Effectiveness of GlaxoSmithKline Biologicals S.A's Meningococcal Group B and Combined ABCWY Vaccines in Healthy Adolescents and Young Adults

Study at a glance

From the registry record, last updated by the sponsor on 5 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

A Phase III, Randomized, Controlled, Observer-blind Study to Demonstrate Effectiveness, Immunogenicity and Safety of GSK's Meningococcal Group B and Combined ABCWY Vaccines When Administered to Healthy Adolescents and Young Adults

ClinicalTrials.gov ID

NCT04502693

Acronym / sponsor ID

205416

Conditions

Infections, Meningococcal

Keywords

Bexsero, Menveo, MenABCWY, Effectiveness, Invasive meningococcal disease, Meningitis

Phase

Phase 3

Study type

Interventional

Recruitment status

Completed

Enrolment

3,657 participants (actual)

Lead sponsor

GlaxoSmithKlineIndustry (pharma, biotech, devices)

Study start

14 Aug 2020 (actual)

Primary completion

13 Sep 2022 (actual)

Study completion

13 Sep 2022 (actual)

First posted

6 Aug 2020 (actual)

Results

Posted 5 Mar 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Prevention

Allocation

Randomised

Intervention model

Parallel groups

Masking

Quadruple blind (participant, care provider, investigator, outcomes assessor)

Number of arms

7

Who may qualify

Ages

10 to 25 years

Sex

All

Healthy volunteers

Accepted

Age groups

Child, Adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Percentage of Blood Samples Without Bactericidal Serum Activity Against Each of the Endemic US N. Meningitidis Serogroup B Strains at 1 Month After the 3-dose (0,2,6-M), 2-dose(0,6-M) Vaccination Schedule of rMenB+OMV and 1 Dose of MenACWY

   Time frame: At 1 month after vaccination schedule (i.e., Day 211 for MenB_0_2_6 group [3-dose schedule] and MenB_0_6 group, and Day 31 for ACWY group)

   The effectiveness (test-based) of rMenB+OMV vaccine at 1 month after the 3 doses in MenB_0_2_6 group and 1 month after the 2 dose schedule in MenB_0_6 group when compared to one dose of MenACWY vaccination in ACWY group, against a panel of N. meningitidis serogroup B strains was measured in terms of percentage of samples without 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. Participants were randomly selected for testing against each strain therefore only a subset of participants were tested for each of the strains.

2. Percentage of Blood Samples Without Bactericidal Serum Activity Against Each of the Endemic US N. Meningitidis Serogroup B Strains at 1 Month After the 2-dose (0,2-M) Vaccination Schedule of rMenB+OMV and 1 Dose of MenACWY

   Time frame: At 1 month after vaccination schedule (i.e., Day 91 for the MenB_0_2_6 group [2-dose schedule] and Day 31 for ACWY group)

   The effectiveness (test-based) of rMenB+OMV vaccine at 1 month after the 2 doses in MenB_0_2_6 group when compared to one dose of MenACWY vaccination in ACWY group, against a panel of N. meningitidis serogroup B strains was measured in terms of percentage of samples without 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. Participants were randomly selected for testing against each strain therefore only a subset of participants were tested for each of the strains.

3. Percentage of Participants Whose Sera Kill Greater Than or Equal to (>=) 70% of the Strains Tested Using Enc-hSBA at 1 Month After the 3-dose (0,2,6-M) Schedule of rMenB+OMV and 2-dose(0,6-M) Schedule of rMenB+OMV

   Time frame: At 1 month after vaccination schedule (i.e., Day 211 for MenB_0_2_6 group [3-dose schedule] and MenB_0_6 group)

   The effectiveness (responder-based) of the rMenB+OMV NZ vaccine was measured in terms of percentage of participants whose sera kill >=70% of the strains tested using enc-hSBA, calculated based on Clopper Pearson method. Effectiveness is demonstrated if Lower Limit (LL) of the two-sided 97.5% CI for the percentages of participants whose sera kill ≥70% of strains is above 65%.

4. Percentage of Participants Whose Sera Kill >=70% of the Strains Tested Using Enc-hSBA at 1 Month After the 2-dose (0,2-M) Schedule of rMenB+OMV

   Time frame: At 1 month after vaccination schedule (i.e., Day 91 for the MenB_0_2_6 group [2-dose schedule])

   The effectiveness (responder-based) of the rMenB+OMV NZ vaccine was measured in terms of percentage of participants whose sera kill >=70% of the strains tested using enc-hSBA, calculated based on Clopper Pearson method. Effectiveness is demonstrated if Lower Limit (LL) of the two-sided 97.5% CI for the percentages of participants whose sera kill ≥70% of strains is above 65%.

5. Geometric Mean Titers (GMTs) Against Serogroups A, C, W and Y for Each Lot (ABCWY-1 Group, ABCWY-2 Group and ABCWY-3 Group) at 1 Month After the Last Vaccination of MenABCWY

   Time frame: At 1 month after the last vaccination of MenABCWY (Day 211)

   Immune response was measured in terms of hSBA GMTs directed against serogroups A, C, W and Y. As pre-specified in the protocol, the data reported in this outcome measures data were presented for individual lots to demonstrate the consistency of the immune response of 3 lots (ABCWY- 1 Group, ABCWY-2 Group, and ABCWY-3 Group) of the ACWY component of the MenABCWY vaccine.

6. Percentage of Participants With 4-fold Rise in hSBA Titers Against N. Meningitidis Serogroups A, C, W and Y at 1 Month After Last MenABCWY Vaccination (Pooled Lots) and MenACWY Vaccination (for the ACWY Group), Relative to Baseline

   Time frame: At 1 month after vaccination schedule (i.e., Day 211 for the ABCWY_Pooled group and Day 31 for the ACWY Group) compared to Day 1 (baseline)

   Four-fold rise is defined as: If the pre-vaccination hSBA titer is < 4, then post-vaccination hSBA titer should be >= 16 . If the pre-vaccination hSBA titer is >= limit of detection (LOD) but < LL of quantification (LLOQ), then post-vaccination hSBA titer should be >= 4 times the LLOQ. If the pre-vaccination hSBA titer is >= LLOQ, then post-vaccination hSBA titer should be >= 4 times the pre-vaccination hSBA titer. As pre-specified in the protocol, data reported in this outcome measure were presented for ACWY group, ABCWY pooled group to evaluate the immunological non-inferiority of 2 doses of the MenABCWY vaccines against MenACWY vaccines, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.

7. Percentage of Blood Samples Without Bactericidal Serum Activity Against Each of the Endemic U.S N. Meningitidis Serogroup B Strains at 1 Month After Last MenABCWY Vaccination (Pooled Lots) and MenACWY Vaccination (for the ACWY Group)

   Time frame: At 1 month after the vaccination schedule (i.e., Day 211 for the ABCWY_Pooled group and Day 31 for the ACWY group)

   The effectiveness (test-based) of 2 doses of MenABCWY vaccine when compared to 1 dose of MenACWY vaccine, against a panel of N. meningitidis serogroup B strains was measured in terms of percentage of samples without bactericidal activity using 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. As pre-specified in the protocol, data reported in this outcome measure were presented for ACWY group and ABCWY pooled group to evaluate the effectiveness of 2 doses of the MenABCWY vaccines against MenACWY vaccines, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.

8. Percentage of Blood Samples With Bactericidal Serum Activity Against Each of the Endemic U.S N. Meningitidis Serogroup B Strains at 1 Month After the Last MenABCWY Dose (Pooled Lots) and 2-dose(0,2-M) Schedule of rMenB+OMV

   Time frame: At 1 month after the vaccination schedule (i.e., Day 211 for the ABCWY_Pooled group and Day 91 for the MenB_0_2_6 Group [2-dose schedule])

   The effectiveness was measured in terms of percentage of samples with bactericidal activity using 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. As pre-specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 Group and ABCWY pooled group to evaluate the effectiveness of 2 doses of the MenABCWY vaccines against MenACWY vaccines, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.

9. Percentage of Participants Whose Sera Kill >=70% of the Strains Tested Using Enc-hSBA at 1 Month After the Last Vaccination in the ABCWY Group (Pooled Lots)

   Time frame: At 1 month after the last vaccination of MenABCWY (Day 211)

   The effectiveness (responder-based) of the MenABCWY vaccine is measured in terms of percentage of participants whose sera kill >=70% of the strains tested using enc-hSBA, being calculated based on Clopper Pearson method. Effectiveness is demonstrated Lower Limit (LL) of the two-sided 97.5% CI for the percentages of participants whose sera kill ≥70% of strains tested for MenABCWY is above 65%.

10. Number of Participants With Any Solicited Local Adverse Events (AEs) After the First Study Intervention Administration

    Time frame: During 7 days after the first study intervention administration occurring at Day 1

    Assessed solicited local adverse events were injection or administration site = pain, erythema, swelling, induration. Any = occurrence of the adverse event regardless of intensity grade. Any erythema and swelling = adverse event reported with a surface diameter greater than 0 millimeters. No solicited AEs were collected after vaccination on Day 211 because these vaccines were administered as part of standard of care and to maintain blinding. As pre- specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group.

11. Number of Participants With Any Solicited Local Adverse Events (AEs) After the Second Study Intervention Administration

    Time frame: During 7 days after the second study intervention administration occurring at Day 61

    Assessed solicited local adverse events were injection or administration site pain, erythema, swelling, induration. Any = occurrence of the adverse event regardless of intensity grade. Any erythema and swelling = adverse event reported with a surface diameter greater than 0 millimeters. No solicited AEs were collected after vaccination on Day 211 because these vaccines were administered as part of standard of care and to maintain blinding. As pre- specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group.

12. Number of Participants With Any Solicited Local Adverse Events (AEs) After the Third Study Intervention Administration

    Time frame: During 7 days after the third study intervention administration occurring at Day 181

    Assessed solicited local adverse events were injection or administration site pain, erythema, swelling, induration. Any = occurrence of the adverse event regardless of intensity grade. Any erythema and swelling = adverse event reported with a surface diameter greater than 0 millimeters. No solicited AEs were collected after vaccination on Day 211 because these vaccines were administered as part of standard of care and to maintain blinding. As pre- specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group.

13. Number of Participants With Any Solicited Systemic AEs After the First Study Intervention Administration

    Time frame: During 7 days after the first study intervention administration occurring at Day 1

    Assessed solicited systemic AEs were fatigue, nausea, myalgia, arthralgia, headache and fever [temperature >= 38.0°C]. Any = occurrence of the adverse event regardless of intensity grade or relation to study vaccination. No solicited AEs were collected after vaccination on Day 211 because these vaccines were administered as part of standard of care and to maintain blinding. As pre- specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group.

14. Number of Participants With Any Solicited Systemic AEs After the Second Study Intervention Administration

    Time frame: During 7 days after the second study intervention administration occurring at Day 61

    Assessed solicited systemic AEs were fatigue, nausea, myalgia, arthralgia, headache and fever [temperature >= 38.0°C]. Any = occurrence of the adverse event regardless of intensity grade or relation to study vaccination. No solicited AEs were collected after vaccination on Day 211 because these vaccines were administered as part of standard of care and to maintain blinding. As pre- specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group.

15. Number of Participants With Any Solicited Systemic AEs After the Third Study Intervention Administration

    Time frame: During 7 days after the third study intervention administration occurring at Day 181

    Assessed solicited systemic AEs were fatigue, nausea, myalgia, arthralgia, headache and fever [temperature >= 38.0°C]. Any = occurrence of the adverse event regardless of intensity grade or relation to study vaccination. No solicited AEs were collected after vaccination on Day 211 because these vaccines were administered as part of standard of care and to maintain blinding. As pre- specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group.

16. Number of Participants With Any Unsolicited AEs After the First Study Intervention Administration

    Time frame: During the 30 days after the first study intervention administration occurring at Day 1

    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 were reported as an unsolicited AE. Any Unsolicited AEs (including Serious adverse events (SAEs), AEs leading to withdrawal, Adverse event of special interest (AESIs) and medically attended AEs were collected during 30 days after vaccination 1-3. For vaccination on Day 211 (Vaccination 4), conducted as part of standard of care and to maintain blinding, no eDiary data or all unsolicited AEs were collected for the 30 days following vaccination. However, SAEs, AEs leading to withdrawal, AESIs and medically attended AEs were collected throughout study duration. As pre-specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group.

17. Number of Participants With Any Unsolicited AEs After the Second Study Intervention Administration

    Time frame: During the 30 days after the second study intervention administration occurring at Day 61

    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 were reported as an unsolicited AE. Any Unsolicited AEs (including Serious adverse events (SAEs), AEs leading to withdrawal, Adverse event of special interest (AESIs) and medically attended AEs were collected during 30 days after vaccination 1-3. For vaccination on Day 211 (Vaccination 4), conducted as part of standard of care and to maintain blinding, no eDiary data or all unsolicited AEs were collected for the 30 days following vaccination. However, SAEs, AEs leading to withdrawal, AESIs and medically attended AEs were collected throughout study duration. As pre-specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group.

18. Number of Participants With Any Unsolicited AEs After the Third Study Intervention Administration

    Time frame: During the 30 days after the third study intervention administration occurring at Day 181

    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 were reported as an unsolicited AE. Any Unsolicited AEs (including Serious adverse events (SAEs), AEs leading to withdrawal, Adverse event of special interest (AESIs) and medically attended AEs were collected during 30 days after vaccination 1-3. For vaccination on Day 211 (Vaccination 4), conducted as part of standard of care and to maintain blinding, no eDiary data or all unsolicited AEs were collected for the 30 days following vaccination. However, SAEs, AEs leading to withdrawal, AESIs and medically attended AEs were collected throughout study duration. As pre-specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group.

19. Number of Participants With SAEs, AEs Leading to Withdrawal, AESIs and Medically Attended AEs

    Time frame: Throughout the study period (Day 1 to 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. Medically attended AEs are symptoms or illnesses requiring hospitalization, or emergency room visit, or visit to/by a health care provider. As pre-specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2024.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Derived from this study: PubMed 39647494Nolan T, Bhusal C, Beran J, Bloch M, Cetin BS, Dinleyici EC, Drazan D, Kokko S, Koski S, Laajalahti O, Langley JM, Ramet M, Richmond PC, Silas P, Tapiero B, Tiong F, Tipton M, Ukkonen B, Ulukol B, Lattanzi M, Trapani M, Willemsen A, Toneatto D; QUINTET study group. Breadth of immune response, immunogenicity, reactogenicity, and safety for a pentavalent meningococcal ABCWY vaccine in healthy adolescents and young adults: results from a phase 3, randomised, controlled observer-blinded trial. Lancet Infect Dis. 2025 May;25(5):560-573. doi: 10.1016/S1473-3099(24)00667-4. Epub 2024 Dec 5.
• Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.

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Referral and contact

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112 sites in 7 countries: see every site and its status.