E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
vaccin against the human papillomavirus |
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E.1.1.1 | Medical condition in easily understood language |
vaccin against the human papillomavirus |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046859 |
E.1.2 | Term | Vaccination |
E.1.2 | System Organ Class | 100000004865 |
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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 define and compare the usage of VDJ and VJ segments in the immunoglobulin heavy (VH) and light (VL) heavy and light chains, respectively, of plasmablasts induced after the 2nd dose of Cervarix and Gardasil.
• To examine and compare the mutational diversity that occurs following vaccine-induced affinity maturation in plasmablasts induced after the 2nd dose of Cervarix and Gardasil.
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E.2.2 | Secondary objectives of the trial |
• To evaluate the cross-reactive pattern of polyclonal serum antibodies generated after the 2nd of a two-dose schedule of Cervarix or Gardasil, given to pairs of twin sisters aged between 9 and 13 years of age, using ELISA- or PBNA-assays.
• To compare the VDJ and VJ segment usage and affinity maturation in HPV-specific antibodies generated after the 2nd dose of a two-dose schedule of either Cervarix or Gardasil, administered to pairs of twin sisters aged between 9 and 13 years of age.
• To compare the cross-reactive potential of monoclonal antibodies obtained by eukaryotic expression of a series of heavy (VH) and light (VL) chains from single ASC isolated after the 2nd dose of a two-dose schedule of either Cervarix or Gardasil, administered to pairs of twin sisters aged between 9 and 13 years of age.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subjects who the investigator believes can and will comply with the requirements of the protocol and 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 13 years of age at the time of the first vaccination.
• Written informed consent obtained from the subject and from the parent(s) or LAR(s) of the subject prior to enrolment in the study.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• To avoid the chance of previous exposure to HPV (any genotype, and HPV-16 and 18 in particular) participants should not have had sexual intercourse (virgin) or other intimate sexual experience)
• Participants of childbearing potential may be enrolled in the study, if the subject:
has a negative pregnancy test on the day of vaccination
has agreed to continue abstinence during the entire study period and for two months after completion of the vaccination series.
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E.4 | Principal exclusion criteria |
• Pregnant or breastfeeding.
• Previous vaccination against HPV or planned administration of another HPV vaccine during the study other than those foreseen in the protocol.
• 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 6).
• 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/product dose. For corticosteroids, this will mean prednisone ≥ 20mg/day or equivalent. Inhaled and topical steroids are allowed.
• 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/product not foreseen by the study protocol within 30 days before each dose of study 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.
• Previous administration of MPL or AS04 adjuvant.
• 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 a temperature of ≥ 37.5°C (99.5°F) measured orally or axillary
Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator. If deemed necessary by the investigator, enrolment will be deferred until condition is resolved.
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E.5 End points |
E.5.1 | Primary end point(s) |
phone call to verify that subjects had no major adverse events: safety follow-up call |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
365 days after the first vaccin |
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E.5.2 | Secondary end point(s) |
blood samples for antibody determination/B lymphocyte analyses |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
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 | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
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 | No |
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.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | No |
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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phone call 1 year after the first dosing of the last subject |
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |