E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prophylaxis Aganist Invasive Meningococcal Disease |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
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 explore the immunogenicity of two and three doses of rMenB ± OMV in healthy adolescents at 30 days after the second and third doses, by evaluation of bactericidal activity (measured by bactericidal complement assay) response against a panel of genetically distinct meningococcal strains.
To explore the immunogenicity of two and three doses of rMenB ± OMV in healthy adolescents at 4 months after the second dose (pre-third dose) and at 6 months after the third dose (a subgroup was also tested 7 days after the third dose) by evaluation of BCA response against a panel of genetically distinct meningococcal strains.
To explore the induction of specific antibody responses by enzyme-linked assay (ELISA) at 30 days after the second and third doses of rMenB ± OMV. In addition, specific antibody responses by ELISA may be explored at other time points.
To explore the safety and tolerability of rMenB ± OMV in healthy adolescents throughout the clinical study relative to a placebo control arm. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. male and female adolescents 11 through 18 years of age at enrollment;
2. able to comprehend and follow all required study procedures (i.e., able to give blood for analysis of safety and immunogenicity);
3. who had given written assent and for whom the parent or legal guardian had provided written informed consent after the nature of the study had been explained;
4. who, with their parent or guardian as required, were available for all the visits scheduled in the study (i.e., not planning to leave the area before the end of the study period);
5. in good health as determined by the outcome of medical history, physical examination, screening laboratory tests and clinical judgment of the investigator. |
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E.4 | Principal exclusion criteria |
1. had a history of any meningococcal B vaccine administration;
2. had a current or previous, confirmed or suspected disease caused by N. meningitidis;
3. had had household contact with and/or intimate exposure to an individual with any laboratory confirmed N. meningitidis infection within 60 days of enrollment;
4. had experienced fever (defined as oral temperature ≥ 38.0°C [100.4°F]) within the previous 3 days or were suffering from a current acute infection;
5. had taken antibiotics within 7 days prior to enrollment (exception: Azithromycin or once daily antibiotics within 14 days prior to enrollment);
6. were pregnant or nursing mothers or females of childbearing age who had not used or did not plan to use acceptable birth control measures, for the 12-month duration of the study. Abstinence, oral, injected or implanted hormonal contraceptive, diaphragm or condom with spermicidal agent or intrauterine device were considered acceptable forms of birth control. If sexually active the subject had to have used one of the accepted birth control methods at least two months prior to study enrollment;
7. had any serious chronic or progressive disease (e.g., any history of neoplasm, diabetes, cardiac disease, hepatic disease, autoimmune disease, HIV infection or AIDS, or blood dyscrasias, signs of cardiac or renal failure or severe malnutrition). (Exception: subjects with mild asthma were eligible for enrollment.) Subjects with moderate or severe asthma requiring chronic use of inhaled or systemic corticosteroids were not eligible for enrollment);
8. had any other serious chronic disease including progressive neurological disease or seizure disorder;
9. had a known or suspected disease of the immune system, or were receiving immunosuppressive therapy, including use of systemic corticosteroids or chronic use of inhaled high-potency corticosteroids within the previous 60 days;
10. had an inherited genetic anomaly (e.g., Down's Syndrome);
11. had received blood, blood products or a parenteral immunoglobulin preparation within the previous 60 days;
12. had a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time;
13. had a history of severe allergic reactions after previous vaccinations, such as anaphylactic shock, asthma, urticaria, or other allergic reaction or hypersensitivity to any vaccine component;
14. had either received, or for whom there was intent to immunize with any other vaccine(s) within 30 days prior, through 30 days following, study injection (Exception: licensed flu-vaccine should not be administered within 14 days prior to enrollment);
15. had any condition which in the opinion of the investigator and/or the medical monitor may interfere with the evaluation of the study objectives;
16. had received another investigational agent within 90 days or before completion of the safety follow-up period in another study, whichever was longer, prior to enrollment and unwilling to refuse participation in another investigational trial through the end of the study;
17. were currently receiving or had received Accutane (Isotretinoin) in the previous 14 days.
18. had a current problem or a history of substance abuse which, in the opinion of the investigator or medical monitor, might interfere with participation in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1.BCA (% ≥1:4) against a panel of genetically distinct meningococcal strains prior to the first and 30 days following the second and third doses.
2.BCA (% ≥1:4), geometric mean response, GMR to baseline and four-fold rise from baseline against a panel of genetically distinct meningococcal strains prior to the first dose and 30days following the second and third doses.
3.BCA (% ≥1:4), geometric mean response, GMR to baseline, four-fold rise from baseline, GMR to pre-third dose, and four-fold rise from pre-third dose) against a panel of genetically distinct meningococcal strains at 4 months after the second immunization, at 6 months after the third immunization and in a subgroup, 7 days
4.To explore the safety and tolerability of rMenB ± OMV in healthy adolescents throughout the clinical study relative to a placebo control arm.
after the third dose. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1.Baseline, 1 month after second Vcacination, 1 Month after third Vaccination.
2. Baseline and 30 days afetr first and second Vaccination.
3. Baseline, 4 months after second vaccination, 6 months after third vaccination, 7 days after 3 vaccination.
4. Day 1 to Day 361. |
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E.5.2 | Secondary end point(s) |
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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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.3 | Single blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 14 |