E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Invasive meningococcal disease (IMD) caused by Neisseria meningitidis
serogroup B |
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E.1.1.1 | Medical condition in easily understood language |
Group B meningococcal disease (e.g. meningitis) |
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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 | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027249 |
E.1.2 | Term | Meningitis meningococcal |
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 describe the immune response as measured by hSBA performed with 4 primary MnB test strains, 2 expressing an LP2086 subfamily A protein and 2 expressing an LP2086 subfamily B protein, measured 1 month after the third vaccination with bivalent rLP2086, in healthy subjects aged ≥24 months to <4 years at study entry.
•To describe the immune response as measured by hSBA performed with 4 primary MnB test strains, 2 expressing an LP2086 subfamily A protein and 2 expressing an LP2086 subfamily B protein, measured 1 month after the third vaccination with bivalent rLP2086, in healthy subjects aged ≥4 years to <10 years at study entry. |
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E.2.2 | Secondary objectives of the trial |
•To describe the immune response as measured by hSBA performed with 4 primary MnB test strains, 2 expressing an LP2086 subfamily A protein and 2 expressing an LP2086 subfamily B protein, measured 1 month after the third vaccination with bivalent rLP2086, in healthy subjects aged ≥24months to <10 years at study entry (ie, in both age strata combined).
•To describe the immune response as measured by hSBA performed with 4 primary MnB test strains, 2 expressing an LP2086 subfamily A protein and 2 expressing an LP2086 subfamily B protein, measured 1 month after the second vaccination and 6 months after the third vaccination with bivalent rLP2086, in healthy subjects aged ≥24 months to <4years at study entry, in healthy subjects aged ≥4 years to <10 years at study entry, and in both age strata combined. |
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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 (ICD) indicating that the subject’s parent(s)/legal guardian has been informed of all pertinent aspects of the study.
2. Parent(s)/legal guardian and subject who are willing and able to comply with scheduled visits, vaccine regimen, laboratory tests, and other study procedures.
3. Male or female subjects aged ≥24 months and <10 years at time of randomization, stratified equally by age (≥24 months to <4 years or ≥4 years to <10 years).
4. Subject is available for the entire study period and subject’s parent(s)/legal guardian can be reached by telephone.
5. Healthy subject as determined by medical history, physical examination, and judgment of the investigator.
6. Subject must have received all vaccinations in the relevant national immunization program (NIP) for their age group.
7. Male and female subjects of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active. Refer to Section 4.5 of the Protocol for further information.
8. Negative urine pregnancy test for all female subjects who are biologically capable of having children. |
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E.4 | Principal exclusion criteria |
Subjects presenting with any of the following will not be included in the study:
1. Previous vaccination with any meningococcal serogroup B vaccine.
2. Subjects who have received prior HAV vaccination.
3. Contraindication to vaccination with any HAV vaccine or known latex allergy.
4. Subjects receiving any allergen immunotherapy with a nonlicensed product or subjects receiving allergen immunotherapy with a licensed product and who are not on stable maintenance doses.
5. A previous anaphylactic reaction to any vaccine or vaccine-related component.
6. Bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate intramuscular injection.
7. 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, those receiving chronic systemic (oral, intravenous, or intramuscular) corticosteroid therapy, or those receiving immunosuppressive therapy. Subjects with terminal complement deficiency may be included. Additional details will be provided in the study reference manual (SRM).
8. History of microbiologically proven disease caused by N meningitidis or Neisseria gonorrhoeae.
9. Significant neurological disorder or history of seizure (excluding simple febrile seizure).
10. Receipt of any blood products, including immunoglobulin, within 6 months before the first study vaccination.
11. Current chronic use of systemic antibiotics.
12. Participation in other studies involving investigational product(s)/device(s) (Phases 1-4) within 28 days before administration of the first study vaccination. Participation in purely observational studies is acceptable.
13. Any neuroinflammatory or autoimmune condition, including but not limited to transverse myelitis, uveitis, optic neuritis, and multiple sclerosis.
14. 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.
15. Pregnant female subjects, breastfeeding female subjects, male subjects with partners who are currently pregnant, or male and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study.
16. Subjects who are children of investigational site staff members directly involved in the conduct of the study and their family members, subjects who are children of site staff members otherwise supervised by the investigator, or subjects who are children of Pfizer employees directly involved in the conduct of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Immunogenicity Endpoints:
•Proportion of subjects aged ≥24 months to <4 years (at study entry) with hSBA titer ≥ LLOQ for each of the 4 primary MnB test strains 1 month after the third vaccination with bivalent rLP2086.
•Proportion of subjects aged ≥4 years to <10 years (at study entry) with hSBA titer ≥ LLOQ for each of the 4 primary MnB test strains 1 month after the third vaccination with bivalent rLP2086.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 month after the third vaccination with bivalent rLP2086. |
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E.5.2 | Secondary end point(s) |
Secondary Immunogenicity Endpoints:
In healthy subjects aged ≥24 months to <10 years at study entry:
•Proportion of subjects with hSBA titer ≥ LLOQ for each of the 4 primary MnB test strains 1 month after the third vaccination with bivalent rLP2086.
In healthy subjects aged ≥24 months to <4 years at study entry, in healthy subjects aged ≥4 years to <10 years at study entry, and in both age strata combined:
• Proportion of subjects with hSBA titer ≥ LLOQ for each of the 4 primary MnB test strains 1 month after the second vaccination and 1 and 6 months after the third vaccination with bivalent rLP2086.
• Proportions of subjects achieving hSBA titers of ≥ 1:4, ≥ 1:8, ≥1:16, ≥1:32, ≥ 1:64, and ≥ 1:128 for each of the 4 primary test strains at baseline, 1 month after the second vaccination, and 1 and 6 months after the third vaccination with bivalent rLP2086.
• hSBA GMTs for each of the 4 primary test strains at baseline, 1 month after the second vaccination, and 1 and 6 months after the third vaccination with bivalent rLP2086. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoints of evaluation for the Secondary Points are included in Section E.5.2 of this form. |
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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 | 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 & Tolerability |
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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 | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 | 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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End of trial in a Member State of the European Union is defined as the time at which it is deemed that sufficient subjects have been recruited and completed the study as stated in the regulatory application (ie, clinical trial application [CTA]) and ethics application in the Member State. Poor recruitment (recruiting less than the anticipated number in the CTA) by a Member State is not a reason for premature termination but is considered a normal conclusion to the study in that Member State. |
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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 | 20 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 20 |