E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10004049 |
E.1.2 | Term | Bacterial meningitis |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
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 the safety profile of rLP2086 vaccine, as measured by adverse events (AEs), during the 6-month vaccination period and 6-month postdose 3 follow-up. |
|
E.2.2 | Secondary objectives of the trial |
To describe the immune response induced by the rLP2086 vaccine as measured by serum bactericidal assays using human complement (hSBAs) performed with MnB strains expressing LP2086 subfamily A and B proteins, measured 1 month after study vaccinations 2 and 3 in a subset of 255 randomly assigned subjects (170 recipients of 120 μg rLP2086 vaccine and 85 control subjects). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Evidence of a personally signed and dated informed consent document indicating that
the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Male or female subjects aged ≥11 and <26 years at time of enrollment.
4. Available for the entire study period and can be reached by telephone.
5. Healthy subject as determined by medical history, physical examination, and judgment of the investigator.
6. Parent/legal guardian and/or subject must be able and willing to complete all relevant study procedures during study participation.
7. All male and female subjects must agree to practice a form of effective contraception,
such as barrier contraception (ie, condom plus spermicide, a female condom, diaphragm, cervical cap or intrauterine device), implants, injectables, combined oral contraceptives or sexual abstinence prior to entering into the study, for the duration of the vaccination period and for 28 days after the last study vaccination. For Denmark: The phrase “sexual abstinence” is not applicable, with the understanding that all male and female subjects of childbearing potential must practice an effective form of contraception during the study.
8. Negative urine pregnancy test for female subjects. |
|
E.4 | Principal exclusion criteria |
Subjects presenting with any of the following will not be included in the study:
1. Subjects who are investigational site staff members or subjects who are Pfizer employees directly involved in the conduct of the trial.
2. Subject is a direct descendant (e.g. child, grandchild or other family member) of study
site personnel.
3. Previous vaccination with any meningococcal serogroup B vaccine.
4. Subjects who have received prior HAV vaccination.
5. Contraindication to vaccination with any HAV vaccine.
6. A previous anaphylactic reaction to any vaccine or vaccine-related component.
7. Bleeding diathesis or condition associated with prolonged bleeding time that would
contraindicate intramuscular injection.
8. A known or suspected defect of the immune system that would prevent an immune response to the vaccine, such as subjects with congenital or acquired defects in B cell function or those receiving immunosuppressive therapy. Subjects with terminal complement deficiency may be included. Please refer to the SRM additional details.
9. History of culture-proven disease caused by Neisseria meningitidis or Neisseria gonorrhoea.
10. Significant neurological disorder or history of seizure (excluding simple febrile seizure).
11. Receipt of any blood products, including immunoglobulin within 6 months before the
first study vaccination.
12. Current participation in another investigational study. Participation in purely
observational studies is acceptable.
13. Received any investigational drugs or devices within 28 days before administration of
the first study vaccination.
14. Any neuroinflammatory and autoimmune condition, including but not limited to transverse myelitis, uveitis, optic neuritis, and multiple sclerosis.
15. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
16. Subject is pregnant or breastfeeding. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints will be the safety related variables, as measured by adverse events (AEs), and serious adverse events (SAEs). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
14 months after last subject last visit. |
|
E.5.2 | Secondary end point(s) |
The secondary endpoints will only be applied to the subset of 255 randomly assigned subjects aged 11 to 18 years (170 recipients of 120 μg rLP2086 vaccine and 85 control subjects) who have hSBA tests.
hSBA titers, as measured by GMTs, for each of the 2 primary strains at each blood draw visit (visits 1, 4 and 6).
The proportion of subjects with an rLP2086-specific hSBA titer ≥1:4 for each of the 2 primary strains, measured prior to the first vaccination with rLP2086, 1 month after the second vaccination with rLP2086 vaccine and 1 month after the third vaccination with rLP2086 vaccine.
The proportion of subjects with an rLP2086-specific hSBA titer ≥1:4, ≥1:8, ≥1:16, ≥1:32, ≥1:64, and ≥1:128 for each of the 2 primary strains at each blood sampling time point.
The proportion of subjects achieving ≥ 4 fold-rise on rLP2086-specific hSBA titer for each of the 2 primary strains, from prior to the first vaccination (visit 1) to 1 month after the second vaccination with rLP2086 vaccine and from prior to the first vaccination (visit 1) to 1 month after the third vaccination with rLP2086 vaccine. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
14 months after last subject last visit. |
|
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 |
Tolerability & Immunogenicity |
|
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 | No |
E.8.1.3 | Single blind | Yes |
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) | Yes |
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
| 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 88 |
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 | No |
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 |
Argentina |
Australia |
Belgium |
Brazil |
Canada |
Chile |
Czech Republic |
Denmark |
Estonia |
Finland |
Germany |
Italy |
Lithuania |
Netherlands |
Poland |
Russian Federation |
Spain |
Sweden |
Turkey |
United States |
|
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
|
|
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 | 2 |
E.8.9.1 | In the Member State concerned days | 21 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 20 |
E.8.9.2 | In all countries concerned by the trial days | 0 |