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Infections, PapillomavirusPhase 3NCT00196937

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

A Phase 3 study testing Cervarix in people with Infections, Papillomavirus, run by GlaxoSmithKline at 6 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 15 to 55 years, women onlyHealthy volunteers can take part
Conditions the study is for
Infections, Papillomavirus
What is being tested?
Cervarix
Could I receive a placebo?
No, everyone receives an active treatment
How many people
667 participants
Where
6 sitesin 2 countries
Study dates
7 Oct 2004to 15 Dec 2005
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 15 to 55 years
  • Women only
  • Healthy volunteers accepted
  • Child, Adult

Who may be able to join

  • 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
  • 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).

Who cannot join

  • 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
Show all 18Show fewer
  • 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.
  • 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.

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

Germany3 sites

  • GSK Investigational Site

    Berlin, 12200

  • GSK Investigational Site

    Munich, Bavaria, 80799

  • GSK Investigational Site

    Würzburg, Bavaria, 97070

Other trials in Germany

Poland3 sites

  • GSK Investigational Site

    Bydgoszcz, 85-021

  • GSK Investigational Site

    Poznan, 60-533

  • GSK Investigational Site

    Poznan, 61-709

Other trials in Poland

About this study

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

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.

Being tested
Cervarix
Keywords
HPV Vaccine Safety
Medical subject headings
Papillomavirus Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CervarixBiological

    Three doses of vaccine administered intramuscularly according to a 0, 1, 6-month schedule.

Study groups in NCT00196937
Study groupRoleWhat they receive
Cervarix (15-25 Years) GroupExperimentalWomen aged 15 to 25 years received 3 doses of Cervarix vaccine administered according to a 0, 1, 6-month schedule.
Receives: Biological: Cervarix
Cervarix (26-45 Years) GroupExperimentalWomen aged 26 to 45 years received 3 doses of Cervarix vaccine administered according to a 0, 1, 6-month schedule.
Receives: Biological: Cervarix
Cervarix (46-55 Years) GroupExperimentalWomen aged 46 to 55 years received 3 doses of Cervarix vaccine administered according to a 0, 1, 6-month schedule.
Receives: Biological: Cervarix

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    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.

    Measured: At Month 7

  2. Anti-HPV-16/18 Antibody Titers Assessed by ELISA Based on the ATP Cohort for Immunogenicity 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.

    Measured: At Months 18, 24, 36 and 48

Secondary outcomes (12)

  1. Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies, in Women 46 - 55 Years of Age

    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.

    Measured: At Month 7

  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

    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.

    Measured: At PRE and Months 2, 7 and 12

  3. Number of Subjects Seroconverted for Anti-HPV-16 and Anti-HPV-18 Antibodies 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.

    Measured: At Month 2 and Month 12

  4. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

    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.

    Measured: During the 7-day period (from the day of vaccination up to 6 subsequent days) following vaccination after each dose and across doses

  5. Number of Subjects With Any and Grade 3 Solicited Local Symptoms

    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.

    Measured: During the 7-day period (from the day of vaccination up to 6 subsequent days) following vaccination after each dose and across doses

  6. Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)

    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.

    Measured: During the 30-day (from the day of vaccination up to 29 subsequent days) post-vaccination period

  7. Number of Subjects Reporting Serious Adverse Events (SAE)

    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.

    Measured: During the entire study period (from Day 0 up to Month 48)

  8. Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs)

    NOCDs assessed include chronic diseases such as autoimmune disorders, diabetes, allergies also asthma and pathognomic signs/symptoms of these diseases.

    Measured: During the entire study period (from Day 0 up to Month 48)

  9. Number of Subjects Reporting Medically Significant Conditions

    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.

    Measured: During the entire study period (from Day 0 up to Month 48)

  10. Anti-HPV-16/18 Antibody Titers Assessed by ELISA in a Subset of Subjects in Cervical Secretions (CVS) Samples

    Anti-HPV 16/18 antibody titers were detected in CVS samples and presented as GMTs, expressed in EL.U/mL based on ELISA.

    Measured: At Months 18 and 24

  11. Number of Subjects Seropositive for Total Immunoglobulin-G (IgG) in Blood (Serum) and in Cervical Samples (Secretion) in a Subset of Subjects

    Seropositivity was defined as total IgG ≥ 0 microgram per milliliter (µg/mL) and was detected in sera and in CVS samples by ELISA.

    Measured: At Months 18 and 24

  12. Number of Subjects Reporting Pregnancies and Outcomes of Reported Pregnancies

    Outcomes of pregnancies were: Abnormal infant / Congenital anomaly, Elective termination, Missed abortion, Normal infant, Premature birth, Spontaneous abortion / Miscarriage and Outcome unknown.

    Measured: During the entire study period (from Day 0 up to Month 48)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Sep 2005 (estimated)
  2. Study start7 Oct 2004
  3. Primary completion15 Dec 2005
  4. Study completion15 Dec 2005

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
667 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00196937
Sponsor's protocol ID
103514
Other IDs
105879, 105880, 105881, 105882, 2004-002083-18, 2004
Status last verified
Dec 2019
First submitted
13 Sep 2005
Last updated
11 Dec 2019
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

  • Descamps D, Hardt K, Spiessens B, Izurieta P, Verstraeten T, Breuer T, Dubin G. Safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for cervical cancer prevention: a pooled analysis of 11 clinical trials. Hum Vaccin. 2009 May;5(5):332-40. doi: 10.4161/hv.5.5.7211. Epub 2009 May 20.

    PubMed 19221517

  • Schwarz TF, Spaczynski M, Schneider A, Wysocki J, Galaj A, Perona P, Poncelet S, Zahaf T, Hardt K, Descamps D, Dubin G; HPV Study Group for Adult Women. Immunogenicity and tolerability of an HPV-16/18 AS04-adjuvanted prophylactic cervical cancer vaccine in women aged 15-55 years. Vaccine. 2009 Jan 22;27(4):581-7. doi: 10.1016/j.vaccine.2008.10.088. Epub 2008 Nov 18.

    PubMed 19022320

  • Schwarz TF, Spaczynski M, Schneider A, Wysocki J, Galaj A, Schulze K, Poncelet SM, Catteau G, Thomas F, Descamps D. Persistence of immune response to HPV-16/18 AS04-adjuvanted cervical cancer vaccine in women aged 15-55 years. Hum Vaccin. 2011 Sep;7(9):958-65. doi: 10.4161/hv.7.9.15999. Epub 2011 Sep 1.

    PubMed 21892005

  • Schwarz TF, Kocken M, Petaja T, Einstein MH, Spaczynski M, Louwers JA, Pedersen C, Levin M, Zahaf T, Poncelet S, Hardt K, Descamps D, Dubin G. Correlation between levels of human papillomavirus (HPV)-16 and 18 antibodies in serum and cervicovaginal secretions in girls and women vaccinated with the HPV-16/18 AS04-adjuvanted vaccine. Hum Vaccin. 2010 Dec;6(12):1054-61. doi: 10.4161/hv.6.12.13399. Epub 2010 Dec 1.

    PubMed 21157180

  • Schwarz T, Spaczynski M, Kaufmann A, Wysocki J, Galaj A, Schulze K, Suryakiran P, Thomas F, Descamps D. Persistence of immune responses to the HPV-16/18 AS04-adjuvanted vaccine in women aged 15-55 years and first-time modelling of antibody responses in mature women: results from an open-label 6-year follow-up study. BJOG. 2015 Jan;122(1):107-18. doi: 10.1111/1471-0528.13070. Epub 2014 Sep 11.

    PubMed 25208608

  • Boxus M, Lockman L, Fochesato M, Lorin C, Thomas F, Giannini SL. Antibody avidity measurements in recipients of Cervarix vaccine following a two-dose schedule or a three-dose schedule. Vaccine. 2014 May 30;32(26):3232-6. doi: 10.1016/j.vaccine.2014.04.005. Epub 2014 Apr 13.

    PubMed 24731816

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cervarix in people with Infections, Papillomavirus, run by GlaxoSmithKline at 6 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Germany, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Aug 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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 Women 15 to 25 Years of Age and Women 26 to 45 Years of Age (time frame: At Month 7). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00196937, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2019.

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