Immunogenicity and Safety of Meningococcal Vaccine GSK 134612 Co-administered With Pneumococcal and DTPa-HBV-IPV/Hib Vaccines
- Conditions
- Meningococcal VaccinesInfections, Meningococcal
- Interventions
- Biological: Nimenrix™Biological: Menjugate®Biological: NeisVac-CTMBiological: Infanrix™ hexaBiological: Synflorix™
- Registration Number
- NCT01144663
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
The purpose of this study is to evaluate immunogenicity and safety of meningococcal conjugate vaccine GSK134612 compared to the licensed vaccines MenC-CRM197 and MenC-TT in infants of 2 months of age. Pneumococcal conjugate vaccine and DTPa-HBV-IPV/Hib vaccines will be co-administered.
- Detailed Description
The study consists of a primary vaccination phase and a booster vaccination phase. The Protocol Posting has been updated due to protocol amendment 2.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 2095
All subjects must satisfy ALL the following criteria at study entry:
- Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visit).
- A male or female between, and including, 6 and 12 weeks (42-90 days) of age at the time of the first vaccination.
- Written informed consent obtained from the parent(s) or guardian of the subject.
- Free of obvious health problems as established by medical history and clinical examination before entering into the study.
- Born after a gestation period of at least 36 weeks.
- Child in care.
- Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
- Extended administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs since birth. For corticosteroids, this will mean prednisone >= 0.5 mg/kg/day, or equivalent. Inhaled and topical steroids are allowed.
- Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting 30 days before the first dose of vaccine(s) until 30 days after the last dose of vaccine(s) (i.e. booster dose), with the exception of rotavirus vaccine which can be administered at any time during the study, according to the national immunisation recommendations. MMR(V) vaccine, if recommended in national immunisation programs, can be given after the last blood sampling time point i.e. after Visit 6. Seasonal or pandemic influenza vaccine can be given at any time during the study, and according to the Summary of Product Characteristics and national recommendations.
- 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 product (pharmaceutical product or device).
- Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b, Streptococcus pneumoniae, Neisseria meningitidis serogroups A, C, W-135 or Y with the exception of vaccines where the first dose may be given within the first two weeks of life according to the national recommendations (for example hepatitis B and BCG).
- History of, or intercurrent, diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b disease, pneumococcal and/or meningococcal disease.
- Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
- Family history of congenital or hereditary immunodeficiency.
- History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s).
- Major congenital defects or serious chronic illness.
- History of any neurologic disorders or seizures (history of a single, simple febrile seizure is permitted).
- Acute disease and/or fever at the time of enrolment. (Fever is defined as temperature ≥ 37.5°C (99.5°F) on oral, axillary or tympanic setting, or ≥ 38.0°C (100.4°F) on rectal setting).
(Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator).
- Administration of immunoglobulins and/ or any blood products since birth or planned administration during the study period.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Nimenrix 2 Group Synflorix™ Healthy male or female subjects aged between and including, 6 and 12 weeks of age, intramuscularly received 2 primary doses of Nimenrix™ vaccine at 2 and 4 months of age, followed by a booster dose of Nimenrix™ vaccine at 12 months of age. Subjects were also administered intramuscular injections of Infanrix™ hexa and Synflorix™ vaccines at 2, 4 and 12 months of age. Menjugate Group Synflorix™ Healthy male or female subjects aged between and including, 6 and 12 weeks of age, intramuscularly received 2 primary doses of Menjugate® vaccine at 2 and 4 months of age, followed by a booster dose of Menjugate® vaccine at 12 months of age. Subjects were also administered intramuscular injections of Infanrix™ hexa and Synflorix™ vaccines at 2, 4 and 12 months of age. Nimenrix 3 Group Nimenrix™ Healthy male or female subjects aged between and including, 6 and 12 weeks of age, intramuscularly received 3 primary doses of Nimenrix™ vaccine at 2, 3 and 4 months of age, followed by a booster dose of Nimenrix™ vaccine at 12 months of age. Subjects were also administered intramuscular injections of Infanrix™ hexa and Synflorix™ vaccines at 2, 3, 4 and 12 months of age. Nimenrix 3 Group Synflorix™ Healthy male or female subjects aged between and including, 6 and 12 weeks of age, intramuscularly received 3 primary doses of Nimenrix™ vaccine at 2, 3 and 4 months of age, followed by a booster dose of Nimenrix™ vaccine at 12 months of age. Subjects were also administered intramuscular injections of Infanrix™ hexa and Synflorix™ vaccines at 2, 3, 4 and 12 months of age. Menjugate Group Menjugate® Healthy male or female subjects aged between and including, 6 and 12 weeks of age, intramuscularly received 2 primary doses of Menjugate® vaccine at 2 and 4 months of age, followed by a booster dose of Menjugate® vaccine at 12 months of age. Subjects were also administered intramuscular injections of Infanrix™ hexa and Synflorix™ vaccines at 2, 4 and 12 months of age. NeisVac-C Group Infanrix™ hexa Healthy male or female subjects aged between and including, 6 and 12 weeks of age, intramuscularly received 2 primary doses of NeisVac-C™ vaccine at 2 and 4 months of age, followed by a booster dose of NeisVac-C™ vaccine at 12 months of age. Subjects were also administered intramuscular injections of Infanrix™ hexa and Synflorix™ vaccines at 2, 4 and 12 months of age. Nimenrix 3 Group Infanrix™ hexa Healthy male or female subjects aged between and including, 6 and 12 weeks of age, intramuscularly received 3 primary doses of Nimenrix™ vaccine at 2, 3 and 4 months of age, followed by a booster dose of Nimenrix™ vaccine at 12 months of age. Subjects were also administered intramuscular injections of Infanrix™ hexa and Synflorix™ vaccines at 2, 3, 4 and 12 months of age. Nimenrix 2 Group Infanrix™ hexa Healthy male or female subjects aged between and including, 6 and 12 weeks of age, intramuscularly received 2 primary doses of Nimenrix™ vaccine at 2 and 4 months of age, followed by a booster dose of Nimenrix™ vaccine at 12 months of age. Subjects were also administered intramuscular injections of Infanrix™ hexa and Synflorix™ vaccines at 2, 4 and 12 months of age. Menjugate Group Infanrix™ hexa Healthy male or female subjects aged between and including, 6 and 12 weeks of age, intramuscularly received 2 primary doses of Menjugate® vaccine at 2 and 4 months of age, followed by a booster dose of Menjugate® vaccine at 12 months of age. Subjects were also administered intramuscular injections of Infanrix™ hexa and Synflorix™ vaccines at 2, 4 and 12 months of age. NeisVac-C Group NeisVac-CTM Healthy male or female subjects aged between and including, 6 and 12 weeks of age, intramuscularly received 2 primary doses of NeisVac-C™ vaccine at 2 and 4 months of age, followed by a booster dose of NeisVac-C™ vaccine at 12 months of age. Subjects were also administered intramuscular injections of Infanrix™ hexa and Synflorix™ vaccines at 2, 4 and 12 months of age. NeisVac-C Group Synflorix™ Healthy male or female subjects aged between and including, 6 and 12 weeks of age, intramuscularly received 2 primary doses of NeisVac-C™ vaccine at 2 and 4 months of age, followed by a booster dose of NeisVac-C™ vaccine at 12 months of age. Subjects were also administered intramuscular injections of Infanrix™ hexa and Synflorix™ vaccines at 2, 4 and 12 months of age. Nimenrix 2 Group Nimenrix™ Healthy male or female subjects aged between and including, 6 and 12 weeks of age, intramuscularly received 2 primary doses of Nimenrix™ vaccine at 2 and 4 months of age, followed by a booster dose of Nimenrix™ vaccine at 12 months of age. Subjects were also administered intramuscular injections of Infanrix™ hexa and Synflorix™ vaccines at 2, 4 and 12 months of age.
- Primary Outcome Measures
Name Time Method Percentage of Subjects With Serum Bactericidal Assay Using Baby Rabbit Complement Against Meningococcal Serogroups A, W-135 and Y (rSBA-MenA, rSBA-MenW-135 and rSBA-Y) Antibody Titers Greater Than or Equal to (≥) the Cut-off Value. One month after the final primary vaccination at Month 3 The cut-off value for the rSBA-MenA, rSBA-MenW-135 and rSBA-Y titers was greater than or equal to (≥) 1:8.
Indication of the immunogenicity of the 2-dose and 3-dose schedules: the lower limit of the two-sided exact 95% CI for the percentage of subjects with post-primary vaccination rSBA antibody titre ≥ 1:8 is greater than or equal to the pre-defined clinical limit of 80%.Number of Subjects With rSBA-MenC Antibody Titers ≥ the Cut-off Value One month after the final primary vaccination at Month 3 The cut-off value for rSBA-MenC titers was ≥ 1:8.
- Secondary Outcome Measures
Name Time Method Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers Above Cut-off Values Pre-primary vaccination at Month 0 The cut-off values for rSBA-Men antibody titers were greater than or equal to (≥) 1:8 and ≥ 1:128 at pre-vaccination
rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titers Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11 Antibody titers were presented as geometric mean titers (GMTs).
hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Antibody Titers Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11 Antibody titers were presented as geometric mean titers (GMTs).
Number of Subjects With Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Concentrations ≥ the Cut-off Values Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3 The cut-off values for anti-PRP antibody concentrations were greater than or equal to (≥) 0.15 micrograms per milliliter (µg/mL) and ≥ 1.0 µg/mL.
Anti-PRP Antibody Concentrations Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11 Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL).
Number of Subjects With Anti-D and Anti-T Antibody Concentrations ≥ the Cut-off Value Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11 The cut-off value for anti-D and anti-T concentrations was greater than or equal to (≥) 0.1 IU/mL
Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11 Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in EL.U/mL.
Number of Subjects With Anti-HBs Antibody Concentrations Above the Cut-off Values Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11 The cut-off values for anti-HBs concentrations were greater than or equal to (≥) 10 mIU/mL and ≥ 100 mIU/mL.
Number of Subjects With Anti-PRP Antibody Concentrations Above the Cut-off Values Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11 The cut-off values for anti-PRP antibody concentrations were greater than or equal to (≥) 0.15 µg/mL and ≥ 1.0 µg/mL.
Number of Subjects With Anti-poliovirus Type 1, 2 and 3 Antibody Concentrations ≥ the Cut-off Value Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3 The cut-off value for anti-poliovirus type 1, 2 and 3 antibody concentrations was greater than or equal to (≥) 1:8.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-meningococcal Vaccination During the 8-day (Days 0-7) post-meningococcal booster vaccination period Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site.
Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135, rSBA-MenY Antibody Titers Above the Cut-off Values Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11 The cut-off values for the rSBA-Men antibody titers were greater than or equal to (≥) 1:8 and ≥ 1:128.
Number of Subjects With Anti-pneumococcal Serotypes (Anti-P) Antibody Concentrations Above the Cut-off Values Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3 The cut-off values for anti-1, anti-4, anti-5, anti-6B, anti-7F, anti-9V, anti-14, anti-18C, anti-19F and anti-23F concentrations were greater than or equal to (≥) 0.15 micrograms per milliliter (µg/mL) and ≥ 0.35 µg/mL
Anti-pneumococcal Serotypes Antibody Concentrations Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11 Anti-1, anti-4, anti-5, anti-6B, anti-7F, anti-9V, anti-14, anti-18C, anti-19F and anti-23F antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in µg/mL.
Anti-D and Anti-T Antibody Concentrations Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11 Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in international units per milliliter (IU/mL).
Number of Subjects With hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Antibody Titers Above the Cut-off Values Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11 The cut-off values for hSBA antibody titers were greater than or equal to (≥) 1:4 and ≥ 1:8.
Number of Subjects With Anti-pneumococcal Serotypes Antibody Concentrations Above the Cut-off Values Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11 The cut-off values for anti-1, anti-4, anti-5, anti-6B, anti-7F, anti-9V, anti-14, anti-18C, anti-19F and anti-23F concentrations were ≥ 0.15 µg/mL and ≥ 0.35 µg/mL
Anti-polio Type 1, 2 and 3 Antibody Titers Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11 Antibody titers were presented as geometric mean titers (GMTs).
Number of Subjects With Any Unsolicited Adverse Events (AEs) Within 31-days (Days 0-30) post-booster vaccination period An unsolicited AE covers 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 and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-Synflorix™ Vaccination During the 8-day (Days 0-7) post-Synflorix™ booster vaccination period Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site.
Number of Subjects With Serum Bactericidal Assay Using Human Complement Against Meningococcal Serogroups (hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY) Antibody Titers Above the Cut-off Values Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3 The cut-off values for hSBA antibody titers were greater than or equal to (≥) 1:4 and ≥ 1:8.
Number of Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Concentrations ≥ the Cut-off Value Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3 The cut-off value for anti-D and anti-T concentrations was greater than or equal to (≥) 0.1 IU/mL
Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Concentrations ≥ the Cut-off Value Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3 The cut-off value for anti-PT, anti-FHA and anti-PRN concentrations was greater than or equal to (≥) 5 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).
Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Concentrations ≥ the Cut-off Value Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11 The cut-off value for anti-PT, anti-FHA and anti-PRN concentrations was greater than or equal to (≥) 5 EL.U/mL.
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above the Cut-off Values Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3 The cut-off values for anti-HBs concentrations were greater than or equal to (≥) 10 milli-international units per milliliter (mIU/mL) and ≥ 100 mIU/mL.
Anti-HBs Antibody Concentrations Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11 Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL).
Number of Subjects With Anti-polio Type 1, 2 and 3 Antibody Concentrations ≥ the Cut-off Value Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11 The cut-off value for anti-poliovirus type 1, 2 and 3 antibody concentrations was greater than or equal to (≥) 1:8.
Number of Subjects With New Onset of Chronic Illnesses (NOCIs) From Booster vaccination (Month 10 to Month 11) up to ESFU (Month 16) NOCIs assessed included asthma, autoimmune disorders, type 1 diabetes and allergies.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms During the 8-day (Days 0-7) post-vaccination period following each dose and across doses from Day 0 to Month 3 (Primary Vaccination) Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site. For the Nimenrix 2, Menjugate and NeisVac-C groups, results corresponding to Dose 2 are for Infanrix hexa and Synflorix vaccination at Visit 2 (Month 1), while results corresponding to Dose 3 refer to the vaccination at Visit 3 (Month 2).
Number of Subjects With Serious Adverse Events (SAEs) From Booster vaccination (Month 10) up to Extended Safety Follow-Up (ESFU) (Month 16) Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-Infanrix™ Hexa Vaccination During the 8-day (Days 0-7) post-Infanrix™ hexa booster vaccination period Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-Synflorix Vaccination During the 8-day (Days 0-7) post-Synflorix vaccination period following each dose and across doses from Day 0 to Month 3 (Primary Vaccination) Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms During the 8-day (Days 0-7) post-booster vaccination period Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and temperature \[defined as rectal temperature greater than or equal to (≥) 38 degrees Celsius (°C)\]. Any = occurrence of any general symptoms, regardless of their intensity grade or relationship to study vaccination. Grade 3 Drowsiness = Drowsiness that prevented normal activity. Grade 3 Irritability = Crying that could not be comforted/prevented normal activity. Grade 3 Loss of appetite = Not eating at all. Grade 3 Temperature= temperature above 40.0 (°C). Related = symptom assessed by the investigator as related to the vaccination.
Trial Locations
- Locations (1)
GSK Investigational Site
🇪🇸Vic, Spain