Meningitis, Meningococcal
Conditions
Keywords
Immunological assays, Human blood donors, Meningococcal vaccination, Meningococcal disease
Brief summary
The purpose of this study was to collect large volumes of matched pairs of pre- and post-vaccination sera from healthy subjects who administered GlaxoSmithKline (GSK) Biologicals' vaccine against meningitis- MenACWY vaccine (Menveo) or rMenB+OMV NZ vaccine (Bexsero), which serves for the development, qualification, validation, and maintenance of immunological assays which supports the preclinical research activities and clinical development of GSK Biologicals' vaccines. The safety of the subjects given one of the two vaccines (Bexsero or Menveo), as per the recommended dosage and schedule were assessed during their participation in the study.
Interventions
BIOLOGICALrMenB+OMV NZ vaccine
Two doses of rMenB+OMV NZ vaccine were administered intramuscularly at Day 1 and Day 61.
One dose of MenACWY vaccine were administered intramuscularly at Day 1.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol. * Written informed consent obtained from the subject prior to performing any study specific procedure. * A male or female between, and including, 18 and 50 years of age at the time of the first study visit. * Healthy subjects as established by medical history and clinical examination before entering into the study. Healthy subjects with no medical conditions that, in the opinion of the investigator, prevents the subject from participating in the study. * Subjects must weigh at least 110 pounds (50 kg), but not to present obesity (BMI \< 32kg/m2). * Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause. * Female subjects of childbearing potential may be enrolled in the study, if the subject: * has practiced adequate contraception for 30 days prior to vaccination, and * has a negative pregnancy test on the day of vaccination and * has agreed to continue adequate contraception during the entire treatment period and for 1 month, after completion of the vaccination series.
Exclusion criteria
* Progressive, unstable or uncontrolled clinical conditions. * Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study. * Clinical conditions representing a contraindication to intramuscular vaccination and blood draws. * Abnormal function of the immune system resulting from: * Clinical conditions. * Systemic administration of corticosteroids (PO/IV/IM) within 90 days prior to informed consent. * Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to informed consent. * Received immunoglobulins or any blood products within 180 days prior to informed consent. * Received an investigational or non-registered medicinal product within 30 days prior to informed consent. * Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study. * Any history of meningococcal vaccination or meningococcal and gonorrhoea diseases. * Enrolment in any activity requiring a blood donation greater than 50 mL during the period starting 30 days before the first study visit (Day -83, Day -60 or Day -30) or for the duration of the study period. * Administration of long-acting immune-modifying drugs at any time during the study period * Subjects with blood disorders. * Subjects with a history of difficulty in providing blood samples * Any antibiotic intake 7 days prior to blood collection. * Subjects who donated \>450 mL of blood within 60 days prior to any blood collection visits. * Subjects who lost \>200 mL during a single apheresis or who lost red blood cells on more than one occasion during apheresis within the previous 60 days. * Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product * Ongoing anaemia as indicated by haemoglobin values below the lower limit of the laboratory-specified reference range. If the finger prick method demonstrates an anaemia, no further protocol procedures will be performed, and the subject will be referred for appropriate medical management. The subject may participate in this study following therapy and evidence that the anaemia has been resolved. * History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. * Pregnant or lactating female. * Female planning to become pregnant or planning to discontinue contraceptive precautions. * Any confirmed or suspected immunosuppressive or immunodeficiency condition based on medical history and physical examination * Family history of congenital or hereditary immunodeficiency. * Serious chronic illness. * History of chronic alcohol consumption and/or drug abuse.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Human Blood Samples Collected for Conversion Into Serum at Day 61 | At Day 61 | The Serum Bactericidal Assay (SBA) using human serum used to measure the induction of functional bactericidal antibodies directed against Neisseria meningitidis. To comply with local health authorities and guidelines \[Australian Red Cross, 2016\], blood samples were collected with the minimum interval of approximately 90 days. For Day 61, blood samples were collected only for MenACWY 3 group. |
| Number of Human Blood Samples Collected for Conversion Into Serum at Day -83 | At Day -83 [83 days before first vaccination (Day 1)] | The Serum Bactericidal Assay (SBA) using human serum used to measure the induction of functional bactericidal antibodies directed against Neisseria meningitidis. To comply with local health authorities and guidelines \[Australian Red Cross, 2016\], blood samples were collected with the minimum interval of approximately 90 days. For Day -83, blood samples were collected only for rMenB+OMV NZ group and MenACWY 1 group. |
| Number of Human Blood Samples Collected for Conversion Into Serum at Day 8 | At Day 8 | The Serum Bactericidal Assay (SBA) using human serum used to measure the induction of functional bactericidal antibodies directed against Neisseria meningitidis. To comply with local health authorities and guidelines \[Australian Red Cross, 2016\], blood samples were collected with the minimum interval of approximately 90 days. For Day 8, blood samples were collected only for rMenB+OMV NZ group and MenACWY 1 group. |
| Number of Human Blood Samples Collected for Conversion Into Serum at Day 98 | At Day 98 | The Serum Bactericidal Assay (SBA) using human serum used to measure the induction of functional bactericidal antibodies directed against Neisseria meningitidis. To comply with local health authorities and guidelines \[Australian Red Cross, 2016\], blood samples were collected with the minimum interval of approximately 90 days. For Day 98, blood samples were collected only for rMenB+OMV NZ group. |
| Number of Human Blood Samples Collected for Conversion Into Serum at Day 151 | At Day 151 | The Serum Bactericidal Assay (SBA) using human serum used to measure the induction of functional bactericidal antibodies directed against Neisseria meningitidis. To comply with local health authorities and guidelines \[Australian Red Cross, 2016\], blood samples were collected with the minimum interval of approximately 90 days. For Day 151, blood samples were collected only for MenACWY 1, 2 and 3 group. |
| Number of Human Blood Samples Collected for Conversion Into Serum at Day -60 | At Day -60 [60 days before first vaccination (Day 1)] | The Serum Bactericidal Assay (SBA) using human serum used to measure the induction of functional bactericidal antibodies directed against Neisseria meningitidis. To comply with local health authorities and guidelines \[Australian Red Cross, 2016\], blood samples were collected with the minimum interval of approximately 90 days. For Day -60, blood samples were collected only for MenACWY 2 group. |
| Number of Human Blood Samples Collected for Conversion Into Serum at Day 31 | At Day 31 | The Serum Bactericidal Assay (SBA) using human serum used to measure the induction of functional bactericidal antibodies directed against Neisseria meningitidis. To comply with local health authorities and guidelines \[Australian Red Cross, 2016\], blood samples were collected with the minimum interval of approximately 90 days. For Day 31, blood samples were collected only for MenACWY 2 group. |
| Number of Human Blood Samples Collected for Conversion Into Serum at Day-30 | At Day -30 [30 days before first vaccination (Day 1)] | The Serum Bactericidal Assay (SBA) using human serum used to measure the induction of functional bactericidal antibodies directed against Neisseria meningitidis. To comply with local health authorities and guidelines \[Australian Red Cross, 2016\], blood samples were collected with the minimum interval of approximately 90 days. For Day -30, blood samples were collected only for MenACWY 3 group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Atleast One Serious Adverse Events (SAEs) Related to Vaccination | Throughout the study period (approximately 4 years) | An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of hospitalization, results in disability/incapacity in a subject or is a congenital anomaly/ birth defect in the offspring of a study subject. AE(s) considered as SAE(s) also include invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, as per the medical or scientific judgement of the physician. Related=AE assessed by the investigator as related to the vaccination. |
Countries
Australia, Germany
Participant flow
Recruitment details
To comply with the local health authorities and guidelines \[Australian Red Cross, 2016\] with a minimum 90-day interval between blood draws, 3 MenACWY groups were formed to ensure blood draw at Days -83 \[83 days before first vaccination (Day 1)\], -60 \[60 days before first vaccination (Day 1), -30 \[30 days before first vaccination (Day 1), 31, 61, and 151. The rMenB+OMV NZ group was not split due to sufficient intervals between the post-vaccination blood sampling time points (Day 8 and Day 98).
Pre-assignment details
Out of 1021 participants enrolled, 60 participants did not receive vaccination as they did not meet the eligibility criteria or withdrew from the study, therefore only 961 participants were included in the Exposed Set and started the study.
Participants by arm
| Arm | Count |
|---|---|
| rMenB+OMV NZ Group Participants vaccinated intramuscularly with Bexsero vaccine at Day 1 and Day 61 and blood samples were collected at Day -83, Day 8, and Day 98. | 470 |
| MenACWY 1 Group Participants vaccinated intramuscularly with Menveo vaccine at Day 1 and blood samples were collected at Day -83, Day 8, and Day 151. | 165 |
| MenACWY 2 Group Participants vaccinated intramuscularly with Menveo vaccine at Day 1 and blood samples were collected at Day -60, Day 31, and Day 151. | 165 |
| MenACWY 3 Group Participants vaccinated intramuscularly with Menveo vaccine at Day 1 and blood samples were collected at Day -30, Day 61, and Day 151. | 161 |
| Total | 961 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 5 | 0 | 0 | 3 |
| Overall Study | Other | 2 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 9 | 3 | 1 | 1 |
Baseline characteristics
| Characteristic | rMenB+OMV NZ Group | Total | MenACWY 3 Group | MenACWY 2 Group | MenACWY 1 Group |
|---|---|---|---|---|---|
| Age, Continuous | 32.8 YEARS STANDARD_DEVIATION 8.8 | 33.0 YEARS STANDARD_DEVIATION 8.9 | 32.9 YEARS STANDARD_DEVIATION 8.8 | 33.3 YEARS STANDARD_DEVIATION 9 | 33.3 YEARS STANDARD_DEVIATION 9.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 29 Participants | 65 Participants | 8 Participants | 15 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 9 Participants | 18 Participants | 6 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 430 Participants | 876 Participants | 147 Participants | 149 Participants | 150 Participants |
| Sex: Female, Male Female | 295 Participants | 608 Participants | 109 Participants | 105 Participants | 99 Participants |
| Sex: Female, Male Male | 175 Participants | 353 Participants | 52 Participants | 60 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 470 | 0 / 165 | 0 / 165 | 0 / 161 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 3 / 470 | 1 / 165 | 1 / 165 | 0 / 161 |
Outcome results
Primary
Number of Human Blood Samples Collected for Conversion Into Serum at Day 151
The Serum Bactericidal Assay (SBA) using human serum used to measure the induction of functional bactericidal antibodies directed against Neisseria meningitidis. To comply with local health authorities and guidelines \[Australian Red Cross, 2016\], blood samples were collected with the minimum interval of approximately 90 days. For Day 151, blood samples were collected only for MenACWY 1, 2 and 3 group.
Time frame: At Day 151
Population: Analysis was performed on blood samples collected from exposed set, which included all participants in the enrolled set who received a study vaccination. The participants included in this outcome measure are based on the data collected at specific blood sampling timepoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| rMenB+OMV NZ Group | Number of Human Blood Samples Collected for Conversion Into Serum at Day 151 | 1869 Blood samples |
| MenACWY 1 Group | Number of Human Blood Samples Collected for Conversion Into Serum at Day 151 | 1866 Blood samples |
| MenACWY 3 Group | Number of Human Blood Samples Collected for Conversion Into Serum at Day 151 | 1752 Blood samples |
Primary
Number of Human Blood Samples Collected for Conversion Into Serum at Day-30
The Serum Bactericidal Assay (SBA) using human serum used to measure the induction of functional bactericidal antibodies directed against Neisseria meningitidis. To comply with local health authorities and guidelines \[Australian Red Cross, 2016\], blood samples were collected with the minimum interval of approximately 90 days. For Day -30, blood samples were collected only for MenACWY 3 group.
Time frame: At Day -30 [30 days before first vaccination (Day 1)]
Population: Analysis was performed on blood samples collected from exposed set, which included all participants in the enrolled set who received a study vaccination. The participants included in this outcome measure are based on the data collected at specific blood sampling timepoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| rMenB+OMV NZ Group | Number of Human Blood Samples Collected for Conversion Into Serum at Day-30 | 1894 Blood samples |
Primary
Number of Human Blood Samples Collected for Conversion Into Serum at Day 31
The Serum Bactericidal Assay (SBA) using human serum used to measure the induction of functional bactericidal antibodies directed against Neisseria meningitidis. To comply with local health authorities and guidelines \[Australian Red Cross, 2016\], blood samples were collected with the minimum interval of approximately 90 days. For Day 31, blood samples were collected only for MenACWY 2 group.
Time frame: At Day 31
Population: Analysis was performed on blood samples collected from exposed set, which included all participants in the enrolled set who received a study vaccination. The participants included in this outcome measure are based on the data collected at specific blood sampling timepoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| rMenB+OMV NZ Group | Number of Human Blood Samples Collected for Conversion Into Serum at Day 31 | 1920 Blood samples |
Primary
Number of Human Blood Samples Collected for Conversion Into Serum at Day -60
The Serum Bactericidal Assay (SBA) using human serum used to measure the induction of functional bactericidal antibodies directed against Neisseria meningitidis. To comply with local health authorities and guidelines \[Australian Red Cross, 2016\], blood samples were collected with the minimum interval of approximately 90 days. For Day -60, blood samples were collected only for MenACWY 2 group.
Time frame: At Day -60 [60 days before first vaccination (Day 1)]
Population: Analysis was performed on blood samples collected from exposed set, which included all participants in the enrolled set who received a study vaccination. The participants included in this outcome measure are based on the data collected at specific blood sampling timepoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| rMenB+OMV NZ Group | Number of Human Blood Samples Collected for Conversion Into Serum at Day -60 | 1957 Blood samples |
Primary
Number of Human Blood Samples Collected for Conversion Into Serum at Day 61
The Serum Bactericidal Assay (SBA) using human serum used to measure the induction of functional bactericidal antibodies directed against Neisseria meningitidis. To comply with local health authorities and guidelines \[Australian Red Cross, 2016\], blood samples were collected with the minimum interval of approximately 90 days. For Day 61, blood samples were collected only for MenACWY 3 group.
Time frame: At Day 61
Population: Analysis was performed on blood samples collected from exposed set, which included all participants in the enrolled set who received a study vaccination. The participants included in this outcome measure are based on the data collected at specific blood sampling timepoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| rMenB+OMV NZ Group | Number of Human Blood Samples Collected for Conversion Into Serum at Day 61 | 1809 Blood samples |
Primary
Number of Human Blood Samples Collected for Conversion Into Serum at Day 8
The Serum Bactericidal Assay (SBA) using human serum used to measure the induction of functional bactericidal antibodies directed against Neisseria meningitidis. To comply with local health authorities and guidelines \[Australian Red Cross, 2016\], blood samples were collected with the minimum interval of approximately 90 days. For Day 8, blood samples were collected only for rMenB+OMV NZ group and MenACWY 1 group.
Time frame: At Day 8
Population: Analysis was performed on blood samples collected from exposed set, which included all participants in the enrolled set who received a study vaccination. The participants included in this outcome measure are based on the data collected at specific blood sampling timepoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| rMenB+OMV NZ Group | Number of Human Blood Samples Collected for Conversion Into Serum at Day 8 | 5396 Blood samples |
| MenACWY 1 Group | Number of Human Blood Samples Collected for Conversion Into Serum at Day 8 | 1907 Blood samples |
Primary
Number of Human Blood Samples Collected for Conversion Into Serum at Day -83
The Serum Bactericidal Assay (SBA) using human serum used to measure the induction of functional bactericidal antibodies directed against Neisseria meningitidis. To comply with local health authorities and guidelines \[Australian Red Cross, 2016\], blood samples were collected with the minimum interval of approximately 90 days. For Day -83, blood samples were collected only for rMenB+OMV NZ group and MenACWY 1 group.
Time frame: At Day -83 [83 days before first vaccination (Day 1)]
Population: Analysis was performed on blood samples collected from exposed set, which included all participants in the enrolled set who received a study vaccination. The participants included in this outcome measure are based on the data collected at specific blood sampling timepoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| rMenB+OMV NZ Group | Number of Human Blood Samples Collected for Conversion Into Serum at Day -83 | 5578 Blood samples |
| MenACWY 1 Group | Number of Human Blood Samples Collected for Conversion Into Serum at Day -83 | 1936 Blood samples |
Primary
Number of Human Blood Samples Collected for Conversion Into Serum at Day 98
The Serum Bactericidal Assay (SBA) using human serum used to measure the induction of functional bactericidal antibodies directed against Neisseria meningitidis. To comply with local health authorities and guidelines \[Australian Red Cross, 2016\], blood samples were collected with the minimum interval of approximately 90 days. For Day 98, blood samples were collected only for rMenB+OMV NZ group.
Time frame: At Day 98
Population: Analysis was performed on blood samples collected from exposed set, which included all participants in the enrolled set who received a study vaccination. The participants included in this outcome measure are based on the data collected at specific blood sampling timepoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| rMenB+OMV NZ Group | Number of Human Blood Samples Collected for Conversion Into Serum at Day 98 | 5204 Blood samples |
Secondary
Number of Participants With Atleast One Serious Adverse Events (SAEs) Related to Vaccination
An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of hospitalization, results in disability/incapacity in a subject or is a congenital anomaly/ birth defect in the offspring of a study subject. AE(s) considered as SAE(s) also include invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, as per the medical or scientific judgement of the physician. Related=AE assessed by the investigator as related to the vaccination.
Time frame: Throughout the study period (approximately 4 years)
Population: Analysis was performed on blood samples collected from exposed set, which included all participants subjects in the exposed set who provide safety data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rMenB+OMV NZ Group | Number of Participants With Atleast One Serious Adverse Events (SAEs) Related to Vaccination | 0 Participants |
| MenACWY 1 Group | Number of Participants With Atleast One Serious Adverse Events (SAEs) Related to Vaccination | 0 Participants |
| MenACWY 3 Group | Number of Participants With Atleast One Serious Adverse Events (SAEs) Related to Vaccination | 0 Participants |
| MenACWY 3 Group | Number of Participants With Atleast One Serious Adverse Events (SAEs) Related to Vaccination | 0 Participants |