A Study on the Safety, Tolerability and Immune Response of Meningococcal Combined ABCWY Vaccine in Healthy Infants

NCT05082285 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 2170432021-001367-24
• Study Type: interventional
• Target: 724
• Locations: 8 countries
• Sites: 33

Brief Summary

The purpose of this study is to assess the safety, tolerability and immunogenicity of the combined meningococcal groups A, B, C, W and Y (MenABCWY-2Gen) vaccine intended to protect against invasive meningococcal disease (IMD) caused by all 5 meningococcal serogroups, in healthy infants 2 months of age (MoA) at enrolment.

Conditions

Infections, Meningococcal

Keywords

MenABCWY-2Gen; MenABCWY-1Gen; Bexsero; Nimenrix; Safety; Tolerability; Immunogenicity; Invasive Meningococcal Disease; Healthy infants

Outcome Measures

Primary Outcomes (18)

• Percentage of participants with solicited administration site events

  The solicited administration site events include tenderness, erythema, induration and swelling.

  During the 7 days (including the day of vaccination) after each vaccination (vaccines administered on Day 1 and 61 and Day 301)

• Percentage of participants with solicited systemic events

  The solicited systemic events include fever, irritability/fussiness, loss of appetite, drowsiness, vomiting and diarrhoea. Fever is defined as temperature \>38.0°C/100.4°F. The preferred location for measuring temperature will be axillary.

  During the 7 days (including the day of vaccination) after each vaccination (vaccines administered on Day 1 and 61 and Day 301)

• Percentage of participants with any unsolicited adverse events (AEs), including all medically attended adverse events (MAEs), serious adverse events (SAEs), AEs leading to withdrawal, and adverse events of special interest (AESIs)

  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. MAEs are defined as symptoms or illnesses requiring a hospitalization, or an emergency room visit, or visit to/by a health care provider. An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity. 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 in order to characterize and understand it.

  During the 30 days (including the day of vaccination) after each vaccination (vaccines administered on Day 1 and 61 and Day 301)

• Percentages of participants with MAEs, SAEs, AEs leading to withdrawal, and AESIs

  MAEs are defined as symptoms or illnesses requiring a hospitalization, or an emergency room visit, or visit to/by a health care provider. An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity. 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 in order to characterize and understand it.

  During the study period (Day 1 through Day 481)

• Percentage of participants with human serum bactericidal assay (hSBA) titers ≥ lower limit of quantitation (LLOQ) for each serogroup B indicator strain

  The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenB vaccine is evaluated by measuring bactericidal activity using an hSBA against all serogroup B indicator strains.

  At 1 month after the second vaccination (Day 91)

• Percentage of participants with hSBA titers ≥ LLOQ for each serogroup B indicator strain

  The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenB vaccine is evaluated by measuring bactericidal activity using an hSBA against all serogroup B indicator strains.

  At pre-third vaccination (Day 301)

• Percentage of participants with hSBA titers ≥ LLOQ for each serogroup B indicator strain

  The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenB vaccine is evaluated by measuring bactericidal activity using an hSBA against all serogroup B indicator strains.

  At 1 month after the third vaccination (Day 331)

• hSBA geometric mean titers (GMTs) for each serogroup B indicator strain

  The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenB vaccine against serogroup B indicator strains is determined using hSBA GMTs. For each serogroup B indicator strain 90% CIs for the GMTs ratio between ABCWY-2Gen low dose/ ABCWY-2Gen high dose and MenB, is created by exponentiating (base 10) the least squares means and the lower and upper limits of the 90% CIs of the log transformed titers (base 10) obtained from a 2-way Analysis of Variance (ANOVA) with factors for arms and center.

  At 1 month after the second vaccination (Day 91)

• hSBA GMTs for each serogroup B indicator strain

  The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenB vaccine against serogroup B indicator strains is determined using hSBA GMTs. For each serogroup B indicator strain 90% CIs for the GMTs ratio between ABCWY-2Gen low dose/ ABCWY-2Gen high dose and MenB, is created by exponentiating (base 10) the least squares means and the lower and upper limits of the 90% CIs of the log transformed titers (base 10) obtained from a 2-way ANOVA with factors for arms and center.

  At pre-third vaccination (Day 301)

• hSBA GMTs for each serogroup B indicator strain

  The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenB vaccine against serogroup B indicator strains is determined using hSBA GMTs. For each serogroup B indicator strain 90% CIs for the GMTs ratio between ABCWY-2Gen low dose/ ABCWY-2Gen high dose and MenB, is created by exponentiating (base 10) the least squares means and the lower and upper limits of the 90% CIs of the log transformed titers (base 10) obtained from a 2-way ANOVA with factors for arms and center.

  At 1 month after the third vaccination (Day 331)

• Within group hSBA geometric mean ratios (GMRs) for each serogroup B indicator strain

  The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenB vaccine against serogroup B indicator strains is determined using hSBA GMRs. Within-group ratios of hSBA GMTs against each of the N.meningitidis serogroup B indicator strain at Day 331 compared to Day 301.

  At 1 month after the third vaccination (Day 331) compared to pre-third vaccination (Day 301)

• Percentage of participants with hSBA titers ≥ LLOQ for each A, C, W and Y serogroup

  The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenACWY-TT vaccine is evaluated by measuring bactericidal activity using an hSBA against serogroups A, C, W and Y. The percentages of participants with hSBA titers ≥ LLOQ and the corresponding exact 2-sided 95% CIs based on Clopper-Pearson method are calculated.

  At 1 month after the second vaccination (Day 91)

• Percentage of participants with hSBA titers ≥ LLOQ for each A, C, W and Y serogroup

  The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenACWY-TT vaccine is evaluated by measuring bactericidal activity using an hSBA against serogroups A, C, W and Y. The percentages of participants with hSBA titers ≥ LLOQ and the corresponding exact 2-sided 95% CIs based on Clopper-Pearson method are calculated.

  At pre-third vaccination (Day 301)

• Percentage of participants with hSBA titers ≥ LLOQ for each A, C, W and Y serogroup

  The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenACWY-TT vaccine is evaluated by measuring bactericidal activity using an hSBA against serogroups A, C, W and Y. The percentages of participants with hSBA titers ≥ LLOQ and the corresponding exact 2-sided 95% CIs based on Clopper-Pearson method are calculated.

  At 1 month after the third vaccination (Day 331)

• hSBA GMTs for each A, C, W and Y serogroup

  The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenACWY-TT vaccine against serogroups A, C, W and Y is determined using hSBA GMTs. For each A, C, W, and Y serogroup 90% CIs for the GMTs ratio between ABCWY-2Gen low dose/ ABCWY-2Gen high dose and MenACWY-TT, is created by exponentiating (base 10) the least squares means and the lower and upper limits of the 90% CIs of the log transformed titers (base 10) obtained from a 2-way ANOVA with factors for arms and center.

  At 1 month after the second vaccination (Day 91)

• hSBA GMTs for each A, C, W and Y serogroup

  The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenACWY-TT vaccine against serogroups A, C, W and Y is determined using hSBA GMTs. For each A, C, W, and Y serogroup 90% CIs for the GMTs ratio between ABCWY-2Gen low dose/ ABCWY-2Gen high dose and MenACWY-TT, is created by exponentiating (base 10) the least squares means and the lower and upper limits of the 90% CIs of the log transformed titers (base 10) obtained from a 2-way ANOVA with factors for arms and center.

  At pre-third vaccination (Day 301)

• hSBA GMTs for each A, C, W and Y serogroup

  The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenACWY-TT vaccine against serogroups A, C, W and Y is determined using hSBA GMTs. For each A, C, W, and Y serogroup 90% CIs for the GMTs ratio between ABCWY-2Gen low dose/ ABCWY-2Gen high dose and MenACWY-TT, is created by exponentiating (base 10) the least squares means and the lower and upper limits of the 90% CIs of the log transformed titers (base 10) obtained from a 2-way ANOVA with factors for arms and center.

  At 1 month after the third vaccination (Day 331)

• Within group hSBA GMRs for each A, C, W and Y serogroup

  The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenACWY-TT vaccine against serogroups A, C, W and Y is determined using hSBA GMRs. Within-group ratios of hSBA GMTs against each of the N.meningitidis A, C, W and Y serogroups at Day 331 compared to Day 301.

  At 1 month after the third vaccination (Day 331) compared to pre-third vaccination (Day 301)

Study Arms (4)

ABCWY-2Gen low dose Group

EXPERIMENTAL

Participants receive 3 doses of the MenABCWY-2Gen low dose vaccine.

Combination Product: MenABCWY-2Gen low dose vaccine

MenB+MenACWY-TT Group

ACTIVE COMPARATOR

Participants receive 3 doses of both the meningococcal group B (MenB) vaccine and the meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate (MenACWY-TT) vaccine.

Combination Product: MenB vaccine; Combination Product: MenACWY-TT vaccine

ABCWY-2Gen high dose Group

EXPERIMENTAL

Participants receive 3 doses of the MenABCWY-2Gen high dose vaccine in.

Combination Product: MenABCWY-2Gen high dose vaccine

ABCWY-1Gen Group

EXPERIMENTAL

Participants receive 3 doses of the MenABCWY-1Gen vaccine.

Combination Product: MenABCWY-1Gen vaccine

Interventions

MenABCWY-2Gen low dose vaccine COMBINATION_PRODUCT

MenABCWY-2Gen low dose vaccine is administered intramuscularly in the upper thigh region of the right leg as 3 doses to participants in study Part I, Step 1 and study Part II.

ABCWY-2Gen low dose Group

MenABCWY-2Gen high dose vaccine COMBINATION_PRODUCT

MenABCWY-2Gen high dose vaccine is administered intramuscularly in the upper thigh region of the right leg as 3 doses to participants in study Part I, Step 2 and study Part II.

ABCWY-2Gen high dose Group

MenABCWY-1Gen vaccine COMBINATION_PRODUCT

MenABCWY-1Gen vaccine is administered intramuscularly in the upper thigh region of the right leg as 3 doses to participants in study Part II.

ABCWY-1Gen Group

MenB vaccine COMBINATION_PRODUCT

MenB vaccine is administered intramuscularly in the upper thigh region of the right leg as 3 doses to participants in study Part I, Step 1 and Step 2 and study Part II.

Also known as: Bexsero

MenB+MenACWY-TT Group

MenACWY-TT vaccine COMBINATION_PRODUCT

MenACWY-TT vaccine is administered intramuscularly in the lower thigh region of the right leg as 3 doses to participants in study Part I, Step 1 and Step 2 and study Part II.

Also known as: Nimenrix

MenB+MenACWY-TT Group

Eligibility Criteria

• Age: 55 Days - 89 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• Written or witnessed/thumb printed informed consent obtained from the parent(s)/LAR(s) of the participant prior to performance of any study specific procedure.
• Healthy participants as established by medical history and clinical examination before entering into the study.
• A male or female between, and including, 55 and 89 days of age (approximately 2 MoA) at the time of the first study vaccination.
• Born after a gestation period of ≥37 weeks, with a birth weight ≥2.5 kg.

You may not qualify if:

• 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 from birth.
• Progressive, unstable or uncontrolled clinical conditions.
• Clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
• Any neuroinflammatory disorders, congenital and peripartum neurological conditions, encephalopathies, seizures.
• Congenital or peripartum disorders resulting in a chronic condition
• Major congenital defects, as assessed by the investigator.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s)/product(s).
• 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:
• Autoimmune disorders or immunodeficiency syndromes.
• Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days starting from birth until Visit 5. This will mean prednisone equivalent ≥0.5 mg/kg/day with maximum 20 mg/day. Inhaled and topical steroids are allowed.
• Administration of antineoplastic and immunomodulating agents or radiotherapy from birth.
• Administration of long-acting immune-modifying drugs at any time during the study period.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (33)

GSK Investigational Site

Santo Domingo Este, Dominican Republic

Location

GSK Investigational Site

Espoo, 02230, Finland

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GSK Investigational Site

Helsinki, 00100, Finland

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GSK Investigational Site

Jarvenpaa, 04400, Finland

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GSK Investigational Site

Kokkola, 67100, Finland

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GSK Investigational Site

Oulu, 90220, Finland

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GSK Investigational Site

Seinäjoki, 60100, Finland

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GSK Investigational Site

Gilching, 82205, Germany

Location

GSK Investigational Site

Schönau am Königssee, 83471, Germany

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GSK Investigational Site

San Pedro Sula, 21101, Honduras

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GSK Investigational Site

Bydgoszcz, 85-048, Poland

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GSK Investigational Site

Krakow, 30-348, Poland

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GSK Investigational Site

Krakow, 30-644, Poland

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GSK Investigational Site

Luboń, 62-030, Poland

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GSK Investigational Site

Siemianowice Śląskie, 41-103, Poland

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GSK Investigational Site

Torun, 87-100, Poland

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GSK Investigational Site

Trzebnica, 55-100, Poland

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GSK Investigational Site

Warsaw, 02-647, Poland

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GSK Investigational Site

Wroclaw, 50368, Poland

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GSK Investigational Site

Parow Valley, 7505, South Africa

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GSK Investigational Site

Soweto Gauteng, 2013, South Africa

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GSK Investigational Site

Almería, 04120, Spain

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GSK Investigational Site

Burgos, 09006, Spain

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GSK Investigational Site

Madrid, 28040, Spain

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GSK Investigational Site

Madrid, 28041, Spain

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GSK Investigational Site

Madrid, 28046, Spain

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GSK Investigational Site

Madrid, 28222, Spain

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GSK Investigational Site

Marbella, 29600, Spain

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GSK Investigational Site

Málaga, 29004, Spain

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GSK Investigational Site

Santiago de Compostela, 15706, Spain

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GSK Investigational Site

Seville, 41013, Spain

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GSK Investigational Site

Exeter, EX2 5DW, United Kingdom

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GSK Investigational Site

Oxford, OX3 7LE, United Kingdom

Location

MeSH Terms

Conditions

Meningococcal Infections

Interventions

Vaccines; 4CMenB vaccine; tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine

Condition Hierarchy (Ancestors)

Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2021
• First Posted: October 18, 2021
• Study Start: November 29, 2021
• Primary Completion: March 31, 2025
• Study Completion: March 31, 2025
• Last Updated: May 18, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

HO (1); PL (9); ES (10); DE (2); ZA (2); FI (6); GB (2); DO (1)