetes. MSCs assessed include AEs prompting emergency room visits and physician office visits not related to common illnesses. An SAE is any untoward medical occurrence that: results in death, is lifethreatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.	During the entire study period (up to Month 18 or up to Month 12)
Number of Subjects With Pregnancies and Their Outcomes	Entire study period = up to Month 18 Cervarix-12 & Month 12 Cervarix-6 Number of pregnancies and pregnancy outcomes.	During the entire study period (up to Month 18 or Month 12)
Number of Subjects Completing the 3-dose Vaccination Schedule		After the third vaccine dose

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Esposito S, Birlutiu V, Jarcuska P, Perino A, Man SC, Vladareanu R, Meric D, Dobbelaere K, Thomas F, Descamps D. Immunogenicity and safety of human papillomavirus-16/18 AS04-adjuvanted vaccine administered according to an alternative dosing schedule compared with the standard dosing schedule in healthy women aged 15 to 25 years: results from a randomized study. Pediatr Infect Dis J. 2011 Mar;30(3):e49-55. doi: 10.1097/INF.0b013e318206c26e.

Helpful 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.

Study record dates

Study Major Dates

• Study Start: November 12, 2007
• Primary Completion (Actual): February 26, 2009
• Study Completion (Actual): July 20, 2009

Study Registration Dates

• First Submitted: October 30, 2007
• First Submitted That Met QC Criteria: October 31, 2007
• First Posted (Estimate): November 1, 2007

Study Record Updates

• Last Update Posted (Actual): June 25, 2018
• Last Update Submitted That Met QC Criteria: May 24, 2018
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: HPV; cervical cancer; Human papillomavirus (HPV) vaccine; papillomavirus
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 109179

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: 109179
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Informed Consent Form
   Information identifier: 109179
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 109179
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 109179
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: 109179
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Annotated Case Report Form
   Information identifier: 109179
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Dataset Specification
   Information identifier: 109179
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No