| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| For active immunization of women from the age of 10 years onwards to prevent persistent HPV-16 and HPV-18 infection and HPV-16 and HPV-18 associated cervical neoplasia. |
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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 |
Long-term follow-up: To evaluate the long-term immunogenicity of the HPV-16/18 L1/AS04 vaccine in all subjects who received the three vaccine doses and completed visit 4 (Month 7) by enzyme-linked immunosorbent assay (ELISA) at each time point (Months 18, 24, 36 and 48).
First primary objective:
To demonstrate lot-to-lot consistency in terms of immunogenicity between three different industrial production lots (80 L scale) of the HPV-16/18 VLP/AS04 vaccine (i.e. Hi5 production process).
Second primary objective:
To demonstrate that the HPV vaccine produced with the Hi5 cell line process (i.e. industrial scale production) is non-inferior in terms of immunogenicity to the HPV vaccine produced with the Hi5/SF9 cell line process. |
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| E.2.2 | Secondary objectives of the trial |
Long-term follow-up: To evaluate the long-term safety and immunogenicty of the candidate vaccine for approximately 48 months after administration of the first vaccine dose.
To evaluate the safety and reactogenicity of all study vaccines after each dose.
To demonstrate that the 10 – 14 years age group is non-inferior to the 15 – 25 years age group in terms of immunogenicity when receiving the same industrial production lot.
To demonstrate that the Hi5-produced HPV vaccine is non-inferior in terms of immunogenicity to the HPV vaccine used in study HPV-001 (i.e. previous Hi5/SF9 manufacturing process). |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Long-term follow-up:
- A female who enrolled in the HPV-012 study in Denmark, Estonia and Finland, received three doses of vaccine and completed Visit 4 (Month 7).
- 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 a parent or legally acceptable representative (LAR) and, in addition, the subject must sign and personally date a written informed assent).
Subjects who the investigator believes that they and/or their parents/legally acceptable representatives can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits).
A female between, and including, 10 and 25 years of age 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 a parent or legally acceptable representative and, in addition, the subject should sign and personally date a written informed assent).
Free of obvious health problems as established by medical history and clinical examination before entering into the study.
Subjects must have a negative urine pregnancy test.
Subject must be of non-childbearing potential, e.g. surgically sterilized, or, if of childbearing potential, she must be abstinent (and if so, this must be documented in the source documents at each vaccination visit) or must be using adequate contraceptive precautions (i.e. intrauterine contraceptive device; oral contraceptives or other equivalent hormonal contraception, e.g. progestogen-only implantable, cutaneous hormonal patch or injectable contraceptives; diaphragm or condom in combination with contraceptive jelly, cream or foam) for 30 days prior to vaccination and must agree to continue such precautions for two months after completion of the vaccination series. Subjects who reach menarche during the study and therefore are of childbearing potential must agree to follow the same precautions.
Has had no more than six lifetime sexual partners prior to enrolment. This criterion may not be applicable in subjects less than 18 years of age, according to local regulatory/ethical requirements. |
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| E.4 | Principal exclusion criteria |
Long-term follow-up:
•Use of any investigational or non-registered product (drug or vaccine) or planned use during the study period.
•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).
•Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs occurring less than three months prior to blood sampling. (For corticosteroids, this will mean prednisone, or equivalent,
greater than or equal to 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
•Administration of immunoglobulins and/or any blood products within the three months preceding blood sampling.
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.
Pregnant or breastfeeding.
A women planning to become pregnant, likely to become pregnant (as determined by the investigator) or planning to discontinue contraceptive precautions during the study period, up to two months after the last vaccine dose (i.e. up to Month 8).
Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose, or planned administration during the study period. (For corticosteroids, this will mean prednisone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed).
Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before and after the first dose of vaccine. Administration of routine vaccines such as 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.
Previous administration of MPL® or AS04 adjuvant (no vaccines currently licensed contain these).
Previous vaccination against HPV.
Any medically diagnosed or suspected immunodeficient condition based on medical history and physical examination (no lab testing required).
History of allergic disease, suspected allergy or reactions likely to be exacerbated by any component of the study vaccine, e.g. aluminium, MPL®.
Hypersensitivity to latex (found in syringe-tip cap and plunger).
Known acute or chronic, clinically significant neurologic, hepatic or renal functional abnormality, as determined by previous physical examination or laboratory tests.
History of chronic condition(s) requiring treatment such as cancer, chronic hepatic or kidney disease(s), diabetes or autoimmune disease.
Administration of immunoglobulins and/or any blood product within three months preceding the first dose of study vaccine or planned administration during the study period. Enrolment will be deferred until the subject is outside of specified window.
Acute disease at the time of enrolment. Acute disease is defined as the presence of a moderate or severe illness with or without fever. Enrolment will be deferred until condition is resolved. All vaccines can be administered to persons with a minor illness such as diarrhoea or mild upper respiratory infection with or without low-grade febrile illness, i.e. oral/axillary temperature <37.5°C (99.5°F). |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Long-term follow-up: Anti-HPV-16 and anti-HPV-18 antibody titers assessed by ELISA in all subjects at each time point (Months 18, 24, 36 and 48).
Anti-HPV-16/18 seroconversion rates and antibody titres for the three consecutive lots of the industrial scale HPV-16/18 VLP/AS04 vaccine (i.e. Hi5-produced vaccine) assessed by enzyme-linked immunosorbent assay (ELISA) at month 7.
Anti-HPV-16/18 seroconversion rates and antibody titres for the Hi5/SF9-produced HPV vaccine assessed by ELISA at month 7. |
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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 | Information not present in EudraCT |
| 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 | Yes |
| E.8.1.4 | Double blind | Yes |
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
| Same composition as PR1 but with AS manufactured with a different process |
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| 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.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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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Long-term follow-up: Month 48
Primary: last telephone contact (at month 12)
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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 | 4 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
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