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

Meningitis, Meningococcal Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03587207
• Other study ID #: 208205
• Secondary ID: 2017-005128-12
• Status: Completed
• Phase: Phase 2
• Start date: July 9, 2018
• Est. completion date: December 19, 2018

Study information

• Verified date: January 2020
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 520
• Est. completion date: December 19, 2018
• Est. primary completion date: December 19, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 10 Years to 25 Years

Eligibility

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.

Related Conditions & MeSH terms

• Meningitis
• Meningitis, Meningococcal

Intervention

Biological:
• MenABCWY vaccine
Two doses administered intramuscularly in the deltoid region of the non-dominant arm.
• 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
• 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

Locations

Country	Name	City	State
Czechia	GSK Investigational Site	Hradec Kralove

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Czechia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	hSBA titers against all of N. meningitidis serogroup B test strains were calculated in terms of GMTs. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA). The serogroup B strains were grouped together to perform a pooled analysis. Adjusted means were obtained from ANCOVA model fitted to all of the Serogroup B test strains, study group, test strain and center as fixed effects; zero-centered pre-vaccination log-transformed titer was included as a continuous covariate.	1 month after last vaccination i.e.: at Day 91 for all groups except for the MenACWY Group
Primary	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.	hSBA titers against each of the N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y were calculated in terms of GMTs. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA). Adjusted means were obtained from ANCOVA model fitted to each Serogroup (Strain) individually, study group and center as fixed effects and zero-centered pre-vaccination log-transformed titer as a continuous covariate.	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.
Primary	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.	Immune responses against N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y, were calculated in terms of percentage of subjects with hSBA titers = LLOQ. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA).	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.
Primary	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.	Immune responses against N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y, were calculated in terms of percentage of subjects with a 4-fold increase in hSBA titers. A 4-fold rise was defined as: a) for individuals whose pre-vaccination titers were less than (<) the limit of detection (LOD), the post-vaccination titers must have been =4-fold the LOD or = the LLOQ, whichever was greater; b) for individuals whose pre-vaccination titers were = the LOD and less than (<) the LLOQ, the post-vaccination titers must have been at least 4 times the LLOQ; and c) for individuals whose pre-vaccination titers were = the LLOQ, the post-vaccination titers must have been at least 4 times the pre-vaccination titer. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA).	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).
Primary	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.	hSBA mean ratios at 1 month after the last vaccination versus baseline were calculated in terms of GMRs i.e. as the anti-logarithm of the mean of the change from baseline of log-transformed titer values at 1 month after last vaccination and Baseline. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA). Adjusted means were obtained from ANCOVA model fitted to each Serogroup (Strain) individually, study group and center as fixed effects and zero-centered pre-vaccination log-transformed titer as a continuous covariate.	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	hSBA Adjusted GMTs Against All of N. Meningitidis Serogroup B Test Strains (Pooled), One Month After First Vaccination	hSBA titers against all of N. meningitidis serogroup B test strains were calculated in terms of GMTs. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA). The serogroup B strains were grouped together to perform a pooled analysis. Adjusted means were obtained from ANCOVA model fitted to all of the Serogroup B test strains, study group, test strain and center as fixed effects; zero-centered pre-vaccination log-transformed titer was included as a continuous covariate.	1 month after first vaccination i.e.: at Day 31 for all groups except for the MenACWY Group
Secondary	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.	hSBA titers against each of the N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y were calculated in terms of GMTs. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA). Adjusted means were obtained from ANCOVA model fitted to each Serogroup (Strain) individually, study group and center as fixed effects and zero-centered pre-vaccination log-transformed titer as a continuous covariate.	1 month after first vaccination i.e.: at Day 31 for all groups except for the MenACWY Group.
Secondary	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	Immune responses against N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y, were calculated in terms of percentage of subjects with hSBA titers = LLOQ. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA).	1 month after first vaccination i.e.: at Day 31 for all groups except for the MenACWY Group
Secondary	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	Immune responses against N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y, were calculated in terms of 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 were less than (<) the limit of detection (LOD), the post-vaccination titers must have been =4-fold the LOD or = the LLOQ, whichever was greater; b) for individuals whose pre-vaccination titers were = the LOD and less than (<) the LLOQ, the post-vaccination titers must have been at least 4 times the LLOQ; and c) for individuals whose pre-vaccination titers were = the LLOQ, the post-vaccination titers must have been at least 4 times the pre-vaccination titer. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA).	1 month after first vaccination versus baseline (i.e.: at Day 31 versus Day 1 for all groups except for the MenACWY Group)
Secondary	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	hSBA mean ratios at 1 month after the first vaccination versus baseline were calculated in terms of GMRs. i.e. as the anti-logarithm of the mean of the change from baseline of log-transformed titer values at 1 month after first vaccination and Baseline. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA). Adjusted mean were obtained from ANCOVA model fitted to each Serogroup (Strain) individually, study group and center as fixed effects and zero-centered pre-vaccination log-transformed titer as a continuous covariate.	1 month after first vaccination versus baseline (i.e.: at Day 31 versus Day 1 for all groups except for the MenACWY Group)
Secondary	Number of Subjects With Any Solicited Local Adverse Events (AEs)	Assessed local AEs were erythema, swelling, induration and pain. Any erythema, swelling and induration is defined as a symptom with a surface diameter equal to or greater than 25 millimeters.	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)
Secondary	Number of Subjects With Any Solicited Systemic AEs	Assessed systemic AEs were arthralgia, fatigue, nausea, headache, myalgia and fever. Any fever is defined as body temperature equal or greater than 38 degrees Celsius.	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)
Secondary	Number of Subjects With Unsolicited AEs	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 AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. An unsolicited AE is an AE that was not solicited using a Subject Diary and that was spontaneously communicated by a subjects/parent(s)/ Legally Acceptable Representative 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.	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)
Secondary	Number of Subjects With Serious Adverse Events (SAEs), Medically Attended AEs (MAEs), AEs Leading to Withdrawal, and Adverse Events of Special Interest (AESIs)	SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability or incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Medically attended AEs are defined as symptoms or illnesses requiring hospitalization, or emergency room visit, or visit to/by a health care provider. 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.	During the whole study period i.e from Day 1 to Day 91