E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cervarix™ is indicated 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. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate, one month after the third dose of hepatitis B vaccine (Month 3), the immune response against hepatitis B with respect to seroprotection rates and GMTs in both study groups. |
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E.2.2 | Secondary objectives of the trial |
To evaluate, one month after the second dose of hepatitis B vaccine (Month 2), the immune response against hepatitis B with respect to seroconversion rates, seroprotection rates and GMTs in both study groups. To evaluate, one month after Dose 2 (Month 2) and Dose 3 (Month 7) of the HPV-16/18 L1 VLP AS04 vaccine, the immune response against HPV-16 and HPV-18 with respect to seroconversion rates and GMTs in the group receiving HPV-16/18 L1 VLP AS04 vaccine. To evaluate, one month after Dose 3 of the hepatitis B vaccine (Month 3), the immune response against hepatitis B with respect to seroconversion rates in both study groups. To evaluate, one month after Dose 4 of the hepatitis B vaccine (Month 13), the immune response against hepatitis B with respect to seroconversion rates, seroprotection rates and GMTs in both study groups. Safety To evaluate the reactogenicity and safety of the study vaccines in both study groups until the last study visit (Month 13).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects who the investigator believes that they can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits) should be enrolled in the study. A female between, and including, 20 and 25 years of age at the time of the first vaccination. Written informed consent obtained from the subject. Healthy subjects as established by medical history and history directed clinical examination before entering into the study. Subjects must not be pregnant. Absence of pregnancy will be verified with a urine pregnancy test. Subjects must be of non-childbearing potential, i.e. have a current tubal ligation, hysterectomy, ovariectomy or be post-menopausal, or if of childbearing potential, subjects must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination series.
Adequate contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly (when applicable, as mentioned in the product label) for example abstinence, combined or progestogen oral contraceptives, injectable progestogen, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches or intrauterine device (IUD) or intrauterine system (IUS), vasectomy with documented azoospermia of the sole male partner or double barrier method (condom or occlusive cap plus spermicidal agent).
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E.4 | Principal exclusion criteria |
Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) 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 >= 0.5 mg/kg/day or equivalent. Inhaled and topical steroids are allowed.) 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) each dose of vaccine. Administration of routine vaccines such as meningococcal, inactivated influenza, inactivated polio, diphtheria/tetanus and/or diphtheria/tetanus-containing vaccines up to 8 days before the first dose of study vaccine is allowed. Concurrently participating in another clinical study, at any time during the study period (up to Month 1213), in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). A subject planning to become pregnant, likely to become pregnant (as determined by the investigator) 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 MPL or AS04 adjuvant. Previous vaccination against hepatitis B or planned administration of any hepatitis B vaccine other than that foreseen by the study protocol during the study period. History of hepatitis B infection. Known exposure to hepatitis 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 (e.g. aluminum, yeast, neomycin, formaldehyde, MPL, phenoxyethanol). Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). 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 diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e., oral/axillary temperature <37.5°C). 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. Enrolment will be postponed until the subject is outside the specified window.
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E.5 End points |
E.5.1 | Primary end point(s) |
Anti-HBs seroprotection status at Month 3 in both groups. Anti-HBs antibody titres at Month 3 in both groups.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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A subject who returns for the concluding visit (Visit 6, Month 7 in the HPV+HepB group and Visit 5, Month 7 in the HepB group) is considered to have completed the active part of the study. A subject who returns for the follow-up conclusion visit (Visit 8, Month 13 in the HPV+HepB group and Visit 7, Month 13 in the HepB group) is considered to have completed the follow-up of the study.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |