A Study to Investigate the Safety and Immunogenicity of Different Formulations of GSK Biologicals' Meningococcal ACWY Conjugate Vaccine (GSK3536820A and Menveo) Administered to Healthy Adolescents and Young Adults 10 to 40 Years of Age

Immunogenicity, Reactogenicity and Safety Study of Different Formulations of GSK Biologicals' Meningococcal ACWY Conjugate Vaccine (GSK3536820A and Menveo) When Administered to Healthy Adolescents and Young Adults 10 to 40 Years of Age

MenACWY (Menveo) is a GSK vaccine intended for protection against disease caused by meningococcal bacteria groups A, C, W and Y in infants, children and adults, licensed in more than 60 countries.

The purpose of this study is to compare the immunogenicity of the currently licensed MenACWY vaccine with the investigational MenACWY liquid vaccine aged for different lengths of time by storage at 2-8ºC.

Study Overview

• Status: Completed
• Conditions: Meningitis, Meningococcal
• Intervention / Treatment: Biological: MenACWY liquid; Biological: MenACWY

• Study Type: Interventional
• Enrollment (Actual): 1707
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 22271-100
    • GSK Investigational Site
  • São Paulo, Brazil, 04266-010
    • GSK Investigational Site
  • São Paulo, Brazil, 01228-200
    • GSK Investigational Site
  • Bahía
    • Salvador, Bahía, Brazil, 40420-000
      • GSK Investigational Site
  • Rio Grande Do Norte
    • Natal, Rio Grande Do Norte, Brazil, 59025-050
      • GSK Investigational Site
• Estonia
  • Tallinn, Estonia, 10117
    • GSK Investigational Site
  • Tallinn, Estonia
    • GSK Investigational Site
  • Tallinn, Estonia, 11313
    • GSK Investigational Site
  • Tartu, Estonia, 50106
    • GSK Investigational Site
• Finland
  • Espoo, Finland, 02230
    • GSK Investigational Site
  • Helsinki, Finland, 00100
    • GSK Investigational Site
  • Jarvenpaa, Finland, 04400
    • GSK Investigational Site
  • Oulu, Finland, 90220
    • GSK Investigational Site
  • Pori, Finland, 28100
    • GSK Investigational Site
  • Tampere, Finland, 33100
    • GSK Investigational Site
• France
  • Angers, France, 49000
    • GSK Investigational Site
  • Nantes cedex 2, France, 44277
    • GSK Investigational Site
  • Nice, France, 06300
    • GSK Investigational Site
  • Rosiers-d'Egletons, France, 19300
    • GSK Investigational Site
  • Tours, France, 37044
    • GSK Investigational Site
• Mexico
  • Durango, Mexico, 34000
    • GSK Investigational Site
  • Yucatán
    • Merida, Yucatán, Mexico, 97070
      • GSK Investigational Site
• Russian Federation
  • Ekaterinburg, Russian Federation, 620028
    • GSK Investigational Site
  • Gatchina, Russian Federation, 188300
    • GSK Investigational Site
  • Moscow, Russian Federation, 115478
    • GSK Investigational Site
  • Murmansk, Russian Federation, 183038
    • GSK Investigational Site
  • Saint Petersburg, Russian Federation, 196240
    • GSK Investigational Site
  • Saint Petersburg, Russian Federation, 197022
    • GSK Investigational Site
  • St.Petersburg, Russian Federation, 191025
    • GSK Investigational Site
  • St.Petersburg, Russian Federation, 197089
    • GSK Investigational Site
  • Tomsk, Russian Federation, 634 050
    • GSK Investigational Site
  • Yaroslavl, Russian Federation, 150051
    • GSK Investigational Site
• South Africa
  • Bellville, South Africa, 7530
    • GSK Investigational Site
  • Gauteng
    • Pretoria, Gauteng, South Africa, 0152
      • GSK Investigational Site
• Spain
  • Barcelona, Spain, 08025
    • GSK Investigational Site
  • Barcelona, Spain
    • GSK Investigational Site
  • Centelles (Barcelona), Spain, 08540
    • GSK Investigational Site
  • Hospitalet de Llobregat, Spain, 08907
    • GSK Investigational Site
  • La Roca Del Valles (Barcelona), Spain, 08430
    • GSK Investigational Site
  • Madrid, Spain, 28050
    • GSK Investigational Site
  • Quart De Poblet, Valencia, Spain, 46930
    • GSK Investigational Site
  • Sevilla, Spain, 41014
    • GSK Investigational Site
  • Valencia, Spain, 46011
    • GSK Investigational Site
  • Valencia, Spain, 46022
    • GSK Investigational Site
  • Valencia, Spain, 46200
    • GSK Investigational Site
  • Valencia, Spain
    • GSK Investigational Site
  • Vic/ Barcelona, Spain, 08500
    • GSK Investigational Site
• Turkey
  • Eskisehir, Turkey, 26040
    • GSK Investigational Site
  • Izmir, Turkey, 35340
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 40 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol or subjects' 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.
2. Written informed consent obtained from the subject/from the parent(s)/LAR(s) of the subject prior to performing any study specific procedure.
3. Written informed assent obtained for subjects below legal age of consent, if required by local regulations at the time of the enrolment.
4. A male or female ≥10 to ≤40 YoA at the time of the vaccination.
5. Healthy subjects as established by medical history and clinical examination before entering into the study.

6. 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

7. 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.

Exclusion Criteria:

1. Child in care
2. Anaphylaxis following the administration of vaccine.
3. Any (clinical) condition that in the judgment of the investigator would make intramuscular injection unsafe &/represents a contraindication to intramuscular vaccination and blood draws.
4. Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV infection.
5. Progressive, unstable or uncontrolled clinical conditions.
6. Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study.
7. Hypersensitivity to the active substances or to any of the excipients of the vaccine, including diphtheria toxoid (CRM197), or a life-threatening reaction after previous administration of a vaccine containing similar components.

8. Abnormal function of the immune system resulting from:

   • Clinical conditions.
   • Systemic administration of corticosteroids within 90 days prior to informed consent, and until the Day 29 blood draw.
   • Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to informed consent, and until the Day 29 blood draw.
9. Received immunoglobulins or any blood products within 180 days prior to informed consent.
10. Received an investigational or non-registered medicinal product within 30 days prior to informed consent.
11. Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study.
12. History of any meningococcal vaccination, with the exception of previous meningococcal C vaccination, if the last dose of MenC was received at ≤24 months of age.

13. Individuals who received any other vaccines within 7 days (for inactivated vaccines) or 14 days prior to enrolment in this study or who are planning to receive any vaccine within 28 days from the study vaccines.*

    * In case an emergency mass vaccination for an unforeseen public health threat is organized by the public health authorities, outside the routine immunization program, the time period described above can be reduced if necessary for that vaccine provided it is licensed and used according to its Prescribing Information and according to the local governmental recommendations and provided a written approval of the sponsor is obtained.

14. Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
15. 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 (pharmaceutical product or device).
16. Current or previous, confirmed or suspected disease caused by N. meningitidis.
17. Household contact with and/or intimate exposure to an individual with any laboratory confirmed N. meningitidis infection within 60 days prior to study vaccination.

18. Acute disease and/or fever within 3 days prior to study vaccination. Note: enrolment may be postponed/delayed until such transient circumstances have ended.

    • Fever is defined as body temperature ≥38.0°C/100.4°F. The preferred location for measuring temperature in this study will be the oral cavity.
    • Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.
19. Received systemic antibiotic treatment within 3 days prior to study vaccination or blood draw.
20. Study personnel as an immediate family or household member.
21. Pregnant or lactating women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GSK3536820A ACWY_Liq24 Group; Healthy subjects receiving a single dose of the investigational MenACWY liquid vaccine formulation aged for approximately 24 months, at Day 1 in the Study Phase1.	Biological: MenACWY liquid; At visit 1 (day 1), each subject will receive a single dose of the investigational MenACWY liquid vaccine (GSK3536820A) aged for approximately 24 months in Phase 1 of the study (subjects randomized to study arm ACWY_Liq24) or vaccine aged for 30 months in Phase 2 of the study (subjects randomized to study arm ACWY_Liq30), administered by intramuscular injection in the deltoid of the non-dominant arm.
Active Comparator: ACWY_1 Group; Healthy subjects receiving a single dose of the licensed GSK's MenACWY vaccine formulation (Menveo), at Day 1 in the Study Phase1.	Biological: MenACWY; At visit 1 (day 1), each subject will receive a single dose of the MenACWY vaccine in the Phase1 of the study (subjects randomized to study arm ACWY_1) or in phase 2 of the study (subjects randomized to study arm ACWY_2), administered by intramuscular injection in the deltoid of the non-dominant arm.; Other Names: Menveo
Experimental: GSK3536820A ACWY_Liq30 Group; Healthy subjects receiving a single dose of the investigational MenACWY liquid vaccine formulation aged for approximately 30 months, at Day 1 in the Study Phase 2.	Biological: MenACWY liquid; At visit 1 (day 1), each subject will receive a single dose of the investigational MenACWY liquid vaccine (GSK3536820A) aged for approximately 24 months in Phase 1 of the study (subjects randomized to study arm ACWY_Liq24) or vaccine aged for 30 months in Phase 2 of the study (subjects randomized to study arm ACWY_Liq30), administered by intramuscular injection in the deltoid of the non-dominant arm.
Active Comparator: ACWY_2 Group; Healthy subjects receiving a single dose of the licensed GSK's MenACWY vaccine formulation (Menveo), at Day 1 in the Study Phase 2.	Biological: MenACWY; At visit 1 (day 1), each subject will receive a single dose of the MenACWY vaccine in the Phase1 of the study (subjects randomized to study arm ACWY_1) or in phase 2 of the study (subjects randomized to study arm ACWY_2), administered by intramuscular injection in the deltoid of the non-dominant arm.; Other Names: Menveo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Human Serum Bactericidal Activity (hSBA) Geometric Mean Titers (GMTs) Against N. Meningitidis Serogroup A for Each Vaccine Group and Between-group Ratios	hSBA titers against N. meningitidis serogroup A are calculated in terms of GMTs adjusted for pre-vaccination titer.	At Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hSBA GMTs Against Each of the N.Meningitidis Serogroups A,C,W and Y for Each Vaccine Group and Between-group Ratios	hSBA titers were calculated in terms of GMTs, at Day 1 and Day 29, against each of the N. meningitidis serogroup A, C, W and Y.	At Day 1 and Day 29
Within-group Geometric Mean Ratios (GMRs) of GMTs Against Each of the N.Meningitidis Serogroups A,C,W and Y for Each Vaccine Group	Within-group ratios of hSBA GMTs against each of the N.meningitidis serogroups A, C, W and Y at Day 29 compared to Day 1.	At Day 29
Percentages of Subjects With ≥4 Fold Rise in hSBA Antibody Titers for Each of the N.Meningitidis Serogroups A, C,W and Y for Each Vaccine Group and Between-group Differences	The percentages of subjects with a ≥ 4-fold rise in post-vaccination hSBA (at Day 29 compared to Day 1) and associated 2-sided 95% Clopper-Pearson CIs are computed by group and N. meningitidis serogroups A, C, W and Y. A 4-fold rise in the hSBA titers is defined as: - for individuals, whose pre-vaccination titers are < the LOD (limit of detection), the post-vaccination titers must be ≥ 4-fold the LOD or ≥ the LLOQ (lower limit of quantitation) whichever is greater; - for individuals whose pre-vaccination titers are ≥ the LOD and ≤ the LLOQ, the post-vaccination titers must be at least four times the LLOQ; - for individuals whose pre-vaccination titers are > the LLOQ, the post-vaccination titers must be at least four times the pre-vaccination titer.	At Day 29
Percentages of Subjects With hSBA Antibody Titers ≥8 Against Each of the N.Meningitidis Serogroups A,C,W and Y for Each Vaccine Group and Between-group Differences	For each vaccine group the percentage of subjects with hSBA titer ≥8 , and its associated two-sided 95% Clopper-Pearson CIs are computed for each of the N. meningitidis serogroups A, C, W and Y.	At Day 1 and Day 29
Percentages of Subjects With hSBA Titers ≥LLOQ Against Each of the N. Meningitidis Serogroups A, C, W and Y for Each Vaccine Group, and Between-group Differences	For each vaccine group the percentages of subjects with hSBA titer ≥LLOQ, and its associated two-sided 95% Clopper-Pearson CIs are computed for each of the N. meningitidis serogroups A, C, W and Y.	At Day 1 and Day 29
Number of Subjects Reported With Any Unsolicited Adverse Events (AEs) Within 30 Minutes After Vaccination	An unsolicited adverse event (AE) is defined as any untoward medical occurrence in a subject or clinical investigation subject administered with a pharmaceutical product at any dose that does not necessarily have to have a causal relationship with this treatment.	Within 30 minutes after vaccination at Day 1
Number of Subjects Reported With Solicited Local and Systemic AEs	Assessed solicited local AEs were erythema, induration and pain at injection site. Assessed solicited systemic AEs were Arthralgia, chills, fatigue, fever (body temperature ≥38.0°C), headache, loss of appetite, myalgia and nausea.	From Day 1 (6 hours) to Day 7 after vaccination
Number of Subjects Reported With Other Indicators of Reactogenicity	Number of subjects reporting other indicators of reactogenicity such as use of analgesics/antipyretics within 7 days after any vaccination	From Day 1 to Day 7 after vaccination
Number of Subjects Reported With Any Unsolicited AEs Within 29 Days After Vaccination	An unsolicited adverse event (AE) is defined as any untoward medical occurrence in a subject or clinical investigation subject administered with a pharmaceutical product at any dose that does not necessarily have to have a causal relationship with this treatment.	From Day 1 to Day 29 after vaccination
Number of Subjects Reported With Serious Adverse Events (SAEs), AEs Leading to Withdrawal and Medically Attended AEs	Medically attended AEs are defined as events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel (medical doctor) for any reason. Any medically attended AE(s) is occurrence of any medically attended AE(s) regardless of intensity grade or relation to vaccination. Serious adverse event is any congenital anomaly/birth defect in the offspring of a study subject or any untoward medical occurrence that results in death or life threatening or requires hospitalization or results in disability or incapacity	From Day 1 to Day 181 (during the entire study period)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Vir Singh P, Tiberi P, Di Domenico GF, Romolini V, Mzolo T, Costantini M, Akhund T, Basile V, Lattanzi M, Pellegrini M. Fully Liquid MenACWY-CRM Vaccine: Results from an Integrated Safety Analysis. Drug Saf. 2022 Nov 11. doi: 10.1007/s40264-022-01242-8. [Epub ahead of print]

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2018
• Primary Completion (Actual): July 26, 2019
• Study Completion (Actual): December 17, 2019

Study Registration Dates

• First Submitted: February 8, 2018
• First Submitted That Met QC Criteria: February 8, 2018
• First Posted (Actual): February 14, 2018

Study Record Updates

• Last Update Posted (Actual): February 17, 2021
• Last Update Submitted That Met QC Criteria: January 27, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Meningitis; Meningococcal disease; Liquid formulation
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Central Nervous System Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Meningitis, Bacterial; Central Nervous System Bacterial Infections; Meningococcal Infections; Neisseriaceae Infections; Meningitis, Meningococcal; Meningitis
• Other Study ID Numbers: 207467; V59_78 (Other Identifier: Novartis); 2017-003456-23 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No