Primary and Booster Vaccination Study With Pneumococcal Vaccine GSK1024850A and Prophylactic Antipyretic Treatment
- Conditions
- Infections, Streptococcal
- Interventions
- Biological: GSK1024850A (SynflorixTM)Biological: Infanrix hexaBiological: Infanrix-IPV/Hib
- Registration Number
- NCT01235949
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
The aim of the current study is to determine whether ibuprofen, given as immediate or delayed prophylactic antipyretic treatment in a standardized manner, significantly impacts the immune response in children receiving primary vaccination with GlaxoSmithKline (GSK) Biologicals' 10-valent pneumococcal conjugate vaccine, co-administered with DTPa-combined vaccines, at 3, 4 and 5 months of age.
In addition, this study will further evaluate the impact of prophylactic administration of paracetamol following primary vaccination with immediate or delayed administration or when given in an immediate manner at the time of the booster dose.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 850
- Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol.
- A male or female between, and including, 12 and 16 weeks (84-118 days) of age at the time of the first vaccination.
- Written informed consent obtained from the parent(s)/LAR(s) 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 36 to 42 weeks inclusive.
- Use of any investigational or non-registered product other than the study vaccines/products within 30 days preceding the first dose of study vaccine/product, or planned use during the study period.
- 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 (.
- Indication, other than specified in the protocol, for prophylactic or therapeutic antipyretic treatment during the study period.
- Treatment with antipyretics in the 24 hours before study vaccination or planned administration of antipyretics in the 24 hours after study vaccination.
- Chronic administration of immunosuppressants or other immune-modifying drugs since birth.
- Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting 30 days before each dose of study vaccine and ending 30 days after with the exception of locally recommended (pandemic) influenza vaccines, and those should be documented in the eCRF.
- Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b and/or Streptococcus pneumoniae with the exception of the vaccines where the first dose may be given within the first two weeks of life according to the national recommendations.
- History of intercurrent diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b disease.
- History of any allergic disease or reaction likely to be exacerbated by any component of the vaccines or prophylactic antipyretic treatment, i.e. ibuprofen or paracetamol, as specified in the protocol.
- History of any seizures or progressive neurological disease.
- Acute disease and/or fever at the time of enrolment. The study entry should be delayed until the illness has improved.
- Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination .
- A family history of congenital or hereditary immunodeficiency.
- Major congenital defects or serious chronic illness.
- Administration of immunoglobulins and/or any blood products since birth or planned administration during entire study period.
- Any contraindication to treatment with ibuprofen as described in the ibuprofen summary of product characteristics (SPC).
- Any contraindication to treatment with paracetamol as described in the paracetamol SPC.
- Body weight < 5 kg at the time of enrolment.
- Child in care.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Group IIBU GSK1024850A (SynflorixTM) Immediate ibuprofen group: subjects receiving immediate ibuprofen treatment after each primary vaccine dose Group IIBU Infanrix hexa Immediate ibuprofen group: subjects receiving immediate ibuprofen treatment after each primary vaccine dose Group IIBU Infanrix-IPV/Hib Immediate ibuprofen group: subjects receiving immediate ibuprofen treatment after each primary vaccine dose Group IIBU Ibuprofen Immediate ibuprofen group: subjects receiving immediate ibuprofen treatment after each primary vaccine dose Group DIBU GSK1024850A (SynflorixTM) Delayed ibuprofen group: subjects receiving delayed ibuprofen treatment after each primary vaccine dose Group DIBU Infanrix hexa Delayed ibuprofen group: subjects receiving delayed ibuprofen treatment after each primary vaccine dose Group DIBU Infanrix-IPV/Hib Delayed ibuprofen group: subjects receiving delayed ibuprofen treatment after each primary vaccine dose Group DIBU Ibuprofen Delayed ibuprofen group: subjects receiving delayed ibuprofen treatment after each primary vaccine dose Group NIBU GSK1024850A (SynflorixTM) No ibuprofen group: subjects receiving no prophylactic ibuprofen treatment after each primary vaccine dose Group NIBU Infanrix hexa No ibuprofen group: subjects receiving no prophylactic ibuprofen treatment after each primary vaccine dose Group NIBU Infanrix-IPV/Hib No ibuprofen group: subjects receiving no prophylactic ibuprofen treatment after each primary vaccine dose Group DPARA Infanrix hexa Delayed paracetamol group: subjects receiving delayed paracetamol treatment after each primary vaccine dose Group DPARA Infanrix-IPV/Hib Delayed paracetamol group: subjects receiving delayed paracetamol treatment after each primary vaccine dose Group NPARA GSK1024850A (SynflorixTM) No paracetamol group: subjects receiving no prophylactic paracetamol treatment after each primary vaccine dose Group NPARA Infanrix hexa No paracetamol group: subjects receiving no prophylactic paracetamol treatment after each primary vaccine dose Group NPARA Infanrix-IPV/Hib No paracetamol group: subjects receiving no prophylactic paracetamol treatment after each primary vaccine dose Group IIBU-IIBU GSK1024850A (SynflorixTM) 1/3 of the subjects from the primary IIBU group receiving immediate ibuprofen treatment after booster vaccination Group IIBU-IIBU Infanrix hexa 1/3 of the subjects from the primary IIBU group receiving immediate ibuprofen treatment after booster vaccination Group IIBU-IIBU Infanrix-IPV/Hib 1/3 of the subjects from the primary IIBU group receiving immediate ibuprofen treatment after booster vaccination Group IIBU-DIBU GSK1024850A (SynflorixTM) 1/3 of the subjects from the primary IIBU group receiving delayed ibuprofen treatment after booster vaccination Group IPARA GSK1024850A (SynflorixTM) Immediate paracetamol group: subjects receiving immediate paracetamol treatment after each primary vaccine dose Group IPARA Infanrix hexa Immediate paracetamol group: subjects receiving immediate paracetamol treatment after each primary vaccine dose Group IPARA Infanrix-IPV/Hib Immediate paracetamol group: subjects receiving immediate paracetamol treatment after each primary vaccine dose Group DPARA GSK1024850A (SynflorixTM) Delayed paracetamol group: subjects receiving delayed paracetamol treatment after each primary vaccine dose Group IIBU-DIBU Infanrix hexa 1/3 of the subjects from the primary IIBU group receiving delayed ibuprofen treatment after booster vaccination Group IIBU-DIBU Infanrix-IPV/Hib 1/3 of the subjects from the primary IIBU group receiving delayed ibuprofen treatment after booster vaccination Group IIBU-NIBU GSK1024850A (SynflorixTM) 1/3 of the subjects from the primary IIBU group receiving no prophylactic ibuprofen treatment after booster vaccination Group IIBU-NIBU Infanrix hexa 1/3 of the subjects from the primary IIBU group receiving no prophylactic ibuprofen treatment after booster vaccination Group IIBU-NIBU Infanrix-IPV/Hib 1/3 of the subjects from the primary IIBU group receiving no prophylactic ibuprofen treatment after booster vaccination Group DIBU-IIBU GSK1024850A (SynflorixTM) 1/3 of the subjects from the primary DIBU group receiving immediate ibuprofen treatment after booster vaccination Group DIBU-IIBU Infanrix hexa 1/3 of the subjects from the primary DIBU group receiving immediate ibuprofen treatment after booster vaccination Group DIBU-DIBU GSK1024850A (SynflorixTM) 1/3 of the subjects from the primary DIBU group receiving delayed ibuprofen treatment after booster vaccination Group DIBU-DIBU Infanrix hexa 1/3 of the subjects from the primary DIBU group receiving delayed ibuprofen treatment after booster vaccination Group DIBU-DIBU Infanrix-IPV/Hib 1/3 of the subjects from the primary DIBU group receiving delayed ibuprofen treatment after booster vaccination Group DIBU-NIBU GSK1024850A (SynflorixTM) 1/3 of the subjects from the primary DIBU group receiving no prophylactic ibuprofen treatment after booster vaccination Group DIBU-NIBU Infanrix hexa 1/3 of the subjects from the primary DIBU group receiving no prophylactic ibuprofen treatment after booster vaccination Group DIBU-NIBU Infanrix-IPV/Hib 1/3 of the subjects from the primary DIBU group receiving no prophylactic ibuprofen treatment after booster vaccination Group DIBU-IIBU Infanrix-IPV/Hib 1/3 of the subjects from the primary DIBU group receiving immediate ibuprofen treatment after booster vaccination Group NIBU-IIBU GSK1024850A (SynflorixTM) 1/3 of the subjects from the primary NIBU group receiving immediate ibuprofen treatment after booster vaccination Group NIBU-IIBU Infanrix hexa 1/3 of the subjects from the primary NIBU group receiving immediate ibuprofen treatment after booster vaccination Group NIBU-IIBU Infanrix-IPV/Hib 1/3 of the subjects from the primary NIBU group receiving immediate ibuprofen treatment after booster vaccination Group NIBU-DIBU GSK1024850A (SynflorixTM) 1/3 of the subjects from the primary NIBU group receiving delayed ibuprofen treatment after booster vaccination Group NIBU-DIBU Infanrix hexa 1/3 of the subjects from the primary NIBU group receiving delayed ibuprofen treatment after booster vaccination Group NIBU-DIBU Infanrix-IPV/Hib 1/3 of the subjects from the primary NIBU group receiving delayed ibuprofen treatment after booster vaccination Group NIBU-NIBU GSK1024850A (SynflorixTM) 1/3 of the subjects from the primary NIBU group receiving no prophylactic ibuprofen treatment after booster vaccination Group NIBU-NIBU Infanrix hexa 1/3 of the subjects from the primary NIBU group receiving no prophylactic ibuprofen treatment after booster vaccination Group NIBU-NIBU Infanrix-IPV/Hib 1/3 of the subjects from the primary NIBU group receiving no prophylactic ibuprofen treatment after booster vaccination Group IPARA-NPARA GSK1024850A (SynflorixTM) subjects from the primary IPARA group receiving no paracetamol treatment after booster vaccination Group IPARA-NPARA Infanrix hexa subjects from the primary IPARA group receiving no paracetamol treatment after booster vaccination Group IPARA-NPARA Infanrix-IPV/Hib subjects from the primary IPARA group receiving no paracetamol treatment after booster vaccination Group DPARA-IPARA GSK1024850A (SynflorixTM) subjects from the primary DPARA group receiving immediate paracetamol treatment after booster vaccination Group DPARA-IPARA Infanrix hexa subjects from the primary DPARA group receiving immediate paracetamol treatment after booster vaccination Group DPARA-IPARA Infanrix-IPV/Hib subjects from the primary DPARA group receiving immediate paracetamol treatment after booster vaccination Group NPARA-IPARA GSK1024850A (SynflorixTM) subjects from the primary NPARA group receiving immediate paracetamol treatment after booster vaccination Group NPARA-IPARA Infanrix hexa subjects from the primary NPARA group receiving immediate paracetamol treatment after booster vaccination Group NPARA-IPARA Infanrix-IPV/Hib subjects from the primary NPARA group receiving immediate paracetamol treatment after booster vaccination Group DPARA Paracetamol Delayed paracetamol group: subjects receiving delayed paracetamol treatment after each primary vaccine dose Group IPARA Paracetamol Immediate paracetamol group: subjects receiving immediate paracetamol treatment after each primary vaccine dose Group IIBU-IIBU Ibuprofen 1/3 of the subjects from the primary IIBU group receiving immediate ibuprofen treatment after booster vaccination Group DIBU-IIBU Ibuprofen 1/3 of the subjects from the primary DIBU group receiving immediate ibuprofen treatment after booster vaccination Group IIBU-NIBU Ibuprofen 1/3 of the subjects from the primary IIBU group receiving no prophylactic ibuprofen treatment after booster vaccination Group DIBU-DIBU Ibuprofen 1/3 of the subjects from the primary DIBU group receiving delayed ibuprofen treatment after booster vaccination Group NIBU-IIBU Ibuprofen 1/3 of the subjects from the primary NIBU group receiving immediate ibuprofen treatment after booster vaccination Group NIBU-DIBU Ibuprofen 1/3 of the subjects from the primary NIBU group receiving delayed ibuprofen treatment after booster vaccination Group DPARA-IPARA Paracetamol subjects from the primary DPARA group receiving immediate paracetamol treatment after booster vaccination Group NPARA-IPARA Paracetamol subjects from the primary NPARA group receiving immediate paracetamol treatment after booster vaccination
- Primary Outcome Measures
Name Time Method Number of Subjects With Antibody Concentrations Against Vaccine Pneumococcal Serotypes Greater Than or Equal to (≥) the Cut-off One month after primary immunization (At Month 3) Antibodies against the vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) have been assessed by 22F-inhibition enzyme-linked immunosorbent assay (ELISA). The cut-off value of the assay was an antibody concentration greater than or equal to (≥) 0.2 micrograms per milliliter (μg/mL).
Antibody Concentrations Against Vaccine Pneumococcal Serotypes One month after primary immunization (At Month 3) Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations have been assessed by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). The seropositivity cut-off for the assay was an antibody concentration ≥ 0.05 μg/mL.
Antibody Concentrations Against Protein D (Anti-PD) One month after primary immunization (At Month 3) Anti-PD antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in ELISA units (EL.U) per milliliter (EL.U/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 100 EL.U/mL.
- Secondary Outcome Measures
Name Time Method Antibody Concentrations Against Pertussis Toxoid (Anti-PT), Filamentous Haemagglutinin (Anti-FHA) and Pertactin (Anti-PRN) Prior to (Month 9) and one month after booster vaccination (Month 10) Antibody concentrations assessed were presented as geometric mean concentrations (GMCs) and expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off for the assay was an antibody concentration ≥ 5 EL.U/mL.
Number of Subjects With Any Unsolicited Adverse Events (AEs) Within 31-days (Day 0-30) following booster vaccination An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Within the 4-day (Days 0-3) period following booster vaccination Solicited local symptoms assessed were pain, redness and swelling. Any = incidence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling above 30 millimeters (mm).
Number of Subjects With Any Serious Adverse Events (SAEs) During the entire study period (Month 0 to 10) SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity.
Antibody Concentrations Against Diphtheria (D) and Tetanus (T) Toxoids One month after primary immunization (Month 3) Anti-D and anti-T antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in international units per milliliter (IU/mL). The seroprotection cut-off for the assay was an antibody concentration ≥ 0.1 IU/mL.
Antibody Concentrations Against Diphteria (D) and Tetanus (T) Toxoids Prior to (Month 9) and one month after booster vaccination (Month 10) Anti-D and anti-T antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in IU/mL. The seroprotection cut-off for the assay was an antibody concentration ≥ 0.1 IU/mL.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Within the 4-day (Days 0-3) period following booster vaccination Solicited general symptoms included drowsiness, irritability, loss of appetite and fever \[rectally, greater than or equal to (≥) 38 degrees Celsius (°C)\]. Any= incidence of any symptom regardless of intensity grade or relationship to vaccination. Grade 3 drowsiness = drowsiness that interfered with 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 fever = fever above (\>) 40.0°C. Related = symptom assessed by the investigator as related to the vaccination.
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Prior to (Month 9) and one month after booster vaccination (Month 10) Anti- pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F antibody concentrations have been assessed by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). The seropositivity cut-off for the assay was an antibody concentration greater than or equal to (≥) 0.05 μg/mL.
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Prior to (Month 9) and one month after booster vaccination (Month 10) OPA titers against pneumococcal serotypes (Opsono-1, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F) were presented as geometric mean titers (GMTs). The seropositivity cut-off for the assay was ≥ 8. When the number of subjects in a group for a specific category equals (=) 1, the lower limit and upper limit of the confidence interval that can't be calculated, are filled in with the GMT value (due to system constraint). Placeholder value "99999.9" has been entered when value to be entered in the system was greater than (\>) 1.0 E10.
Antibody Concentrations Against Protein D (Anti-PD) Prior to (Month 9) and one month after booster vaccination (Month 10) Anti-PD antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U//mL). The seroprotection cut-off for the assay was an antibody concentration ≥ 100 EL.U/mL.
Antibody Concentrations Against Hepatitis B Surface Antigen (HBs) One month after primary immunization (Month 3) Antibody concentrations assessed were presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL). The seroprotection cut-off for the assay was an antibody concentration ≥ 10 mIU/mL.
Antibody Concentrations Against Hepatitis B Surface Antigen Prior to (Month 9) and one month after booster vaccination (Month 10) Antibody concentrations assessed were presented as geometric mean concentrations (GMCs) and expressed in mIU/mL. The seroprotection cut-off for the assay was an antibody concentration ≥ 10 mIU/mL.
Antibody Concentrations Against Polyribosyl-ribitol-phosphate (PRP) Prior to (Month 9) and one month after booster vaccination (Month 10) Antibody concentrations assessed were presented as geometric mean concentrations (GMCs) and expressed in µg/mL. The seroprotection cut-off for the assay was an antibody concentration ≥ 0.15 µg/mL.
Antibody Titers Against Poliovirus Type 1, 2 and 3 Prior to (Month 9) and one month after booster vaccination (Month 10) Antibody titers assessed were presented as geometric mean titers (GMTs). The seroprotection cut-off for the assay was a titer ≥ the value of 8.
Antibody Concentrations Against Cross-reactive Pneumococcal Serotypes 6A and 19A One month after primary immunization (At Month 3) Anti-pneumococcal serotype 6A and 19A antibody concentrations have been assessed by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). The seropositivity cut-off for the assay was an antibody concentration ≥ 0.05 μg/mL.
Trial Locations
- Locations (1)
GSK Investigational Site
🇷🇴Timisoara, Romania