Study to Assess the Safety and Immunogenicity of GSK Meningococcal Group B Vaccine When Administered Concomitantly With GSK Meningococcal MenACWY Conjugate Vaccine in Healthy Subjects of 16-18 Years of Age
- Conditions
- Infections, Meningococcal
- Interventions
- Combination Product: Meningococcal Group B Vaccine (GSK3536829A) (rMenB+OMV NZ)Biological: Meningococcal MenACWY Conjugate Vaccine (GSK3536820A) (MenA lyo + MenCWY liquid)Combination Product: Placebo
- Registration Number
- NCT04318548
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
The purpose of this study is to evaluate the immunogenicity, safety and tolerability of rMenB+OMV NZ and MenACWY vaccines when concomitantly administered to healthy subjects 16-18 years of age.
- Detailed Description
As per the recommendation from Center for Biologics Evaluation and Research (CBER) the study has been amended to include a new "agar-overlay" serum bactericidal assay using human serum complement (hSBA). Additional changes include validation of the MenB manual to measure immunogenicity of the meningococcal group B vaccine, a modification in the definition of 4-fold increase in post-vaccination hSBA titer definition when the pre-vaccination titer is below the limit of detection, and a modification in the population set to be used for safety analysis wherein the exposed set is to be used for all safety analyses.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 945
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Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol or/and participants' parent(s)/Legally Acceptable Representative(s) [LAR(s)] who, in the opinion of the investigator, can and will comply, with the requirements of the protocol.
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Previous vaccination with 1 dose of quadrivalent meningococcal conjugate vaccine (MenACWY, Menveo or Menactra) at least 4 years prior to informed consent and assent as applicable.
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Written or /witnessed/thumb printed informed consent obtained from the participant/parent(s)/LAR(s) of the participant prior to performance of any study specific procedure.
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Written informed assent obtained from the participant (if applicable) along with informed consent from the participant's parent(s)/LAR(s) prior to performing any study specific procedure.
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A male or female between, and including, 16 and 18 years of age at the time of the first vaccination.
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Healthy participants as established by medical history and clinical examination before entering the study.
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Female participants 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.
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Female participants of childbearing potential may be enrolled in the study if the participant:
- 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 2 months after completion of the vaccination series.
Medical conditions
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Progressive, unstable, or uncontrolled clinical conditions.
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Clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
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Abnormal function of the immune system resulting from:
- Clinical conditions.
- Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days within 90 days prior to study vaccination. This will mean prednisone ≥ 20 mg/day (for adult participants) or ≥ 0.5 mg/kg/day or 20 mg/day whichever is the maximum dose for pediatric participants, or equivalent. Inhaled and topical steroids are allowed.
- Administration of antineoplastic or immunomodulating agents or radiotherapy within 90 days prior to informed consent.
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Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.
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History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
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History of any reaction or hypersensitivity likely to be exacerbated by any medicinal products or medical equipment whose use is foreseen in this study.
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Current or previous, confirmed, or suspected disease caused by N. meningitidis.
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Known contact to an individual with any laboratory-confirmed N. meningitidis infection within 60 days, prior to enrolment.
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History of neuroinflammatory or autoimmune condition.
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Recurrent history or un-controlled neurological disorders or seizures.
Prior/Concomitant therapy
- Use of any investigational or non-registered product other than the study vaccine(s) during the period starting 30 days before the informed consent or planned use during the study period.
- Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 180 days before the informed consent or planned administration during the study period.
- Previous vaccination with any group B meningococcal vaccine at any time prior to informed consent and assent as applicable.
- Previous vaccination with 2 doses of quadrivalent meningococcal conjugate vaccine (MenACWY, Menveo, Menactra or MenQuadfi).
Prior/Concurrent clinical study experience
• Participant concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational vaccine/product, will not be enrolled.
Other exclusions
- Child in care.
- Pregnant or lactating female.
- Female planning to become pregnant or planning to discontinue contraceptive precautions.
- Any study personnel or immediate dependents, family, or household member.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MenB+MenACWY Group Meningococcal Group B Vaccine (GSK3536829A) (rMenB+OMV NZ) Participants received 1 dose of rMenB+OMV NZ vaccine administered concomitantly with 1 dose of MenACWY vaccine, as separate injections in each arm at Day 1, 1 dose of rMenB+OMV NZ vaccine at Day 61 and 1 dose of placebo at Day 91. MenB+MenACWY Group Meningococcal MenACWY Conjugate Vaccine (GSK3536820A) (MenA lyo + MenCWY liquid) Participants received 1 dose of rMenB+OMV NZ vaccine administered concomitantly with 1 dose of MenACWY vaccine, as separate injections in each arm at Day 1, 1 dose of rMenB+OMV NZ vaccine at Day 61 and 1 dose of placebo at Day 91. MenB+MenACWY Group Placebo Participants received 1 dose of rMenB+OMV NZ vaccine administered concomitantly with 1 dose of MenACWY vaccine, as separate injections in each arm at Day 1, 1 dose of rMenB+OMV NZ vaccine at Day 61 and 1 dose of placebo at Day 91. MenB Group Meningococcal Group B Vaccine (GSK3536829A) (rMenB+OMV NZ) Participants received 1 dose of rMenB+OMV NZ vaccine administered concomitantly with 1 dose of placebo, as separate injections in each arm at Day 1, 1 dose of rMenB+OMV NZ vaccine at Day 61 and 1 dose of MenACWY at Day 91. MenB Group Meningococcal MenACWY Conjugate Vaccine (GSK3536820A) (MenA lyo + MenCWY liquid) Participants received 1 dose of rMenB+OMV NZ vaccine administered concomitantly with 1 dose of placebo, as separate injections in each arm at Day 1, 1 dose of rMenB+OMV NZ vaccine at Day 61 and 1 dose of MenACWY at Day 91. MenB Group Placebo Participants received 1 dose of rMenB+OMV NZ vaccine administered concomitantly with 1 dose of placebo, as separate injections in each arm at Day 1, 1 dose of rMenB+OMV NZ vaccine at Day 61 and 1 dose of MenACWY at Day 91. MenACWY Group Meningococcal Group B Vaccine (GSK3536829A) (rMenB+OMV NZ) Participants received 1 dose of MenACWY vaccine administered concomitantly with 1 dose of placebo, as separate injections in each arm at Day1, 1 dose of rMenB+OMV NZ vaccine each administered at Day 61 and at Day 91. MenACWY Group Meningococcal MenACWY Conjugate Vaccine (GSK3536820A) (MenA lyo + MenCWY liquid) Participants received 1 dose of MenACWY vaccine administered concomitantly with 1 dose of placebo, as separate injections in each arm at Day1, 1 dose of rMenB+OMV NZ vaccine each administered at Day 61 and at Day 91. MenACWY Group Placebo Participants received 1 dose of MenACWY vaccine administered concomitantly with 1 dose of placebo, as separate injections in each arm at Day1, 1 dose of rMenB+OMV NZ vaccine each administered at Day 61 and at Day 91.
- Primary Outcome Measures
Name Time Method Number of Participants With Solicited Local Adverse Events (AEs) After the Vaccination With rMenB+OMV NZ During 7 days after the rMenB+OMV NZ vaccination at Day 91 Solicited local adverse events assessed are injection site pain, erythema, swelling, induration. Any solicited local AEs = occurrence of the symptom regardless of intensity grade.
Number of Participants With Solicited Local AEs After the Vaccination With MenACWY During 7 days after the MenACWY vaccination at Day 91 Solicited local adverse events assessed are injection site pain, erythema, swelling, induration. Any solicited local AEs= occurrence of the symptom regardless of intensity grade.
Number of Participants With Solicited Local AEs After the Vaccination With Placebo During 7 days after the Placebo vaccination at Day 91 Solicited local adverse events assessed are injection site pain, erythema, swelling, induration. Any solicited local AEs = occurrence of the symptom regardless of intensity grade.
Number of Participants With Solicited Systemic AEs During 7 days after the third study intervention administration occurring at Day 91 Solicited systemic adverse events assessed are fever \[temperature \>= 38.0°C\], nausea, fatigue, myalgia, arthralgia, and headache.
Number of Participants With Any Unsolicited AEs (Including All Serious Adverse Events) During 30 days after the third study intervention administration occurring at Day 91 Unsolicited adverse events are defined as any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms are reported as an unsolicited adverse event. Any solicited AE that has not resolved within 30 days post vaccination and is reported during clinic visits or safety follow-up calls is entered into the subject's electronic Case Report Form (eCRF) as an unsolicited AE. Serious Adverse Events (SAEs) are any untoward medical occurrence that result in death, are life-threatening, require hospitalization or prolongation of existing hospitalization, result in disability/incapacity and is a congenital anomaly/birth defect in the offspring of a study subject.
Number of Participants With Any AEs/SAEs Leading to Withdrawal During 30 days after the third study intervention administration occurring at Day 91 Unsolicited AEs are defined as any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms are reported as an unsolicited adverse event. Any solicited AE that has not resolved within 30 days post vaccination and is reported during clinic visits or safety follow-up calls is entered into the subject's electronic Case Report Form (eCRF) as an unsolicited AE. SAEs are any untoward medical occurrence that result in death, are life-threatening, require hospitalization or prolongation of existing hospitalization, result in disability/incapacity and is a congenital anomaly/birth defect in the offspring of a study subject. A participant was considered a 'withdrawal' from the study when no study procedure has occurred, no follow-up has been performed and no further information has been collected for this participant from the date of withdrawal/last contact.
Number of Participants With Any Medically Attended AEs During 30 days after the third study intervention administration occurring at Day 91 Medically attended AEs are symptoms or illnesses requiring hospitalization, or emergency room visit, or visit to/by a health care provider.
Number of Participants With Any SAEs, AEs Leading to Withdrawal and Medically Attended AEs Throughout the study period (Day 1 to Day 271) SAEs, AEs leading to withdrawal and medically attended AEs were assessed throughout the study period are reported in this outcome measure.
Number of Participants Who Received rMenB+OMV NZ With Adverse Events of Special Interest (AESI) Throughout the study period (Day 1 to Day 271) AESIs are predefined (serious or non-serious) adverse events of scientific and medical concern specific to the product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate, because such an event might warrant further investigation in order to characterize and understand it.
Number of Participants With Any SAEs and AEs Leading to Withdrawal During safety follow-up (Day 271 to Day 451) Unsolicited AEs are defined as any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms are reported as an unsolicited adverse event. Any solicited AE that has not resolved within 30 days post vaccination and is reported during clinic visits or safety follow-up calls is entered into the subject's electronic Case Report Form (eCRF) as an unsolicited AE. SAEs are any untoward medical occurrence that result in death, are life-threatening, require hospitalization or prolongation of existing hospitalization, result in disability/incapacity and is a congenital anomaly/birth defect in the offspring of a study subject. A participant was considered a 'withdrawal' from the study when no study procedure has occurred, no follow-up has been performed and no further information has been collected for this participant from the date of withdrawal/last contact.
Number of Participants Who Received rMenB+OMV NZ With AESI During safety follow-up (Day 271 to Day 451) AESIs are predefined (serious or non-serious) adverse events of scientific and medical concern specific to the product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate, because such an event might warrant further investigation in order to characterize and understand it.
Human Serum Bactericidal Assay (hSBA) Geometric Mean Titers (GMTs) Against Each of the N. Meningitidis Serogroup B Strains at 1 Month After the Second Vaccination With rMenB+OMV NZ (Groups MenB+MenACWY and MenB), and Between-group GMT Ratios At Day 91 (1 month after the second vaccination with rMenB+OMV NZ in MenB+MenACWY and MenB groups) hSBA titers were measured by serum bactericidal assay and expressed as Geometric Mean Titers (GMTs) against N. meningitidis serogroup B indicator strains (M14459 \[fHbp\], 96217 \[NadA\], NZ98/254 \[PorA\] and M13520 \[NHBA\]).
hSBA GMTs Against Each of the N. Meningitidis Serogroups A, C, W and Y After Vaccination With MenACWY (Groups MenB+MenACWY and MenACWY), and Between-group GMT Ratios At Day 31 (1 month after the vaccination with MenACWY in MenACWY and MenB+MenACWY groups) hSBA titers were measured by serum bactericidal assay and expressed as GMTs against each of the 4 serogroups Men A, Men C, Men W and Men Y.
- Secondary Outcome Measures
Name Time Method hSBA Geometric Mean Concentrations (GMCs) Measured by ECL Against Each of the N. Meningitidis Serogroups After MenACWY Vaccination At Day 31 (1 month after the vaccination of MenACWY in MenACWY and MenB+MenACWY groups) Immune response to MenACWY given with or without rMenB+OMV NZ, as measured by ectrochemiluminescence-based multiplex (ECL) GMCs against each of the serogroups A, C, W and Y. ECL (validated assay) was used because ELISA is not validated.
hSBA GMTs Against Each of the Serogroup B Strains in Both MenB+MenACWY and MenB Groups After First rMenB+OMV NZ Vaccination and Between-group GMT Ratios At Day 31 (1 month after first vaccination with rMenB+OMV NZ) hSBA titers were measured by bactericidal activity against N. meningitidis serogroup B indicator strains (M14459 \[fHbp\], 96217 \[NadA\], NZ98/254 \[PorA\] and M13520 \[NHBA\]) and expressed in GMTs.
Geometric Mean Ratios (GMRs) Against Each of the N. Meningitidis Serogroup B Strains in Both MenB+MenACWY and MenB Groups After the First rMenB+OMV NZ Vaccination At Dya 31 (1 month after first rMenB+OMV NZ vaccination) compared to the baseline (Day 1) The immune response to rMenB+OMV NZ was measured by bactericidal activity against N. meningitidis serogroup B indicator strains (M14459 \[fHbp\], 96217 \[NadA\], NZ98/254 \[PorA\] and M13520 \[NHBA\]) in terms of GMRs (after vaccination/baseline).
GMRs Against Each of the N. Meningitidis Serogroup B Strains in Both MenB+MenACWY and MenB Groups After the Second rMenB+OMV NZ Vaccination At Day 91 (1 month after the second rMenB+OMV NZ vaccination) compared to the baseline (Day 1) The immune response to rMenB+OMV NZ was measured by bactericidal activity against N. meningitidis serogroup B indicator strains (M14459 \[fHbp\], 96217 \[NadA\], NZ98/254 \[PorA\] and M13520 \[NHBA\]) in terms of GMRs (after vaccination/baseline).
Percentage of Participants With hSBA Titers >= Lower Limit of Quantitation (LLOQ) for Each and All Serogroup B Test Strains in Both MenB+MenACWY and MenB Groups After the First rMenB+OMV NZ Vaccination At Day 31 (one month after the first rMenB+OMV NZ vaccination) The immune response to rMenB+OMV NZ vaccine is evaluated by measuring bactericidal activity in terms of participants with hSBA titers \>= LLOQ against N. meningitidis serogroup B test strains (M14459 \[fHbp\], 96217 \[NadA\], NZ98/254 \[PorA\] and M13520 \[NHBA\]).
Percentage of Participants With hSBA Titers >= LLOQ for Each and All of the Serogroup B Test Strains in Both MenB+MenACWY and MenB Groups After the Second rMenB+OMV NZ Vaccination At Day 91 (1 month after the second rMenB+OMV NZ vaccination) The immune response to rMenB+OMV NZ vaccine is evaluated by measuring bactericidal activity in terms of participants with hSBA titers \>= LLOQ against N. meningitidis serogroup B test strains (M14459 \[fHbp\], 96217 \[NadA\], NZ98/254 \[PorA\] and M13520 \[NHBA\]).
Percentage of Participants With 4-fold Increase in hSBA Titers Relative to Baseline in Both MenB+MenACWY and MenB Groups After the First rMenB+OMV NZ Vaccination At 1 month after the first rMenB+OMV NZ vaccination (i.e at Day 31) relative to baseline (i.e. Day 1) The immune response to rMenB+OMV NZ vaccine is evaluated by measuring bactericidal activity against each of N. meningitidis serogroup B test strains (M14459 \[fHbp\], 96217 \[NadA\], NZ98/254 \[PorA\] and M13520 \[NHBA\]) in terms of the Four-fold increase defined as: - For a pre-vaccination titer \< limit of detection (LOD), a post-vaccination titer of \>= 4-fold the LOD or \>= LLOQ, whichever is greater, - For a pre-vaccination titer \>= LOD but \<LLOQ, a post vaccination titer of at least 4-fold the LLOQ, - For a pre-vaccination titer \>= LLOQ, a post vaccination titer of at least 4-fold the pre-vaccination titer.
Percentage of Participants With 4-fold Increase in hSBA Titers Relative to Baseline in Both MenB+MenACWY and MenB Groups After the Second rMenB+OMV NZ Vaccination At 1 month after the second rMenB+OMV vaccination (i.e at Day 91) relative to baseline (i.e. Day 1) The immune response to rMenB+OMV NZ vaccine is evaluated by measuring bactericidal activity against each of the N. meningitidis serogroup B test strains (M14459 \[fHbp\], 96217 \[NadA\], NZ98/254 \[PorA\] and M13520 \[NHBA\]) in terms of the Four-fold increase defined as: - For a pre-vaccination titer \<LOD, a post-vaccination titer of \>= 4-fold the LOD or \>= LLOQ, whichever is greater, - For a pre-vaccination titer \>=LOD but \<LLOQ, a post vaccination titer of at least 4-fold the LLOQ, - For a pre-vaccination titer \>=LLOQ, a post vaccination titer of at least 4-fold the pre-vaccination titer.
Percentage of Participants With hSBA Titers >=LLOQ for Each of the Serogroup A, C, W and Y in Both MenB+MenACWY and MenACWY Groups After MenACWY Vaccination At baseline (Day 1) and at one month after the MenACWY vaccination (i.e. Day 31) The immune response to MenACWY vaccines is expressed in terms of percentage of participants with hSBA titers \>=LLOQ for each of the serogroup Men A, Men C, Men W and Men Y.
GMRs Against Each of the N. Meningitidis Serogroup Men A, Men C, Men W and Men Y in Both MenB+MenACWY and MenACWY Groups After MenACWY Vaccination At 1 month after MenACWY vaccination (i.e.at Day 31) compared to the baseline (Day 1) Immune response to MenACWY given with or without rMenB+OMV NZ was measured by bactericidal activity against the four serogroups Men A, Men C, Men W and Men Y in terms of GMRs at one month after MenACWY vaccination compared to the baseline at Day 1/Month 0. GMR was measured within-group.
Percentage of Participants With 4-fold Increase in hSBA Titers Against Each of the N. Meningitidis Serogroup Men A, Men C, Men W and Men Y Relative to Baseline in Both MenB+MenACWY and MenACWY Groups After MenACWY Vaccination At 1 month after MenACWY vaccination (i.e at Day 31) relative to baseline (i.e. Day 1) The immune response to MenACWY vaccine is evaluated by measuring percentage of participants with 4-fold increase for the four serogroups Men A, Men C, Men W and Men Y. The Four-fold increase defined as: - For a pre-vaccination titer \<LOD, a post-vaccination titer of \>= 4-fold the LOD or \>= LLOQ, whichever is greater, - For a pre-vaccination titer \>=LOD but \<LLOQ, a post vaccination titer of at least 4-fold the LLOQ, - For a pre-vaccination titer \>= LLOQ, a post vaccination titer of at least 4-fold the pre-vaccination titer
Trial Locations
- Locations (1)
GSK Investigational Site
🇮🇹Milano, Italy