Cervical Intraepithelial NeoplasiaPhase 3NCT00316706

Human Papilloma Virus (HPV) Vaccine Trial in Young Adolescent Women With GlaxoSmithKline Biologicals' (GSK Bio) HPV-16/18 Vaccine

A Phase 3 study testing GSK Biologicals' HPV-16/18 Vaccine (Cervarix™) and Havrix™ in people with Cervical Intraepithelial Neoplasia and Papillomavirus Infection, run by GlaxoSmithKline at 28 sites in 5 countries.

Completed

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

Official record

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Trial summary

This protocol posting deals with objectives \& outcome measures of the extension phase up to Month 48. The objective of the extension study is to evaluate the long-term immunogenicity of the HPV 16/18 L1 VLP AS04 vaccine (for all subjects in the HPV Vaccine Group) by enzyme-linked immunosorbent assay (ELISA). Read more about this study

Who is it for?: Ages 10 to 14 years, women onlyHealthy volunteers can take part
Conditions the study is for: Cervical Intraepithelial Neoplasia, Papillomavirus Infection
What is being tested?: GSK Biologicals' HPV-16/18 Vaccine (Cervarix™) and Havrix™
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1,245 participants
Where: 28 sitesin 5 countries
Study dates: Oct 2005to Jan 2009
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 10 to 14 years
Women only
Healthy volunteers accepted
Child

Who may be able to join

A female who enrolled in the immunological subset of the 580299-013 study, received the three doses of vaccine/control according to the treatment allocation and completed the 580299-013 study.
Written informed assent obtained from the subject and written informed consent obtained from a parent or legally acceptable representative of the subject.

Who cannot join

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).
Use of any investigational or non-registered product (drug or vaccine) or planned use during the study period.
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 3 months preceding blood sampling.

Trial locations and contacts

28 sites in 5 countries.

Country

City, postcode or hospital

28 sites in 5 countries

Germany22 sites

GSK Investigational Site
Berlin, State of Berlin, 10315
GSK Investigational Site
Berlin, State of Berlin, 10967
GSK Investigational Site
Bochum, North Rhine-Westphalia, 44866
GSK Investigational Site
Brunsbüttel, Schleswig-Holstein, 25541
GSK Investigational Site
Bützow, Mecklenburg-Vorpommern, 18246
GSK Investigational Site
Deggingen, Baden-Wurttemberg, 73326
GSK Investigational Site
Ettenheim, Baden-Wurttemberg, 77955
GSK Investigational Site
Flensburg, Schleswig-Holstein, 24937
GSK Investigational Site
Hamburg, Free and Hanseatic City of Hamburg, 22307
GSK Investigational Site
Harrislee, Schleswig-Holstein, 24955
GSK Investigational Site
Husum, Schleswig-Holstein, 25813
GSK Investigational Site
Kehl, Baden-Wurttemberg, 77694
GSK Investigational Site
Mannheim, Baden-Wurttemberg, 68167
GSK Investigational Site
Niebüll, Schleswig-Holstein, 25899
GSK Investigational Site
Rostock, Mecklenburg-Vorpommern, 18109
GSK Investigational Site
Tauberbischofsheim, Baden-Wurttemberg, 97941
GSK Investigational Site
Trier, Rhineland-Palatinate, 54290
GSK Investigational Site
Weilheim, Bavaria, 82362
GSK Investigational Site
Weimar, Thuringia, 99425
GSK Investigational Site
Willich, North Rhine-Westphalia, 47877
GSK Investigational Site
Wolfenbüttel, Lower Saxony, 38302
GSK Investigational Site
Würzburg, Bavaria, 97070

Other trials in Germany

Colombia2 sites

GSK Investigational Site
Bogotá, 805
GSK Investigational Site
Bogotá

Other trials in Colombia

Taiwan2 sites

GSK Investigational Site
Taipei, 100
GSK Investigational Site
Tao Yuan County, 333

Other trials in Taiwan

Honduras1 site

GSK Investigational Site
Comayagüela

Other trials in Honduras

Panama1 site

GSK Investigational Site
La Chorrera, Provincia de Panamá

Other trials in Panama

About this study

Official title: A Long-term, Open Follow-up of the Immunogenicity and Safety of GSK Biologicals' HPV Vaccine (580299) in Healthy Female Subjects Vaccinated in Study HPV-013

The long-term follow-up study will be blinded until the primary study is unblinded and will be open for all visits subsequent to unblinding of primary study HPV-013 (NCT00196924). During the open phase, only subjects who received the HPV-16/18 VLP/AS04 vaccine during the primary study will continue their participation in the follow-up study until Month 48. Subjects in the Control group (Havrix®) will attend one further visit as their last study visit.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Conditions: Cervical Intraepithelial Neoplasia, Papillomavirus Infection
Being tested: GSK Biologicals' HPV-16/18 Vaccine (Cervarix™), Havrix™
Keywords: Prophylaxis HPV-16/18 infections and cervical neoplasia
Medical subject headings: Uterine Cervical Dysplasia, Papillomavirus Infections

What participants receive

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

GSK Biologicals' HPV-16/18 Vaccine (Cervarix™)Biological
Three doses of vaccine administrerd intramuscularly according to 0, 1, 6 month schedule
Havrix™Biological
Three doses of vaccine administrerd intramuscularly according to 0, 1, 6 month schedule.

Study groups in NCT00316706
Study group	Role	What they receive
Cervarix Group	Experimental	Subjects received 3 doses of GSK Biologicals' HPV-16/18 Vaccine (Cervarix™) during the primary study (NCT00196924). Subjects from this group continued the long-term follow-up study until Month 48. Receives: Biological: GSK Biologicals' HPV-16/18 Vaccine (Cervarix™)
Havrix Group	Active comparator	Subjects received 3 doses of Havrix™ (hepatitis A vaccine [HAV]) during the primary study (NCT00196924). Subjects from the this group completed the study at Month 24. Receives: Biological: Havrix™

What is being measured

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

Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies
Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL).
Measured: At 18, 24, 36 and 48 months

Secondary outcomes (4)

Titers of Anti-3-O-desacyl-4'-Monophosphoryl Lipid A (Anti-MPL) Antibodies During the Initial 2 Years Follow-up
Titers are given as Geometric Mean Titers (GMTs) expressed as EL.U/mL.
Measured: At Months 18 and 24
Titers of Anti-3-O-desacyl 4'-Monophosphoryl Lipid A (Anti-MPL) Antibodies During the Last 2 Years Follow-up
Titers are given as Geometric Mean Titers (GMTs) expressed as EL.U/mL.
Measured: At Month 36 and 48
Number of Subjects Reporting Pregnancies, Serious Adverse Events (SAEs), New Onset Chronic Diseases (NOCDs), and Conditions Prompting Emergency Room (ER) Visits or Physician Visits That Are Not Related to Common Diseases During the First 2 Years Follow-up
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
New onset of chronic diseases (NOCDs) assessed include e.g. autoimmune disorders, asthma, type I diabetes.
Measured: From Month 18 to Month 24
Number of Subjects Reporting Pregnancies, Serious Adverse Events (SAEs), New Onset Chronic Diseases (NOCDs), and Conditions Prompting Emergency Room During the Last 2 Years Follow-up
Serious adverse events assessed include medical occurrences that result in death, is life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
New onset of chronic diseases (NOCDs) assessed include e.g. autoimmune disorders, asthma, type I diabetes.
Measured: From Month 24 to Month 48

Timeline

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

Oct 2005Jan 2009

First posted21 Apr 2006 (estimated)
Study startOct 2005
Primary completionJan 2009
Study completionJan 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Cervical Intraepithelial NeoplasiaStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: 1,245 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00316706
Sponsor's protocol ID: 104896 (month 18 FU)
Other IDs: 104902, 104904, 104918
Status last verified: Sep 2012
First submitted: 19 Apr 2006
Last updated: 18 Sep 2012
Results posted: Yes, on ClinicalTrials.gov

Publications

Schwarz TF, Huang LM, Medina DM, Valencia A, Lin TY, Behre U, Catteau G, Thomas F, Descamps D. Four-year follow-up of the immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine when administered to adolescent girls aged 10-14 years. J Adolesc Health. 2012 Feb;50(2):187-94. doi: 10.1016/j.jadohealth.2011.11.004.
PubMed 22265115

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 18 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Long-term, Open Follow-up of the Immunogenicity and Safety of GSK Biologicals' HPV Vaccine (580299) in Healthy Female Subjects Vaccinated in Study HPV-013
ClinicalTrials.gov ID: NCT00316706
Acronym / sponsor ID: 104896 (month 18 FU)
Conditions: Cervical Intraepithelial Neoplasia, Papillomavirus Infection
Keywords: Prophylaxis HPV-16/18 infections and cervical neoplasia
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,245 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: Oct 2005
Primary completion: Jan 2009 (actual)
Study completion: Jan 2009 (actual)
First posted: 21 Apr 2006 (estimated)
Results: Posted 1 Mar 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Study design

Primary purpose: Prevention
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Cervarix Group	Experimental	Biological: GSK Biologicals' HPV-16/18 Vaccine (Cervarix™)Subjects received 3 doses of GSK Biologicals' HPV-16/18 Vaccine (Cervarix™) during the primary study (NCT00196924). Subjects from this group continued the long-term follow-up study until Month 48.
Havrix Group	Active comparator	Biological: Havrix™Subjects received 3 doses of Havrix™ (hepatitis A vaccine [HAV]) during the primary study (NCT00196924). Subjects from the this group completed the study at Month 24.

Who may qualify

Ages: 10 to 14 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Child

Key inclusion criteria (2 listed)

A female who enrolled in the immunological subset of the 580299-013 study, received the three doses of vaccine/control according to the treatment allocation and completed the 580299-013 study.
Written informed assent obtained from the subject and written informed consent obtained from a parent or legally acceptable representative of the subject.

Key exclusion criteria (4 listed)

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).
Use of any investigational or non-registered product (drug or vaccine) or planned use during the study period.
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 3 months preceding blood sampling.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GSK Biologicals' HPV-16/18 Vaccine (Cervarix™)Three doses of vaccine administrerd intramuscularly according to 0, 1, 6 month schedule	Biological	Cervarix Group
Havrix™Three doses of vaccine administrerd intramuscularly according to 0, 1, 6 month schedule.	Biological	Havrix Group

Primary outcome

Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies
Time frame: At 18, 24, 36 and 48 months
Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL).

4 secondary outcomes

Titers of Anti-3-O-desacyl-4'-Monophosphoryl Lipid A (Anti-MPL) Antibodies During the Initial 2 Years Follow-up
Time frame: At Months 18 and 24
Titers of Anti-3-O-desacyl 4'-Monophosphoryl Lipid A (Anti-MPL) Antibodies During the Last 2 Years Follow-up
Time frame: At Month 36 and 48
Number of Subjects Reporting Pregnancies, Serious Adverse Events (SAEs), New Onset Chronic Diseases (NOCDs), and Conditions Prompting Emergency Room (ER) Visits or Physician Visits That Are Not Related to Common Diseases During the First 2 Years Follow-up
Time frame: From Month 18 to Month 24
Number of Subjects Reporting Pregnancies, Serious Adverse Events (SAEs), New Onset Chronic Diseases (NOCDs), and Conditions Prompting Emergency Room During the Last 2 Years Follow-up
Time frame: From Month 24 to Month 48

Results and safety

Results posted to the registry on 1 Mar 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cervarix Group	626	588
Havrix Group	619	571

Primary outcome: Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies

Time frame: At 18, 24, 36 and 48 months. Geometric mean (95% Confidence Interval). Unit: EL.U/mL

Measure	Cervarix Group n = 588	Havrix Group n = 0
Anti-HPV-16 at Month 18 (n= 588)	3901.6 (3626.2 to 4198.0)	–
Anti-HPV-16 at Month 24 (n= 549)	3226.3 (2988.4 to 3483.1)	–
Anti-HPV-16 at Month 36 (n= 571)	2688.6 (2503.6 to 2887.3)	–
Anti-HPV-16 at Month 48 (n= 559)	2395.8 (2230.5 to 2573.3)	–
Anti-HPV-18 at Month 18 (n= 587)	1570.8 (1448.3 to 1703.7)	–
Anti-HPV-18 at Month 24 (n= 548)	1263.4 (1165.1 to 1370.1)	–
Anti-HPV-18 at Month 36 (n= 570)	995.0 (918.1 to 1078.4)	–
Anti-HPV-18 at Month 48 (n= 559)	885.6 (816.3 to 960.8)	–

Population analysed: Analysis was performed on the According-to-Protocol (ATP) cohort for analysis of immunogenicity, on those subjects from the Cervarix Group with available data for the defined time point.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: From Month 18 up to Month 24 in Havrix group and up to Month 48 in Cervarix group. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cervarix Group	33 of 626 (5.3%)	0 of 626 (0%)	Not reported
Havrix Group	5 of 619 (0.8%)	0 of 619 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 22265115Schwarz TF, Huang LM, Medina DM, Valencia A, Lin TY, Behre U, Catteau G, Thomas F, Descamps D. Four-year follow-up of the immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine when administered to adolescent girls aged 10-14 years. J Adolesc Health. 2012 Feb;50(2):187-94. doi: 10.1016/j.jadohealth.2011.11.004.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

28 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 2 inclusion and 4 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 18 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in Germany, Colombia, Taiwan, Honduras, Panama. 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 1 Mar 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?

Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies (time frame: At 18, 24, 36 and 48 months). 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 NCT00316706, which also lists 1 linked publication.

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 18 Sep 2012.