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Infections, PapillomavirusPhase 3NCT01462357

Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' Human Papillomavirus (HPV) Vaccine (GSK-580299) and Merck's Gardasil Vaccine When Administered According to Alternative 2-dose Schedules in 9-14 Year Old Females

A Phase 3 study testing Cervarix and Gardasil in people with Infections, Papillomavirus, run by GlaxoSmithKline at 21 sites in 4 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

The purpose of this study is to evaluate the immunogenicity and the safety of Cervarix administered according to a 2-dose schedule at 0, 6 months compared to Gardasil, administered according to a 2-dose schedule at 0, 6 months or the standard 3-dose schedule of 0, 2, 6 months in 9-14 years old healthy females. Read more about this study

Who is it for?
Ages 9 to 14 years, women onlyHealthy volunteers can take part
Conditions the study is for
Infections, Papillomavirus
What is being tested?
Cervarix and Gardasil
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,079 participants
Where
21 sitesin 4 countries
Study dates
21 Nov 2011to 27 Oct 2015
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 9 to 14 years
  • Women only
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • Subjects who the investigator believes can and will comply with the requirements of the protocol 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 14 years of age at the time of the first vaccination.
  • Written informed consent obtained from the parent(s)/LAR(s) of the subject prior to enrolment in the study. In addition, if capable, the subject should sign and personally date a written informed assent.
  • Healthy subjects as established by medical history and clinical examination before entering into the study.
  • 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:
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  • 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 treatment period and for two months after completion of the vaccination series.

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 vaccination phase of the study, i.e. up to two months after the last vaccine dose.
  • Previous vaccination against HPV or planned administration of another HPV vaccine during the study other than those foreseen in the protocol.
  • Child in care.
  • 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 36).
  • Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
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  • 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 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 (pharmaceutical product or device).
  • Previous administration of vaccine components.
  • Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
  • 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.
  • Drug and/or alcohol abuse.

Trial locations and contacts

21 sites in 4 countries.

21 sites in 4 countries

France10 sites

  • GSK Investigational Site

    Dax, 40100

  • GSK Investigational Site

    Draguignan, 83300

  • GSK Investigational Site

    Essey-lès-Nancy, 54270

  • GSK Investigational Site

    Le Havre, 76620

  • GSK Investigational Site

    Nice, 06300

  • GSK Investigational Site

    Paris, 75970

  • GSK Investigational Site

    Rosiers-d'Égletons, 19300

  • GSK Investigational Site

    Saint Cyr Sur Loir, 37540

  • GSK Investigational Site

    Seysses, 31600

  • GSK Investigational Site

    Tours, 37100

Other trials in France

Singapore6 sites

  • GSK Investigational Site

    Singapore, 119074

  • GSK Investigational Site

    Singapore, 169608

  • GSK Investigational Site

    Singapore, 228510

  • GSK Investigational Site

    Singapore, 229899

  • GSK Investigational Site

    Singapore, 529889

  • GSK Investigational Site

    Singapore, 768826

Other trials in Singapore

Sweden3 sites

  • GSK Investigational Site

    Eskilstuna, SE-631 88

  • GSK Investigational Site

    Linköping, SE-581 85

  • GSK Investigational Site

    Örebro, SE-701 16

Other trials in Sweden

Hong Kong2 sites

  • GSK Investigational Site

    Pokfulam

  • GSK Investigational Site

    Shatin

Other trials in Hong Kong

About this study

Official title: Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' HPV-16/18 L1 AS04 Vaccine and Merck's Gardasil Vaccine When Administered According to Alternative 2-dose Schedules in 9-14 Year Old Females

The purpose of this study is to evaluate the immunogenicity and the safety of Cervarix administered according to a 2-dose schedule at 0, 6 months compared to Gardasil, administered according to a 2-dose schedule at 0, 6 months or the standard 3-dose schedule of 0, 2, 6 months in 9-14 years old healthy females.

Being tested
Cervarix, Gardasil, Placebo
Keywords
Human papillomavirus, Safety, HPV vaccine, Immune response
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

    2 doses of 0.5 mL supplied as a liquid in individual pre-filled syringes to be administered intramuscularly in the deltoid muscle of the non-dominant arm at Day 0 and Month 6.

  • GardasilBiological

    2 or 3 doses of 0.5 mL supplied as a liquid in individual pre-filled syringes or vials to be administered intramuscularly in the deltoid muscle of the non-dominant arm at Day 0 and Month 6 (Gardasil 2 dose Group) or at Day 0, Month 2 and Month 6 (Gardasil 3 dose Group), respectively.

  • PlaceboDrug

    2 doses of 0.5 mL supplied as a liquid in individual pre-filled syringes to be administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 2 to maintain blinding.

Study groups in NCT01462357
Study groupRoleWhat they receive
Cervarix 2 dose GroupExperimentalSubjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Receives: Biological: Cervarix; Drug: Placebo
Gardasil 2 dose GroupExperimentalSubjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Receives: Biological: Gardasil; Drug: Placebo
Gardasil 3 dose GroupExperimentalSubjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Receives: Biological: Gardasil

What is being measured

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

  1. Number of Seroconverted Subjects for Anti-HPV-16/18 Antibodies as Assessed by Enzyme-Linked Immunosorbent Assay (ELISA) at Month 7 Based on the ATP Cohort for Immunogenicity

    Seroconversion was defined as the appearance of antibodies (i.e. anti-HPV-16 and anti-HPV-18 antibody titers greater than or equal to (≥) 19 and 18 ELISA units per milliliter (EL.U/mL), respectively), in the serum of subjects seronegative before vaccination.

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

  2. Anti-HPV-16/18 Antibody Titers as Assessed by ELISA at Month 7 Based on the ATP Cohort for Immunogenicity

    Anti-HPV 16/18 antibody titers were presented as Geometric Mean Titers (GMTs) and expressed in EL.U/mL.

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

  3. Anti-HPV-16/18 Antibody Titers as Assessed by ELISA at Month 7 Based on the Total Vaccinated Cohort (TVC)

    Anti-HPV 16/18 antibody titers were presented as Geometric Mean Titers (GMTs) and expressed in EL.U/mL.

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

Secondary outcomes (19)

  1. Anti-HPV-16/18 Seroconversion Rates as Assessed by ELISA

    Seroconversion was defined as the appearance of antibodies (i.e. anti-HPV-16 and anti-HPV-18 antibody titers ≥ 19 and 18 EL.U/mL, respectively) in the serum of subjects seronegative before vaccination.

    Measured: At Day 0 and Months 12, 18, 24 and 36

  2. Anti-HPV-16/18 Antibody Titers as Assessed by ELISA

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

    Measured: At Day 0 and Months 12, 18, 24 and 36

  3. Anti-HPV-16/18 Antibody Titers as Assessed by ELISA at Month 36

    Data at Month 36 were also expressed as International Units per milliliter (IU/mL). Conversion factor from EU/mL to IU/mL was determined to be 1/6.1 for HPV-16 and 1/5.7 for HPV-18, using the WHO International Standards (NIBSC codes 05-134 and 10-140 for HPV-16 and HPV-18, respectively). The assay cut-offs were therefore 3.1 IU/mL and 3.2 IU/mL for anti-HPV-16 and anti-HPV-18 antibodies, respectively.

    Measured: At Month 36

  4. Anti-HPV-16/18 Seroconversion Rates as Assessed by Pseudovirion-based Neutralization Assay (PBNA) in a Subset of Subjects, Based on the Month 36 ATP Cohort for Immunogenicity

    Seroconversion was defined as the appearance of antibodies (i.e. anti-HPV-16 and anti-HPV-18 antibody titers ≥40 ED50) in the serum of subjects seronegative before vaccination. The assay was performed on a subset of approximately 100 subjects per study group.

    Measured: At Day 0 and Months 7, 12, 18, 24 and 36

  5. Anti-HPV-16/18 Antibody Titers as Assessed by PBNA in a Subset of Subjects, Based on the Month 36 ATP Cohort for Immunogenicity

    Anti-HPV 16/18 antibody titers were presented as GMT and expressed in titers using the PBNA. The assay was performed on a subset of approximately 100 subjects per study group.

    Measured: At Day 0 and Months 7, 12, 18, 24 and 36

  6. Anti-HPV-16/18 Seroconversion Rates as Assessed by PBNA in a Subset of Subjects, Based on the Month 36 TVC

    Seroconversion was defined as the appearance of antibodies (i.e. anti-HPV-16 and anti-HPV-18 antibody titers ≥40 ED50) in the serum of subjects seronegative before vaccination. The assay was performed on a subset of approximately 100 subjects per study group.

    Measured: At Day 0 and Months 7, 12, 18, 24 and 36

  7. Anti-HPV-16/18 Antibody Titers as Assessed by PBNA in a Subset of Subjects, Based on the Month 36 TVC

    Anti-HPV 16/18 antibody titers were presented as GMT and expressed in titers using the PBNA. The assay was performed on a subset of approximately 100 subjects per study group.

    Measured: At Day 0 and Months 7, 12, 18, 24 and 36

  8. T-cell-mediated Immune Responses in the Sub-cohort for Cell-Mediated Immunity (CMI)

    Among immune markers expressed were Interleukin-2 (IL-2), Interferon-gamma (IFN-γ), Tumour necrosis factor-alpha (TNF-α) and CD40-ligand (CD40-L). The assay was performed on a sub-cohort of approximately 100 subjects per study group.

    Measured: At Day 0 and Months 7, 12, 24 and 36

  9. B-cell-mediated Immune Responses in the Sub-cohort for CMI

    The frequency of B-cell Elispot response to HPV-16/18 by overall status was presented. The assay was performed on a sub-cohort of approximately 100 subjects per study group.

    Measured: At Day 0 and Months 7, 12, 24 and 36

  10. 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

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

    Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, rash, temperature [defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)] 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

  12. 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

  13. Number of Subjects With Potentially Immune Mediated Diseases (pIMDs)

    pIMDs were defined as a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.

    Measured: From Day 0 up to Month 12

  14. Number of Subjects With Medically Significant Conditions (MSCs)

    MSCs were defined as AEs prompting emergency room (ER) or physician visits that were not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs not related to common diseases. Common diseases include: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury.

    Measured: From Day 0 up to Month 36 (throughout the study period)

  15. Number of Subjects With Serious Adverse Events (SAEs)

    SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.

    Measured: From Day 0 up to Month 36 (throughout the study period)

  16. Number of Subjects With SAEs Related to the Investigational Product, to Study Participation, to GSK Concomitant Products or Any Fatal SAE

    SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity. Related = an event assessed by the investigator as causally related to the investigational product, to study participation or to GSK concomitant products.

    Measured: From Day 0 up to Month 36 (throughout the study period)

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

    Outcomes of pregnancies were Live infant NO apparent congenital anomaly (ACA), Live infant congenital anomaly (CA), Elective termination NO ACA, Elective termination CA, Ectopic pregnancy, Spontaneous abortion NO ACA, Stillbirth NO ACA, Stillbirth CA, Lost to follow up and Pregnancy ongoing.

    Measured: From Day 0 up to Month 36 (throughout the study period)

  18. Number of Subjects Using a Concomitant Medication Throughout the Study Period

    The number of subjects who have used any concomitant medication, as well as any antipyretic, any prophylactic antipyretic and any antibiotic.

    Measured: From Day 0 up to Month 36 (throughout the study period) following vaccination after each dose and across doses

  19. Number of Subjects Completing the Vaccination Schedule

    The number of subjects who have completed the three-dose vaccination schedule in all groups.

    Measured: From Day 0 up to Month 36 (throughout the study period)

Timeline

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

  1. First posted31 Oct 2011 (estimated)
  2. Study start21 Nov 2011
  3. Primary completion27 Oct 2015
  4. Study completion27 Oct 2015

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
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
1,079 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01462357
Sponsor's protocol ID
115411
Other IDs
2011-002035-26
Status last verified
Oct 2019
First submitted
27 Oct 2011
Last updated
15 Nov 2019
Individual data sharing
Yes: IPD is available via the Clinical Study Data Request site (click on the link provided below).

Publications

  • Leung TF, Liu AP, Lim FS, Thollot F, Oh HM, Lee BW, Rombo L, Tan NC, Rouzier R, Friel D, De Muynck B, De Simoni S, Suryakiran P, Hezareh M, Folschweiller N, Thomas F, Struyf F. Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine administered according to 2- and 3-dose schedules in girls aged 9-14 years: Results to month 12 from a randomized trial. Hum Vaccin Immunother. 2015;11(7):1689-702. doi: 10.1080/21645515.2015.1050570.

    PubMed 26062002

  • Leung TF, Liu AP, Lim FS, Thollot F, Oh HML, Lee BW, Rombo L, Tan NC, Rouzier R, De Simoni S, Suryakiran P, Hezareh M, Thomas F, Folschweiller N, Struyf F. Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and 4vHPV vaccine administered according to two- or three-dose schedules in girls aged 9-14 years: Results to month 36 from a randomized trial. Vaccine. 2018 Jan 2;36(1):98-106. doi: 10.1016/j.vaccine.2017.11.034. Epub 2017 Nov 23.

    PubMed 29174109

  • Bergman H, Henschke N, Arevalo-Rodriguez I, Buckley BS, Crosbie EJ, Davies JC, Dwan K, Golder SP, Loke YK, Probyn K, Petkovic J, Villanueva G, Morrison J. Human papillomavirus (HPV) vaccination for the prevention of cervical cancer and other HPV-related diseases: a network meta-analysis. Cochrane Database Syst Rev. 2025 Nov 24;11(11):CD015364. doi: 10.1002/14651858.CD015364.pub2.

    PubMed 41276263

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cervarix and Gardasil in people with Infections, Papillomavirus, run by GlaxoSmithKline at 21 sites in 4 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 9 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 15 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in France, Singapore, Sweden, Hong Kong. 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 28 Mar 2016). 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-HPV-16/18 Antibodies as Assessed by Enzyme-Linked Immunosorbent Assay (ELISA) at Month 7 Based on the ATP Cohort for Immunogenicity (time frame: At Month 7 (i.e. one month after the last dose of study vaccine)). The study lists 3 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 NCT01462357, which also lists 3 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 15 Nov 2019.

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