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Study to Assess Potential Immune Interference When GlaxoSmithKline (GSK) Biologicals' MenABCWY Vaccine is Administered to Healthy Subjects Aged 10-25 Years

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ClinicalTrials.gov Identifier: NCT03587207
Recruitment Status : Completed
First Posted : July 16, 2018
Last Update Posted : June 5, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

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.

Condition or disease Intervention/treatment Phase
Meningitis, Meningococcal Biological: MenABCWY vaccine Biological: rMenB+OMV NZ (Bexsero) vaccine Biological: MenACWY (Menveo) vaccine Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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
Actual Study Start Date : July 9, 2018
Actual Primary Completion Date : December 19, 2018
Actual Study Completion Date : December 19, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Meningitis

Arm Intervention/treatment
Experimental: MenABCWY Group
Approximately 100 subjects (50 subjects aged 10 to 17 years and 50 subjects aged 18 to 25 years) will receive one dose of MenABCWY twice, 2 months apart (Day 1 and Day 61).
Biological: MenABCWY vaccine
Two doses administered intramuscularly in the deltoid region of the non-dominant arm.

Active Comparator: rMenBOMV+ACWY_S Group
Approximately 100 subjects (50 subjects aged 10 to 17 years and 50 subjects aged 18 to 25 years) will concomitantly receive one dose of rMenB+OMV NZ (Bexsero) and one dose of MenACWY (Menveo) in the same arm twice, 2 months apart (Day 1 and Day 61).
Biological: rMenB+OMV NZ (Bexsero) vaccine
Two doses administered 2 months apart intramuscularly in the deltoid region of the non-dominant arm to subjects randomised to the rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group and rMenBOMV Group

Biological: MenACWY (Menveo) vaccine
Two doses administered intramuscularly in the deltoid region of the dominant/non-dominant arm to subjects randomised to the rMenBOMV+ACWY_S Group and rMenBOMV+ACWY_D Group and one dose administered intramuscularly in the deltoid region of the dominant/non-dominant arm to subjects randomised to the MenACWY Group

Active Comparator: rMenBOMV+ACWY_D Group
Approximately 100 subjects (50 subjects aged 10 to 17 years and 50 subjects aged 18 to 25 years) will concomitantly receive one dose of rMenB+OMV NZ (Bexsero) and one dose of MenACWY (Menveo) in 2 different arms twice, 2 months apart (Day 1 and Day 61).
Biological: rMenB+OMV NZ (Bexsero) vaccine
Two doses administered 2 months apart intramuscularly in the deltoid region of the non-dominant arm to subjects randomised to the rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group and rMenBOMV Group

Biological: MenACWY (Menveo) vaccine
Two doses administered intramuscularly in the deltoid region of the dominant/non-dominant arm to subjects randomised to the rMenBOMV+ACWY_S Group and rMenBOMV+ACWY_D Group and one dose administered intramuscularly in the deltoid region of the dominant/non-dominant arm to subjects randomised to the MenACWY Group

Active Comparator: rMenBOMV Group
Approximately 100 subjects (50 subjects aged 10 to 17 years and 50 subjects aged 18 to 25 years) will receive one dose of rMenB+OMV NZ (Bexsero) twice, 2 months apart (Day 1 and Day 61).
Biological: rMenB+OMV NZ (Bexsero) vaccine
Two doses administered 2 months apart intramuscularly in the deltoid region of the non-dominant arm to subjects randomised to the rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group and rMenBOMV Group

Active Comparator: MenACWY Group
Approximately 100 subjects (50 subjects aged 10 to 17 years and 50 subjects aged 18 to 25 years) will receive one dose of MenACWY (Menveo) once (Day 1).
Biological: MenACWY (Menveo) vaccine
Two doses administered intramuscularly in the deltoid region of the dominant/non-dominant arm to subjects randomised to the rMenBOMV+ACWY_S Group and rMenBOMV+ACWY_D Group and one dose administered intramuscularly in the deltoid region of the dominant/non-dominant arm to subjects randomised to the MenACWY Group




Primary Outcome Measures :
  1. Human Serum Bactericidal Activity (hSBA) Geometric Mean Titres (GMTs) against each of the N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y. [ Time Frame: At 1 month after last vaccination (Day 91) ]

    hSBA titers against each of the N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y are calculated in terms of GMTs.

    Serogroup B strains tested are M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M07 0241084 (Neisseria heparin binding antigen; NHBA)


  2. hSBA GMTs against all of N. meningitidis serogroup B test strains (pooled). [ Time Frame: At 1 month after last vaccination (Day 91) ]
    hSBA titers against all of N. meningitidis serogroup B test strains. Serogroup B strains tested are M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M07 0241084 (Neisseria heparin binding antigen; NHBA)

  3. Percentages of subjects with hSBA titres greater than or equal to (≥) the lower limit of quantitation (LLOQ) against each of the N. meningitidis serogroup B test strains and against N. meningitidis serogroups A, C, W-135, and Y [ Time Frame: At 1 month after last vaccination (Day 91) ]

    Immune responses against N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y, as measured by percentage of subjects with hSBA titers ≥ LLOQ.

    Serogroup B strains tested are M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M07 0241084 (Neisseria heparin binding antigen; NHBA)


  4. Percentages of subjects with a 4-fold increase in hSBA titres against each of the N. meningitidis serogroup B test strains and against N. meningitidis serogroups A, C, W-135, and Y [ Time Frame: At 1 month after last vaccination (Day 91) ]

    Immune responses against N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y, as measured by percentage of subjects with a 4-fold increase in hSBA titers.

    A 4-fold rise is defined as: a) for individuals whose pre-vaccination titers are less than (<) the limit of detection (LOD), the post-vaccination titers must be ≥4-fold the LOD or ≥ the LLOQ, whichever is greater; b) for individuals whose pre vaccination titers are ≥ the LOD and less than(<) the LLOQ, the post vaccination titers must be at least 4 times the LLOQ; and c) for individuals whose pre-vaccination titers are ≥ the LLOQ, the post vaccination titers must be at least 4 times the pre-vaccination titer.

    Serogroup B strains tested are M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M07 0241084 (Neisseria heparin binding antigen; NHBA)


  5. hSBA 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. [ Time Frame: At 1 month after last vaccination (Day 91) versus baseline (Day 1) ]

    hSBA mean ratios at 1 month after the last vaccination versus baseline are calculated in terms of GMRs.

    The ratios of GMTs between study groups are analyzed to evaluate effect of treatment as described below:

    1. Immune interference due to stress to lymph nodes (lymph-node effect) in rMenBOMV+ACWY_S versus rMenBOMV+ACWY_D Group, on the pooled B strains, and individually by serogroup A, C, W 135, Y, and B test strains.
    2. Other unknown interference in the MenABCWY versus rMenBOMV+ACWY_S Group, by serogroup A, C, W 135, Y, and B test strains.
    3. The difference in immune response compared to control groups in rMenBOMV+ACWY_S versus rMenBOMV and MenACWY Groups, rMenBOMV+ACWY_D versus rMenBOMV and MenACWY Groups, and MenABCWY versus rMenBOMV and MenACWY Groups, by serogroup A, C, W 135, Y, and B test strains.

    Serogroup B strains tested are M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M07 0241084 (Neisseria heparin binding antigen; NHBA)



Secondary Outcome Measures :
  1. Human Serum Bactericidal Activity (hSBA) Geometric Mean Titres (GMTs) against each of the N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y. [ Time Frame: At 1 month after first vaccination (Day 31) ]

    hSBA titers against each of the N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y are calculated in terms of GMTs.

    Serogroup B strains tested are M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M07 0241084 (Neisseria heparin binding antigen; NHBA)


  2. hSBA GMTs against all of N. meningitidis serogroup B test strains (pooled). [ Time Frame: At 1 month after first vaccination (Day 31) ]
    hSBA titers against all of N. meningitidis serogroup B test strains. Serogroup B strains tested are M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M07 0241084 (Neisseria heparin binding antigen; NHBA)

  3. Percentages of subjects with hSBA titres ≥ the lower limit of quantitation (LLOQ) against each of the N. meningitidis serogroup B test strains and against N. meningitidis serogroups A, C, W-135, and Y [ Time Frame: At 1 month after first vaccination (Day 31) ]

    Immune responses against N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y, as measured by percentage of subjects with hSBA titers ≥ LLOQ.

    Serogroup B strains tested are M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M07 0241084 (Neisseria heparin binding antigen; NHBA)


  4. Percentages of subjects with a 4-fold increase in hSBA titres against each of the N. meningitidis serogroup B test strains and against N. meningitidis serogroups A, C, W-135, and Y [ Time Frame: At 1 month after first vaccination (Day 31) ]

    Immune responses against N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y, as measured by percentage of subjects with a 4-fold increase in hSBA titers.

    A 4-fold rise is defined as: a) for individuals whose pre-vaccination titers are < the limit of detection (LOD), the post-vaccination titers must be ≥4-fold the LOD or ≥ the LLOQ, whichever is greater; b) for individuals whose pre vaccination titers are ≥ the LOD and < the LLOQ, the post vaccination titers must be at least 4 times the LLOQ; and c) for individuals whose pre-vaccination titers are ≥ the LLOQ, the post vaccination titers must be at least 4 times the pre-vaccination titer.

    Serogroup B strains tested are M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M07 0241084 (Neisseria heparin binding antigen; NHBA)


  5. hSBA 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. [ Time Frame: At 1 month after first vaccination (Day 31) versus baseline (Day 1) ]

    hSBA mean ratios at 1 month after first vaccination versus baseline are calculated in terms of GMRs.

    The ratios of GMTs between study groups are analyzed to evaluate effect of treatment as described below:

    1. Immune interference due to stress to lymph nodes (lymph-node effect) in rMenBOMV+ACWY_S versus rMenBOMV+ACWY_D Group, on the pooled B strains, and individually by serogroup A, C, W 135, Y, and B test strains.
    2. Other unknown interference in the MenABCWY versus rMenBOMV+ACWY_S Group, by serogroup A, C, W 135, Y, and B test strains.
    3. The difference in immune response compared to control groups in rMenBOMV+ACWY_S versus rMenBOMV and MenACWY Groups, rMenBOMV+ACWY_D versus rMenBOMV and MenACWY Groups, and MenABCWY versus rMenBOMV and MenACWY Groups, by serogroup A, C, W 135, Y, and B test strains.

    Serogroup B strains tested are M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M07 0241084 (Neisseria heparin binding antigen; NHBA)


  6. Occurrence of solicited local and systemic Adverse Events (AEs) [ Time Frame: During the 7 days (including the day of vaccination) after each vaccination (Day 1 to Day 7 and Day 61 to Day 67 [Day 1 to Day 7 only for subjects in the MenACWY Group]) ]
    Number and percentage of subjects with solicited local and systemic AEs during the 7-days period (including the day of vaccination) after the vaccination.

  7. Occurrence of unsolicited local and systemic AEs [ Time Frame: During the 30 days (including the day of vaccination) after each vaccination (Day 1 to Day 31 and Day 61 to Day 91 [Day 1 to Day 31 only for subjects in the MenACWY Group]) ]

    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE is 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 is reported as an unsolicited adverse event.

    An AE that was not solicited using a Subject Diary and that was spontaneously communicated by a subjects/parent(s)/ Legally Acceptable Representative (LAR(s)) who has signed the informed consent or a solicited local or systemic adverse event that continues beyond the solicited period at day 7 after vaccination.


  8. Occurrence of AEs, Serious Adverse Events (SAEs), medically attended AEs, AEs leading to withdrawal, and Adverse events of special interest (AESIs) [ Time Frame: From informed consent signature (Day 1) to Visit 4 (Day 91) ]

    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.

    SAE is defined as any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, is a congenital anomaly/birth defect in the offspring of a study subject, or results in disability or incapacity.

    AESIs are predefined (serious or non-serious) adverse events 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.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   10 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03587207


Locations
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Czechia
GSK Investigational Site
Hradec Kralove, Czechia, 50002
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03587207     History of Changes
Other Study ID Numbers: 208205
2017-005128-12 ( EudraCT Number )
First Posted: July 16, 2018    Key Record Dates
Last Update Posted: June 5, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Meningitis
Concomitantly
Adolescent
Neisseria meningitidis
Healthy subjects
Adult
Additional relevant MeSH terms:
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Meningitis, Meningococcal
Meningitis
Central Nervous System Diseases
Nervous System Diseases
Meningitis, Bacterial
Central Nervous System Bacterial Infections
Bacterial Infections
Meningococcal Infections
Neisseriaceae Infections
Gram-Negative Bacterial Infections
Central Nervous System Infections
Vaccines
Immunologic Factors
Physiological Effects of Drugs