For active immunization of females for the prevention of cervical cancer by protecting against persistent infections, cytological abnormalities including atypical squamous cells of undetermined significance (ASC-US), cervical intraepithelial neoplasia (CIN) and pre-cancerous lesions (CIN 2/3) caused by oncogenic human papillomavirus (HPV) types 16 and 18. MedDRA version: 14.1 Level: LLT Classification code 10063001 Term: Human papilloma virus infection System Organ Class: 100000004862
Conditions
Interventions
Product Name: Prophylactic HPV-16/18 L1 VLP (40µg/40µg) AS04 vaccine
Product Code: HPV-16/18 L1 VLP (40µg/40µg) AS04 vaccine
Pharmaceutical Form: Suspension for injection
Other descriptive name: HPV-
Sponsors
GlaxoSmithKline Biologicals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Subjects who the investigator believes that they and/or their parents can and will comply with the requirements of the protocol should be enrolled in the study. •A female subject between, and including, 9 and 25 years of age at the time of the first vaccination. •Written informed consent/assent obtained from the subject prior to enrolment. For subjects above the legal age of consent, written informed consent must be obtained from the subject. For subjects below the legal age of consent, written informed consent from the subject’s parents/legally acceptable representative, and written informed assent must be obtained from the subject. •Healthy subjects as established by medical history and history-oriented clinical examination before entering into the study. •Subjects must be of non-childbearing potential, i.e. have a current tubal ligation, hysterectomy, ovariectomy or be pre-menarcheal; or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for two months after completion of the vaccination series. Are the trial subjects under 18? yes Number of subjects for this age range: 480 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 480 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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. •Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. (For corticosteroids, this will mean prednisone, or equivalent,>0.5 mg/kg/day. Inhaled and topical steroids are allowed.) •Concurrently participating in another clinical study, at any time during the study period (up to Month 24), in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). •Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before and 30 days after (i.e. Days 0 - 29) the first dose of vaccine. Planned administration/administration of routine meningococcal, hepatitis A or B, inactivated influenza, diphtheria/tetanus and/or diphtheria/tetanus-containing vaccines, up to 8 days before the first dose of study vaccine is allowed. Enrolment will be deferred until the subject is outside of specified window. •Pregnant or breastfeeding female. •A woman planning to become pregnant or planning to discontinue contraceptive precautions during the study period, up to two months after the last vaccine dose. •Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period (up to Month 24). •Previous administration of MPL or AS04 adjuvant. •Cancer or autoimmune disease under treatment. •Any medically diagnosed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). •History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. MPL, AS04. •Hypersensitivity to latex (found in syringe-tip cap and plunger). •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°/Axillary temperature < 37.5°C). •Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory tests. •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 (up to Month 24).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the immunogenicity of the HPV-16/18 L1 VLP AS04 vaccine one month after the last dose when administered at different dosages (20 or 40 µg of each HPV antigen) and on different schedules (0, 2- or 0, 6-months) compared with the standard HPV-16/18 L1 VLP AS04 vaccine administered on a 3-dose schedule (0, 1, 6-months). To evaluate the reactogenicity of the HPV-16/18 L1 VLP AS04 vaccine when administered at different dosages (20 or 40 µg of each HPV type) and on different schedules (0, 2- or 0, 6-months) with respect to the occurrence, intensity and relationship to vaccination of solicited local and general symptoms reported within 7 days (Days 0 - 6) after each and any vaccination. ;Secondary Objective: To evaluate the safety of the HPV-16/18 L1 VLP AS04 vaccine when administered at different dosages and on different schedules up to Month 60.To demonstrate the non-inferiority of the antibody response to the 2-dose schedule of the HPV-16/18 L1 VLP AS04 vaccine in the 9-14, then in the 15-19 and then in the 20-25 year age strata (these 3 objectives will be assessed sequentially) when administered at different dosages and on different schedules as compared to the standard 3-dose schedule in subjects 15-25 years of age, one month after the last dose of vaccine.If any of the above secondary objectives for immunogenicity are demonstrated:To examine pair-wise comparisons of the antibody response between each 2-dose schedule group and the standard 3-dose schedule, one month after the last dose of vaccine within each age stratum.To evaluate the antibody response to all dose schedules and dosages of the HPV-16/18 L1 VLP AS04 vaccine in each age stratum during the extended follow-up period. ;Primary end point(s): •HPV-16 and HPV-18 antibody titres (by ELISA) assessed one month after the last dose of vaccine when administered at different dosages (20 or 40 µg of each HPV type) and on different schedules (0, 2- or 0, 6 or 0, 1, 6-months). Safety •Occurre | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Occurrence, intensity and causal relationship to vaccination of unsolicited symptoms within 30 days (Days 0 - 29) after any vaccination. •Occurrence of serious adverse events (SAEs) up to Month 7 and during the extended safety follow-up period (up to Month 60). •Occurrence of medically significant conditions (MSCs) up to Month 7 and during the extended safety follow-up period (up to Month 60), regardless of causal relationship to vaccination and intensity. •Occurrence of New Onset Chronic Diseases (NOCD)/New Onset Autoimmune Diseases (NOAD) (e.g. autoimmune disorders, asthma, type I diabetes, allergies, etc…), regardless of causal relationship to vaccination and intensity. •Occurrence of pregnancies and pregnancy outcomes. •Changes in haematological and biochemical parameters from blood samples taken from all subjects at Month 0 and Month 7. •HPV-16 and HPV-18 antibody titres (by ELISA) assessed one month after the last dose of vaccine (Month 7) in all study groups and in all age strata. •HPV-16 and HPV-18 antibody titre (by ELISA) assessed one month after the second dose of vaccine in the 2-dose schedule groups (Month 3). •HPV-16 and HPV-18 antibody titres (by ELISA) and seroconversion status assessed during the extended follow-up period ( up to Month 60).;Timepoint(s) of evaluation of this end point: Unsolicited symptoms: 30-day period following each vaccination. SAEs, MSCs, NOCD/NOAD and pregnancy: Throughout the study period. Haematological and biochemical parameters: At Day 0 and Month 7. ELISA: At Day 0 and Months 3, 7, 12, 18, 24, 36, 48 and 60 (in the 2-dose schedule groups), or at Day 0 and Months 7, 12, 18, 24, 36, 48 and 60 (in the 3-dose schedule group). | — |
Countries
Canada, Germany
Contacts
Public ContactClinical Disclosure Advisor
GlaxoSmithKline Biologicals
Outcome results
None listed