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

NCT ID: NCT04502693

Last Updated: 2024-03-05

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

3657 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-14

Study Completion Date

2022-09-13

Brief Summary

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The purpose of this study was to evaluate the effectiveness of 2 doses or 3 doses of GSK's licenced meningococcal group B Bexsero (rMenB+OMV NZ) vaccine and of 2 doses of GSK's investigational combined meningococcal (MenABCWY) vaccine (GSK3536819A) in healthy adolescents and young adults. The immunogenicity and safety were evaluated in the study.

Detailed Description

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As per the feedback from the Center for Biologics Evaluation and Research (CBER), the scope of this post-marketing commitment study was extended to demonstrate the effectiveness, immunogenicity, and safety of GSK's investigational combined meningococcal ABCWY vaccine along with the rMenB+OMV NZ vaccine. Note that the rMenB+OMV and MenACWY vaccines provided to the MenB\_0\_2\_6, MenB\_0\_6 group, and MenACWY group, respectively, at day 211 were only as part of the standard care of treatment and to maintain blinding. These vaccination schedules were not considered for any endpoint evaluations.

Conditions

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Infections, Meningococcal

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Observer-blinded study. Recipients \& study evaluators will be unaware of vaccine administered.

Study Groups

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MenB_0_2_6 Group

Participants received 3 doses of rMenB+OMV NZ vaccine on Day 1, Day 61 and Day 181. Participants received 1 dose of MenACWY vaccine at Day 211 as a standard of care.

Group Type EXPERIMENTAL

rMenB+OMV NZ vaccine

Intervention Type COMBINATION_PRODUCT

rMenB+OMV NZ vaccine was administered intramuscularly.

Meningococcal Groups A, C, W and Y Conjugate Vaccine (MenACWY)

Intervention Type BIOLOGICAL

MenACWY vaccine was administered intramuscularly.

MenB_0_6 Group

Participants received 2 doses of rMenB+OMV NZ vaccine on Day 1, and Day 181, 1 dose of MenACWY vaccine on Day 61. Participants received 1 dose of Placebo on Day 211 to maintain blinding.

Group Type EXPERIMENTAL

rMenB+OMV NZ vaccine

Intervention Type COMBINATION_PRODUCT

rMenB+OMV NZ vaccine was administered intramuscularly.

Meningococcal Groups A, C, W and Y Conjugate Vaccine (MenACWY)

Intervention Type BIOLOGICAL

MenACWY vaccine was administered intramuscularly.

Placebo

Intervention Type COMBINATION_PRODUCT

Placebo was administered intramuscularly.

ABCWY-1 Group

Participants received 2 doses of MenABCWY lot 1 vaccine at Day 1 and Day 181 and 2 doses of placebo at Day 61 and Day 211.

Group Type EXPERIMENTAL

Placebo

Intervention Type COMBINATION_PRODUCT

Placebo was administered intramuscularly.

MenABCWY-1

Intervention Type COMBINATION_PRODUCT

Lot 1 of the MenABCWY vaccine was administered intramuscularly.

ABCWY-2 Group

Participants received 2 doses of MenABCWY lot 2 vaccine at Day 1 and Day 181 and 2 doses of placebo at Day 61 and Day 211.

Group Type EXPERIMENTAL

Placebo

Intervention Type COMBINATION_PRODUCT

Placebo was administered intramuscularly.

MenABCWY-2

Intervention Type COMBINATION_PRODUCT

Lot 2 of the MenABCWY vaccine was administered intramuscularly.

ABCWY-3 Group

Participants received 2 doses of MenABCWY lot 3 vaccine at Day 1 and Day 181 and 2 doses of placebo at Day 61 and Day 211.

Group Type EXPERIMENTAL

Placebo

Intervention Type COMBINATION_PRODUCT

Placebo was administered intramuscularly.

MenABCWY-3

Intervention Type COMBINATION_PRODUCT

Lot 3 of the MenABCWY vaccine was administered intramuscularly.

ACWY Group

Participants received 1 dose of MenACWY vaccine at Day 1,1 dose of placebo at Day 61 and 1 dose of rMenB+OMV NZ vaccine on Day 181. Participants received 1 dose of rMenB+OMV NZ vaccine on Day 211 as standard of care.

Group Type ACTIVE_COMPARATOR

rMenB+OMV NZ vaccine

Intervention Type COMBINATION_PRODUCT

rMenB+OMV NZ vaccine was administered intramuscularly.

Meningococcal Groups A, C, W and Y Conjugate Vaccine (MenACWY)

Intervention Type BIOLOGICAL

MenACWY vaccine was administered intramuscularly.

Placebo

Intervention Type COMBINATION_PRODUCT

Placebo was administered intramuscularly.

ABCWY_Pooled

Participants received 2 doses of either MenABCWY Lot 1, Lot 2, or Lot 3 vaccine on Day 1 and Day 181 and 1 dose of placebo on Day 61. Participants received 1 dose of placebo on Day 211 to maintain blinding.

To evaluate the effectiveness of 2 doses of the MenABCWY vaccines against rMenB+OMV and MenACWY vaccines, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.

Group Type EXPERIMENTAL

MenABCWY-1

Intervention Type COMBINATION_PRODUCT

Lot 1 of the MenABCWY vaccine was administered intramuscularly.

MenABCWY-2

Intervention Type COMBINATION_PRODUCT

Lot 2 of the MenABCWY vaccine was administered intramuscularly.

MenABCWY-3

Intervention Type COMBINATION_PRODUCT

Lot 3 of the MenABCWY vaccine was administered intramuscularly.

Interventions

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rMenB+OMV NZ vaccine

rMenB+OMV NZ vaccine was administered intramuscularly.

Intervention Type COMBINATION_PRODUCT

Meningococcal Groups A, C, W and Y Conjugate Vaccine (MenACWY)

MenACWY vaccine was administered intramuscularly.

Intervention Type BIOLOGICAL

Placebo

Placebo was administered intramuscularly.

Intervention Type COMBINATION_PRODUCT

MenABCWY-1

Lot 1 of the MenABCWY vaccine was administered intramuscularly.

Intervention Type COMBINATION_PRODUCT

MenABCWY-2

Lot 2 of the MenABCWY vaccine was administered intramuscularly.

Intervention Type COMBINATION_PRODUCT

MenABCWY-3

Lot 3 of the MenABCWY vaccine was administered intramuscularly.

Intervention Type COMBINATION_PRODUCT

Other Intervention Names

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Bexsero Menveo NaCl, saline solution

Eligibility Criteria

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Inclusion Criteria

* Subjects or/and 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.
* Written or witnessed/thumb printed informed consent obtained from the subject/parent(s)/LAR(s) of the subject prior to performance of any study specific procedure.
* Written informed assent obtained from the subject (if applicable) prior to performing any study specific procedure.
* A male or female between, and including, 10 and 25 years of age (i.e. 25 years + 364 days) at the time of the first vaccination.
* Healthy subjects as established by medical history physical examination and clinical judgment of the investigator before entering into the study.
* Subjects who are either unvaccinated with MenACWY vaccine or have received a single previous dose of MenACWY vaccine can participate in the study, if they have received it at least 4 years prior to informed consent and assent as applicable (with the exception of meningococcal C vaccination, if the last dose of MenC was received at ≤24 months of age).
* 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\*.
* 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 until 30 days after completion of Visit 6.

* A female is considered to be of non-childbearing potential prior to menarche and after natural or induced menopause. Natural menopause is recognized to have occurred after 12 consecutive months of amenorrhea for which there is no other obvious pathological or physiological cause. Induced menopause is recognized to have occurred after hysterectomy, after bilateral oophorectomy, or iatrogenic ablation of ovarian function.

Exclusion Criteria

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 within 60 days of enrolment.
* Progressive, unstable or uncontrolled clinical conditions.
* Clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
* Any neuroinflammatory, congenital neurological conditions, encephalopathies, seizures. History of febrile convulsions should not lead to exclusion.
* 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 (CRM 197) 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 within 90 days prior to study vaccination until the post-vaccination 3 blood sample (Visit 6). This will mean prednisone - ≥20 mg/day (for adult subjects) or ≥0.5 mg/kg/day (for paediatric subjects), or equivalent. Inhaled and topical steroids are allowed.
* Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to study vaccination.
* Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.

Prior/Concomitant therapy

* Use of any investigational or non-registered product other than the study vaccine(s)/product(s) during the period starting 30 days before the first dose of study vaccine(s)/product(s) (Day -29 to Day 1), or planned use during the study period.
* Previous vaccination against any group B meningococcal vaccine at any time prior to informed consent and assent as applicable.
* Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 90 days before the first dose of study vaccine/ product or planned administration during the study period until the post-vaccination 3 blood sample (Visit 6).
* Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 90 days prior to the vaccine/product dose(s) until the post-vaccination 3 blood sample (Visit 6). For corticosteroids, this will mean prednisone ≥20 mg/day (for adult subjects) or ≥0.5 mg/kg/day (for paediatric subjects), or equivalent. Inhaled and topical steroids are allowed.

Prior/Concurrent clinical study experience

• 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.

Other exclusions

* Child in care.
* Pregnant or lactating female.
* Female planning to become pregnant or planning to discontinue contraceptive precautions.
* History of /current chronic alcohol abuse and/or drug abuse as determined by the investigator.
* Any study personnel or immediate dependants, family, or household member.
Minimum Eligible Age

10 Years

Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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GSK Investigational Site

Chandler, Arizona, United States

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Glendale, Arizona, United States

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Jonesboro, Arkansas, United States

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Bell Gardens, California, United States

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Canoga Park, California, United States

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Garden Grove, California, United States

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Inglewood, California, United States

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Los Gatos, California, United States

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Cutler Bay, Florida, United States

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Lake City, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Orlando, Florida, United States

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Orlando, Florida, United States

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Oviedo, Florida, United States

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West Palm Beach, Florida, United States

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Adairsville, Georgia, United States

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Buford, Georgia, United States

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Columbus, Georgia, United States

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Hinesville, Georgia, United States

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Nampa, Idaho, United States

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Oak Brook, Illinois, United States

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Wichita, Kansas, United States

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Wichita, Kansas, United States

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Bardstown, Kentucky, United States

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Louisville, Kentucky, United States

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Metairie, Louisiana, United States

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Beverly, Massachusetts, United States

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Fall River, Massachusetts, United States

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Grosse Pointe Woods, Michigan, United States

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Minneapolis, Minnesota, United States

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Petal, Mississippi, United States

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Missoula, Montana, United States

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Missoula, Montana, United States

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The Bronx, New York, United States

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Dayton, Ohio, United States

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Dayton, Ohio, United States

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Grants Pass, Oregon, United States

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Greenville, South Carolina, United States

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North Charleston, South Carolina, United States

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West Columbia, South Carolina, United States

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Laredo, Texas, United States

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Plano, Texas, United States

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San Antonio, Texas, United States

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Kaysville, Utah, United States

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Layton, Utah, United States

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Murray, Utah, United States

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Orem, Utah, United States

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Roy, Utah, United States

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Salt Lake City, Utah, United States

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Salt Lake City, Utah, United States

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South Jordan, Utah, United States

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Syracuse, Utah, United States

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Falls Church, Virginia, United States

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Newport News, Virginia, United States

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Richmond, Virginia, United States

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Suffolk, Virginia, United States

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Cheney, Washington, United States

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Spokane, Washington, United States

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Marshfield, Wisconsin, United States

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Sydney, New South Wales, Australia

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Gold Coast, Queensland, Australia

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Taringa, Queensland, Australia

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Tarragindi, Queensland, Australia

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Geelong, Victoria, Australia

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Melbourne, Victoria, Australia

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Nedlands, Western Australia, Australia

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Calgary, Alberta, Canada

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Edmonton, Alberta, Canada

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Vancouver, British Columbia, Canada

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Halifax, Nova Scotia, Canada

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London, Ontario, Canada

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Sarnia, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Pointe-Claire, Quebec, Canada

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Québec, Quebec, Canada

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Québec, , Canada

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České Budejovice, , Czechia

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České Budějovice, , Czechia

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Hradec Králové, , Czechia

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Jindřichův Hradec, , Czechia

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Kladno, , Czechia

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Mělník, , Czechia

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Pardubice, , Czechia

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Pardubice, , Czechia

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Prague, , Czechia

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Příbram, , Czechia

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Trutnov, , Czechia

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Týnec nad Sázavou, , Czechia

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Tallinn, , Estonia

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Tallinn, , Estonia

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Espoo, , Finland

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Helsinki, , Finland

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Helsinki, , Finland

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Järvenpää, , Finland

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Kokkola, , Finland

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Oulu, , Finland

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Pori, , Finland

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Seinäjoki, , Finland

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Tampere, , Finland

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Turku, , Finland

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Adana, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Eskişehir, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Kayseri, , Turkey (Türkiye)

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Countries

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United States Australia Canada Czechia Estonia Finland Turkey (Türkiye)

References

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Nolan 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.

Reference Type DERIVED
PMID: 39647494 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2019-001666-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

205416

Identifier Type: -

Identifier Source: org_study_id

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