Safety and Immunogenicity of GSK Meningococcal Group B Vaccine and 13-valent Pneumococcal Vaccine Administered Concomitantly With Routine Infant Vaccines to Healthy Infants
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| ClinicalTrials.gov Identifier: NCT03621670 |
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Recruitment Status :
Recruiting
First Posted : August 8, 2018
Last Update Posted : January 12, 2023
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| Condition or disease | Intervention/treatment | Phase |
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| Infections, Meningococcal | Biological: Bexsero (GSK Biologicals' Meningococcal group-B vaccine/ rMenB+OMV NZ) Biological: Prevnar13 Biological: Pediarix Biological: Hiberix Biological: Rotarix Biological: M-M-R II Biological: Varivax Biological: Placebo (saline water) | Phase 3 |
This study will be divided into 3 timepoints:
- Epoch 1- Primary- From Day 1 to Day 301
- Epoch 2-Secondary-From Day 301 to Day 331
- Epoch 3-Safety follow up -From Day 331 to study end (Day 481 or Day 661). For subjects who have not yet reached the 6-month safety follow-up after the last dose at the time protocol amendment 7 takes effect, Visit 7 will take place on Day 481.
In addition to receiving the study vaccines, infants will also receive non-study vaccines such as Diphtheria, tetanus toxoids and acellular pertussis adsorbed vaccine (DTPa, Infanrix) and Haemophilus influenzae type b Conjugate Vaccine (Hib, Hiberix), to ease the disruption to the standard infant vaccine schedule caused by participating in this study.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 1200 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Masking Description: | Observer-blind study Data will be collected in an observer-blind manner. By observer blind, it is meant that during the course of the study, the subject/parent/caregiver, site and sponsor personnel involved in the clinical evaluation of the subjects are blinded while other study personnel are aware of the treatment assignment. To do so, vaccine preparation and administration will be done by authorized medical personnel who will not participate in any of the study clinical evaluation assays or procedures. The serological data, which would lead to the unblinding of the study groups, will not be available during the course of the study to any investigator or any person involved in the clinical conduct of the study. The laboratory in charge of the laboratory testing will be blinded to the treatment, subject and visit number, and codes will be used to link the subject, visit and study to each sample. |
| Primary Purpose: | Prevention |
| Official Title: | Safety and Immunogenicity of GSK Meningococcal Group B Vaccine and 13-valent Pneumococcal Vaccine Administered Concomitantly With Routine Infant Vaccines to Healthy Infants |
| Actual Study Start Date : | July 27, 2018 |
| Estimated Primary Completion Date : | August 20, 2024 |
| Estimated Study Completion Date : | August 20, 2024 |
| Arm | Intervention/treatment |
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Experimental: MenB+PCV Group
Approximately 800 subjects enrolled in this group will receive rMenB+OMV NZ (Bexsero) concomitantly with PCV13 (Prevnar13) and other RIV (Pediarix, Hiberix, Rotarix, M-M-R II, Varivax) at 2, 4, 6 and 12 months of age.
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Biological: Bexsero (GSK Biologicals' Meningococcal group-B vaccine/ rMenB+OMV NZ)
Bexsero is to be administered intramuscularly on upper side of the right thigh as a 4-dose schedule on Visit 1 (Day 1), Visit 2 (Day 61), Visit 3 (Day 121) and Visit 5 (Day 301) to all subjects in the MenB+PCV group. Biological: Prevnar13 Prevnar13 (PCV13) is to be administered intramuscularly on upper side of the left thigh as a 4-dose schedule on Visit 1 (Day 1), Visit 2 (Day 61), Visit 3 (Day 121) and Visit 5 (Day 301) to all subjects in the MenB+PCV group and Placebo+PCV group. Biological: Pediarix Pediarix (DTPa-HBV-IPV) is to be administered intramuscularly on lower side of the left thigh as a 3-dose schedule on Visit 1 (Day 1), Visit 2 (Day 61) and Visit 3 (Day 121) to all subjects in the MenB+PCV group and Placebo+PCV group. Biological: Hiberix Hiberix (Hib) is to be administered intramuscularly on lower side of the right thigh as a 3-dose schedule on Visit 1 (Day 1), Visit 2 (Day 61) and Visit 3 (Day 121) to all subjects in the MenB+PCV group and Placebo+PCV group. Biological: Rotarix Rotarix (HRV) is to be administered orally as a 2-dose schedule on Visit 1 (Day 1), Visit 2 (Day 61) to all subjects in the MenB+PCV group and Placebo+PCV group. Biological: M-M-R II M-M-R II (MMR) is to be administered subcutaneously on upper side of the right arm as a single dose on Visit 5 (Day 301) to all subjects in the MenB+PCV group and Placebo+PCV group. Biological: Varivax Varivax (VV) is to be administered subcutaneously on upper side of the left arm as a single dose on Visit 5 (Day 301) to all subjects in the MenB+PCV group and Placebo+PCV group. |
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Placebo Comparator: Placebo+PCV Group
Approximately 400 subjects enrolled in this group will receive PCV13 concomitantly with placebo and other RIV at 2, 4, 6 and 12 months of age.
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Biological: Prevnar13
Prevnar13 (PCV13) is to be administered intramuscularly on upper side of the left thigh as a 4-dose schedule on Visit 1 (Day 1), Visit 2 (Day 61), Visit 3 (Day 121) and Visit 5 (Day 301) to all subjects in the MenB+PCV group and Placebo+PCV group. Biological: Pediarix Pediarix (DTPa-HBV-IPV) is to be administered intramuscularly on lower side of the left thigh as a 3-dose schedule on Visit 1 (Day 1), Visit 2 (Day 61) and Visit 3 (Day 121) to all subjects in the MenB+PCV group and Placebo+PCV group. Biological: Hiberix Hiberix (Hib) is to be administered intramuscularly on lower side of the right thigh as a 3-dose schedule on Visit 1 (Day 1), Visit 2 (Day 61) and Visit 3 (Day 121) to all subjects in the MenB+PCV group and Placebo+PCV group. Biological: Rotarix Rotarix (HRV) is to be administered orally as a 2-dose schedule on Visit 1 (Day 1), Visit 2 (Day 61) to all subjects in the MenB+PCV group and Placebo+PCV group. Biological: M-M-R II M-M-R II (MMR) is to be administered subcutaneously on upper side of the right arm as a single dose on Visit 5 (Day 301) to all subjects in the MenB+PCV group and Placebo+PCV group. Biological: Varivax Varivax (VV) is to be administered subcutaneously on upper side of the left arm as a single dose on Visit 5 (Day 301) to all subjects in the MenB+PCV group and Placebo+PCV group. Biological: Placebo (saline water) Placebo is to be administered intramuscularly on upper side of the right thigh as a 4-dose schedule on Visit 1 (Day 1), Visit 2 (Day 61), Visit 3 (Day 121) and Visit 5 (Day 301) to all subjects in the Placebo+PCV group. |
- Percentages of subjects with solicited local and systemic Adverse Events (AEs) [ Time Frame: During the 7-day follow-up period after the 1st vaccination ]
Assessed solicited local AEs are hardness and swelling of the skin and redness, tenderness or discomfort to touch at injection site.
Assessed solicited systemic AEs are decreased eating, increased sleepiness, vomiting/throwing up, loose stools/diarrhea, irritability, persistent/continuous crying and fever, defined as body temperature greater than or equal to (≥)38.0°C/100.4°F.
Each solicited local and systemic AE are summarized as "any". Any=Occurrence of the solicited local/systemic AE regardless of the intensity grade.
- Percentages of subjects with solicited local and systemic AEs [ Time Frame: During the 7-day follow-up period after the 2nd vaccination ]
Assessed solicited local AEs are hardness and swelling of the skin and redness, tenderness or discomfort to touch at injection site.
Assessed solicited systemic AEs are decreased eating, increased sleepiness, vomiting/throwing up, loose stools/diarrhea, irritability, persistent/continuous crying and fever, defined as body temperature ≥38.0°C/100.4°F.
Each solicited local and systemic AE are summarized as "any". Any=Occurrence of the solicited local/systemic AE regardless of the intensity grade.
- Percentages of subjects with solicited local and systemic AEs [ Time Frame: During the 7-day follow-up period after the 3rd vaccination ]
Assessed solicited local AEs are hardness and swelling of the skin and redness, tenderness or discomfort to touch at injection site.
Assessed solicited systemic AEs are decreased eating, increased sleepiness, vomiting/throwing up, loose stools/diarrhea, irritability, persistent/continuous crying and fever, defined as body temperature ≥38.0°C/100.4°F.
Each solicited local and systemic AE are summarized as "any". Any=Occurrence of the solicited local/systemic AE regardless of the intensity grade.
- Percentages of subjects with solicited local and systemic AEs [ Time Frame: During the 7-day follow-up period after the 4th vaccination ]
Assessed solicited local AEs are hardness and swelling of the skin and redness, tenderness or discomfort to touch at injection site.
Assessed solicited systemic AEs are decreased eating, increased sleepiness, vomiting/throwing up, loose stools/diarrhea, irritability, persistent/continuous crying and fever, defined as body temperature ≥38.0°C/100.4°F.
Each solicited local and systemic AE are summarized as "any". Any=Occurrence of the solicited local/systemic AE regardless of the intensity grade.
- Percentages of subjects with solicited systemic AEs [ Time Frame: During the 30-day (Day 1 - Day 30) follow-up period after the 4th vaccination ]For MMR and VV-specific solicited systemic AEs assessed are parotid/salivary gland swelling, fever and rash and are summarized. Each solicited systemic AE are further summarized as "any". "Any" = Occurrence of the solicited systemic AE regardless of intensity grade.
- Percentages of subjects with all unsolicited AEs [ Time Frame: During the 30-day follow-up period after the 1st vaccination ]
An unsolicited AEs is an AE that is not solicited using a subject diary and that is spontaneously communicated by the parent(s)/LAR(s) who has signed the informed consent or a solicited local or systemic AE that continues beyond the solicited period after vaccination.
Assessed unsolicited AEs include serious adverse events (SAEs), AEs leading to withdrawal, AEs of special interest (AESIs), and medically attended AEs.
- Percentages of subjects with all unsolicited AEs [ Time Frame: During the 30-day follow-up period after the 2nd vaccination ]
An unsolicited AEs is an AE that is not solicited using a subject diary and that is spontaneously communicated by the parent(s)/LAR(s) who has signed the informed consent or a solicited local or systemic AE that continues beyond the solicited period after vaccination.
Assessed unsolicited AEs include serious adverse events (SAEs), AEs leading to withdrawal, AEs of special interest (AESIs), and medically attended AEs.
- Percentages of subjects with all unsolicited AEs [ Time Frame: During the 30-day follow-up period after the 3rd vaccination ]
An unsolicited AEs is an AE that is not solicited using a subject diary and that is spontaneously communicated by the parent(s)/LAR(s) who has signed the informed consent or a solicited local or systemic AE that continues beyond the solicited period after vaccination.
Assessed unsolicited AEs include serious adverse events (SAEs), AEs leading to withdrawal, AEs of special interest (AESIs), and medically attended AEs.
- Percentages of subjects with all unsolicited AEs [ Time Frame: During the 30-day follow-up period after the 4th vaccination ]
An unsolicited AEs is an AE that is not solicited using a subject diary and that is spontaneously communicated by the parent(s)/LAR(s) who has signed the informed consent or a solicited local or systemic AE that continues beyond the solicited period after vaccination.
Assessed unsolicited AEs include serious adverse events (SAEs), AEs leading to withdrawal, AEs of special interest (AESIs), and medically attended AEs.
- Percentages of subjects with SAEs, AEs leading to withdrawal, AESIs and medically attended AEs [ Time Frame: Throughout the study period [Day 1 up to study end (Day 481 or Day 661)] ]
A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization and that results in disability/incapacity.
An AE leading to withdrawal includes any AEs/SAEs collected and recorded from the time of the 1st receipt of study vaccines until study end which are identified as reasons for withdrawal of the subject from the study.
Adverse events of special interest (AESIs) are pre-defined (serious or non-serious) AEs of scientific and medical concern specific to the product or program which might warrant further investigation in order to characterize and understand it.
A medically attended AE includes any AEs that requires medical visit.
- Percentages of subjects with human serum bactericidal assay (hSBA) antibody titers ≥ Lower Limit of Quantitation (LLOQ) for each of the M14459, 96217, NZ98/254 and M13520 test strains [ Time Frame: At 1 month after the 3rd vaccination (Day 151) ]
The 4 selected meningococcal B strains are M14459, 96217, NZ98/254 and M13520 respectively. Each of these strains measures bactericidal activity primarily directed against one of the major bactericidal antigens included in the vaccine.
The sufficiency of the immune response to rMenB+OMV NZ at 1 month after the 3rd vaccination is demonstrated if the adjusted lower confidence limit for the percentage of subjects achieving hSBA titers ≥LLOQ is ≥60% for the N. meningitidis serogroup B test strains M14459, 96217, NZ98/254, M13520 (individually).
- Percentages of subjects with hSBA antibody titers ≥LLOQ for all strains combined (M14459, 96217, NZ98/254 and M13520) [ Time Frame: At 1 month after the 3rd vaccination (Day 151) ]
The 4 selected meningococcal B strains are M14459, 96217, NZ98/254 and M13520 respectively. Each of these strains measures bactericidal activity primarily directed against one of the major bactericidal antigens included in the vaccine.
The sufficiency of the immune response to rMenB+OMV NZ at 1 month after the 3rd vaccination is demonstrated if the adjusted lower confidence limit for the percentage of subjects achieving hSBA titers ≥LLOQ is ≥ 50% for all strains combined (composite endpoint).
- Percentages of subjects with hSBA titers ≥ 8 (for strains M14459, NZ98/254, M13520) and ≥16 (for strain 96217) for each of the test strains [ Time Frame: At 1 month after the 4th vaccination (Day 331) ]
The 4 selected meningococcal B strains are M14459, 96217, NZ98/254 and M13520 respectively. Each of these strains measures bactericidal activity primarily directed against one of the major bactericidal antigens included in the vaccine.
The sufficiency of the immune response to rMenB+OMV NZ is demonstrated if the adjusted lower confidence limit for the percentage of subjects with hSBA titers ≥ 8 (for strains M14459, NZ98/254, M13520) and ≥16 (for strain 96217) is ≥75% for the individual N. meningitidis serogroup B test strains.
- Percentages of subjects with hSBA titers ≥ 8 (for strains M14459, NZ98/254, M13520) and ≥16 (for strain 96217) for all strains combined (composite endpoint) [ Time Frame: At 1 month after the 4th vaccination (Day 331) ]
The 4 selected meningococcal B strains are M14459, 96217, NZ98/254 and M13520 respectively. Each of these strains measures bactericidal activity primarily directed against one of the major bactericidal antigens included in the vaccine.
The sufficiency of the immune response to rMenB+OMV NZ is demonstrated if the adjusted lower confidence limit for the percentage of subjects with hSBA titers ≥ 8 (for strains M14459, NZ98/254, M13520) and ≥16 (for strain 96217) is ≥65% for all strains combined (composite endpoint).
- Antibody Geometric Mean Concentrations (GMC) using electrochemiluminescence (ECL) assay for each of the 13 PCV13 antigens [ Time Frame: At 1 month after the 3rd vaccination (Day 151) ]Pneumococcal serotype-specific immunoglobin G (IgG) antibodies is measured by validated multiplex assays (ECL1 and ECL2 assays).
- Antibody GMCs using ECL for each of the 13 PCV13 serotypes [ Time Frame: At 1 month after the 4th vaccination (Day 331) ]Pneumococcal serotype-specific IgG antibodies is measured by validated multiplex assays (ECL1 and ECL2 assays).
- Percentages of subjects with serum pneumococcal anti-capsular polysaccharide IgG ≥0.35 μg/mL [ Time Frame: At one month after the 3rd vaccination (Day 151) and one month after 4th vaccination (Day 331) ]Pneumococcal serotype-specific IgG antibodies is measured by validated multiplex assays (ECL1 and ECL2 assays).
- GMCs against 3 pertussis antigens (pertussis toxin [PT], pertactin [PRN], filamentous hemagglutinin [FHA]) [ Time Frame: At 1 month after the 3rd vaccination (Day 151) ]
Antibodies (IgG's) against the pertussis components PT, PRN and FHA having 2.693, 2.187, 2.046 assay cut-off, respectively. The antibodies GMCs are measured by Enzyme linked immunosorbent assay (ELISA) expressed as International Units per millilitre (IU/mL) to evaluate the immunogenicity of acellular B. pertussis containing vaccines. The seropositivity for all 3 pertussis antibodies is based on new respective ELISA cut-off, where subjects with antibody concentration below the cut-off being considered seronegative.
For the analysis of the immune responses to the Routine Infant Vaccine (RIV) antigens, subjects in each of the 2 study groups are randomly assigned to different immunogenicity subsets. The assignment of the immunogenicity subsets are performed by a second randomization, whereas the first randomization is performed at the enrolment to assign subjects to Group MenB+PCV or Group Placebo+PCV.
- Percentages of subjects with antibodies concentrations against hepatitis B surface antigen (AntiHBsAg) ≥10 mIU/mL [ Time Frame: At 1 month after the 3rd vaccination (Day 151) ]
Antibodies against the anti-HBs are measured using a ChemiLuminescence ImmunoAssay (CLIA) expressed as milli-international units per millilitre. The cut-off of the test has been set at 6.2 mIU/mL. An antibody concentration ≥10 mIU/mL defines seroprotection.
For the analysis of the immune responses to the Routine Infant Vaccine (RIV) antigens, subjects in each of the 2 study groups are randomly assigned to different immunogenicity subsets. The assignment of the immunogenicity subsets are performed by a second randomization, whereas the first randomization is performed at the enrolment to assign subjects to Group MenB+PCV or Group Placebo+PCV.
- Percentages of subjects with anti-diphtheria and anti-tetanus antibody concentrations ≥0.1 IU/mL [ Time Frame: At 1 month after the 3rd vaccination (Day 151) ]
Specific antibodies against diphtheria toxoid (anti-diphtheria IgG's) and tetanus toxoid (anti-tetanus IgG's) are measured by ELISA. The clinical acceptable cut-off of ELISA was set at 0.1 IU/mL, which provided a conservative estimate of the percentage of subjects deemed to be protected.
For the analysis of the immune responses to the Routine Infant Vaccine (RIV) antigens, subjects in each of the 2 study groups are randomly assigned to different immunogenicity subsets. The assignment of the immunogenicity subsets is performed by a second randomization, whereas the first ran-domization is performed at the enrolment to assign subjects to Group MenB+PCV or Group Placebo+PCV.
- Percentages of subjects with anti-polyribosyl-ribitol phosphate (PRP) concentration ≥0.15 µg/mL and ≥1 µg/mL [ Time Frame: At 1 month after the 3rd vaccination (Day 151) ]
Concentrations of IgG antibodies against the Hib polysaccharide PRP is measured by ELISA. An immunological correlate of protection has been established when anti-PRP concentrations ≥0.15 µg/mL.
For the analysis of the immune responses to the Routine Infant Vaccine (RIV) antigens, subjects in each of the 2 study groups are randomly assigned to different immunogenicity subsets. The assignment of the immunogenicity subsets are performed by a second randomization, whereas the first randomization is performed at the enrolment to assign subjects to Group MenB+PCV or Group Placebo+PCV.
- GMCs for anti-Varicella (VV) antibodies [ Time Frame: At 1 month after the 4th vaccination (Day 331) ]A suitable ELISA assay for analysis of anti-VV antibody concentrations is yet to be selected and/or developed. For the analysis of the immune responses to the Routine Infant Vaccine (RIV) antigens, subjects in each of the 2 study groups are randomly assigned to different immunogenicity subsets. The assignment of the immunogenicity subsets are performed by a second randomization, whereas the first randomization is performed at the enrolment to assign subjects to Group MenB+PCV or Group Placebo+PCV.
- GMCs for anti-measles antibodies [ Time Frame: At 1 month after the 4th vaccination (Day 331) ]A suitable ELISA assay for analysis of anti-measles virus antibody concentrations is yet to be selected and/or developed. For the analysis of the immune responses to the Routine Infant Vaccine (RIV) antigens, subjects in each of the 2 study groups are randomly assigned to different immunogenicity subsets. The assignment of the immunogenicity subsets are performed by a second randomization, whereas the first randomization is performed at the enrolment to assign subjects to Group MenB+PCV or Group Placebo+PCV.
- GMCs for anti-mumps antibodies [ Time Frame: At 1 month after the 4th vaccination (Day 331) ]
A suitable ELISA assay for analysis of anti-mumps virus anti-body concentrations is yet to be selected and/or developed.
For the analysis of the immune responses to the Routine Infant Vaccine (RIV) antigens, subjects in each of the 2 study groups are randomly assigned to different immunogenicity subsets. The assignment of the immunogenicity subsets are performed by a second randomization, whereas the first randomization is performed at the enrolment to assign subjects to Group MenB+PCV or Group Placebo+PCV.
- GMCs for anti-rubella antibodies [ Time Frame: At 1 month after the 4th vaccination (Day 331) ]
A suitable ELISA assay for analysis of anti-rubella virus antibody concentrations is yet to be selected and/or developed.
For the analysis of the immune responses to the Routine Infant Vaccine (RIV) antigens, subjects in each of the 2 study groups are randomly assigned to different immunogenicity subsets. The assignment of the immunogenicity subsets are performed by a second randomization, whereas the first randomization is performed at the enrolment to assign subjects to Group MenB+PCV or Group Placebo+PCV.
- Percentages of subjects with hSBA antibody titers ≥5 and ≥8 and ≥16 for each of the M14459, 96217, NZ98/254 and M13520 test strains [ Time Frame: At 1 month after the 3rd vaccination (Day 151) ]
The 4 selected meningococcal B strains are M14459, 96217, NZ98/254 and M13520. The number of subjects having antibody titers ≥5, and ≥8 and ≥16 for each of the strains are presented.
Each of these strains measures bactericidal activity primarily directed against one of the major bactericidal antigens included in the vaccine.
- Percentages of subjects with hSBA antibody titers ≥5 and ≥8 for each of the M14459, 96217, NZ98/254 and M13520 test strains [ Time Frame: At 6 months after the 3rd vaccination (Day 301) ]
The 4 selected meningococcal B strains are M14459, 96217, NZ98/254 and M13520. The number of subjects having antibody titers ≥5 and ≥8 for each of the strains are presented.
Each of these strains measures bactericidal activity primarily directed against one of the major bactericidal antigens included in the vaccine.
- Percentages of subjects with hSBA antibody titers ≥5 for each of the M14459, 96217, NZ98/254 and M13520 test strains [ Time Frame: At 1 month after the 4th vaccination (Day 331) ]
The 4 selected meningococcal B strains are M14459, 96217, NZ98/254 and M13520. The number of subjects having antibody titers ≥5 for each of the strains are presented.
Each of these strains measures bactericidal activity primarily directed against one of the major bactericidal antigens included in the vaccine.
- hSBA Geometric Mean Titers for the M14459, 96217, NZ98/254 and M13520 test strains [ Time Frame: At 1 month after the 3rd vaccination (Day 151) and 6 months after 3rd vaccination (Day 301) and 1 month after 4th vaccination (Day 331) ]Serum antibody titers are presented as hSBA GMTs.The 4 selected meningococcal B strains are M14459, 96217, NZ98/254 and M13520. The GMTs calculated is described for the four strains.
- Percentages of subjects with hSBA antibody titers ≥LLOQ for each of the M14459, 96217, NZ98/254 and M13520 test strains [ Time Frame: At 6 months after the 3rd vaccination (Day 301) and 1 month after 4th vaccination (Day 331) ]
The 4 selected meningococcal B strains are M14459, 96217, NZ98/254 and M13520 respectively.
Each of these strains measures bactericidal activity primarily directed against one of the major bactericidal antigens included in the vaccine.
- hSBA Geometric Mean Ratios (GMR) of GMTs over pre 4th vaccination for the M14459, 96217, NZ98/254 and M13520 test strains [ Time Frame: At 1 month after the 4th vaccination (Day 331) versus pre-4th vaccination (Day 301) ]The 4 selected meningococcal B strains are M14459, 96217, NZ98/254 and M13520. The GMR calculated at one month post 4th vaccination versus pre-4th vaccination is described for the four strains.
- Percentages of subjects with 4-fold rise in hSBA titers (from pre-4th vaccination) for each of the M14459, 96217, NZ98/254 and M13520 test strains [ Time Frame: At 1 month after the 4th vaccination (Day 331) ]
The 4 selected meningococcal B strains are M14459, 96217, NZ98/254 and M13520 respectively.
A 4-fold rise in hSBA titers is defined as:
- if pre-vaccination titer < LOD, then a post-vaccination titer ≥ 4 times the LOD or ≥ LLOQ, whichever is greater;
- if pre-vaccination titer is ≥LOD but <LLOQ, then a post-vaccination titer ≥4 times the LLOQ;
- if pre-vaccination titer is ≥LLOQ, then a post-vaccination titer ≥4 times the pre-vaccination titer, where pre-vaccination titer=pre-4th dose titers (Day 301).
- Percentages of subjects with anti-HBs antibody concentrations ≥100 mIU/mL [ Time Frame: At 1 month after the 3rd vaccination (Day 151) ]Antibodies against the anti-HBs are measured using CLIA expressed as milli-international units per millilitre. The cut-off of the test has been set at 6.2 mIU/mL. An antibody concentration ≥10 mIU/mL defines seroprotection.
- GMCs for Anti-HBsAg antibodies [ Time Frame: At 1 month after the 3rd vaccination (Day 151) ]Antibodies against the anti-HBs is measured using CLIA. The cut-off of the test has been set at 6.2 mIU/mL. An antibody concentration ≥10 mIU/mL defines seroprotection.
- Percentages of subjects with anti-diphtheria and anti-tetanus antibody concentrations ≥1 IU/mL [ Time Frame: At 1 month after the 3rd vaccination (Day 151) ]Specific antibodies against diphtheria toxoid (anti-diphtheria IgG's) and tetanus toxoid (anti-tetanus IgG's) are measured by ELISA. The clinical acceptable cut-off of ELISA was set at 0.1 IU/mL, which provided a conservative estimate of the percentage of subjects deemed to be protected.
- GMCs for anti-diphtheria and anti-tetanus antibodies [ Time Frame: At 1 month after the 3rd vaccination (Day 151) ]Specific antibodies against diphtheria toxoid (anti-diphtheria IgG's) and tetanus toxoid (anti-tetanus IgG's) are measured by ELISA. The clinical acceptable cut-off of ELISA was set at 0.1 IU/mL, which provided a conservative estimate of the percentage of subjects deemed to be protected.
- Percentages of subjects with anti-polio type 1, 2 and 3 neutralization antibody titers ≥8 [ Time Frame: At 1 month after the 3rd vaccination (Day 151) ]Antibodies against poliovirus types 1, 2 and 3 are determined by a virus micro neutralization test. Titers are expressed in terms of the reciprocal of the dilution resulting in 50% inhibition (ED50TR). The assay cut-off for anti-polio 1, 2 and 3 is 8 ED50.
- Percentages of subjects showing seroresponse for anti-Varicella (VV), anti-measles virus, anti-mumps virus and anti-rubella virus antibodies [ Time Frame: At 1 month after the 4th vaccination (Day 331) ]
Seroresponse is defined as post-vaccination anti-VV virus, anti-measles virus, anti-mumps virus and anti-rubella virus antibody concentration ≥ a protective threshold among subjects who were seronegative (antibody concentration <assay cut-off) before vaccination.
A suitable ELISA assay for analysis of anti-VZV, anti-measles virus, anti-mumps virus and anti-rubella virus antibody concentrations is yet to be selected and/or developed.
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.
| Ages Eligible for Study: | 6 Weeks to 12 Weeks (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
All subjects must satisfy all the following criteria at study entry:
- 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 (e.g. completion of the eDiary, return for follow-up visits).
- Written informed consent obtained from the parent(s)/LAR(s) of the subject prior to performing any study specific procedure.
- A male or female between, and including, 42 and 84 days of age (i.e., 6 through 12 weeks) at the time of the 1st vaccination.
- Healthy subjects as established by medical history and clinical examination before entering into the study.
- Born full-term (i.e. after a gestation period of ≥ 38 weeks).
Exclusion Criteria:
If any exclusion criterion applies, the subject must not be included in the study:
• Child in care
Each subject must not have:
- Progressive, unstable or uncontrolled clinical conditions.
- Hypersensitivity, including allergy to any component of vaccines, medicinal product or medical equipment whose use is foreseen in this study.
- Hypersensitivity to latex.
- Clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
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Abnormal function of the immune system resulting from:
- Clinical conditions.
- Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days from birth.
- Administration of antineoplastic and immunomodulating agents or radiotherapy for any duration from birth.
- Autoimmune disorders (including, but not limited to: blood, endocrine, hepatic, muscular, nervous system or skin autoimmune disorders; lupus erythematosus and associated conditions; rheumatoid arthritis and associated conditions; scleroderma and associated disorders) or immunodeficiency syndromes (including, but not limited to: acquired immunodeficiency syndromes and primary immunodeficiency syndromes).
- Received immunoglobulins or any blood products from birth.
- Received an investigational or non-registered medicinal product from birth.
- Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study.
- Neuroinflammatory disorders (including but not limited to: demyelinating disorders, encephalitis or myelitis of any origin), congenital and peripartum neurological conditions, encephalopathies, seizures (including all subtypes such as: absence seizures, generalised tonic-clonic seizures, partial complex seizures, partial simple seizures or febrile convulsions).
- Congenital or peripartum disorders resulting in a chronic condition (including but not limited to: chromosomal abnormalities, cerebral palsy, metabolism or synthesis disorders, cardiac disorders).
- Study personnel as an immediate family or household member.
- Current or previous, confirmed or suspected disease caused by N. meningitidis
- Household contact with and/or intimate exposure from birth to an individual with laboratory confirmed N. meningitidis and/or Streptococcus pneumoniae infection or colonization.
- Previous administration of meningococcal B or pneumococcal vaccine at any time prior to informed consent.
- Received a dose of DTPa-HBV-IPV, HRV, MMR, VV and/or Hib at any time prior to informed consent. Receipt of one dose of HBV up to 4 weeks prior to informed con-sent is allowed.
- Serious chronic illness.
- Uncorrected congenital malformation (such as Meckel's diverticulum) of the gastrointestinal tract that would predispose for Intussusception (IS).
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): NCT03621670
| Contact: US GSK Clinical Trials Call Center | 877-379-3718 | GSKClinicalSupportHD@gsk.com | |
| Contact: EU GSK Clinical Trials Call Center | +44 (0) 20 89904466 | GSKClinicalSupportHD@gsk.com |
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| Study Director: | GSK Clinical Trials | GlaxoSmithKline |
| Responsible Party: | GlaxoSmithKline |
| ClinicalTrials.gov Identifier: | NCT03621670 |
| Other Study ID Numbers: |
205239 2016-003268-37 ( EudraCT Number ) V72_57 ( Other Identifier: Novartis ) |
| First Posted: | August 8, 2018 Key Record Dates |
| Last Update Posted: | January 12, 2023 |
| Last Verified: | January 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | IPD for this study will be made available via the Clinical Study Data Request site. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (CSR) |
| Time Frame: | IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study |
| Access Criteria: | Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months. |
| URL: | https://clinicalstudydatarequest.com |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
|
Meningitis Immune response Sufficiency Neisseria meningitides Bexsero |
|
Meningococcal Infections Neisseriaceae Infections Gram-Negative Bacterial Infections Bacterial Infections Bacterial Infections and Mycoses |
Infections Heptavalent Pneumococcal Conjugate Vaccine Immunologic Factors Physiological Effects of Drugs |