E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Inflammation of the liver due to viral infection |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10021881 |
E.1.2 | Term | Infections and infestations |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 assess the anti-HBs antibody response, in terms of subjects with antibody concentrations >= 100 mIU/ml, to a single challenge dose of HBV vaccine (Engerix-B Kinder) in subjects 12–13 years of age, previously vaccinated with four doses of Infanrix hexa in the first two years of life. |
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E.2.2 | Secondary objectives of the trial |
•To assess the persistence of anti-HBs antibodies, in terms of seroprotection status and antibody concentrations, in subjects 12–13 years of age, previously vaccinated with four doses of Infanrix hexa in the first two years of life.
•To assess the immunological response to the hepatitis B antigen, in terms of seroprotection status and antibody concentrations, one month after the single challenge dose of the HBV vaccine in subjects 12–13 years of age, previously vaccinated with four doses of Infanrix hexa in the first two years of life.
•To evaluate the safety and reactogenicity of a single challenge dose of HBV vaccine (Engerix-B Kinder) in terms of solicited symptoms (local and general), unsolicited symptoms and serious adverse events (SAEs). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Subjects’ parent(s)/LAR(s) who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visit).
•A male or female between the ages of 12 to 13 (from and including the 12th birthday, up to but excluding the 14th birthday) at the time of enrolment.
•Subjects with documented evidence of previous vaccination with four consecutive doses of Infanrix hexa as part of routine vaccination in Germany: three doses of primary vaccination received by 9 months of age and one booster dose received between 11 and 18 months of age.
•Written informed consent obtained from the parents/LAR(s) of the subject.
-In addition to the informed consent that will be signed by the parents/LAR(s), written informed assent of the subject will be sought.
•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.
-Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.
•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 2 months after completion of the vaccination series. |
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E.4 | Principal exclusion criteria |
•Child in care
•Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the dose of study vaccine, or planned use during the study period.
•Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
•Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within six months prior to the vaccination. Inhaled and topical steroids are allowed.
•Administration of any chronic drug therapy to be continued during the study period.
•Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting from 30 days before and ending 30 days after the HBV challenge dose, with the exception of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (dTpa) vaccine, which can be given as part of routine vaccination practice.
•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 vaccine/product (pharmaceutical product or device).
•Evidence of previous hepatitis B booster vaccination since administration of the fourth dose of Infanrix hexa booster in the second year of life.
•History of or intercurrent hepatitis B disease.
•Hepatitis B vaccination at birth.
•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.
•History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
•Major congenital defects or serious chronic illness including thrombocytopenia and bleeding disorders.
•History of any neurological disorders or seizures.
•Acute disease and/or fever at the time of enrolment.
-Fever is defined as temperature >=37.5°C for oral, axillary or tympanic route, or >= 38.0°C on rectal route. The preferred route for recording temperature in this study will be 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.
•Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests
•Administration of immunoglobulins and/or any blood products within the 3 months preceding the dose of study vaccine or planned administration during the study period.
•Pregnant or lactating female.
•Female planning to become pregnant or planning to discontinue contraceptive precautions. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
One month after the single challenge dose of HBV vaccine (Month 1) |
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E.5.2 | Secondary end point(s) |
Anti-HBs antibody persistence at 12-13 years of age, after previous vaccination with Infanrix hexa
Anti-HBs immune response.
Solicited local and general symptoms
Unsolicited Adverse Events (AEs)
Serious Adverse Events (SAEs) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Anti-HBs antibody persistence at 12-13 years of age, after previous vaccination with Infanrix hexa: Before the challenge dose of HBV vaccine (Day 0)
Anti-HBs immune response: One month after the challenge dose of HBV vaccine (Month 1)
Solicited local and general symptoms: During the 4-day (Day 0–3) follow-up period after the single challenge dose of HBV vaccine
Unsolicited Adverse Events (AEs): During the 31-day (Day 0–30) follow-up period after the single challenge dose of HBV vaccine
Serious Adverse Events (SAEs): After challenge dose, up to study end (Month 1) |
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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 | Yes |
E.6.5 | Efficacy | Yes |
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 |
Immunogenicity and persistence |
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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 | No |
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.8.3 |
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 | 11 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |