Clinical trial NCT00578227: Evaluation of Safety and Immunogenicity of Co-administering Human Papillomavirus Vaccine With Another Vaccine in Healthy Female Subjects
Official title: Immunogenicity and Safety Study of GSK Biologicals' HPV Vaccine (GSK-580299) Co-administered With a Commercially Available Vaccine in Healthy Female Adolescents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Papillomavirus
Keywords: Human papillomavirus infection,
cervical cancer
HPV vaccine,
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-12-21
Enrollment: 814
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 central 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, and so HPV vaccination could complement the existing pre-adolescent/adolescent vaccination programs. Therefore, this Phase IIIb study is designed to evaluate the safety and immunogenicity of co-administering a commercially available vaccine with GSK Biologicals' HPV-16/18 L1 AS04 (Cervarix ®) vaccine as compared to the administration of either vaccine alone. This Protocol Posting has been updated in order to comply with the FDA AA, Sept 2007.


Eligibility criteria: Inclusion Criteria:

* Subjects who the investigator believes that they and/or their legally acceptable representatives (LARs) can and will comply with the requirements of the protocol 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 prior to enrolment. For subjects below the legal age of consent, written informed consent must be obtained from the subject's LAR, and 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.
* Subjects must be of non-childbearing potential, or if the subject is of childbearing potential, she must be abstinent or use adequate contraception for 30 days prior to vaccination and must agree to continue such precautions for two months after completion of the vaccination series.

Exclusion Criteria:

* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period (up to Month 12).
* 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).
* 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(s). Administration of routine vaccines may be allowed up to 8 days before the first dose
* A subject planning to become pregnant, likely to become pregnant 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 A or B planned administration of any hepatitis A or B vaccine other than that foreseen by the study protocol during the study period.
* History of hepatitis A or B infection.
* Known exposure to hepatitis A or 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 Seroconverted for Anti-hepatitis A (Anti-HAV) Antibodies
timeFrame: At Month 7
measure: Anti-Heptatis A (HAV) Antibody Titers.
timeFrame: At Month 7
measure: Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies
timeFrame: At Month 7
measure: Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies
timeFrame: At Month 7
measure: Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers
timeFrame: At Month 7
Secondary outcomes:
measure: Anti-HBs Antibody Titers
timeFrame: At Month 7
measure: Number of Subjects Seroconverted for Anti-HBs Antibodies
timeFrame: At month 7
measure: Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies in Vaccine Recipients Aged 9 Years
timeFrame: At Month 7
measure: Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers in Vaccine Recipients Aged 9 Years
timeFrame: At Month 7
measure: Number of Subjects Seroconverted for Anti-HAV Antibodies
timeFrame: One month after the second dose of vaccine
measure: Anti-HAV Antibody Titers
timeFrame: One month after the second dose of vaccine
measure: Number of Subjects Seroconverted and Number of Subjects Seroprotected for Anti-HBs Antibodies
timeFrame: One month after the second dose of vaccine
measure: Anti-HBs Antibody Titers
timeFrame: One month after the second dose of vaccine
measure: Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies
timeFrame: One month after the second dose of vaccine
measure: Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers
timeFrame: One month after the second dose of vaccine
measure: Number of Subjects Reporting Solicited Local Symptoms
timeFrame: During the 7-day period (Day 0-6) following vaccination
measure: Number of Subjects Reporting Solicited General Symptoms
timeFrame: During the 7-day period following vaccination
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 (from Month 7 up to Month 12)
measure: Number of Subjects Reporting Unsolicited Adverse Events
timeFrame: During the 30-day period following any vaccination
measure: Number of Subjects Reporting Serious Adverse Events (SAE)
timeFrame: Throughout the study (up to Month 12)
Other outcomes:
Locations:
city: Surrey
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Brampton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Newmarket
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Sarnia
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Sudbury
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Hoersholm
country: Denmark
facility: GSK Investigational Site
city: Odense C
country: Denmark
facility: GSK Investigational Site
city: Bordány
country: Hungary
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: Győr
country: Hungary
facility: GSK Investigational Site
city: Hódmezővásárhely
country: Hungary
facility: GSK Investigational Site
city: Szeged
country: Hungary
facility: GSK Investigational Site
city: Szombathely
country: Hungary
facility: GSK Investigational Site
city: Karlskrona
country: Sweden
facility: GSK Investigational Site
city: Linköping
country: Sweden
facility: GSK Investigational Site
city: Lycksele
country: Sweden
facility: GSK Investigational Site
city: Umeå
country: Sweden
facility: GSK Investigational Site
city: Örebro
country: Sweden
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Pedersen C, Breindahl M, Aggarwal N, Berglund J, Oroszlan G, Silfverdal SA, Szuts P, O'Mahony M, David MP, Dobbelaere K, Dubin G, Descamps D. Randomized trial: immunogenicity and safety of coadministered human papillomavirus-16/18 AS04-adjuvanted vaccine and combined hepatitis A and B vaccine in girls. J Adolesc Health. 2012 Jan;50(1):38-46. doi: 10.1016/j.jadohealth.2011.10.009.
citation: Pederson C et al. Co-administration of ASO4- adjuvanted human papillomavirus- 16/18 cervical cancer vaccine with inactivated hepatitis A ans B vaccine in girls aged 9-15 years. Abstract presented at the 6th World Congress of the World Society for Pediatric Infectious Diseases (WSPID). Beunos Aires, Argentina, 19-22 November 2009.