Meningococcal Vaccine, rLP2086, Repevax, N Meningitidis Serogroup B, Meningitis
Conditions
Keywords
Healthy adolescents
Brief summary
This study is to look at a new vaccine that might prevent meningococcal disease, and to look at the safety of the new vaccine as well as how it is tolerated when given together with Repevax. The study will be done in healthy adolescents.
Interventions
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
11 Years to 18 Years
Healthy volunteers
Yes
Inclusion criteria
* Evidence of a personally signed and dated informed consent document indicating that the parent/legally acceptable representative and/or subject has been informed of all pertinent aspects of the study. * Parent/legally acceptable representative and/or subjects who are willing and able to comply with scheduled visits, laboratory tests, and other study procedures. * Male or female subject aged ≥11 and \<19 years at the time of enrollment. * Available for the entire study period and can be reached by telephone. * Healthy subject as determined by medical history, physical examination, and judgment of the investigator. * Has received full series of diphtheria, tetanus, and pertussis (DTP)/DTaP vaccines and oral poliomyelitis virus (OPV)/IPV vaccines per country-specific recommendations applicable at the time of receipt. * 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 Germany: The phrase sexual abstinence is not applicable, with the understanding that all male and all female subjects of childbearing potential must practice an effective form of contraception during the study. * Negative urine pregnancy test for female subjects.
Exclusion criteria
* Previous vaccination with any meningococcal serogroup B vaccine. * Vaccination with any diphtheria, tetanus, pertussis, or poliomyelitis virus vaccine within 5 years of the first study vaccination. * A previous anaphylactic reaction to any vaccine or vaccine-related component. * Contraindication to vaccination with diphtheria, tetanus, pertussis, or poliomyelitis virus vaccine. * Bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate intramuscular injection. * A known or suspected disease of the immune system or those receiving immunosuppressive therapy. * History of culture-proven disease caused by Neisseria meningitidis or Neisseria gonorrhoeae. * Significant neurological disorder or history of seizure (excluding simple febrile seizure). * Receipt of any blood products, including immunoglobulin within 6 months before the first study vaccination. * Current chronic use of systemic antibiotics. * Participation in other studies during study participation. Participation in purely observational studies is acceptable. * Received any investigational drugs, vaccines or devices within 28 days before administration of the first study vaccination. * Any neuroinflammatory or autoimmune condition, including, but not limited to, transverse myelitis, uveitis, optic neuritis, and multiple sclerosis. * 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. * Subjects who are investigational site staff members or subjects who are Pfizer employees directly involved in the conduct of the trial. * Subject is a direct descendant (eg, child, grandchild or other family member) of study site or Pfizer personnel. * Subject is pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants Achieving Prespecified Criteria for the Concomitant Antigen | 1 month after Vaccination 1 |
| Percentage of Participants With at Least One Adverse Event (AE) | Vaccination 1 up to 1 month after Vaccination 3 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| GMC for Acellular Pertussis Antigens | 1 month after Vaccination 1 | Enzyme-linked immunosorbent assay (ELISA) units per milliliter (EU/mL) |
| Percentage of Participants Achieving Serum Bactericidal Assay Using Human Complement (hSBA) Titer Level Greater Than or Equal to (>=) Prespecified Titer Level | 1 month after Vaccination 3 | — |
| Geometric Mean Titer (GMT) for Poliomyelitis Antigens | 1 month after Vaccination 1 | — |
| Geometric Mean Concentration (GMC) for Diphtheria and Tetanus Antigens | 1 month after Vaccination 1 | — |
Other
| Measure | Time frame |
|---|---|
| Immunoglobulin G (IgG) Measured by Geometric Mean Titer (GMT) | Before vaccination 1, 1 month after Vaccination 2, 3 |
| Geometric Mean Fold-Rise (GMFR) for IgG | Before Vaccination 1, 1 month after Vaccination 2, 3 |
Countries
Finland, Germany, Poland
Participant flow
Pre-assignment details
A total of 753 participants were enrolled in this study. Of these, 4 participants were not randomized but were vaccinated rLP2086 vaccine or Repevax or Saline at Vaccination 1. These participants were included in safety population and not intent-to-treat population.
Participants by arm
| Arm | Count |
|---|---|
| Group 1: rLP2086 + Repevax Randomized to receive rLP2086 at 0-,2-6-month and Repevax at 0-month. | 373 |
| Group 2: Saline+Repevax Randomized to receive Saline at 0-,2-6-month and Repevax at 0-month. | 376 |
| Total | 749 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 0 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 4 | 6 |
| Overall Study | Not eligible | 1 | 1 |
| Overall Study | Other | 0 | 3 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Protocol Violation | 9 | 7 |
| Overall Study | Randomized, but not vaccinated | 1 | 0 |
| Overall Study | Withdrawal by Subject | 19 | 10 |
Baseline characteristics
| Characteristic | Group 1: rLP2086 + Repevax | Group 2: Saline+Repevax | Total |
|---|---|---|---|
| Age, Customized >=14 years-<19 years | 156 participants | 161 participants | 317 participants |
| Age, Customized Greater than or equal (>=)11-less than (<)14years | 217 participants | 215 participants | 432 participants |
| Sex: Female, Male Female | 183 Participants | 184 Participants | 367 Participants |
| Sex: Female, Male Male | 190 Participants | 192 Participants | 382 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 98 / 374 | 118 / 378 |
| serious Total, serious adverse events | 12 / 374 | 9 / 378 |
Outcome results
Primary
Percentage of Participants Achieving Prespecified Criteria for the Concomitant Antigen
Time frame: 1 month after Vaccination 1
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1: rLP2086 + Repevax | Percentage of Participants Achieving Prespecified Criteria for the Concomitant Antigen | Tetanus | 100.0 percentage of participants |
| Group 1: rLP2086 + Repevax | Percentage of Participants Achieving Prespecified Criteria for the Concomitant Antigen | Pertussis fimbrial agglutinogens types 2+3 | 97.6 percentage of participants |
| Group 1: rLP2086 + Repevax | Percentage of Participants Achieving Prespecified Criteria for the Concomitant Antigen | Pertussis filamentous hemagglutinin | 100.0 percentage of participants |
| Group 1: rLP2086 + Repevax | Percentage of Participants Achieving Prespecified Criteria for the Concomitant Antigen | Poliovirus type 1 | 100.0 percentage of participants |
| Group 1: rLP2086 + Repevax | Percentage of Participants Achieving Prespecified Criteria for the Concomitant Antigen | Pertussis toxoid | 94.7 percentage of participants |
| Group 1: rLP2086 + Repevax | Percentage of Participants Achieving Prespecified Criteria for the Concomitant Antigen | Poliovirus type 2 | 100.0 percentage of participants |
| Group 1: rLP2086 + Repevax | Percentage of Participants Achieving Prespecified Criteria for the Concomitant Antigen | Pertussis pertactin | 100.0 percentage of participants |
| Group 1: rLP2086 + Repevax | Percentage of Participants Achieving Prespecified Criteria for the Concomitant Antigen | Poliovirus type 3 | 100.0 percentage of participants |
| Group 1: rLP2086 + Repevax | Percentage of Participants Achieving Prespecified Criteria for the Concomitant Antigen | Diphtheria | 99.4 percentage of participants |
| Group 2: Saline+Repevax | Percentage of Participants Achieving Prespecified Criteria for the Concomitant Antigen | Poliovirus type 3 | 100.0 percentage of participants |
| Group 2: Saline+Repevax | Percentage of Participants Achieving Prespecified Criteria for the Concomitant Antigen | Diphtheria | 99.4 percentage of participants |
| Group 2: Saline+Repevax | Percentage of Participants Achieving Prespecified Criteria for the Concomitant Antigen | Tetanus | 100.0 percentage of participants |
| Group 2: Saline+Repevax | Percentage of Participants Achieving Prespecified Criteria for the Concomitant Antigen | Pertussis toxoid | 96.0 percentage of participants |
| Group 2: Saline+Repevax | Percentage of Participants Achieving Prespecified Criteria for the Concomitant Antigen | Pertussis filamentous hemagglutinin | 100.0 percentage of participants |
| Group 2: Saline+Repevax | Percentage of Participants Achieving Prespecified Criteria for the Concomitant Antigen | Pertussis pertactin | 100.0 percentage of participants |
| Group 2: Saline+Repevax | Percentage of Participants Achieving Prespecified Criteria for the Concomitant Antigen | Pertussis fimbrial agglutinogens types 2+3 | 98.9 percentage of participants |
| Group 2: Saline+Repevax | Percentage of Participants Achieving Prespecified Criteria for the Concomitant Antigen | Poliovirus type 1 | 100.0 percentage of participants |
| Group 2: Saline+Repevax | Percentage of Participants Achieving Prespecified Criteria for the Concomitant Antigen | Poliovirus type 2 | 100.0 percentage of participants |
Comparison: Diphtheria: Exact 2-sided confidence interval (based on Chan and Zhang) was reported for the difference in proportions, expressed as a percentage.95% CI: [-1.6, 1.5]
Comparison: Tetanus: Exact 2-sided confidence interval (based on Chan and Zhang) was reported for the difference in proportions, expressed as a percentage.95% CI: [-1.1, 1.1]
Comparison: Pertussis toxoid: Exact 2-sided confidence interval (based on Chan and Zhang) was reported for the difference in proportions, expressed as a percentage.95% CI: [-4.7, 1.9]
Comparison: Pertussis filamentous hemagglutinin: Exact 2-sided confidence interval (based on Chan and Zhang) was reported for the difference in proportions, expressed as a percentage.95% CI: [-1.1, 1.1]
Comparison: Pertussis pertactin: Exact 2-sided confidence interval (based on Chan and Zhang) was reported for the difference in proportions, expressed as a percentage.95% CI: [-1.1, 1.1]
Comparison: Pertussis fimbrial agglutinogens types 2+3: Exact 2-sided confidence interval (based on Chan and Zhang) was reported for the difference in proportions, expressed as a percentage.95% CI: [-3.6, 0.8]
Comparison: Poliovirus type 1: Exact 2-sided confidence interval (based on Chan and Zhang) was reported for the difference in proportions, expressed as a percentage.95% CI: [-1.1, 1.1]
Comparison: Poliovirus type 2: Exact 2-sided confidence interval (based on Chan and Zhang) was reported for the difference in proportions, expressed as a percentage.95% CI: [-1.1, 1.1]
Comparison: Poliovirus type 3: Exact 2-sided confidence interval (based on Chan and Zhang) was reported for the difference in proportions, expressed as a percentage.95% CI: [-1.1, 1.1]
Primary
Percentage of Participants With at Least One Adverse Event (AE)
Time frame: Vaccination 1 up to 1 month after Vaccination 3
Population: Summary was performed for participants as per vaccine administration.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: rLP2086 + Repevax | Percentage of Participants With at Least One Adverse Event (AE) | 37.4 percentage of participants |
| Group 2: Saline+Repevax | Percentage of Participants With at Least One Adverse Event (AE) | 40.2 percentage of participants |
Secondary
Geometric Mean Concentration (GMC) for Diphtheria and Tetanus Antigens
Time frame: 1 month after Vaccination 1
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group 1: rLP2086 + Repevax | Geometric Mean Concentration (GMC) for Diphtheria and Tetanus Antigens | Diphtheria | 1.4 International Units per milliliter |
| Group 1: rLP2086 + Repevax | Geometric Mean Concentration (GMC) for Diphtheria and Tetanus Antigens | Tetanus | 12.3 International Units per milliliter |
| Group 2: Saline+Repevax | Geometric Mean Concentration (GMC) for Diphtheria and Tetanus Antigens | Diphtheria | 1.5 International Units per milliliter |
| Group 2: Saline+Repevax | Geometric Mean Concentration (GMC) for Diphtheria and Tetanus Antigens | Tetanus | 12.4 International Units per milliliter |
Secondary
Geometric Mean Titer (GMT) for Poliomyelitis Antigens
Time frame: 1 month after Vaccination 1
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group 1: rLP2086 + Repevax | Geometric Mean Titer (GMT) for Poliomyelitis Antigens | Poliovirus type 1 | 662.1 titer |
| Group 1: rLP2086 + Repevax | Geometric Mean Titer (GMT) for Poliomyelitis Antigens | Poliovirus type 2 | 840.5 titer |
| Group 1: rLP2086 + Repevax | Geometric Mean Titer (GMT) for Poliomyelitis Antigens | Poliovirus type 3 | 2237.4 titer |
| Group 2: Saline+Repevax | Geometric Mean Titer (GMT) for Poliomyelitis Antigens | Poliovirus type 1 | 672.6 titer |
| Group 2: Saline+Repevax | Geometric Mean Titer (GMT) for Poliomyelitis Antigens | Poliovirus type 2 | 995.8 titer |
| Group 2: Saline+Repevax | Geometric Mean Titer (GMT) for Poliomyelitis Antigens | Poliovirus type 3 | 2450.1 titer |
Secondary
GMC for Acellular Pertussis Antigens
Enzyme-linked immunosorbent assay (ELISA) units per milliliter (EU/mL)
Time frame: 1 month after Vaccination 1
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group 1: rLP2086 + Repevax | GMC for Acellular Pertussis Antigens | Pertussis toxoid | 27.1 EU/mL |
| Group 1: rLP2086 + Repevax | GMC for Acellular Pertussis Antigens | Pertussis filamentous hemagglutinin | 119.4 EU/mL |
| Group 1: rLP2086 + Repevax | GMC for Acellular Pertussis Antigens | Pertussis pertactin | 317.0 EU/mL |
| Group 1: rLP2086 + Repevax | GMC for Acellular Pertussis Antigens | Pertussis fimbrial agglutinogens types 2+3 | 339.1 EU/mL |
| Group 2: Saline+Repevax | GMC for Acellular Pertussis Antigens | Pertussis fimbrial agglutinogens types 2+3 | 364.5 EU/mL |
| Group 2: Saline+Repevax | GMC for Acellular Pertussis Antigens | Pertussis toxoid | 26.5 EU/mL |
| Group 2: Saline+Repevax | GMC for Acellular Pertussis Antigens | Pertussis pertactin | 336.1 EU/mL |
| Group 2: Saline+Repevax | GMC for Acellular Pertussis Antigens | Pertussis filamentous hemagglutinin | 122.9 EU/mL |
Secondary
Percentage of Participants Achieving Serum Bactericidal Assay Using Human Complement (hSBA) Titer Level Greater Than or Equal to (>=) Prespecified Titer Level
Time frame: 1 month after Vaccination 3
Population: Serum samples from approximately 50% of the participants had hSBA performed with primary MnB test strains expressing rLP2086 variants A22 and B24 and the other 50% of participants had hSBAs performed with strains expressing variants A56 and B44. The number of participants shown for each test strain represents the number with valid and determinant assay result for that strain.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1: rLP2086 + Repevax | Percentage of Participants Achieving Serum Bactericidal Assay Using Human Complement (hSBA) Titer Level Greater Than or Equal to (>=) Prespecified Titer Level | PMB80 [A22] 1:16 (N=158, 166) | 95.6 percentage of participants |
| Group 1: rLP2086 + Repevax | Percentage of Participants Achieving Serum Bactericidal Assay Using Human Complement (hSBA) Titer Level Greater Than or Equal to (>=) Prespecified Titer Level | PMB2001 [A56] 1:8 (N=148, 152) | 100.0 percentage of participants |
| Group 1: rLP2086 + Repevax | Percentage of Participants Achieving Serum Bactericidal Assay Using Human Complement (hSBA) Titer Level Greater Than or Equal to (>=) Prespecified Titer Level | PMB2948 [B24] 1:8 (N=157, 170) | 96.8 percentage of participants |
| Group 1: rLP2086 + Repevax | Percentage of Participants Achieving Serum Bactericidal Assay Using Human Complement (hSBA) Titer Level Greater Than or Equal to (>=) Prespecified Titer Level | PMB2707 [B44] 1:8 (N=146, 159) | 81.5 percentage of participants |
| Group 2: Saline+Repevax | Percentage of Participants Achieving Serum Bactericidal Assay Using Human Complement (hSBA) Titer Level Greater Than or Equal to (>=) Prespecified Titer Level | PMB2707 [B44] 1:8 (N=146, 159) | 8.2 percentage of participants |
| Group 2: Saline+Repevax | Percentage of Participants Achieving Serum Bactericidal Assay Using Human Complement (hSBA) Titer Level Greater Than or Equal to (>=) Prespecified Titer Level | PMB80 [A22] 1:16 (N=158, 166) | 19.9 percentage of participants |
| Group 2: Saline+Repevax | Percentage of Participants Achieving Serum Bactericidal Assay Using Human Complement (hSBA) Titer Level Greater Than or Equal to (>=) Prespecified Titer Level | PMB2948 [B24] 1:8 (N=157, 170) | 12.9 percentage of participants |
| Group 2: Saline+Repevax | Percentage of Participants Achieving Serum Bactericidal Assay Using Human Complement (hSBA) Titer Level Greater Than or Equal to (>=) Prespecified Titer Level | PMB2001 [A56] 1:8 (N=148, 152) | 26.3 percentage of participants |
Other Pre-specified
Geometric Mean Fold-Rise (GMFR) for IgG
Time frame: Before Vaccination 1, 1 month after Vaccination 2, 3
Population: A decision was made, a priori, that the hSBA MnB immunogenicity assay will be used instead of the IgG assay originally planned . Therefore only hSBA assay results will be disclosed.
Other Pre-specified
Immunoglobulin G (IgG) Measured by Geometric Mean Titer (GMT)
Time frame: Before vaccination 1, 1 month after Vaccination 2, 3
Population: A decision was made, a priori, that the hSBA MnB immunogenicity assay will be used instead of the IgG assay originally planned . Therefore only hSBA assay results will be disclosed.