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Human Papilloma Virus (HPV) Vaccine Immunogenicity and Safety Trial in Young and Adult Women With GSK Biologicals' HPV-16/18

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00196937
Recruitment Status : Completed
First Posted : September 20, 2005
Results First Posted : August 6, 2010
Last Update Posted : December 11, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
Infection with human papillomavirus (HPV) has been clearly established as the central cause of cervical cancer. Indeed, certain oncogenic types of HPV can infect the cervix (part of the uterus or womb). This infection may go away by itself, but if it does not go away (this is called persistent infection), it can lead in women over a long period of time to cancer of the cervix. This study will evaluate the immunogenicity and safety of GSK Biologicals HPV-16/18 vaccine over 12 months, in women up to 55 years of age at study start. Approximately 660 study subjects will receive the HPV vaccine administered intramuscularly according to a 0-1-6 month schedule. The study will be extended to assess long-term safety and immunogenicity of the HPV-16/18 vaccine.

Condition or disease Intervention/treatment Phase
Infections, Papillomavirus Biological: Cervarix Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 667 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Phase 3, Open, Age-stratified Study to Assess Immunogenicity and Safety of GSK Biologicals' HPV-16/18 Vaccine Administered Intramuscularly According to 3-dose Schedule (0,1,6 Months) in Healthy Female Subjects Aged 15 - 55 Years and Long Term Follow-up
Actual Study Start Date : October 7, 2004
Actual Primary Completion Date : December 15, 2005
Actual Study Completion Date : December 15, 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Safety Vaccines

Arm Intervention/treatment
Experimental: Cervarix (15-25 Years) Group
Women aged 15 to 25 years received 3 doses of Cervarix vaccine administered according to a 0, 1, 6-month schedule.
Biological: Cervarix
Three doses of vaccine administered intramuscularly according to a 0, 1, 6-month schedule.

Experimental: Cervarix (26-45 Years) Group
Women aged 26 to 45 years received 3 doses of Cervarix vaccine administered according to a 0, 1, 6-month schedule.
Biological: Cervarix
Three doses of vaccine administered intramuscularly according to a 0, 1, 6-month schedule.

Experimental: Cervarix (46-55 Years) Group
Women aged 46 to 55 years received 3 doses of Cervarix vaccine administered according to a 0, 1, 6-month schedule.
Biological: Cervarix
Three doses of vaccine administered intramuscularly according to a 0, 1, 6-month schedule.




Primary Outcome Measures :
  1. Number of Seroconverted Subjects for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies, in Women 15 to 25 Years of Age and Women 26 to 45 Years of Age [ Time Frame: At Month 7 ]
    Seroconversion was defined as the appearance of anti-HPV-16 and/or anti-HPV-18 antibodies [i.e. antibody titer greater than or equal to (≥) the cut-off value] in the sera of subjects seronegative before vaccination. Cut-off values were 8 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies. Data for the Cervarix (46-55 Years) Group are presented in the Secondary Outcomes as per Protocol.

  2. Anti-HPV-16/18 Antibody Titers Assessed by ELISA Based on the ATP Cohort for Immunogenicity at Months 18, 24, 36 and 48 [ Time Frame: At Months 18, 24, 36 and 48 ]
    Anti-HPV 16/18 antibody titers were detected in sera samples and presented as Geometric Mean Titers (GMT), expressed in EL.U/mL. Data for pre-vaccination, Month 2, Month 7 and Month 12 are presented in the Secondary Outcomes as per Protocol.


Secondary Outcome Measures :
  1. Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies, in Women 46 - 55 Years of Age [ Time Frame: At Month 7 ]
    Seroconversion was 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 EL.U/mL for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies. Seroconversion results at Month 7 for the Cervarix (15-25 Years) Group and for the Cervarix (26-45 Years) Group are presented in the Primary Outcome Measure 1.

  2. Anti-HPV-16/18 Antibody Titers Assessed by ELISA Based on the ATP Cohort for Immunogenicity at Pre-vaccination (PRE) and Months 2, 7 and 12 [ Time Frame: At PRE and Months 2, 7 and 12 ]
    Anti-HPV 16/18 antibody titers were detected in sera samples and presented as GMT, expressed in EL.U/mL. Data for Months 18, 24, 36 and 48 are presented in the Primary Outcome Measure 2 as per Protocol.

  3. Number of Subjects Seroconverted for Anti-HPV-16 and Anti-HPV-18 Antibodies at Month 2 and Month 12 [ Time Frame: At Month 2 and Month 12 ]
    Seroconversion was 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 EL.U/mL for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies. Seroconversion results at Month 7 are presented in the Primary Outcome Measure 1 for Cervarix (15-25 Years) Group and Cervarix (26-45 Years) Group and in the Secondary Outcome Measure 3 for the Cervarix (46-55 Years) Group.

  4. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [ Time Frame: During the 7-day period (from the day of vaccination up to 6 subsequent days) following vaccination after each dose and across doses ]
    Assessed solicited general symptoms were arthralgia, fatigue, fever, gastrointestinal symptoms, headache, myalgia, rash and urticaria. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever above (>) 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.

  5. Number of Subjects With Any and Grade 3 Solicited Local Symptoms [ Time Frame: During the 7-day period (from the day of vaccination up to 6 subsequent days) following vaccination after each dose and across doses ]
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimetres (mm) of injection site.

  6. Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) [ Time Frame: During the 30-day (from the day of vaccination up to 29 subsequent days) post-vaccination period ]
    An unsolicited AE covers 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 and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.

  7. Number of Subjects Reporting Serious Adverse Events (SAE) [ Time Frame: During the entire study period (from Day 0 up to Month 48) ]
    An SAE is any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study subject, or may have evolved into one of the outcomes listed above.

  8. Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs) [ Time Frame: During the entire study period (from Day 0 up to Month 48) ]
    NOCDs assessed include chronic diseases such as autoimmune disorders, diabetes, allergies also asthma and pathognomic signs/symptoms of these diseases.

  9. Number of Subjects Reporting Medically Significant Conditions [ Time Frame: During the entire study period (from Day 0 up to Month 48) ]
    Medically significant conditions are AEs prompting emergency room or physician visits that were not related to common diseases or routine visits for physical examination or vaccination, or SAEs that were not related to common diseases.

  10. Anti-HPV-16/18 Antibody Titers Assessed by ELISA in a Subset of Subjects in Cervical Secretions (CVS) Samples [ Time Frame: At Months 18 and 24 ]
    Anti-HPV 16/18 antibody titers were detected in CVS samples and presented as GMTs, expressed in EL.U/mL based on ELISA.

  11. Number of Subjects Seropositive for Total Immunoglobulin-G (IgG) in Blood (Serum) and in Cervical Samples (Secretion) in a Subset of Subjects [ Time Frame: At Months 18 and 24 ]
    Seropositivity was defined as total IgG ≥ 0 microgram per milliliter (µg/mL) and was detected in sera and in CVS samples by ELISA.

  12. Number of Subjects Reporting Pregnancies and Outcomes of Reported Pregnancies [ Time Frame: During the entire study period (from Day 0 up to Month 48) ]
    Outcomes of pregnancies were: Abnormal infant / Congenital anomaly, Elective termination, Missed abortion, Normal infant, Premature birth, Spontaneous abortion / Miscarriage and Outcome unknown.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   15 Years to 55 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria for primary study:

  • A woman who the investigator believes that she and/or her parents/legally acceptable representative can and will comply with the requirements of the protocol.
  • A woman between, and including, 15 and 55 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 a parent or legally acceptable representative and, in addition, the subject should sign and personally date a written informed assent).
  • Free of obvious health problems.
  • Subject must have a negative urine pregnancy test.
  • Subject must be of non-childbearing potential or, if of childbearing potential, she must be abstinent or must be using adequate contraceptive precautions for 30 days prior to vaccination and must agree to continue such precautions for two months after completion of the vaccination series. Subjects who reach menarche during the study and therefore become of childbearing potential must agree to follow the same precautions

Inclusion criteria for extension studies

  • A female who enrolled in the primary study and received three doses of vaccine.
  • 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 a parent or legally acceptable representative and, in addition, the subject must sign and personally date a written informed assent).

Exclusion criteria for primary study:

  • Pregnant or breastfeeding.
  • A woman planning to become pregnant, likely to become pregnant (as determined by the investigator) or planning to discontinue contraceptive precautions during the study period, up to two months after the last vaccine dose.
  • 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 (up to Month 12).
  • Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose, or planned administration during the study period.
  • Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before and 30 days after the first dose of study 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 subject is outside of specified window.
  • Previous administration of components of the investigational vaccine
  • Previous vaccination against HPV.
  • Any medically diagnosed or suspected immunodeficient condition based on medical history and physical examination.
  • History of allergic disease, suspected allergy or reactions likely to be exacerbated by any component of the study vaccine.
  • Hypersensitivity to latex.
  • Known acute or chronic, clinically significant neurologic, hepatic or renal functional abnormality, as determined by previous physical examination or laboratory tests.
  • History of chronic condition(s) requiring treatment.
  • Administration of immunoglobulins and/or any blood product within 3 months preceding the first dose of study vaccine or planned administration during the study period. Enrolment will be deferred until the subject is outside of specified window.
  • Acute disease at the time of enrolment.

Exclusion criteria for extension studies

  • Use of any investigational or non-registered product (drug or vaccine) or planned use during the study period.
  • 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).
  • Chronic administration of immunosuppressants or other immune-modifying drugs occurring less than 3 months prior to blood sampling.
  • Administration of immunoglobulins and/or any blood products within the three months preceding blood sampling.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00196937


Locations
Layout table for location information
Germany
GSK Investigational Site
Muenchen, Bayern, Germany, 80799
GSK Investigational Site
Wuerzburg, Bayern, Germany, 97070
GSK Investigational Site
Berlin, Germany, 12200
Poland
GSK Investigational Site
Bydgoszcz, Poland, 85-021
GSK Investigational Site
Poznan, Poland, 60-533
GSK Investigational Site
Poznan, Poland, 61-709
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Layout table for investigator information
Study Director: GSK Clinical Trials GlaxoSmithKline
Additional Information:
Study Data/Documents: Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 103514
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 103514
For additional information about this study please refer to the GSK Clinical Study Register. The results of this study 103514 are summarised with studies 105880 and 105881 on the GSK Clinical Study Register.
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 103514
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 103514
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 103514
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 103514
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 103514
For additional information about this study please refer to the GSK Clinical Study Register

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00196937    
Obsolete Identifiers: NCT00332358, NCT00332475, NCT00332501, NCT00332527
Other Study ID Numbers: 103514
105879 ( Other Identifier: GSK )
105880 ( Other Identifier: GSK )
105881 ( Other Identifier: GSK )
105882 ( Other Identifier: GSK )
2004-002083-18 ( EudraCT Number )
First Posted: September 20, 2005    Key Record Dates
Results First Posted: August 6, 2010
Last Update Posted: December 11, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.
URL: https://www.clinicalstudydatarequest.com/Posting.aspx?ID=1513
Keywords provided by GlaxoSmithKline:
HPV Vaccine Safety