Study to Assess the Immunological Long-term Persistence of Antibodies (Abs) 2 Years After GlaxoSmithKline (GSK) Meningococcal ABCWY Vaccination in the V102_15 (NCT02212457) and Response to a Booster in Adolescents

Infections, Meningococcal Clinical Trial

Official title:

A Phase 2b Open-Label Multi-Center Study Assessing the Immunological Persistence of Antibodies at Approximately 2 Years After the Last Meningococcal Vaccination in Study V102_15 (NCT02212457) and the Response to a Booster Dose of GSK MenABCWY or Meningococcal Serogroup B Vaccines, in Healthy Adolescents

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02946385
• Other study ID #: 205613
• Secondary ID: V102_15E12016-00
• Status: Completed
• Phase: Phase 2
• Start date: November 15, 2016
• Est. completion date: February 13, 2018

Study information

• Verified date: August 2019
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the persistence of 2 or 3 doses of the GSK MenABCWY vaccine, or 2 doses of GSK rMenB+OMV vaccine (Bexsero) administered to healthy adolescents at approximately 24 months after the last meningococcal vaccination in the parent study V102_15(NCT02212457), compared with baseline antibody levels in vaccine naïve subjects at similar age at enrolment.

Description:

Naive subjects will be randomized 1:1 to receive MenABCWY or rMenB+OMV at Day 1. No randomization to treatment arm for follow-on subjects is required as vaccine groups remain the same as in the parent study V102_15 (NCT02212457).

Response to a booster dose of MenABCWY vaccine will also be assessed in follow-on subjects who received 2 or 3 doses of MenABCWY (at 0.2-, 0,.6- or 0,.2,.6-month schedules) in the parent study, and will be compared with responses to a single dose of MenABCWY in naive subjects (subjects who are meningococcal vaccine-naive and of similar age to subjects enrolled from the parent study).

Response to a booster dose of GSK Meningococcal B Recombinant vaccine (rMenB+OMV) will be assessed in subjects who received 2 doses of rMenB+OMV (at 0, 2-month schedule) in the parent study, and will be compared with responses to a single dose of rMenB+OMV in naive subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 604
• Est. completion date: February 13, 2018
• Est. primary completion date: February 13, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years to 20 Years

Eligibility

Inclusion Criteria:

Follow-on Participants

• Subjects from Finland and Poland previously enrolled in study V102_15 (NCT02212457) who have received all planned meningococcal vaccinations in the study

• Who have not received any additional meningococcal vaccination since the last meningococcal vaccination administered in the parent trial.

• Who have given written informed consent or assent after the nature of the study has been explained according to local regulatory requirements, prior to study entry. If the subject is under age 18 at the time of enrollment, the parent(s)/ legal guardian(s) of the subject should have given their written consent.

• Individuals of who the investigator believes can and will comply with the requirements of the protocol.

• Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator.

Naive Group

• Male and female individuals of similar age (approximately 12-20 years) to follow-on subjects from V102_15 (NCT02212457) trial.

• Who have not received any meningococcal vaccination since birth

• Individuals who have given their written informed consent or assent after the nature of the study has been explained according to local regulatory requirements, prior to study entry. If the subject is under age 18 at the time of enrollment, the parent(s)/ legal guardian(s) of the subject should have given their written consent.

• Individuals of who the investigator believes can and will comply with the requirements of the protocol.

• Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator.

Exclusion Criteria:

Follow-on Participants:

• Follow-on individuals not eligible to be enrolled in the study are those with:

• History of any meningococcal vaccine administration since last meningococcal vaccination administered in V102_15 (NCT02212457) parent study.

• Current or previous, confirmed or suspected disease caused by N. meningitidis, since termination from parent study.

• Household contact with and/or intimate exposure to an individual with any laboratory confirmed N. meningitidis infection within 60 days of enrollment.

• If the subject is female of childbearing potential, sexually active, and has not used any of the acceptable contraceptive methods for at least 2 months prior to study entry and for the duration of the trial.

• Pregnancy or breast-feeding

• History of severe allergic reactions after previous vaccinations or hypersensitivity to any vaccine component including diphtheria toxoid (CRM197) and latex.

• Progressive, unstable or uncontrolled clinical conditions.

• Any confirmed or suspected condition with impaired/altered function of immune system.

• Chronic administration of immunosuppressants or other immune-modifying drugs within three months prior to the study vaccination or planned use throughout the study period. (For corticosteroids, this means prednisone, or equivalent, = 20 mg/day. Inhaled, intranasal and topical steroids are allowed).

• Administration of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the 3 months prior to study enrolment.

• Received an investigational or non-registered medicinal product within 30 days prior to informed consent.

• Administration of any vaccine within 14 days or 28 days prior to enrollment in the study, or within 7 days after vaccination in the study.

• Clinical conditions representing a contraindication to intramuscular vaccination and/or blood draws.

• Who have received systemic antibiotic treatment within 3 days prior to any blood draw

• Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study.

Naive Individuals

• Naive individuals not eligible to be enrolled in the study are those with:

• History of any meningococcal vaccine administration since birth.

• Current or previous, confirmed or suspected disease caused by N. meningitidis.

• Household contact with and/or intimate exposure to an individual with any laboratory confirmed N. meningitidis infection within 60 days of enrollment.

• If the subject is female of childbearing potential, sexually active, and has not used any of the acceptable contraceptive methods for at least 2 months prior to study entry and for the duration of the trial.

• Pregnancy or breast-feeding.

• History of severe allergic reactions after previous vaccinations or hypersensitivity to any vaccine component including diphtheria toxoid (CRM197) and latex.

• Progressive, unstable or uncontrolled clinical conditions.

• Any confirmed or suspected condition with impaired/altered function of immune system.

• Chronic administration of immunosuppressants or other immune-modifying drugs within 30 days prior to the study enrolment. (For corticosteroids, this means prednisone, or equivalent, = 20 mg/kg/day. Inhaled, intranasal and topical steroids are allowed).

• Administration of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 3 months or planned use throughout the study period.

• Received an investigational or non-registered medicinal product within 30 days prior to informed consent.

• Individuals who are part of study personnel or close family members conducting this study.

• Administration of any vaccine within 14 days or 28 days prior to enrollment in the study, or within 7 days after first vaccination, and/or planned use of any vaccine 7 days prior to and 7 days after second vaccination.

• Clinical conditions representing a contraindication to intramuscular vaccination and/or blood draws.

• Who have received systemic antibiotic treatment within 3 days prior to any blood draw

• Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study.

Related Conditions & MeSH terms

• Infections, Meningococcal
• Meningococcal Infections

Intervention

Biological:
• Meningococcal ABCWY Vaccine
Intramuscular injection of one booster dose at Day 1 to follow-on subjects in the ABCWY_ 0_2 Group, ABCWY_ 0_2_6 Group and ABCWY_ 0_6 Group, primed with 2 or 3 doses of the study vaccine and 2 doses at Days 1 and 61 to naïve subjects in the ABCWY naïve group.
• Meningococcal B Recombinant vaccine
Intramuscular injection of one booster dose of the rMenB+OMV vaccine to subjects in the B_0_2 group, primed with 2 doses of the vaccine and intramuscular injection of 2 doses at Days 1 and 61 in the deltoid area of the non-dominant arm to naïve subjects in the rMenB+OMV Naïve group.

Locations

Country	Name	City	State
Finland	GSK Investigational Site	Espoo
Finland	GSK Investigational Site	Helsinki
Finland	GSK Investigational Site	Helsinki
Finland	GSK Investigational Site	Jarvenpaa
Finland	GSK Investigational Site	Kokkola
Finland	GSK Investigational Site	Oulu
Finland	GSK Investigational Site	Pori
Finland	GSK Investigational Site	Seinajoki
Finland	GSK Investigational Site	Tampere
Finland	GSK Investigational Site	Turku
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Debica
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Siemianowice Slaskie
Poland	GSK Investigational Site	Wroclaw

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Finland,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentages of Subjects With hSBA Titers =LLOQ Against 4 Serogroup B Test Strains, and Against N. Meningitidis Serogroups A, C, W and Y at 24 Months After Last Meningococcal Vaccination in Follow-on Subjects in V102_15 and at Day 1 in Naive Subjects	The immunogenicity of MenABCWY or rMenB+OMV vaccines, is measured as the percentage of subjects with High-Throughput Human Serum Bactericidal Assay (HT-hSBA) titers greater or equal than (=) Lower limit of quantification (LLOQ) against N. meningitidis serogroup B test strains and serogroups A,C, W and Y. The test strains assessed were Meningitis B NZ98/254 Ab, Meningitis B M14459 Ab, Meningitis B M07-0241084 Ab and Meningitis B 96217 Ab.	At 24 months after the last meningococcal vaccination for all follow-on subjects and at Day 1 in the extension study for naive subjects
Primary	hSBA GMTs Against Each of Four Serogroup B Test Strains, and Against N. Meningitidis Serogroups A, C, W and Y at 24 Months After Last Meningococcal Vaccination in Follow-on Subjects in V102_15 and at Day 1 in Naive Subjects	The immunogenicity of MenABCWY or rMenB+OMV vaccines, is measured as the HT-hSBA geometric mean titers (GMTs) against N. meningitidis serogroup B test strains and serogroups A,C, W and Y. The test strains assessed were Meningitis B NZ98/254 Ab, Meningitis B M14459 Ab, Meningitis B M07-0241084 Ab and Meningitis B 96217 Ab.	At 24 months after the last meningococcal vaccination for all follow-on subjects and at Day 1 in the extension study for naive subjects
Secondary	Percentages of Subjects With HT-hSBA Titers = LLOQ Against 4 Serogroup B Test Strains, and Against N. Meningitidis Serogroups A, C, W and Y at Day 31 After MenABCWY Vaccination in V102_15E1	The immunogenicity of MenABCWY vaccine, was measured as the percentages of subjects with HT-hSBA titers greater than or equal to (=) Lower limit of quantification (LLOQ) against N. meningitidis serogroup B test strains and serogroups A,C, W and Y. The test strains assessed were Meningitis B NZ98/254 Ab, Meningitis B M14459 Ab, Meningitis B M07-0241084 Ab and Meningitis B 96217 Ab.	Day 31: One month after a booster dose of MenABCWY given at 24 months after last MenABCWY vaccination in groups: ABCWY_0_2, ABCWY_0_6 and ABCWY_0_2_6 and after first dose of MenABCWY in Naive_ABCWY Group
Secondary	Percentages of Subjects With 4-Fold Increase in HT-hSBA Titers Against 4 Serogroup B Test Strains, and Against N. Meningitidis Serogroups A, C, W and Y at Day 31 After MenABCWY Vaccination in V102_15E1	The immunogenicity of MenABCWY vaccine, was measured as the percentages of subjects with 4-Fold Increase in HT-hSBA Titers against N. meningitidis serogroup B test strains and serogroups A,C, W and Y. The test strains assessed were Meningitis B NZ98/254 Ab, Meningitis B M14459 Ab, Meningitis B M07-0241084 Ab and Meningitis B 96217 Ab. The 4-fold titer rise is defined as: a) for subjects with pre-vaccination hSBA titers ? LLOQ, a post-vaccination hSBA = 4 LLOQ; b) for subjects with a pre-vaccination hSBA titers = LLOQ, an increase of at least 4 times of the pre-vaccination hSBA.	Day 31: One month after a booster dose of MenABCWY given at 24 months after last MenABCWY vaccination in groups: ABCWY_0_2, ABCWY_0_6 and ABCWY_0_2_6 and after first dose of MenABCWY in Naive_ABCWY Group
Secondary	hSBA GMTs Against Each of Four Serogroup B Test Strains, and Against N. Meningitidis Serogroups A, C, W and Y at Day 31 After MenABCWY Vaccination in V102_15E1	The immunogenicity of MenABCWY vaccine, was measured as the HT-hSBA Geometric Mean Titers (GMTs) against N. meningitidis serogroup B test strains and serogroups A,C, W and Y . The test strains assessed were Meningitis B NZ98/254 Ab, Meningitis B M14459 Ab, Meningitis B M07-0241084 Ab and Meningitis B 96217 Ab.	Day 31: One month after a booster dose of MenABCWY given at 24 months after last MenABCWY vaccination in groups: ABCWY_0_2, ABCWY_0_6 and ABCWY_0_2_6 and after first dose of MenABCWY in Naive_ABCWY Group
Secondary	Percentages of Subjects With hSBA Titers =LLOQ Against 4 Serogroup B Test Strains, and N. Meningitidis Serogroups A, C, W and Y at 24 Months At Days 1, 6, 31 in V102_15 Follow-on Subjects and at Day 1, 66, 91 in Naive Subjects, in MenABCWY Groups	The immunogenicity of MenABCWY vaccine, was measured as the percentages of subjects with HT-hSBA titers greater or equal than (=) Lower limit of quantification (LLOQ) against N. meningitidis serogroup B test strains and serogroups A,C, W and Y. The test strains assessed were Meningitis B NZ98/254 Ab, Meningitis B M14459 Ab, Meningitis B M07-0241084 Ab and Meningitis B 96217 Ab.	At Day 1, Day 6 and 31(after booster dose of MenABCWY given at 24 months after last MenABCWY vaccination) in ABCWY_0_2, ABCWY_0_6 and ABCWY_0_2_6 groups and at Day 1, Day 66 and 91(i.e. day 6 and 1 month after dose 2 of MenABCWY) in Naive_ABCWY Group
Secondary	Percentages of Subjects With 4-Fold Increase in HT-hSBA Titers Against 4 Serogroup B Test Strains, and Against N. Meningitidis Serogroups A, C, W and Y At Days 6, 31 in Follow-on Subjects in V102_15 and at Day 66, 91 in Naive Subjects, in MenABCWY Groups	The immunogenicity of MenABCWY vaccine, was measured as the percentages of subjects with 4-Fold Increase in HT-hSBA Titers against N. meningitidis serogroup B test strains and serogroups A,C, W and Y. The test strains assessed were Meningitis B NZ98/254 Ab, Meningitis B M14459 Ab, Meningitis B M07-0241084 Ab and Meningitis B 96217 Ab. The 4-fold titer rise is defined as: a) for subjects with pre-vaccination hSBA titers ? LLOQ, a post-vaccination hSBA = 4 LLOQ; b) for subjects with a pre-vaccination hSBA titers = LLOQ, an increase of at least 4 times of the pre-vaccination hSBA.	At Day 6 and 31(after booster dose of MenABCWY given at 24 months after last MenABCWY vaccination) in ABCWY_0_2, ABCWY_0_6 and ABCWY_0_2_6 groups and at Day 66 and 91(i.e. day 6 and 1 month after dose 2 of MenABCWY) in Naive_ABCWY Group
Secondary	hSBA GMTs Against Each of Four Serogroup B Test Strains, and Against N. Meningitidis Serogroups A, C, W and Y At Days 1, 6, 31 in Follow-on Subjects in V102_15 and at Day 1, 66, 91 in Naive Subjects, in MenABCWY Groups	The immunogenicity of MenABCWY vaccine, was measured as the HT-hSBA geometric mean titers (GMTs) against N. meningitidis serogroup B test strains and serogroups A,C, W and Y . The test strains assessed were Meningitis B NZ98/254 Ab, Meningitis B M14459 Ab, Meningitis B M07-0241084 Ab and Meningitis B 96217 Ab.	At Day 1, Day 6 and 31(after booster dose of MenABCWY given at 24 months after last MenABCWY vaccination) in ABCWY_0_2, ABCWY_0_6 and ABCWY_0_2_6 groups and at Day 1, Day 66 and 91(i.e. day 6 and 1 month after dose 2 of MenABCWY) in Naive_ABCWY Group
Secondary	Percentages of Subjects With HT-hSBA Titers = LLOQ Against 4 Serogroup B Test Strains at Day 31 After rMenB+OMV Vaccination in V102_15E1	The immunogenicity of rMenB+OMV vaccine, was measured as the percentages of subjects with HT-hSBA titers greater or equal than (=) Lower limit of quantification (LLOQ) against N. meningitidis serogroup B test strains. The test strains assessed were Meningitis B NZ98/254 Ab, Meningitis B M14459 Ab, Meningitis B M07-0241084 Ab and Meningitis B 96217 Ab.	Day 31: One month after a booster dose of rMenB+OMV given at 24 months after last rMenB+OMVl vaccination in B_0_2 Group and after first dose of rMenB+OMV in Naive_B Group
Secondary	Percentages of Subjects With 4-Fold Increase in HT-hSBA Titers Against 4 Serogroup B Test Strains at Day 31 After rMenB+OMV Vaccination in V102_15E1	The immunogenicity of rMenB+OMV vaccine, was measured as the percentages of subjects with 4-Fold Increase in HT-hSBA Titers against N. meningitidis serogroup B test strains. The test strains assessed were Meningitis B NZ98/254 Ab, Meningitis B M14459 Ab, Meningitis B M07-0241084 Ab and Meningitis B 96217 Ab. The 4-fold titer rise is defined as: a) for subjects with pre-vaccination hSBA titers ? LLOQ, a post-vaccination hSBA = 4 LLOQ; b) for subjects with a pre-vaccination hSBA titers = LLOQ, an increase of at least 4 times of the pre-vaccination hSBA.	Day 31: One month after a booster dose of rMenB+OMV given at 24 months after last rMenB+OMV vaccination in B_0_2 Group and after first dose of rMenB+OMV in Naive_B Group
Secondary	hSBA GMTs Against Each of Four Serogroup B Test Strains, at Day 31 After rMenB+OMV Vaccination in V102_15E1	The immunogenicity of rMenB+OMV vaccine, was measured as the HT-hSBA geometric mean titers (GMTs) against N. meningitidis serogroup B test strains. The test strains assessed were Meningitis B NZ98/254 Ab, Meningitis B M14459 Ab, Meningitis B M07-0241084 Ab and Meningitis B 96217 Ab.	Day 31: One month after a booster dose of rMenB+OMV given at 24 months after last rMenB+OMV vaccination in B_0_2 Group and after first dose of rMenB+OMV in Naive_B Group
Secondary	Percentages of Subjects With hSBA Titers =LLOQ Against 4 Serogroup B Test Strains at 24 Months At Days 1, 6, 31 in Follow-on Subjects in V102_15 and at Day 1, 66, 91 in Naive Subjects, in rMenB+OMV Groups	The immunogenicity of rMenB+OMV vaccine, was measured as the percentages of subjects with HT-hSBA titers greater or equal than (=) Lower limit of quantification (LLOQ) against N. meningitidis serogroup B test strains. The test strains assessed were Meningitis B NZ98/254 Ab, Meningitis B M14459 Ab, Meningitis B M07-0241084 Ab and Meningitis B 96217 Ab.	At Day 1, at Day 6 and 31(after a booster dose of rMenB+OMV given at 24 months after last rMenB+OMV vaccination) in B_0_2 Group, and at Day 1, at Day 66 and 91(i.e. day 6 and 1 month after second dose of rMenB+OMV) in Naive_B Group
Secondary	Percentages of Subjects With 4-Fold Increase in HT-hSBA Titers Against 4 Serogroup B Test Strains At Days 6, 31 in Follow-on Subjects in V102_15 and at Day 66, 91 in Naive Subjects, in rMenB+OMV Groups	The immunogenicity of rMenB+OMV vaccine, was measured as the percentages of subjects with 4-Fold Increase in HT-hSBA Titers against N. meningitidis serogroup B test strains. The test strains assessed were Meningitis B NZ98/254 Ab, Meningitis B M14459 Ab, Meningitis B M07-0241084 Ab and Meningitis B 96217 Ab. The 4-fold titer rise is defined as: a) for subjects with pre-vaccination hSBA titers ? LLOQ, a post-vaccination hSBA = 4 LLOQ; b) for subjects with a pre-vaccination hSBA titers = LLOQ, an increase of at least 4 times of the pre-vaccination hSBA.	At Day 6 and 31(after a booster dose of rMenB+OMV given at 24 months after last rMenB+OMV vaccination) in B_0_2 Group, and at Day 66 and 91(i.e. day 6 and 1 month after second dose of rMenB+OMV) in Naive_B Group
Secondary	hSBA GMTs Against Each of Four Serogroup B Test Strains At Days 1, 6, 31 in Follow-on Subjects in V102_15 and at Day 1, 66, 91 in Naive Subjects, in rMenB+OMV Groups	The immunogenicity of rMenB+OMV vaccine, was measured as the HT-hSBA geometric mean titers (GMTs) against N. meningitidis serogroup B test strains. The test strains assessed were Meningitis B NZ98/254 Ab, Meningitis B M14459 Ab, Meningitis B M07-0241084 Ab and Meningitis B 96217 Ab.	At Day 1, at Day 6 and 31(after a booster dose of rMenB+OMV given at 24 months after last rMenB+OMV vaccination) in B_0_2 Group, and at Day 1, at Day 66 and 91(i.e. day 6 and 1 month after second dose of rMenB+OMV) in Naive_B Group
Secondary	Number of Subjects With Any Solicited Local or Systemic AEs and Other Indicators of Reactogenicity Within 30 Minutes After Vaccination	Assessed solicited symptoms were Pain, erythema and induration. Assessed solicited systemic symptoms were Fatigue, headache, myalgia, arthralgia, loss of appetite, nausea, chills, and fever (body temperature =38.0°C).	within 30 minutes after vaccination at Day 1 (for all subjects) and also Day 61 (for naive subjects only)
Secondary	Number of Subjects With Any Unsolicited AEs Within 30 Minutes After Vaccination	An unsolicited adverse event is an adverse event that was not solicited and that was spontaneously communicated by a subject and/or parent/legal guardian who has signed the informed consent. Number of subjects reporting any unsolicited AE within 30 minutes after each vaccination. Note: unsolicited AEs within 30 minutes were not collected	Within 30 minutes after vaccination at Day 1 (for all subjects) and also Day 61 (for naive subjects only)
Secondary	Number of Subjects With Any Solicited Local or Systemic Adverse Events (AEs) and Other Indicators of Reactogenicity From Day 1 to Day 7.	Assessed solicited symptoms were pain, erythema and induration. Assessed solicited systemic symptoms were Fatigue, headache, myalgia, arthralgia, loss of appetite, nausea, chills, and fever (body temperature =38.0°C).	At Day 1 (6 hours) to Day 7 after vaccination at Day 1 (for all subjects) and Day 61 to Day 67 (for naive subjects only)
Secondary	Number of Subjects With Unsolicited AEs, 30 Days After Any Vaccination	An unsolicited adverse event is an adverse event that was not solicited and that was spontaneously communicated by a subject and/or parent/legal guardian who has signed the informed consent. Number of subjects reporting any unsolicited AE within 30 minutes after each vaccination.	From Day 1 to Day 31 for all subjects and Day 61 to Day 91 for naive subjects
Secondary	Number of Subjects With Any Serious AE (SAE), Medically Attended AEs (MAAEs), AEs Leading to Premature Withdrawal	Serious adverse events (SAEs), medically attended adverse events and AEs leading to withdrawal are reported. A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in one or more of the following: -Death, -Is life-threatening,-Required or prolonged hospitalization, -Persistent or significant disability/incapacity, -Congenital anomaly/or birth defect, -An important and significant medical event that may not be immediately life threatening or resulting in death or hospitalization but, based upon appropriate medical judgment, may jeopardize the subject or may require intervention to prevent one of the other outcomes listed above.	During the entire study period (up to Day 181 for follow-on subjects and up to Day 241 for naive subjects)