Cervarix is indicated in females from 9 years of age onwards for the prevention of persistent infection, premalignant genital (cervical, vulvar and vaginal) lesions and cervical, vulvar and vaginal cancers (squamous-cell carcinoma and adenocarcinoma) caused by oncogenic Human Papillomaviruses (HPV). MedDRA version: 17.0 Level: LLT Classification code 10033723 Term: Papilloma viral infection NOS System Organ Class: 100000004862 MedDRA version: 17.0 Level: LLT Classification code 10008229 Term:
Conditions
Sponsors
GlaxoSmithKline Biologicals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Subjects who the investigator believes can and will comply with the requirements of the protocol and subjects who the investigator believes their parent(s)/Legally Acceptable Representative(s) (LAR[s]) can and will comply with the requirements of the protocol. - A female between, and including, 9 and 14 years of age at the time of the first vaccination. - Written informed consent obtained from the parent(s)/LAR(s) of the subject prior to enrolment in the study. In addition, if capable, the subject should sign and personally date a written informed assent. - Healthy subjects as established by medical history and clinical examination before entering into the study. - Female subjects of non-childbearing potential may be enrolled in the study. - Female subjects of childbearing potential may be enrolled in the study, if the subject: ? • has practiced adequate contraception for 30 days prior to vaccination, and ? • has a negative pregnancy test on the day of vaccination, and ? • has agreed to continue adequate contraception during the entire treatment period and for two months after completion of the vaccination series. Are the trial subjects under 18? yes Number of subjects for this age range: 1074 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: - Pregnant or breastfeeding. - A woman planning to become pregnant, likely to become pregnant (as determined by the investigator) or planning to discontinue contraceptive precautions during the vaccination phase of the study, i.e. up to two months after the last vaccine dose. - Previous vaccination against HPV or planned administration of another HPV vaccine during the study other than those foreseen in the protocol. - Child in care. - 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 36). - Chronic administration (defined as more than 14 consecutive days in total) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. - History of allergic disease, suspected allergy or reactions likely to be exacerbated by any component of the study vaccines. - Cancer or autoimmune disease under treatment. - Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before each dose of vaccine. Administration of routine meningococcal, hepatitis B, hepatitis A, inactivated influenza, diphtheria/tetanus and/or diphtheria/tetanus-containing vaccine up to 8 days before each dose of study vaccine is allowed. Enrolment will be deferred until the subject is outside of specified window. - Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). - Previous administration of vaccine components. - 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. - Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). - Family history of congenital or hereditary immunodeficiency. - Major congenital defects or serious chronic illness. - Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests, which in the opinion of the investigator precludes administration of the study vaccine. - Acute disease and/or fever at the time of enrolment. • Fever is defined as temperature = 37.5°C on oral, axillary or tympanic setting, or = 38.0°C on rectal setting. ? • Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator. Enrolment can be deferred until condition is resolved. - Drug and/or alcohol abuse.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To evaluate sequentially if the immunogenicity (as determined by ELISA) of GSK Biologicals’ HPV-16/18 L1 VLP AS04 vaccine administered according to a 2-dose schedule at 0, 6 months is non-inferior/superior to that of Merck's HPV-6/11/16/18 L1 VLP recombinant vaccine administered according to a 2-dose schedule at 0, 6 months in 9-14 years old females, one month after the last dose (Month 7).;Secondary Objective: - To evaluate sequentially non-inferiority/superiority of GSK Biologicals' HPV vaccine administered on a 2-dose schedule at 0, 6 months compared to Merck's HPV vaccine administered on a 2-dose schedule at 0, 6 months at Months 12, 18, 24 and 36. - To evaluate sequentially non-inferiority/superiority of GSK Biologicals’ HPV vaccine administered on a 2-dose schedule at 0, 6 months compared to Merck’s HPV vaccine administered on the standard 3-dose schedule at 0, 2, 6 months at Months 7, 12, 18, 24 and 36. - To assess the immune responses to HPV-16/18 by ELISA at Day 0 and Months 7, 12, 18, 24 and 36. - To assess the immune responses to HPV-16/18 by PBNA at Day 0 and Months 7, 12, 18, 24 and 36. - To assess T- and B-cell-mediated immune responses specific to HPV-16/18 at Day 0, Months 7, 12, 24 and 36. - To assess the reactogenicity and safety of the administered vaccines in all groups. - To evaluate compliance with completion of vaccination in all groups.;Primary end point(s): Immunogenicity with respect to components of the investigational vaccine: - Anti-HPV-16/18 serconversion rates and antibody titres assessed by ELISA.;Timepoint(s) of evaluation of this end point: One month after the last dose of study vaccine (Month 7). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Humoral immunogenicity with respect to components of the investigational vaccine: - Anti-HPV-16/18 serconversion rates and antibody titres assessed by ELISA. - Anti-HPV-16/18 serconversion rates and antibody titres assessed by PBNA in a subset of subjects. Cellular immunogenicity with respect to components of the investigational vaccine: - T-cell and B-cell-mediated immune responses (frequency of cytokine(s)-positive CD4 or CD8 T lymphocytes and frequency of HPV-specific memory B-cells) in the sub-cohort for CMI. - The occurrence and intensity of solicited local symptoms during the 7-day period (Days 0-6) following each vaccination in all groups. - The occurrence, intensity and causal relationship to vaccination of solicited general symptoms during the 7-day period (Days 0-6) following each vaccination in all groups. - The occurrence, intensity and causal relationship to vaccination of unsolicited symptoms during the 30-day period (Days 0-29) following each vaccination in all groups. - The occurrence of pIMDs from first vaccination to six months after the last vaccine dose (from Day 0 up to Month 12) in all groups. - The occurrence of MSCs throughout the study period (from Day 0 up to Month 36) in all groups. - The occurrence of SAEs throughout the study period (from Day 0 up to Month 36) in all groups. - The occurrence of SAEs related to the investigational product, to study participation, to GSK concomitant products or any fatal SAE throughout the study period (from Day 0 up to Month 36) in all groups. - The occurrence of pregnancies and pregnancy outcomes throughout the study period (from Day 0 up to Month 36) in all groups. - Use of concomitant medication (e.g. prophylactic use of antibiotics or antipyretics) throughout the study period (from Day 0 up to Month 36) in all groups.;Timepoint(s) of evaluation of this end point: Humoral immunogenicity: Day 0, Months 7, 12, 18, 24 and 36 after the first vaccine dose. Cell | — |
Countries
Brazil, Hong Kong, Singapore, Sweden
Contacts
Public ContactClinical Disclosure Advisor
GlaxoSmithKline Biologicals
Outcome results
None listed