Clinical trial NCT00652938: Evaluation of Immunogenicity and Safety of Human Papillomavirus (HPV) Vaccine Co-administered With Another Vaccine in Healthy Female Subjects
Official title: Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' HPV Vaccine (580299) Co-administrated With a Commercially Available Vaccine in Healthy Female Adolescents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Papillomavirus
Keywords: Co-administration
HPV vaccine
Cervical cancer
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-04-04
Enrollment: 744
Sex: FEMALE
Minimum age (years): 9
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Infection with human papillomavirus (HPV) has been clearly established as the necessary cause of cervical cancer. Vaccination of pre-teens and adolescents, ideally before sexual debut and thus before exposure to oncogenic HPV, is a rational strategy for prevention of cervical cancer. Thus, HPV vaccination could complement the existing pre-adolescent/adolescent vaccination programs. This Phase IIIb study is designed to evaluate the immunogenicity and safety of co-administering a commercially available vaccine with GSK Biologicals' HPV-16/18 L1 VLP AS04 (Cervarix TM) vaccine as compared to the administration of either vaccine alone.


Eligibility criteria: Inclusion Criteria:

* Subjects who the investigator believes that they and/or their parents/legally acceptable representatives (LARs) can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits) should be enrolled in the study.
* A female between, and including, 9 and 15 years of age (has not attained her 16th birthday) at the time of the first vaccination.
* Written informed consent obtained from the subject's parent/LAR prior to the enrolment. In addition, written informed assent must be obtained from the subject.
* Healthy subjects as established by medical history and clinical examination before entering into the study.
* Subjects must not be pregnant. Absence of pregnancy should be verified with a urine pregnancy test.
* If the subject is female, she must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for at least 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for two months after completion of the vaccination series. Subjects who reach menarche (begin menstruating) during the study, and therefore become of childbearing potential, must agree to follow the same precautions.

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 (up to Month 12).
* 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 each dose of vaccine. Administration of routine vaccines such as meningococcal, inactivated influenza, diphtheria/tetanus and/or diphtheria/tetanus-containing vaccines up to 8 days before the first dose of study vaccine is allowed.
* Concurrently participating in another clinical study, at any time during the study period (up to the Month 12 telephone contact), in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
* A subject planning to become pregnant, likely to become pregnant (as determined by the investigator) or planning to discontinue contraceptive precautions during the study period and up to two months after the last vaccine dose.
* Pregnant or breastfeeding women.
* 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.
* Previous vaccination against hepatitis B or planned administration of any hepatitis B vaccine other than that foreseen by the study protocol during the study period.
* History of hepatitis B infection.
* Known exposure to hepatitis B within the previous 6 weeks.
* Known acute or chronic, clinically significant neurologic, hepatic or renal functional abnormality, as determined by previous physical examination or laboratory tests.
* Cancer or autoimmune disease under treatment.
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* Acute disease at the time of enrolment.
* 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.

Primary outcomes:
measure: Number of Subjects With Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above the Cut-off Value for Seroprotection
timeFrame: Month 7
measure: Number of Subjects With Anti-human Papillomavirus 16 and 18 (Anti-HPV-16 and Anti-HPV-18) Antibody Concentrations Above the Cut-off Value for Seroconversion
timeFrame: Month 7
measure: Anti-HPV-16/18 Antibody Titres
timeFrame: Month 7
Secondary outcomes:
measure: Number of Subjects With Anti-HBs Antibody Concentrations Above the Cut-off Value for Seroconversion
timeFrame: Month 7
measure: Anti-HBs Antibody Titres
timeFrame: Month 7
measure: Number of Subjects With Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations Above the Cut-off Value for Seroconversion
timeFrame: Month 2
measure: Anti-HPV-16/18 Antibody Titres
timeFrame: Month 2
measure: Number of Subjects With Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above the Cut-off Value for Seroconversion
timeFrame: Month 2
measure: Number of Subjects With Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above the Cut-off Value for Seroprotection
timeFrame: Month 2
measure: Anti-HBs Antibody Titers
timeFrame: Month 2
measure: Number of Subjects Reporting Any Solicited Local Symptoms
timeFrame: During the 7-day period (Days 0 - 6) following vaccination
measure: Number of Subjects Reporting Grade 3 Solicited Local Symptoms
timeFrame: During the 7-day period (Days 0-6) following vaccination
measure: Number of Subjects Reporting Any Solicited General Symptoms
timeFrame: During the 7-day (Days 0-6) period following vaccination.
measure: Number of Subjects Reporting Grade 3 Solicited General Symptoms
timeFrame: During the 7-day (Days 0-6) period following vaccination
measure: Number of Subjects Reporting Related Solicited General Symptoms
timeFrame: During the 7-day period (Days 0 - 6) following vaccination
measure: Number of Subjects Reporting Any, Grade 3 and Causally Related to Vaccination Unsolicited Adverse Events (AEs)
timeFrame: During the 30-day period (Days 0 - 29) following any vaccination
measure: Number of Subjects Reporting Any and Causally Related to Vaccination Serious Adverse Events (SAEs)
timeFrame: Throughout the active phase of the study (up to Month 7).
measure: Number of Subjects Reporting Any and Causally Related to Vaccination SAEs
timeFrame: Throughout the safety follow-up (month 7 up to Month 12).
measure: Number of Subjects Reporting Medically Significant Conditions
timeFrame: Throughout the active phase of the study (up to Month 7)
measure: Number of Subjects Reporting Medically Significant Conditions
timeFrame: Throughout the safety follow-up (month 7 up to Month 12)
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Linköping
country: Sweden
facility: GSK Investigational Site
city: Luleå
country: Sweden
facility: GSK Investigational Site
city: Malmö
country: Sweden
facility: GSK Investigational Site
city: Norrköping
country: Sweden
facility: GSK Investigational Site
city: Skene
country: Sweden
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Schmeink C et al. Co-administration of AS04-adjuvanted human papillomavirus-16/18 vaccine with hepatitis B vaccine in healthy female subjects aged 9-15 years. Abstract presented at the 28th Annual Meeting of European Society for Paediatric Infectious Diseases (ESPID). Nice, France, 4-8 May 2010.
citation: Schmeink CE, Bekkers RL, Josefsson A, Richardus JH, Berndtsson Blom K, David MP, Dobbelaere K, Descamps D. Co-administration of human papillomavirus-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine: randomized study in healthy girls. Vaccine. 2011 Nov 15;29(49):9276-83. doi: 10.1016/j.vaccine.2011.08.037. Epub 2011 Aug 19.