| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Active immunization to prevent invasive disease caused by Neisseria meningitidis serogroups A, B, C, W and Y in individuals 10 through 25 years of age. |
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| 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 | 20.0 |
| 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 |
|
| 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 |
Primary Immunogenicity objective:
To assess the immune response induced by bivalent rLP2086 as measured by serum bactericidal assay using human complement (hSBA) performed with 4 primary MnB test strains, 2 expressing a lipoproten 2086 (LP2086) subfamily A protein and 2 expressing an LP2086 subfamily B protein, measured 1 month after the second vaccination, in the bivalent rLP2086 arms (Group 2 and 4 subjects) combined.
Primary Safety Objectives:
- To describe the safety profile of bivalent rLP2086, as measured by local reactions, systemic events, adverse events (AEs), serious adverse events (SAEs), newly diagnosed chronic medical conditions, medically attended AEs, and immediate AEs, following Vaccinations 1 and 2 in the bivalent rLP2086 arms (Group 2 and 4 subjects) combined.
- To describe the safety profile of MenABCWY after the booster
vaccination.
- To describe the safety profile of bivalent rLP2086 after the booster
vaccination. |
|
| E.2.2 | Secondary objectives of the trial |
Secondary immunogenicity objectives:
- To describe the immune response induced by bivalent rLP2086 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, in the bivalent rLP2086 arms (Group 2 and 4 subjects) combined.
- To describe the MenB immune response as measured by hSBA performed with secondary MenB test strains measured 1 month after the second vaccination in
Groups 2 and 4 combined.
- To describe the immune response induced by 1 dose of MenABCWY compared to the immune response induced by 1 dose of MenACWY-CRM, as measured by hSBA performed with ACWY test strains, in ACWY-naive and ACWY-experienced subjects separately.
Additional secondary immunogenicity objectives and all secondary safety objectives are listed in the study Protocol. |
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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 (or parent(s)/legal guardian) has been informed of all pertinent aspects of the study.
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Male and femle subject aged ≥10 and <26 years, at the time of randomization.
4. Subjects who have never received a prior dose, or who have received not more than 1 prior dose no sooner than 4 years prior to the date of randomization, of a vaccine containing 1 or more ACWY groups. Written confirmation of ACWY vaccination history should be obtained prior to randomization; however, if written ACWY vaccination history is not available, history obtained verbally from the subject (or parent(s)/legal guardian) is acceptable, if deemed reliable by the investigator.
5. Available for the entire study period and can be reached by telephone.
6. Healthy subject as determined by medical history, physical examination, and judgment of the investigator.
7. Male and female subjects of childbearing potential must agree to use a highly effective method of contraception throughout Stage 1 (through the follow-up telephone contact at Month 12), and from Visit 10 (booster vaccination) to Visit 11. 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.
8. Negative urine pregnancy test for all female subjects.
|
|
| E.4 | Principal exclusion criteria |
Subjects with any of the following characteristics/conditions will not be included in the study:
1. Previous vaccination with any meningococcal group B vaccine or any purely polysaccharide (nonconjugate) meningococcal vaccine. Written vaccination history should be obtained prior to randomization; however, if written vaccination history is not available, history obtained verbally from the subject (or parent(s)/legal guardian) is acceptable, if deemed reliable by the investigator.
2. Previous vaccination with >1 dose of a vaccine containing 1 or more ACWY group.
3. Subjects having received 1 prior dose of a vaccine containing 1 or more ACWY group <4 years prior to the date of randomization.
4. A previous anaphylactic reaction to any vaccine or vaccine-related component.
5. Subjects receiving any allergen immunotherapy with a nonlicensed product or receiving allergen immunotherapy with a licensed product and are not on stable maintenance doses.
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 in the United States with terminal complement deficiency are
excluded from participation in this study. Please refer to the study reference manual (SRM) for additional details.
8. History of microbiologically proven disease caused by Neisseria 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 drug(s) within 28 days prior to study entry and/or during study participation.
13. Any neuroinflammatory or autoimmune condition, including, but not limited to, transverse myelitis, uveitis, optic neuritis, and multiple sclerosis.
14. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior 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. Investigator site staff members directly involved in the conduct of the study and their embers, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study.
16. Pregnant female subjects; breastfeeding female subjects; fertile male subjects and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in the Protocol Section 4.5. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary immunogenicity endpoints:
Five (5) coprimary endpoints are defined for the primary objective; they are defined for hSBA performed with each of the 4 primary test strains: PMB80 (A22), PMB2001 (A56), PMB2948 (B24), and PMB2707 (B44).
•One (1) of the 5 coprimary endpoints is the composite endpoint defined as the proportion of subjects achieving an hSBA titer ≥lower limit of quantitation (LLOQ: 1:16 for A22 and 1:8 for A56, B24, and B44)) for all 4 primary test strains combined, 1 month after the second vaccination in the bivalent rLP2086 arms (Group 2 and 4 subjects) combined.
•Four (4) of the coprimary endpoints are defined as the proportion of subjects achieving at least a 4-fold increase in hSBA titer from baseline to 1 month after the second vaccination in the bivalent rLP2086 arms (Group 2 and 4 subjects) combined for each of the 4 primary test strains.
•For subjects with a baseline hSBA titer below the limit of detection (LOD, or an hSBA titer of <1:4), a 4-fold response is defined as an hSBA titer of ≥1:16 or the LLOQ (whichever titer is higher).
•For subjects with a baseline hSBA titer of ≥LOD (ie, hSBA titer of ≥1:4) and < LLOQ, a 4-fold response is defined as an hSBA titer of ≥4
times the LLOQ.
•For subjects with a baseline hSBA titer of ≥LLOQ, a 4-fold response is defined as an hSBA titer of ≥4 times the baseline titer.
Primary Safety endpoints:
The following endpoints will be described after Vaccinations 1 and 2 in the bivalent rLP2086 arms (Group 2 and 4 subjects) combined.
•Percentage of subjects reporting local reactions (pain, redness, and swelling) and by severity within 7 days after each vaccination visit.
•Percentage of subjects reporting systemic events (fever, vomiting, diarrhea, headache, fatigue, chills, muscle pain other than muscle pain at any injection site, and joint pain) and by severity within 7 days after each vaccination visit.
•Percentage of subjects reporting the use of antipyretic medication within 7 days after each vaccination visit.
•Percentage of subjects with at least 1 SAE during the following time periods:
•30 Days after each vaccination.
•30 Days after any vaccination.
•During the Stage 1 vaccination phase (from the first study vaccination [Visit 1] through 1 month after the second study vaccination [Visit 4]).
•During the Stage 1 follow-up phase (from 1 month after the second study vaccination [Visit 4] through 6 months after the second study vaccination [Visit 5]).
•Throughout Stage 1 (from the first study vaccination [Visit 1] through 6 months after the second study vaccination [Visit 5]).
•Percentage of subjects with at least 1 medically attended AE occurring during the following time periods:
•30 Days after each vaccination.
•30 Days after any vaccination.
•During the Stage 1 vaccination phase (from the first study vaccination [Visit 1] through 1 month after the second study vaccination [Visit 4]).
•During the Stage 1 follow-up phase (from 1 month after the second study vaccination [Visit 4] through 6 months after the second study vaccination [Visit 5]).
•Throughout Stage 1 (from the first study vaccination [Visit 1] through 6 months after the second study vaccination [Visit 5]).
•Percentage of subjects with at least 1 newly diagnosed chronic medical condition occurring during the following time periods:
•30 Days after each vaccination.
•30 Days after any vaccination.
•During the Stage 1 vaccination phase (from the first study vaccination [Visit 1] through 1 month after the second study vaccination [Visit 4]).
•During the Stage 1 follow-up phase (from 1 month after the second study vaccination [Visit 4] through 6 months after the second study vaccination [Visit 5]).
•Throughout Stage 1 (from the first study vaccination [Visit 1] through 6 months after the second study vaccination [Visit 5]).
•Percentage of subjects with at least 1 AE occurring during the following time periods:
•30 Days after each vaccination.
•30 Days after any vaccination.
•During the Stage 1 vaccination phase (from the first study vaccination [Visit 1] through 1 month after the second study vaccination [Visit 4]).
•Percentage of subjects reporting at least 1 immediate AE after each vaccination.
•Subject days missing school or work because of AEs during the Stage 1 vaccination phase (Visit 1 though Visit 4).
Please refer to the protocol for additional endpoints that will be described after the booster vaccination in Groups 1 through 4. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Timepoints are detailed above. Please refer to the protocol for the timepoints for the additional endpoints that will be described after the booster vaccination in Groups 1 through 4. |
|
| E.5.2 | Secondary end point(s) |
Secondary Immunogenicity endpoints -
- Proportions of subjects with hSBA titers ≥LLOQ, ≥1:4,≥1:8, ≥1:16, ≥1:32, ≥1:64, and ≥1:128 for each of the 4 primary MenB test strains at Visit 4.
- hSBA geometric mean titers (GMTs) for each of the 4 primary MnB test strains at Visit 4.
The secondary immunogenicity endpoints for the subsets tested with the additional hSBA test strains are as follows:
-Proportions of subjects with hSBA titers ≥LLOQ (1:16 for A06, A12, and A19 and 1:8 for A07, A15, A29, B03,B09, B15, and B16) for each of the secondary test strains 1 month after the second vaccination.
-Proportions of subjects with hSBA titers ≥1:4, ≥1:8, ≥1:16, ≥1:32, ≥1:64, and ≥1:128 for each of the secondary test strains 1 month after the second vaccination.
-hSBA GMTs for each of the secondary test strains 1 month after the second vaccination.
-Proportions of subjects with hSBA-MenA, hSBA-MenC, hSBA-MenW, and hSBA-MenY titers ≥1:8 (or LLOQ, whichever is higher) at Visit 2.
-Proportions of subjects with hSBA-MenA, hSBA-MenC, hSBA-MenW, and hSBA-MenY titers ≥1:4, ≥1:8, ≥1:16, ≥1:32, ≥1:64, and ≥1:128 at Visit 2.
-hSBA GMTs for each of the ACWY test strains at Visit 2.
- Proportions of subjects with hSBA-MenA, hSBA-MenC, hSBA-MenW, and hSBA-MenY titers ≥1:8 (or LLOQ, whichever is higher) at Visit 4 in Groups 1 and 3 and at Visit 2 in Groups 2 and 4.
-Proportions of subjects with hSBA-MenA, hSBA-MenC, hSBA-MenW, and hSBA-MenY titers ≥1:4, ≥1:8, ≥1:16, ≥1:32, ≥1:64, and ≥1:128 at Visit 4 in Groups 1 and 3 and Visit 2 in Groups 2 and 4.
-hSBA GMTs for each of the ACWY test strains at Visit 4 in Groups 1 and 3 and Visit 2 in Groups 2 and 4.
- Proportions of subjects who achieve the 5 MnB endpoints 1 month after the second vaccination, which are defined for hSBA performed with each of the 4 primary test strains: PMB80 (A22), PMB2001 (A56), PMB2948 (B24), and PMB2707 (B44), as detailed below:
-One (1) of the 5 endpoints is the composite endpoint defined as the proportion of subjects achieving an hSBA titer ≥LLOQ (1:16 for A22 and 1:8 for A56, B24, and B44) for all 4 primary test strains combined, 1 month after the second vaccination.
-Four (4) of the endpoints are defined as the proportion of subjects achieving at least a 4-fold increase in hSBA titer from baseline to 1 month after the second vaccination for each of the 4 primary test strains.
-For subjects with a baseline hSBA titer below the LOD (ie, an hSBA titer of <1:4), a 4-fold response is defined as an hSBA titer of ≥1:16 or the LLOQ (whichever titer is higher).
-For subjects with a baseline hSBA titer of ≥LOD (ie, hSBA titer of ≥1:4) and < LLOQ, a 4-fold response is defined as an hSBA titer of ≥4 times the LLOQ.
-For subjects with a baseline hSBA titer of ≥LLOQ, a 4-fold response is defined as an hSBA titer of ≥4 times the baseline titer.
-Proportions of subjects with hSBA titers ≥LLOQ, ≥1:4, ≥1:8, ≥1:16, ≥1:32, ≥1:64, and ≥1:128 for each of the 4 primary MenB test strains at Visit 4.
-hSBA GMTs for each of the 4 primary MnB test strains at Visit 4.
- Proportions of subjects with hSBA-MenA, hSBA-MenC, hSBA-MenW, and hSBA-MenY titers ≥1:8 (or LLOQ, whichever is higher) at Visits 1, 3, 7, 8, 9, and 10, in the
ACWY-naive and ACWY-experienced subjects separately.
- Proportions of subjects with hSBA-MenA, hSBA-MenC, hSBA-MenW, and hSBA-MenY titers ≥1:4, ≥1:8, ≥1:16, ≥1:32, ≥1:64, and ≥1:128 at Visits 1, 3, 7, 8, 9, and 10, in the ACWY-naive and ACWY-experienced subjects separately.
- hSBA GMTs for each of the ACWY test strains at Visits 1, 3, 7, 8, 9, and 10, in the ACWY-naive and ACWYexperienced subjects separately.
- Proportions of subjects with hSBA titers ≥ LLOQ, ≥1:4, ≥1:8, ≥1:16, ≥1:32, ≥1:64, and ≥1:128 for each of the 4 primary MenB test strains at Visits 1, 3, 7, 8, 9, and 10, in the ACWY-naive and ACWY-experienced subjects combined.
- hSBA GMTs for each of the 4 primary MenB test strains at Visits 1, 3, 7, 8, 9, and 10, in the ACWY-naive and ACWY-experienced subjects combined.
- Proportions of subjects with hSBA-MenA, hSBA-MenC, hSBA-MenW, and hSBA-MenY titers ≥1:8 (or LLOQ, whichever is higher) at Visit 11.
- Proportions of subjects with hSBA-MenA, hSBA-MenC, hSBA-MenW, and hSBA-MenY titers ≥1:4, ≥1:8, ≥1:16, ≥1:32, ≥1:64, and ≥1:128 at Visit 11.
- hSBA GMTs for each of the ACWY test strains at Visit 11.
- Proportion of subjects who achieve the 5 MnB endpoints at Visit 11.
- Proportions of subjects with hSBA titers ≥ LLOQ, ≥1:4, ≥1:8, ≥1:16, ≥1:32, ≥1:64, and ≥1:128 for each of the 4 primary MenB test strains at Visit 11.
- hSBA GMTs for each of the 4 primary MnB test strains at Visit 11.
- Proportion of subjects who achieve the 5 MnB endpoints 1 month after the booster vaccination.
Additional secondary immunogenicity endpoint and all secondary safety end points detailed in the Protocol |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Timepoints are detailed above |
|
| 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) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| 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) | 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 | 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 | Yes |
| E.8.1.7.1 | Other trial design description |
|
| 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 | 4 |
| 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 | No |
| 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 | 15 |
| 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 |
| Czechia |
| Finland |
| Poland |
| 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
|
End of trial in a Member State of the EU is defined as the time at which it is deemed that a sufficient number of 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 | 5 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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