For the prevention of high-grade cervical intraepithelial neoplasia (CIN grades 2 and 3) and cervical cancer causally related to human papillomavirus (HPV) types 16 and 18. MedDRA version: 17.0 Level: HLT Classification code 10008230 Term: Cervix neoplasms malignant System Organ Class: 100000004864
Conditions
Interventions
Product Name: Prophylactic HPV-16/18 L1 VLP AS04 vaccine
Product Code: HPV-16/18 L1 VLP AS04 vaccine
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: HPV-16 L1 VLP antigen
Other desc
Sponsors
GlaxoSmithKline Biologicals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria for community selection:•A Finnish urban community including between 1000 and 9000 male and female adolescents when pooling birth cohorts from four consecutive years (1992 - 1995);•Geographically distinct communities;•Minimal distance between communities had to be at least of 50 kilometres (35 kilometers in the Helsinki metropolitan area) (to decrease risk acquisition of HPV infection between adolescents residing in different communities);•Communities with appropriate study personnel available to conduct the trial;•Availability of an HPV vaccine registry, to monitor opportunistic vaccination with a licensed HPV vaccine. Inclusion criteria for study participants during the immunisation phase: • Study participants who the investigator believes that they and/or their parents/legally acceptable representative can and will comply with the requirements of the protocol (should be enrolled in the study. •A male or female between, and including, 12 and 15 years of age at the time of the first vaccination. •A written informed consent/assent must be obtained from all study participants prior to enrolment. In addition, for study participants below legal age of consent (15 years) a written informed consent must be obtained from the parent or legally acceptable representative. •A written informed assent must be obtained from all study participants prior to enrolment. In addition, a written informed consent must be obtained from the study participants’ parent or legally acceptable representative. As according to the Finnish law legal age of consent is 15 years, a written informed consent form can be obtained from study participants aged 15 years old and their parent(s)/legally acceptable representative(s) will receive a letter informing them of their child participation to the study. •Healthy male and female study participants as established by medical history before entering into the study. If needed, an history-directed clinical examination will be performed by the investigator or delegate (e.g. study nurse). •Subjects should not be pregnant. Absence of pregnancy should be verified (e.g. urine pregnancy test) as per investigator’s clinical judgement. •If the study participant is female, she must be of non-childbearing potential, i.e. be abstinent, have a current tubal ligation, hysterectomy, ovariectomy or be post-menopausal or pre-menarcheal, or if she is of childbearing potential and has not practiced adequate contraception for 30 days prior to vaccination, she must have a negative pregnancy test and continue adequate contraception for 2 months after completion of the vaccination series. Are the trial subjects under 18? yes Number of subjects for this age range: 36000 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Immunization phase: •Previous vaccination against HPV or Hepatitis B virus. •History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. •Acute disease at the time of enrolment. (Acute disease is defined as the presence of a moderate or severe illness with or without fever. All vaccines can be administered to persons with a minor illness such as diarrhoea, mild upper respiratory infection with or without low-grade febrile illness, i.e. Oral temperature <37.5°C (99.5°F) / Axillary temperature <37.5°C (99.5°F) / Rectal temperature <38°C (100.4°F).) •Pregnant or lactating female.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: CO-PRIMARY OBJECTIVES • To demonstrate the overall (direct and indirect) effectiveness of GSK Biologicals’ HPV-16/18 vaccine in reducing the prevalence of HPV-16/18 genital infection in females approximately 18.5 years of age following community-based vaccination of 12 - 15 year old females only (Arm B versus Arm C). • To demonstrate the overall (direct and indirect) effectiveness of GSK Biologicals’ HPV-16/18 vaccine in reducing the prevalence of HPV-16/18 genital infection in females approximately 18.5 years of age, following community-based vaccination of 12 - 15 year old females and males (Arm A versus Arm C). ;Secondary Objective: • Compare overall effectiveness of GSKs HPV-16/18 vaccine in reducing the prevalence of HPV-16/18 genital infection - In females approx. 18.5 YOA following community-based HPV vaccination of 12-15 yr old females vs. HPV vaccination of 12-15 yr old females and males (Arm A vs. Arm B). - with oncogenic HPV types in females approx. 18.5 YOA, following community-based vaccination of 12-15 yr old females only (Arm B vs. Arm C) and 12-15 yr old females and males (Arm A vs. Arm C) • Evaluate the direct effectiveness of GSKs HPV-16/18 vaccine in reducing the prevalence of HPV-16/18 oropharyngeal infection: - In females following community-based HPV vaccination of 12-15 yr old females/females and males. - and with oncogenic HPV types in females following community-based HPV vaccination of 12-15 yr old females/females and males. • To monitor the safety of HPV-16/18 vaccination in males and females and assess the immunogenicity of the HPV-16/18 vaccine in Arm A immuno subset.;Primary end point(s): • Genital HPV-16 and/or HPV-18 DNA positivity (by PCR) in females approximately 18.5 years of age in Arm B vs C. •Genital HPV-16 and/or HPV-18 DNA positivity (by PCR) in females approximately 18.5 years of age in Arm A vs C. ;Timepoint(s) of evaluation of this end point: At final analysis. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Genital HPV-16 and/or HPV-18 DNA positivity (by PCR) in females approximately 18.5 years of age in Arm A vs B. •Genital oncogenic HPV DNA positivity (by PCR) (overall and individually) in females approximately 18.5 years of age. •Oropharyngeal HPV-16 and/or HPV-18 DNA positivity (by PCR) in females in Arms A, B and C. •Oropharyngeal oncogenic HPV DNA positivity (by PCR) in females in Arms A, B, and C. •Occurrence, intensity and causal relationship to vaccination of solicited (local and general) symptoms within 7 days (Days 0 - 6) after any vaccination (study participants in the Diary Card subset). •Occurrence, intensity and causal relationship to vaccination of unsolicited symptoms within 30 days (Days 0 - 29) after any vaccination (study participants in the Diary Card subset). •Occurrence of rash and urticaria within 30 minutes following vaccination (study participants in the Diary Card subset). •Occurrence of medically significant conditions from dose 1 until Month 12 (study participants in the Diary Card subset). •Occurrence and causal relationship to vaccination of SAEs from dose 1 until Month 12 (male study participants in the Diary Card subset and remaining Arm A male study participants) •Occurrence of SAEs assessed by the investigator as possibly related to vaccination reported during the entire study period up to Visit 5 (all study participants) •Occurrence of new onset of autoimmune diseases between Visit 1 and Visit 5 retrieved from Care Register for Social Welfare and Health (HILMO) (all study participants) •Occurrence of pregnancies with onset between Visit 1 and Visit 5, and their outcomes, retrieved from medical birth registry (all female study participants). •Anti-HPV-16/18 antibody levels and quality assessed at the time of serum withdrawal (Visits 1, 4, and 5) (study participants in the immunogenicity subset). ;Timepoint(s) of evaluation of this end point: At interim analysis of immunogenicity and safety and/ | — |
Countries
Finland
Contacts
Public ContactClinical Disclosure Advisor
GlaxoSmithKline Biologicals
Outcome results
None listed