A Phase I/II, Randomised, Controlled Study to Assess the Safety, Effectiveness and Immune Response of Meningococcal Combined ABCWY Vaccine When Administered to Healthy Adults (Phase I) and to Healthy Adolescents and Adults (Phase II)
Overview
- Phase
- Phase 1
- Intervention
- MenACWY vaccine
- Conditions
- Infections, Meningococcal
- Sponsor
- GlaxoSmithKline
- Enrollment
- 1440
- Locations
- 1
- Primary Endpoint
- Number of Participants With Solicited Administration Site Events in Study Phase I (Safety Lead-in)
- Status
- Completed
- Last Updated
- 11 months ago
Overview
Brief Summary
The purpose of this study was to assess the safety, effectiveness, and immune response of the meningococcal combined ABCWY vaccine (GSK4023393A) intended to protect against invasive meningococcal disease (IMD) caused by all 5 meningococcal serogroups. The first time-in-human (FTIH), Phase I part of this study was conducted in healthy adults in a dose-escalating fashion with 2 formulations of the investigational MenABCWY-2Gen vaccine and served as a safety lead-in to the Phase II study. The Phase II part of the study was conducted in 2 parts: The 'formulation and schedule-finding' part followed in healthy adolescents and young adults and was designed to select the vaccine formulation and the schedule to be tested in Phase III. The 'blood sourcing' part was conducted in healthy adults in order to collect sufficient serum samples for the development of assays to be used in the MenABCWY-2Gen vaccine clinical development program.
Investigators
Eligibility Criteria
Inclusion Criteria
- •All inclusion criteria are applicable for both study phases, except where specified otherwise.
- •Participants and/or participants' parent(s)/Legally Acceptable Representative(s) (LAR) who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the eDiaries, return for follow-up visits).
- •Written or witnessed/thumb printed informed consent obtained from the participant or /parent(s)/LAR(s) of the participant prior to performance of any study specific procedure.
- •Written informed assent obtained from the participant (if applicable) prior to performing any study specific procedure.
- •Phase I only: A male or female between, and including, 18 and 40 years of age (i.e. 40 years + 364 days) at the time of the first study intervention administration.
- •Phase II (Formulation and Schedule-finding) only: A male or female between, and including, 10 and 25 years of age (i.e. 25 years + 364 days) at the time of the first study intervention administration.
- •Phase II (Sourcing) only: A male or female between, and including, 18 and 50 years of age (i.e. 50 years + 364 days) at the time of the first study intervention administration.
- •Participants who are either unvaccinated with MenACWY vaccine or have received a single previous dose of MenACWY vaccine can participate in the study, if they have received it at least 4 years prior to informed consent and assent as applicable (with the exception of meningococcal C vaccination, if the last dose of MenC was received at ≤24 months of age).
- •Healthy participants as established by medical history and clinical examination before entering into the study.
- •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.
Exclusion Criteria
- •Medical conditions
- •Current or previous, confirmed or suspected disease caused by N. meningitidis.
- •Household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis infection within 60 days of enrolment.
- •Progressive, unstable or uncontrolled clinical conditions.
- •Clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
- •Are obese at enrolment (e.g. for participants from 20 years of age a body mass index (BMI) ≥ 30 kg/m2, for participants up to 19 years of age a BMI ≥ 95th percentile for age and gender or as applicable per country recommendations).
- •Any neuroinflammatory (including but not limited to: demyelinating disorders, encephalitis or myelitis of any origin), congenital neurological conditions, encephalopathies, seizures (including all subtypes such as: absence seizures, generalised tonic-clonic seizures, partial complex seizures, partial simple seizures). History of febrile convulsions should not lead to exclusion.
- •History of any reaction or hypersensitivity likely to be exacerbated by any component of the study interventions.
- •Hypersensitivity, including allergy, to any component of vaccines, including diphtheria toxoid (CRM197) and latex medicinal products or medical equipment whose use is foreseen in this study.
- •Abnormal function or modification of the immune system resulting from:
Arms & Interventions
Control Group
Participants randomized to the control group received two doses of the Bexsero (MenB) vaccine on Day 1 and Day 181, following a 0, 6-month schedule, and one dose of Menveo (MenACWY) on Day 1 during Study Phase II (Formulation and Schedule-Finding).
Intervention: MenACWY vaccine
ABCWY low dose_01 Group
Participants received two doses of MenABCWY-2Gen low dose vaccine on Day 1 and Day 31, following a 0, 1-month schedule during study Phase II (Sourcing).
Intervention: MenABCWY-2Gen low dose vaccine
ABCWY high dose_01 Group
Participants received two doses of MenABCWY-2Gen high dose vaccine on Day 1 and Day 31, following a 0, 1-month schedule during study Phase II (Sourcing).
Intervention: MenABCWY-2Gen high dose vaccine
ABCWY low dose Group
Participants received two doses of the MenABCWY-2Gen low-dose vaccine on Day 1 and Day 31, following a 0, 1-month schedule during Study Phase I (Safety Lead-In).
Intervention: MenABCWY-2Gen low dose vaccine
Placebo low dose Group
Participants received two doses of a placebo on Day 1 and Day 31, following a 0, 1-month schedule during Study Phase I (Safety Lead-In), as the control group for the ABCWY low-dose group.
Intervention: Placebo
ABCWY high dose Group
Participants received two doses of the MenABCWY-2Gen high-dose vaccine on Day 1 and Day 31, following a 0, 1-month schedule during Study Phase I (Safety Lead-In).
Intervention: MenABCWY-2Gen high dose vaccine
Placebo high dose Group
Participants received two doses of a placebo on Day 1 and Day 31, following a 0, 1-month schedule during Study Phase I (Safety Lead-In), as the control group for the ABCWY high-dose group.
Intervention: Placebo
ABCWY low dose_06 Group
Participants received two doses of the MenABCWY-2Gen low-dose vaccine on Day 1 and Day 181, following a 0, 6-month schedule, along with one dose of a placebo on Day 121 during Phase II (Formulation and Schedule-Finding).
Intervention: MenABCWY-2Gen low dose vaccine
ABCWY low dose_06 Group
Participants received two doses of the MenABCWY-2Gen low-dose vaccine on Day 1 and Day 181, following a 0, 6-month schedule, along with one dose of a placebo on Day 121 during Phase II (Formulation and Schedule-Finding).
Intervention: Placebo
ABCWY low dose_02 Group
Participants received two doses of the MenABCWY-2Gen low-dose vaccine on Day 121 and Day 181, following a 0, 2-month schedule, along with one dose of a placebo on Day 1 during Phase II (Formulation and Schedule-Finding).
Intervention: MenABCWY-2Gen low dose vaccine
ABCWY low dose_02 Group
Participants received two doses of the MenABCWY-2Gen low-dose vaccine on Day 121 and Day 181, following a 0, 2-month schedule, along with one dose of a placebo on Day 1 during Phase II (Formulation and Schedule-Finding).
Intervention: Placebo
ABCWY high dose_06 Group
Participants received two doses of the MenABCWY-2Gen high-dose vaccine on Day 1 and Day 181, following a 0, 6-month schedule, along with one dose of a placebo on Day 121 during Phase II (Formulation and Schedule-Finding).
Intervention: MenABCWY-2Gen high dose vaccine
ABCWY high dose_06 Group
Participants received two doses of the MenABCWY-2Gen high-dose vaccine on Day 1 and Day 181, following a 0, 6-month schedule, along with one dose of a placebo on Day 121 during Phase II (Formulation and Schedule-Finding).
Intervention: Placebo
ABCWY high dose_02 Group
Participants received two doses of the MenABCWY-2Gen high-dose vaccine on Day 121 and Day 181, following a 0, 2-month schedule, along with one dose of a placebo on Day 1 during Phase II (Formulation and Schedule-Finding).
Intervention: MenABCWY-2Gen high dose vaccine
ABCWY high dose_02 Group
Participants received two doses of the MenABCWY-2Gen high-dose vaccine on Day 121 and Day 181, following a 0, 2-month schedule, along with one dose of a placebo on Day 1 during Phase II (Formulation and Schedule-Finding).
Intervention: Placebo
Control Group
Participants randomized to the control group received two doses of the Bexsero (MenB) vaccine on Day 1 and Day 181, following a 0, 6-month schedule, and one dose of Menveo (MenACWY) on Day 1 during Study Phase II (Formulation and Schedule-Finding).
Intervention: MenB vaccine
ABCWY low doseS_02 Group
Participants received two doses of MenABCWY-2Gen low dose vaccine on Day 1 and day 61 following a 0, 2-month schedule during study Phase II (Sourcing).
Intervention: MenABCWY-2Gen low dose vaccine
ABCWY high doseS_02 Group
Participants received two doses of MenABCWY-2Gen high dose vaccine on Day 1 and day 61 following a 0, 2-month schedule during study Phase II (Sourcing).
Intervention: MenABCWY-2Gen high dose vaccine
ABCWY low doseS_06 Group
Participants received two doses of MenABCWY-2Gen low dose vaccine on Day 1 and day 181 following a 0, 6-month schedule during study Phase II (Sourcing).
Intervention: MenABCWY-2Gen low dose vaccine
ABCWY high doseS_06 Group
Participants received two doses of MenABCWY-2Gen high dose vaccine on Day 1 and day 181 following a 0, 6-month schedule during study Phase II (Sourcing).
Intervention: MenABCWY-2Gen high dose vaccine
Outcomes
Primary Outcomes
Number of Participants With Solicited Administration Site Events in Study Phase I (Safety Lead-in)
Time Frame: During the 7 days (including the day of vaccination) following vaccination at Day 31
The solicited administration site events include injection site pain, erythema (redness), swelling and induration. Any solicited administration site AEs = occurrence of the symptom regardless of intensity grade.
Number of Participants With Solicited Systemic Events in Study Phase I (Safety Lead-in)
Time Frame: During the 7 days (including the day of vaccination) following vaccination at Day 31
The solicited systemic events include fever (temperature ≥ 38.0°C), nausea, fatigue, myalgia, arthralgia and headache.
Number of Participants With Any Unsolicited Adverse Events (AEs), Including All Serious Adverse Events (SAEs), AEs Leading to Withdrawal and AEs of Special Interest (AESIs) in Study Phase I (Safety Lead-in)
Time Frame: During the 30 days (including the day of vaccination) following vaccination at Day 1
Unsolicited AEs includes 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 is reported as an unsolicited adverse event. A SAE is any untoward medical occurrence that results in death, is life-threatening, requires or prolongs hospitalization, results in disability/incapacity and is a congenital anomaly/birth defect in a subject's offspring. AESIs are predefined (serious or non-serious) AEs 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 to characterize and understand it. A participant was considered withdrawn if no study procedures occurred, and no follow-up or further information has been collected from the date of withdrawal or last contact.
Number of Participants With Any Unsolicited AEs, Including All SAEs, AEs Leading to Withdrawal and AESIs in Study Phase I (Safety Lead-in)
Time Frame: During the 30 days (including the day of vaccination) following vaccination at Day 31
Unsolicited AEs includes 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 is reported as an unsolicited adverse event. A SAE is any untoward medical occurrence that results in death, is life-threatening, requires or prolongs hospitalization, results in disability/incapacity and is a congenital anomaly/birth defect in a subject's offspring. AESIs are predefined (serious or non-serious) AEs 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 to characterize and understand it. A participant was considered withdrawn if no study procedures occurred, and no follow-up or further information has been collected from the date of withdrawal or last contact.
Number of Participants With SAEs, AEs Leading to Withdrawal and AESIs in Study Phase I (Safety Lead-in)
Time Frame: Throughout the Phase 1 study period (Day 1 through Day 211)
A SAEs is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity and is a congenital anomaly/birth defect in the offspring of a study subject. AESIs are predefined (serious or non-serious) AEs 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 to characterize and understand it. A participant was considered withdrawn if no study procedures occurred, and no follow-up or further information has been collected from the date of withdrawal or last contact.
Number of Participants With Change From Baseline in Haematological and Biochemical Laboratory Values, in Study Phase I (Safety Lead-in)
Time Frame: At Day 8 (7 days after the first vaccination)
The safety laboratory data included haematological parameters (basophils, eosinophils, Erythrocytes, hemoglobin, leukocytes, lymphocytes, monocytes, platelets and neutrophils), and chemical parameters (Alanine Aminotransferase \[ALT\], Aspartate Aminotransferase \[AST\], Creatinine) Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.
Number of Participants With Clinically Significant Haematological and Biochemical Laboratory Values, in Study Phase I (Safety Lead-in)
Time Frame: At Day 8 (7 days after the first vaccination)
Clinical laboratory testing included hematological and biochemical laboratory values. Any abnormal laboratory test result (e.g., in hematology or clinical chemistry) that was deemed clinically significant by the investigator's medical and scientific judgment, and not related to an underlying disease, was reported as an unsolicited adverse event (AE) unless it was considered by the investigator to be more severe than expected for the participant's condition. The safety laboratory data included hematological parameters (basophils, eosinophils, erythrocytes, hemoglobin, leukocytes, lymphocytes, monocytes, platelets, and neutrophils) and chemical parameters (Alanine Aminotransferase \[ALT\], Aspartate Aminotransferase \[AST\], and creatinine).
Percentage of Blood Samples With Bactericidal Serum Activity Using Enc-hSBA Against a Panel of 110 Randomly Selected Endemic US N. Meningitidis Serogroup B Invasive Disease Strains at Study Phase II (Formulation and Schedule-finding)
Time Frame: At Day 211 (1 month after the last vaccination)
The effectiveness of the MenABCWY-2Gen (low \& high dose) vaccine when administered at 0,2- or 0,6-months schedule compared to MenB vaccine administered at 0,6-months schedule, against a panel of 110 randomly selected endemic N. meningitidis serogroup B strains is measured in terms of percentage of samples with bactericidal activity using endogenous complement human Serum Bactericidal Assay (enc-hSBA), which provides a qualitative assessment (yes/no) of the presence of sufficient bactericidal antibodies in human sera to kill a meningococcal strain at a specific dilution of 1:4.
Number of Participants With a 4-fold Rise in hSBA Titers Against Serogroups A, C, W and Y in Study Phase II (Formulation and Schedule-finding)
Time Frame: At Day 211 for ABCWY groups (1 month after the last MenABCWY-2Gen vaccination) and at Day 31 for Control group (1 month after the last MenACWY vaccination)
The immune response to the MenABCWY-2Gen (low and high dose) vaccine when administered at 0,2- or 0,6-months schedule compared to MenACWY vaccine (single dose), relative to day 1 in the ABCWY and control groups (0, 6 month schedule) and day 31 in ABCWY (0, 2 month schedule) is measured in terms of number of participants achieving a 4-fold rise in hSBA titers against serogroups A, C, W and Y. The 4-fold rise is defined as: -a post-vaccination hSBA titer ≥ 16 for participants with a pre-vaccination hSBA titer \< 4, -a post-vaccination hSBA titer ≥ 4 times the lower limit of quantitation (LLOQ) for participants with a pre-vaccination hSBA titer ≥LOD but \<LLOQ, and. -a post-vaccination hSBA titer ≥ 4 times the pre-vaccination hSBA titer for participants with a pre-vaccination hSBA titer ≥LLOQ.
Number of Participants With Solicited Administration Site Events in Study Phase II (Formulation and Schedule-finding)
Time Frame: During the 7 days (including the day of vaccination) following vaccination at Day 181
Assessed solicited administration site events included injection site pain, erythema (redness), swelling and induration. Any = occurrence of the event regardless of intensity grade.
Number of Participants With Solicited Systemic Events in Study Phase II (Formulation and Schedule-finding)
Time Frame: During the 7 days (including the day of vaccination) following vaccination at Day 181
Assessed solicited systemic events included fever (temperature ≥ 38.0°C), nausea, fatigue, myalgia, arthralgia and headache. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.
Number of Participants With Any Unsolicited AEs (Including All SAEs, AEs Leading to Withdrawal, and AESIs) in Study Phase II (Formulation and Schedule-finding)
Time Frame: During the 30 days (including the day of vaccination) following vaccination at Day 181
Unsolicited AEs includes 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 is reported as an unsolicited adverse event. A SAE is any untoward medical occurrence that results in death, is life-threatening, requires or prolongs hospitalization, results in disability/incapacity and is a congenital anomaly/birth defect in a subject's offspring. AESIs are predefined (serious or non-serious) AEs 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 to characterize and understand it. A participant was considered withdrawn if no study procedures occurred, and no follow-up or further information has been collected from the date of withdrawal or last contact.
Number of Participants With SAEs, AEs Leading to Withdrawal and AESIs in Study Phase II (Formulation and Schedule-Finding)
Time Frame: Throughout the Phase II FSF study period (Day 1 through Day 541)
A SAEs is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity and is a congenital anomaly/birth defect in the offspring of a study subject. AESIs are predefined (serious or non-serious) AEs 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 to characterize and understand it. A participant was considered withdrawn if no study procedures occurred, and no follow-up or further information has been collected from the date of withdrawal or last contact.
Number of Participants With Solicited Administration Site Events in Study Phase II (Sourcing)
Time Frame: During the 7 days (including the day of vaccination) following vaccination at Day 181
Assessed solicited administration site events included injection site pain, erythema (redness), swelling and induration. Any = occurrence of the event regardless of intensity grade.
Number of Participants With Solicited Systemic Events in Study Phase II (Sourcing)
Time Frame: During the 7 days (including the day of vaccination) following vaccination at Day 181
Assessed solicited systemic events included fever (temperature ≥ 38.0°C), nausea, fatigue, myalgia, arthralgia and headache. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.
Number of Participants With Any Unsolicited AEs (Including All SAEs, AEs Leading to Withdrawal, and AESIs) in Study Phase II (Sourcing)
Time Frame: During the 30 days (including the day of vaccination) following vaccination at Day 181
Unsolicited AEs includes 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 is reported as an unsolicited adverse event. A SAE is any untoward medical occurrence that results in death, is life-threatening, requires or prolongs hospitalization, results in disability/incapacity and is a congenital anomaly/birth defect in a subject's offspring. AESIs are predefined (serious or non-serious) AEs 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 to characterize and understand it. A participant was considered withdrawn if no study procedures occurred, and no follow-up or further information has been collected from the date of withdrawal or last contact.
Number of Participants With SAEs, AEs Leading to Withdrawal and AESIs in Study Phase II (Sourcing)
Time Frame: Throughout the study period (Day 1 through Day 361)
A SAEs is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity and is a congenital anomaly/birth defect in the offspring of a study subject. AESIs are predefined (serious or non-serious) AEs 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 to characterize and understand it. A participant was considered withdrawn if no study procedures occurred, and no follow-up or further information has been collected from the date of withdrawal or last contact.
Secondary Outcomes
- Percentage of Participants Classified by Percentages of Serogroup B Invasive Disease Strains Killed Using Enc-hSBA in Each Participant in Study Phase II (Formulation and Schedule-finding)(At Day 211 (1 month after the last vaccination))
- Number of Participants With hSBA Titers ≥ LLOQ for Each and All Serogroup B Indicator Strains in Study Phase II (Formulation and Schedule-finding)(At Day 1 in ABCWY (0,6-months) and Control groups, Day 31 in ABCWY groups (0,2-months) and Day 211 in all study groups)
- Number of Participants With 4-fold Rise in hSBA Titers Against Serogroup B Indicator Strains in Study Phase II (Formulation and Schedule-finding)(At Day 211 (1 month after the last vaccination))
- hSBA Geometric Mean Titers (GMTs) Against Serogroup B Indicator Strains in Study Phase II (Formulation and Schedule-finding)(At Day 1 in ABCWY groups (0,6-months) and Control groups, Day 31 in ABCWY groups (0,2-months) and Day 211 in all study groups)
- Number of Participants With hSBA Titers ≥ LLOQ for Serogroups A, C, W and Y in Study Phase II (Formulation and Schedule-finding)(Day 1 in ABCWY (0,6 Months) & Control; Day 31 pre-vaccination in ABCWY (0,2 Months); Day 31 post-first MenABCWY-2Gen in ABCWY (0,6 Months); Day 211 post-last MenABCWY-2Gen in all ABCWY; Day 31 post-MenACWY in Control)
- hSBA Geometric Mean Ratios (GMRs) Against Serogroup B Indicator Strains in Study Phase II (Formulation and Schedule-finding)(At Day 211 in all study groups versus Day 1 in ABCWY (0,6-months) and Control groups and Day 31 in ABCWY groups (0,2-months))
- Number of Participants With a 4-fold Rise in hSBA Titers Against Serogroups A, C, W and Y in Study Phase II (Formulation and Schedule-finding)(At Day 31 (1 month after the first MenABCWY-2Gen vaccination) in ABCWY (0,6-months) groups)
- hSBA GMTs Against Serogroups A, C, W and Y in Study Phase II (Formulation and Schedule-finding)(Day 1 in ABCWY (0,6 Months) & Control; Day 31 pre-vaccination in ABCWY (0,2 Months); Day 31 post-first MenABCWY-2Gen in ABCWY (0,6 Months); Day 211 post-last MenABCWY-2Gen in all ABCWY; Day 31 post-MenACWY in Control)
- hSBA GMRs Against Serogroups A, C, W and Y in Study Phase II (Formulation and Schedule-finding)(At Day 31 [for ABCWY (0,6-months) and Control group compared to Day 1 (Baseline)], at Day 211 [for ABCWY (0,6-months) groups compared to Day 1 (baseline) and for ABCWY (0,2-months) groups compared to Day 31])
- Immunoglobulin G (IgG) Antibodies Against Serogroups A, C, W and Y in Study Phase II (Formulation and Schedule-finding)(Day 1 in ABCWY (0,6 Months) & Control; Day 31 pre-vaccination in ABCWY (0,2 Months); Day 31 post-first MenABCWY-2Gen in ABCWY (0,6 Months); Day 211 post-last MenABCWY-2Gen in all ABCWY; Day 31 post-MenACWY in Control)