E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of invasive meningococcal disease caused by Neisseria meningitidis serogroup B (MnB) in adolescents and young adults, aged 10 through 25 years. |
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E.1.1.1 | Medical condition in easily understood language |
Prevent invasive disease caused by Neisseria meningitidis serogroup B |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10004049 |
E.1.2 | Term | Bacterial meningitis |
E.1.2 | System Organ Class | 100000004862 |
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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 demonstrate the immune response (based on geometric mean titer [GMT]) induced by Gardasil given with bivalent rLP2086 vaccine (Group1) is noninferior to the immune response induced by Gardasil alone (Group3) as measured 1month after the 3rd vaccination (Visit5) with Gardasil in both groups. The immune response to all 4 components of Gardasil will be assessed
To demonstrate the immune response (based on GMT) induced by bivalent rLP2086 vaccine given with Gardasil (Group1) is noninferior to the immune response induced by bivalent rLP2086 vaccine alone (Group2) as measured by serum bactericidal assay using human complement performed with 2 MnB test strains, 1 expressing LP2086 subfamily A and 1 expressing LP2086 subfamily B proteins, when measured 1 month after the third vaccination (Visit5) with bivalent rLP2086 vaccine in both groups
To evaluate the safety profile of bivalent rLP2086 vaccine as measured by proportion of subjects reporting local reactions, systemic events and AEs |
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E.2.2 | Secondary objectives of the trial |
To describe the immune response as measured by serum bactericidal assay using human complement (hSBA) performed with 4 MnB test strains, 2 expressing LP2086 subfamily A and 2 expressing LP2086 subfamily B proteins, measured 1 month after the third vaccination (Visit 5) with bivalent rLP2086 vaccine (Group 2)
To describe the immune response as measured by serum bactericidal assay using human complement (hSBA) performed with 4 MnB test strains, 2 expressing LP2086 subfamily A and 2 expressing LP2086 subfamily B proteins, measured 1 month after the second vaccination (Visit 3) with bivalent rLP2086 vaccine (Group 2)
To demonstrate that the immune response induced by Gardasil given with bivalent rLP2086 vaccine (Group 1) as measured by seroconversion, is non-inferior to the immune response induced by Gardasil® alone (Group 3) when measured 1 month after the third vaccination (Visit 5) with Gardasil® in both groups. The immune response to all 4 serotypes of Gardasil will be assessed
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Evidence of a personally signed and dated informed consent document (ICD) indicating that the subject (and a legally authorized representative) has been informed of all pertinent aspects of the study.
2. Parent/legally authorized representative and subjects who are willing and able to comply with scheduled visits, laboratory tests, and other study procedures.
3. Male or female subject aged ≥11 and <18 years at the 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. Male and female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study (through the follow-up phone contact at month 12). 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 for further information.
7. Negative urine pregnancy test for all female subjects. |
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E.4 | Principal exclusion criteria |
1. Previous vaccination with any meningococcal serogroup B vaccine.
2. Previous vaccination with any HPV vaccine.
3. A previous anaphylactic reaction to any vaccine or vaccine-related component.
4. Contraindication to vaccination with Gardasil® or any HPV vaccine.
5. Subjects receiving any allergen immunotherapy with a non-licensed 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 with terminal complement deficiency may not be included.
8. History of any sexually transmitted disease.
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 chronic use of systemic antibiotics.
13. Participation in other studies during study participation. Participation in purely observational studies is acceptable.
14. Received any investigational drugs, vaccines or devices within 28 days before administration of the first study vaccination.
15. Any neuroinflammatory or autoimmune condition, including, but not limited to, transverse myelitis, uveitis, optic neuritis, and multiple sclerosis.
16. 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.
17. Subjects who are investigational site staff members or relatives of those site staff members, or who are Pfizer employees directly involved in the conduct of the trial or relatives of those Pfizer employees.
18. Subject is pregnant or breastfeeding. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints for the first co-primary objective are the geometric mean titers (GMTs) of the 4 HPV antigens (HPV 6, HPV 11, HPV 16, and HPV 18) measured at 1 month after the third vaccination (Visit 5) of Gardasil®, among subjects in Groups 1 and 3. Both baseline seropositive and baseline seronegative subjects will be included in the comparison
The primary endpoints for the second co-primary objective are the hSBA geometric mean titers (GMTs) of the 2 primary strains (PMB80 [A22], PMB2948 [B24]), measured at 1-month after the third vaccination (Visit 5) of bivalent rLP2086 vaccine, among subjects in Groups 1 and 2.
All of the safety endpoints will be applied to each group.
• Proportion of subjects reporting local reactions (pain, redness and swelling) and by severity after each vaccination visit.
• Proportion 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 after each vaccination visit.
• Proportion of subjects reporting the use of antipyretic medication after each vaccination visit.
• Proportion of subjects with at least one SAE during the following time periods:
• 30 days after each vaccination
• 30 days after any vaccination
• During the vaccination phase [from the first study vaccination (Visit 1) through 1 month after the last study vaccination (Visit 5)]
• During the follow-up phase [from 1 month after the last study vaccination (Visit 5) through 6 months after the third study vaccination (Visit 6)]
• Throughout the study period [from the first study vaccination (Visit 1) through 6 months after the third study vaccination (Visit 6)].
• Proportion of subjects who develop at least one adverse event occurring during the following time periods:
• 30 days after each vaccination
• 30 days after any vaccination
• During the vaccination phase [from the first study vaccination (Visit 1) through 1 month after the last study vaccination (Visit 5)]
• Proportion of subjects reporting at least one immediate adverse event after each vaccination.
Proportion of subjects reporting at least one newly diagnosed major illnesses, during the follow-up phase [from 1 month after the last study vaccination (Visit 5) through 6 months after the third study vaccination (Visit 6)]
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1month post last vaccination(Visit5)for co-primary immunogenicity endpoints
Local Reactions,Systemic Events,Antipyretic Use 7days after each vaccination
SAE’s: 30days after each/any vaccination
During vaccination from first (Visit1)through 1month after last study vaccination (Visit5)
During follow-up from 1month after last (Visit5)through 6months after third study vaccination(Visit6)
Throughout study period from first(Visit1)through 6months after third study vaccination(Visit6)
AE’s 30 days after each vaccination,30 days after any vaccination
During vaccination from first(Visit1)through 1month after last study vaccination(Visit5)
Immediate AE’s 30Min after each vaccination
Newly Diagnosed Major Illness 1month after last(Visit5)through 6months after third study vaccination (Visit6) |
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E.5.2 | Secondary end point(s) |
• The seroconversion rate for each of the 4 HPV antigens, 1 month after the third vaccination (Visit 5) of Gardasil® for subjects with baseline seronegative in Groups 1 and 3. The seroconversion rate is defined as anti HPV serum competitive Luminex® immunoassay (cLIA) levels ≥20 mMU/mL for HPV 6, ≥16 mMU/mL for HPV 11, ≥20 mMU/mL for HPV 16, and ≥24 mMU/mL for HPV 18. A subject having anti HPV serum cLIA levels less than these cutoff points at Visit 1 will be considered baseline seronegative; a subject having anti HPV serum cLIA levels greater than or equal to these cutoff points at Visit 1 will be considered baseline seropositive
• Proportion of subjects with baseline seropositive for each of the 4 HPV antigens.
• Proportion of subjects with hSBA titers ≥ lower limit of quantitation (LLOQ), ≥1:4, ≥1:8, ≥1:16, ≥1:32, ≥1:64, ≥1:128 for each of the 4 primary strains (PMB80 [A22], PMB2001 [A56], PMB2948 [B24], PMB2707 [B44]) at each applicable blood draw time point.
• hSBA geometric mean titers (GMTs) for each of the 4 primary strains (PMB80 [A22], PMB2001 [A56], PMB2948 [B24], PMB2707 [B44]) at each applicable blood sampling time point
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• One month after third vaccination
• Pre-bleed at visit 1
• One month after second and third vaccination
• One month after second and third vaccination
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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 | 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 |
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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 | Yes |
E.8.2.3.1 | Comparator description |
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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?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
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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The end of the clinical phase of the study will be the telephone contact to the last subject. At this time, sites will be closed out, the institutional review board/independent ethics committee (IRB/IEC) will be informed, and no further Council for International Organizations of Medical Sciences (CIOMS) reports will be sent. For other purposes, the end of the study will be last serology sample assayed. |
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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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |