Safety and Immunogenicity of GlaxoSmithKline Biologicals Meningococcal Group B Vaccine When Administered Concomitantly With GlaxoSmithKline Biologicals MenACWY Conjugate Vaccine to Healthy Infants

Study Overview
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Brief Summary
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The purpose of this trial is to evaluate the immunogenicity, the safety and the tolerability of rMenB+OMV NZ and MenACWY vaccines in healthy infants, when concomitantly administered at 3, 5, 7 and 13 months of age, compared to either alone.

Official Title
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A Phase 3b, Open-Label, Randomized, Multicenter Study to Assess the Safety and Immunogenicity of GlaxoSmithKline Biologicals Meningococcal Group B Vaccine When Administered Concomitantly With GlaxoSmithKline Biologicals MenACWY Conjugate Vaccine to Healthy Infants

Conditions
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Infections, Meningococcal

Intervention / Treatment
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* Biological: Meningococcal group B Vaccine, rMenB+OMV NZ
* Biological: Meningococcal ACWY Conjugate Vaccine, MenACWY


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy 3-month old infants (85-119 days, inclusive) at time of Visit 1 whose parents/legal guardians have given written informed consent after the nature of the study has been explained. Available for all the visits scheduled in the study. In good health as determined by medical history, physical examination and clinical judgment of the investigator. Exclusion Criteria: History of any previous immunization with a meningococcal vaccine or vaccine containing meningococcal antigen(s) at the time of enrollment. Previous known or suspected disease caused by N. meningitidis. Household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis infection or colonization. History of severe allergic reaction after previous vaccinations, or hypersensitivity to any component of the vaccine. Known or suspected autoimmune disease or impairment/alteration of the immune system resulting from, for ex-ample: Chronic administration of immunosuppressants or other immune-modifying drugs since birth (3 months prior). (For corticosteroids, this means prednisone, or equivalent, ≥ 0.5 mg/kg/day or ≥ 10 mcg/day for children below 2 years. Inhaled and topical steroids are allowed), Immune deficiency disorder, or known HIV infection. Receipt of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation since birth. History of any progressive or severe neurologic disorder, or seizure disorder or Guillan Barré syndrome (exception: one self-limited febrile seizure is acceptable). History of any bleeding disorder considered as a contraindication to intramuscular injection or blood draw. Child's parent(s) or legal guardian(s) are not able to comprehend and to follow all required study procedures for the whole period of the study. Receipt of any investigational or non-registered product since birth (3 month prior) or are expected to receive during the study period. Family members or household members of site research staff. Any clinically-significant chronic or progressive disease according to judgment of the investigator (pulmonary, cardiovascular, renal, hepatic or endocrine functional abnormality) or a congenital anomaly/known cytogenic disorder (e.g., Down's syndrome). History or any illness/condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subjects due to participation in the study.

Ages Eligible for Study
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Minimum Age: 85 Days
Maximum Age: 119 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rMenB+ACWY<br>Approximately 250 healthy infants who will be vaccinated at 3, 5, 7 and 13 months of age. | Biological: Meningococcal group B Vaccine, rMenB+OMV NZ<br>* 4 doses administered intramuscularly on Days 1, 61, 121 and 301 with blood draw visits at Days 1, 151, 301 and 331 and who will receive reminder calls at 2 and 4 days after each vaccination visit and safety calls on Days 201 and 251.<br>* Other names: Bexsero®;Biological: Meningococcal ACWY Conjugate Vaccine, MenACWY<br>* 4 doses administered intramuscularly on Days 1, 61, 121 and 301 with blood draw visits at Days 1, 151, 301 and 331 and who will receive reminder calls at 2 and 4 days after each vaccination visit and safety calls on Days 201 and 251.<br>* Other names: Menveo®;|
| Active Comparator: rMENB<br>Approximately 250 healthy infants who will be vaccinated at 3, 5, 7 and 13 months of age. | Biological: Meningococcal group B Vaccine, rMenB+OMV NZ<br>* 4 doses administered intramuscularly on Days 1, 61, 121 and 301 with blood draw visits at Days 1, 151, 301 and 331 and who will receive reminder calls at 2 and 4 days after each vaccination visit and safety calls on Days 201 and 251.<br>* Other names: Bexsero®;|
| Active Comparator: MenACWY<br>Approximately 250 healthy infants who will be vaccinated at 3, 5, 7 and 13 months of age. | Biological: Meningococcal ACWY Conjugate Vaccine, MenACWY<br>* 4 doses administered intramuscularly on Days 1, 61, 121 and 301 with blood draw visits at Days 1, 151, 301 and 331 and who will receive reminder calls at 2 and 4 days after each vaccination visit and safety calls on Days 201 and 251.<br>* Other names: Menveo®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Human Serum Bactericidal Activity (hSBA) Geometric Mean Titers (GMTs) Against Each of the Serogroup B Indicator Strains | Human serum bactericidal activity (hSBA) titers against each of the serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 after receiving 4 doses of rMenB+OMV NZ / MenACWY vaccines, concomitantly administered, versus corresponding response in subjects who received rMenB+OMV NZ administered alone, were presented in terms of vaccine group specific geometric mean titers (GMTs). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B indicator strains were assessed only for these two groups. | At Day 331 (one month after the fourth vaccination) | 
| hSBA Geometric Mean Titers (GMTs) Against Each of the Serogroups A, C, W-135 and Y | hSBA titers against N. meningitidis serogroups A, C, W-135 and Y after receiving four doses of either rMenB+OMV NZ / MenACWY concomitantly administered versus corresponding response in subjects who received MenACWY administered alone were presented in terms of vaccine group specific GMTs. This outcome measure applies to only rMenB+ACWY and MenACWY groups as the serogroups A,C,W-135 & Y were assessed only for these two groups. | At Day 331 (one month after the fourth vaccination) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hSBA Geometric Mean Titers Against Each of the Serogroup B Indicator Strains. | hSBA GMTs against each of the N. meningitidis serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 at baseline (Day 1). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B strains were assessed only for these two groups. | At Day 1 | 
| hSBA Geometric Mean Titers Against Each of the Serogroup B Indicator Strains. | hSBA GMTs against each of the N. meningitidis serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 at one month after the third vaccination (Day 151). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B strains were assessed only for these two groups. | At Day 151 (one month after the third vaccination) | 
| hSBA Geometric Mean Titers Against Each of the Serogroup B Indicator Strains. | hSBA GMTs against each of the N. meningitidis serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 before the fourth vaccination (Day 301). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B strains were assessed only for these two groups. | At Day 301 (before the fourth vaccination) | 
| hSBA Geometric Mean Titers Against Each of the Serogroup B Indicator Strains. | hSBA GMTs against each of the N. meningitidis serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 at one month after the fourth vaccination (Day 331). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B strains were assessed only for these two groups. | At Day 331 (one month after the fourth vaccination) | 
| hSBA Geometric Mean Titers Against Each of the Serogroups A,C,W-135 & Y. | hSBA GMTs against each of the N. meningitidis serogroups A, C, W-135, Y at baseline (Day 1). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups A,C,W-135 & Y were assessed only for these two groups. | At Day 1 | 
| hSBA Geometric Mean Titers Against Each of the Serogroups A, C, W-135 and Y | hSBA GMTs against each of the N. meningitidis serogroups A, C, W-135, Y at one month after the third vaccination (Day 151). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups A,C,W-135 & Y were assessed only for these two groups. | At Day 151 (one month after the third vaccination) | 
| hSBA Geometric Mean Titers Against Each of the Serogroups A,C,W-135 & Y. | hSBA GMTs against each of the N. meningitidis serogroups A, C, W-135, Y before the fourth vaccination (Day 301). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups A,C,W-135 & Y were assessed only for these two groups. | At Day 301 (before the fourth vaccination) | 
| hSBA Geometric Mean Titers Against Each of the Serogroups A,C,W-135 & Y. | hSBA GMTs against each of the N.meningitidis serogroups A, C, W-135, Y at one month after the fourth vaccination (Day 331). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups A,C,W-135 & Y were assessed only for these two groups. | At Day 331 (one month after the fourth vaccination) | 
| Percentage of Subjects With hSBA Titers ≥1:5 Against Each of the Serogroup B Indicator Strains | Percentage of subjects with hSBA titers≥ 1:5 against each of the N. meningitidis serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 before the first vaccination (Day 1). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B strains were assessed only for these two groups. | At Day 1 | 
| Percentage of Subjects With hSBA Titers ≥1:5 Against Each of the Serogroup B Indicator Strains | Percentage of subjects with hSBA titers ≥ 1:5 against each of the N. meningitidis serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 one month after the third vaccination (Day 151). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B indicator strains were assessed only for these two groups. | At Day 151 (one month after the third vaccination) | 
| Percentage of Subjects With hSBA Titers ≥1:5 Against Each of the Serogroup B Strains. | Percentage of subjects with hSBA titers ≥ 1:5 against each of the N. meningitidis serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 before the fourth vaccination (Day 301). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B indicator strains were assessed only for these two groups. | At Day 301 (before the fourth vaccination) | 
| Percentage of Subjects With hSBA Titers ≥1:5 Against Each of the Serogroup B Strains. | Percentage of subjects with hSBA titers ≥ 1:5 against each of the N. meningitidis serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 one month after the fourth vaccination (Day 331). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B indicator strains were assessed only for these two groups. | At Day 331 (One month after the fourth vaccination) | 
| Percentage of Subjects With hSBA Titers ≥1:8 Against Each of the Serogroup B Indicator Strains | Percentage of subjects with hSBA titers ≥ 1:8 against each of the N. meningitidis serogroup B indicator strains at baseline (Day 1). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B indicator strains were assessed only for these two groups. | At Day 1 | 
| Percentage of Subjects With hSBA Titers ≥1:8 Against Each of the Serogroup B Indicator Strains | Percentage of subjects with hSBA titers ≥ 1:8 against each of the N. meningitidis serogroup B indicator strains at one month after third vaccination (Day 151). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B indicator strains were assessed only for these two groups. | At Day 151 (one month after the third vaccination) | 
| Percentage of Subjects With hSBA Titers ≥1:8 Against Each of the Serogroup B Indicator Strains | Percentage of subjects with hSBA titers ≥ 1:8 against each of the N. meningitidis serogroup B indicator strains before the fourth vaccination (Day 301). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B indicator strains were assessed only for these two groups. | At Day 301 (before the fourth vaccination) | 
| Percentage of Subjects With hSBA Titers≥1:8 Against Each of the Serogroup B Indicator Strains | Percentage of subjects with hSBA titers≥ 1:8 against each of the N. meningitidis serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 at one month after the fourth vaccination (Day 331). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B indicator strains were assessed only for these two groups. | At Day 331 (one month after the fourth vaccination) | 
| Percentage of Subjects With hSBA Titers ≥1:4 Against Each of the Serogroups A, C, W-135 and Y | Percentage of subjects with hSBA titers≥ 1:4 against each of the N. meningitidis serogroups A, C, W-135 and Y before the first vaccination (Day 1). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups were assessed only for these two groups. | At Day 1 | 
| Percentage of Subjects With hSBA Titers≥1:4 Against Each of the Serogroups A, C, W-135 and Y | Percentage of subjects with hSBA titers≥ 1:4 against each of the N. meningitidis serogroups A, C, W-135 and Y at one month after the third vaccination (Day 151). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups were assessed only for these two groups. | At Day 151 (one month after the third vaccination) | 
| Percentage of Subjects With hSBA Titers≥1:4 Against Each of the Serogroups A, C, W-135 and Y | Percentage of subjects with hSBA titers≥ 1:4 against each of the N. meningitidis serogroups A, C, W-135 and Y before the fourth vaccination (Day 301). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups were assessed only for these two groups. | At Day 301 (before the fourth vaccination) | 
| Percentage of Subjects With hSBA Titers≥1:4 Against Each of the Serogroups A, C, W-135 and Y | Percentage of subjects with hSBA titers≥ 1:4 against each of the N. meningitidis serogroups A, C, W-135 and Y at one month after the fourth vaccination (Day 331). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups were assessed only for these two groups. | At Day 331 (one month after the fourth vaccination) | 
| Within-subject Geometric Mean Ratios (GMRs) Against Each of the Serogroup B Indicator Strains | Geometric Mean Ratios(GMRs) of GMTs against each of the serogroup B indicator strains- H44/76, 5/99, N98/254 & M10713 were calculated at one month after the fourth vaccination (Day 331) versus pre fourth vaccination(Day 301). | At Day 331 (one month after fourth vaccination) | 
| Within-subject Geometric Mean Ratios (GMRs) Against Each of Serogroups A, C, W-135 and Y | Geometric Mean Ratios(GMRs) of GMTs against each of the serogroups A,C,W-135 & Y were calculated at one month after the fourth vaccination (Day 331) versus pre fourth vaccination (Day 301). | At Day 331 (one month after the fourth vaccination) | 
| Percentage of Subjects With Four-fold Increases in hSBA Titers Against Each of the Serogroup B Indicator Strains | Percentage of subjects with four-fold increase in hSBA titers against each of the N. meningitidis serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 at one month after the fourth vaccination (Day 331) over pre-fourth vaccination (Day 301). This outcome measure applies to only groups rMenB+ACWY and rMenB as the serogroup B indicator strains were assessed only for these two groups. For serogroup B strains, 4-fold increase in titers was defined as post 4th vaccination titer ≥8 (if pre 4th vaccination titer was <2) or post 4th vaccination titer ≥ 4 x pre 4th vaccination titer (if pre 4th vaccination titer was ≥2). | At Day 331 (one month after the fourth vaccination) | 
| Percentage of Subjects With Four-fold Increases in hSBA Titers Against Each of the Serogroups A, C, W-135 and Y | Percentages of subjects with four-fold increases in hSBA against each of the N. meningitidis serogroups A,C,W & Y at one month after the fourth vaccination (Day 331) over pre-fourth vaccination(Day 301). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups were assessed only for these two groups. For serogroups A, C, W and Y, 4-fold increase in titers was defined as post 4th vaccination titer ≥16 (if pre 4th vaccination titer was <4) or post 4th vaccination titer ≥ 4 x pre 4th vaccination titer (if pre 4th vaccination titer was ≥4). | At Day 331 (one month after the fourth vaccination) | 
| Percentage of Subjects With hSBA Titers≥1:8 Against Each of the Serogroups A, C, W-135 and Y | Percentage of subjects with hSBA titers≥ 1:8 against each of the N. meningitidis serogroups A, C, W-135 and Y at baseline (Day 1). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups were assessed only for these two groups. | At Day 1 | 
| Percentage of Subjects With hSBA Titers≥1:8 Against Each of the Serogroups A, C, W-135 and Y | Percentage of subjects with hSBA titers≥ 1:8 against each of the N. meningitidis serogroups A, C, W-135 & Y at one month after the third vaccination (Day 151). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups were assessed only for these two groups. | At Day 151 (one month before the third vaccination) | 
| Percentage of Subjects With hSBA Titers≥1:8 Against Each of the Serogroups A, C, W-135 and Y | Percentage of subjects with hSBA titers≥ 1:8 against each of the N. meningitidis serogroups A, C, W-135 & Y before the fourth vaccination (Day 301). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups were assessed only for these two groups. | At Day 301 (before the fourth vaccination) | 
| Percentage of Subjects With hSBA Titers≥1:8 Against Each of the Serogroups A, C, W-135 and Y | Percentage of subjects with hSBA titers≥ 1:8 against each of the N. meningitidis serogroups A, C, W-135 & Y at one month after the fourth vaccination (Day 331). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups were assessed only for these two groups. | At Day 331 (one month after the fourth vaccination) | 
| Number of Subjects With Solicited Local and Systemic Adverse Events (AEs) | Number of subjects with solicited local and systemic AEs during the 7 days (including the day of vaccination) after any vaccination | From Day 1 (6 hours) to Day 7 after each vaccination (Days 1, 61, 121 and 301) | 
| Number of Subjects With Unsolicited Adverse Events | An unsolicited adverse event (AE) is defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product at any dose that does not necessarily have to have a causal relationship with this treatment. | From Day 1 to Day 7 after each vaccination (Days 1, 61, 121 and 301) | 
| Number of Subjects With SAEs, AEs Leading to Withdrawal and Medically Attended AEs (MAEs) | A serious adverse event is any untoward medical occurrence that at any dose results in death/ is life threatening/requires prolonged hospitalization/Persistent or significant disability/incapacity/congenital anomaly/or birth defect. | Throughout the whole study period (from Day 1 upto Day 331) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Central Nervous System Diseases, Nervous System Diseases, Meningitis