Evaluation of Safety and Immunogenicity of Co-administering Human Papillomavirus Vaccine With Another Vaccine in Healthy Female Subjects

Infections, Papillomavirus Clinical Trial

Official title:

Immunogenicity and Safety Study of GSK Biologicals' HPV Vaccine (GSK-580299) Co-administered With a Commercially Available Vaccine in Healthy Female Adolescents

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00578227
• Other study ID #: 110886
• Status: Completed
• Phase: Phase 3
• Start date: December 15, 2007
• Est. completion date: April 28, 2009

Study information

• Verified date: October 2016
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 814
• Est. completion date: April 28, 2009
• Est. primary completion date: December 1, 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 9 Years to 15 Years

Eligibility

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.

Related Conditions & MeSH terms

• Infections, Papillomavirus

Intervention

Biological:
• Cervarix™
Three doses of vaccine administered intramuscularly with the second and third dose given one month and six months after the first dose
• Twinrix ™ Paediatric
Three doses of vaccine administered intramuscularly with the second and third dose given one month and six months after the first dose

Locations

Country	Name	City	State
Canada	GSK Investigational Site	Brampton	Ontario
Canada	GSK Investigational Site	Newmarket	Ontario
Canada	GSK Investigational Site	Sarnia	Ontario
Canada	GSK Investigational Site	Sudbury	Ontario
Canada	GSK Investigational Site	Surrey	British Columbia
Denmark	GSK Investigational Site	Hoersholm
Denmark	GSK Investigational Site	Odense C
Hungary	GSK Investigational Site	Bordány
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Gyor
Hungary	GSK Investigational Site	Hódmezovásárhely
Hungary	GSK Investigational Site	Szeged
Hungary	GSK Investigational Site	Szombathely
Sweden	GSK Investigational Site	Karlskrona
Sweden	GSK Investigational Site	Linköping
Sweden	GSK Investigational Site	Lycksele
Sweden	GSK Investigational Site	Örebro
Sweden	GSK Investigational Site	Umeå

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Canada,  Denmark,  Hungary,  Sweden, 

References & Publications (2)

Pedersen C, Breindahl M, Aggarwal N, Berglund J, Oroszlán G, Silfverdal SA, Szüts 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. — View 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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects Seroconverted for Anti-hepatitis A (Anti-HAV) Antibodies	Seroconversion is defined as the appearance of anti-HAV antibodies [i.e., antibody titer greater than or equal to 15 milli-international units/milliliter (mIU/mL)] in the sera of subjects seronegative (antibody titer below 15 mIU/mL) before vaccination.	At Month 7
Primary	Anti-Heptatis A (HAV) Antibody Titers.	Titers are given as Geometric Mean Titers (GMTs) expressed as mIU/mL.	At Month 7
Primary	Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies	A subject seroprotected against HBs is a subject with antibody titers greater than or equal to 10 mIU/mL.	At Month 7
Primary	Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies	Seroconversion is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off values = 8 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies.	At Month 7
Primary	Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers	Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL).	At Month 7
Secondary	Anti-HBs Antibody Titers	Titers are given as Geometric Mean Titers (GMTs)expressed as mIU/mL.	At Month 7
Secondary	Number of Subjects Seroconverted for Anti-HBs Antibodies	Seroconversion is defined as the appearance of anti-HBs antibodies (i.e., antibody titer greater than or equal to 3.3 mIU/mL) in the sera of subjects seronegative (with antibody titers below 3.3 mIU/mL) before vaccination.	At month 7
Secondary	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	Seroconversion is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off values = 8 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies.	At Month 7
Secondary	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	Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL).	At Month 7
Secondary	Number of Subjects Seroconverted for Anti-HAV Antibodies	Seroconversion is defined as the appearance of anti-HAV antibodies (i.e., antibody titer greater than or equal to 15 mIU/mL) in the sera of subjects seronegative (antibody titer below 15 mIU/mL) before vaccination.	One month after the second dose of vaccine
Secondary	Anti-HAV Antibody Titers	Titers are given as geometric mean titers (GMTs) expressed as mIU/mL.	One month after the second dose of vaccine
Secondary	Number of Subjects Seroconverted and Number of Subjects Seroprotected for Anti-HBs Antibodies	Seroconversion is defined as the appearance of anti-HBs antibodies (i.e., antibody titer greater than or equal to 3.3 mIU/mL) in the sera of subjects seronegative (with antibody titers below 3.3 mIU/mL) before vaccination.; A seroprotected subject against HBs is a subject with antibody titers greater than or equal to 10 mIU/mL.	One month after the second dose of vaccine
Secondary	Anti-HBs Antibody Titers	Titers are given as geometric mean titers (GMTs) expressed as mIU/mL.	One month after the second dose of vaccine
Secondary	Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies	Seroconversion is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off values assessed include 8 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies.	One month after the second dose of vaccine
Secondary	Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers	Titers are given as Geometric Mean Titers (GMTs) expressed as EL.U/mL.	One month after the second dose of vaccine
Secondary	Number of Subjects Reporting Solicited Local Symptoms	Solicited local symptoms assessed include injection site pain, redness and swelling. Data are presented across doses.	During the 7-day period (Day 0-6) following vaccination
Secondary	Number of Subjects Reporting Solicited General Symptoms	Solicited general symptoms assessed include arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, rash, temperature [axillary route, greater than or equal to 37.5 degree Celsius (°C)] and urticaria.	During the 7-day period following vaccination
Secondary	Number of Subjects Reporting Medically Significant Conditions	Medically significant conditions include adverse events (AEs) prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.	Throughout the active phase of the study (up to Month 7)
Secondary	Number of Subjects Reporting Medically Significant Conditions	Medically significant conditions include adverse events (AEs) prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.	Throughout the safety follow-up (from Month 7 up to Month 12)
Secondary	Number of Subjects Reporting Unsolicited Adverse Events	Unsolicited adverse events include any adverse event 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.	During the 30-day period following any vaccination
Secondary	Number of Subjects Reporting Serious Adverse Events (SAE)	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.	Throughout the study (up to Month 12)

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