Clinical trial NCT03587207: Study to Assess Potential Immune Interference When GlaxoSmithKline (GSK) Biologicals' MenABCWY Vaccine is Administered to Healthy Subjects Aged 10-25 Years
Official title: Immunogenicity and Safety of Meningococcal MenABCWY Vaccine, and of rMenB+OMV NZ and MenACWY Administered Concomitantly in the Same Arm or in 2 Different Arms, or Alone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Meningitis, Meningococcal
Keywords: Meningitis
Concomitantly
Adolescent
Neisseria meningitidis
Healthy subjects
Adult
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2018-07-16
Enrollment: 520
Sex: ALL
Minimum age (years): 10
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of the current study is to evaluate whether there is immune interference when MenABCWY \[consisting of MenACWY lyophilized component and rMenB+OMV NZ (Bexsero) liquid component\] is administered to healthy adolescents and adults following a 2-dose vaccination schedule with MenABCWY administered 2 months apart.


Eligibility criteria: Inclusion Criteria:

* Subjects and/or subjects' parent(s)/Legally Acceptable Representative(s) (LARs) who, in the opinion of the investigator, can and will comply, with the requirements of the protocol (e.g. completion of the paper diary (pDiary), return for follow-up visits, availability for all visits scheduled in the study).
* Written informed consent obtained from the subject and/or from the parent(s)/LAR(s) of the subject prior to performing any study specific procedure.
* Written informed assent obtained from subjects below the legal age of consent prior to performing any study specific procedure.
* A male or female between, and including, 10 to 25 years of age at the time of the first vaccination.
* Healthy subjects as established by medical history and clinical examination before entering into the study.
* 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, or bilateral ovariectomy.
* Female subjects of childbearing potential may be enrolled in the study, if the subject:

  * has practiced highly effective contraception for 30 days prior to vaccination, and
  * has a negative pregnancy test on the day of vaccination, and
  * has agreed to continue highly effective contraception during the entire treatment period and for 2 months after completion of the vaccination series.

Exclusion Criteria:

* Female planning to become pregnant or planning to discontinue contraceptive precautions
* Pregnant or lactating female
* Child in care
* Current or previous, confirmed or suspected disease caused by N. meningitidis.
* Known contact to an individual with any laboratory confirmed N. meningitidis infection within 60 days prior to enrolment.
* Previous vaccination against N. meningitidis at any time prior to informed consent.
* Progressive, unstable or uncontrolled clinical conditions.
* Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study.
* Clinical conditions representing a contraindication to IM vaccination and blood draws.
* Abnormal function of the immune system resulting from:

  * Clinical conditions.
  * Systemic administration of corticosteroids (oral/intravenous/IM) for more than 14 consecutive days within 90 days prior to informed consent.
  * Administration of antineoplastic and immune modulating agents or radiotherapy within 90 days prior to informed consent.
* Received immunoglobulins or any blood products within 180 days prior to informed consent.
* Received an investigational or non registered medicinal product within 30 days prior to informed consent.
* Any other clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study.
* 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.
* Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by physical examination.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* Are obese at screening.
* Family history of congenital or hereditary immunodeficiency.
* History of neuroinflammatory or autoimmune condition.
* History of significant neurological disorder or seizure.
* Serious chronic illness.
* History of chronic alcohol consumption and/or drug abuse.
* Any study personnel as an immediate family or household member.
* Administration of a vaccine not foreseen by the study protocol in the period starting 14 days (for inactivated vaccines), 28 days (for live vaccines), or 7 days (for influenza vaccines) before each dose and ending 14 days (for inactivated vaccines), 28 days (for live vaccines), or 7 days (for influenza vaccines) after each dose of study vaccine(s) administration.
* Thrombocytopenia, bleeding disorders, or be receiving anticoagulant therapy.

Primary outcomes:
measure: Human Serum Bactericidal Activity (hSBA) Adjusted Geometric Mean Titers (GMTs) Against All of N. Meningitidis Serogroup B Test Strains (Pooled), One Month After Last Vaccination.
timeFrame: 1 month after last vaccination i.e.: at Day 91 for all groups except for the MenACWY Group
measure: hSBA Adjusted GMTs Against Each of the N. Meningitidis Serogroup B Test Strains and N. Meningitidis Serogroups A, C, W-135, and Y, One Month After Last Vaccination.
timeFrame: 1 month after last vaccination i.e.: at Day 91 for all groups except the MenACWY Group, and at Day 31 for the MenACWY Group.
measure: Percentage of Subjects With hSBA Titers Greater Than or Equal to(≥) the Lower Limit of Quantitation (LLOQ) Against Each of the N. Meningitidis Serogroup B Test Strains and Serogroups A, C, W-135 and Y,One Month After Last Vaccination.
timeFrame: 1 month after last vaccination i.e.: at Day 91 for all groups except the MenACWY Group, and at Day 31 for the MenACWY Group.
measure: Percentage of Subjects With a 4-fold Increase in hSBA Titers Against Each of the N. Meningitidis Serogroup B Test Strains and Against N. Meningitidis Serogroups A, C, W-135 and Y, One Month After Last Vaccination.
timeFrame: 1 month after last vaccination versus baseline (i.e.: at Day 91 versus Day 1 for all groups except the MenACWY Group, and at Day 31 versus Day 1 for the MenACWY Group).
measure: hSBA Adjusted Geometric Mean Ratios (GMRs) Against Each of the N. Meningitidis Serogroup B Test Strains and Against N. Meningitidis Serogroups A, C, W-135 and Y, One Month After Last Vaccination.
timeFrame: 1 month after last vaccination versus baseline (i.e.: at Day 91 versus Day 1 for all groups except the MenACWY Group, and at Day 31 versus Day 1 for the MenACWY Group).
Secondary outcomes:
measure: hSBA Adjusted GMTs Against All of N. Meningitidis Serogroup B Test Strains (Pooled), One Month After First Vaccination
timeFrame: 1 month after first vaccination i.e.: at Day 31 for all groups except for the MenACWY Group
measure: hSBA Adjusted GMTs Against Each of the N. Meningitidis Serogroup B Test Strains and N. Meningitidis Serogroups A, C, W-135 and Y, One Month After First Vaccination.
timeFrame: 1 month after first vaccination i.e.: at Day 31 for all groups except for the MenACWY Group.
measure: Percentage of Subjects With hSBA Titers Greater Than or Equal to (≥) the LLOQ Against Each of the N. Meningitidis Serogroup B Test Strains and Against Serogroups A, C, W-135, and Y, One Month After First Vaccination
timeFrame: 1 month after first vaccination i.e.: at Day 31 for all groups except for the MenACWY Group
measure: Percentage of Subjects With a 4-fold Increase in hSBA Titers Against Each of the N. Meningitidis Serogroup B Test Strains and Against N. Meningitidis Serogroups A, C, W-135, and Y, One Month After First Vaccination
timeFrame: 1 month after first vaccination versus baseline (i.e.: at Day 31 versus Day 1 for all groups except for the MenACWY Group)
measure: hSBA Adjusted GMRs Against Each of the N. Meningitidis Serogroup B Test Strains and Against N. Meningitidis Serogroups A, C, W-135, and Y, One Month After First Vaccination
timeFrame: 1 month after first vaccination versus baseline (i.e.: at Day 31 versus Day 1 for all groups except for the MenACWY Group)
measure: Number of Subjects With Any Solicited Local Adverse Events (AEs)
timeFrame: During the 7 days (including the day of vaccination) after each vaccination i.e after Dose 1 administered at Day 1 (for all groups) and after Dose 2 administered at Day 61 (for all groups except for MenACWY Group)
measure: Number of Subjects With Any Solicited Systemic AEs
timeFrame: During the 7 days (including the day of vaccination) after each vaccination i.e after Dose 1 administered at Day 1 (for all groups) and after Dose 2 administered at Day 61 (for all groups except for MenACWY Group)
measure: Number of Subjects With Unsolicited AEs
timeFrame: During the 30 days (including the day of vaccination) after each vaccination i.e after Dose 1 administered at Day 1 (for all groups) and after Dose 2 administered at Day 61 (for all groups except for MenACWY Group)
measure: Number of Subjects With Serious Adverse Events (SAEs), Medically Attended AEs (MAEs), AEs Leading to Withdrawal, and Adverse Events of Special Interest (AESIs)
timeFrame: During the whole study period i.e from Day 1 to Day 91
Other outcomes:
Locations:
city: Hradec Kralove
country: Czechia
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Beran J, Drazan D, Enweonye I, Bhusal C, Toneatto D. Immunogenicity and Safety of Investigational MenABCWY Vaccine and of 4CMenB and MenACWY Vaccines Administered Concomitantly or Alone: a Phase 2 Randomized Study of Adolescents and Young Adults. mSphere. 2021 Dec 22;6(6):e0055321. doi: 10.1128/mSphere.00553-21. Epub 2021 Nov 17.