Primary and Booster Vaccination Study With Pneumococcal Vaccine GSK1024850A and Prophylactic Antipyretic Treatment

Infections, Streptococcal Clinical Trial

Official title:

Impact of Immediate or Delayed Prophylactic Antipyretic Treatment on the Immunogenicity, Reactogenicity and Safety of GlaxoSmithKline Biologicals' Pneumococcal Vaccine 1024850A and the Co-administered DTPa-combined Vaccines

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01235949
• Other study ID #: 112921
• Secondary ID: 2010-019761-28
• Status: Completed
• Phase: Phase 4
• Start date: November 12, 2010
• Est. completion date: December 8, 2012

Study information

• Verified date: April 2019
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 850
• Est. completion date: December 8, 2012
• Est. primary completion date: March 28, 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Weeks to 16 Weeks

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Infections, Streptococcal
• Streptococcal Infections

Intervention

Biological:
• GSK1024850A (SynflorixTM)
Intramuscular injection, 4 doses
• Infanrix hexa
Intramuscular injection, 3 doses
• Infanrix-IPV/Hib
Intramuscular injection, 1 dose

Drug:
• Ibuprofen
Oral administration, 3 doses in the 24 hours following vaccination with an interval of 6-8 hours between doses and with dosage based on the subject's body weight
• Paracetamol
Oral administration, 3 doses in the 24 hours following vaccination with an interval of 6-8 hours between doses and with dosage based on the subject's body weight

Locations

Country	Name	City	State
Romania	GSK Investigational Site	Bacau
Romania	GSK Investigational Site	Braila
Romania	GSK Investigational Site	Braila
Romania	GSK Investigational Site	Brasov
Romania	GSK Investigational Site	Brasov
Romania	GSK Investigational Site	Brasov
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Calarasi
Romania	GSK Investigational Site	Cluj-Napoca
Romania	GSK Investigational Site	Constanta
Romania	GSK Investigational Site	Constanta
Romania	GSK Investigational Site	Galati
Romania	GSK Investigational Site	Galati
Romania	GSK Investigational Site	Galati
Romania	GSK Investigational Site	Galati
Romania	GSK Investigational Site	Galati
Romania	GSK Investigational Site	Iasi
Romania	GSK Investigational Site	Pantelimon
Romania	GSK Investigational Site	Sibiu
Romania	GSK Investigational Site	Timisoara

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Romania, 

References & Publications (1)

Falup-Pecurariu O, Man SC, Neamtu ML, Chicin G, Baciu G, Pitic C, Cara AC, Neculau AE, Burlea M, Brinza IL, Schnell CN, Sas V, Lupu VV, François N, Swinnen K, Borys D. Effects of prophylactic ibuprofen and paracetamol administration on the immunogenicity and reactogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugated vaccine (PHiD-CV) co-administered with DTPa-combined vaccines in children: An open-label, randomized, controlled, non-inferiority trial. Hum Vaccin Immunother. 2017 Mar 4;13(3):649-660. doi: 10.1080/21645515.2016.1223001. Epub 2016 Aug 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Antibody Concentrations Against Vaccine Pneumococcal Serotypes Greater Than or Equal to (=) the Cut-off	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).	One month after primary immunization (At Month 3)
Primary	Antibody Concentrations Against Vaccine Pneumococcal Serotypes	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.	One month after primary immunization (At Month 3)
Primary	Antibody Concentrations Against Protein D (Anti-PD)	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.	One month after primary immunization (At Month 3)
Secondary	Antibody Concentrations Against Cross-reactive Pneumococcal Serotypes 6A and 19A	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.	One month after primary immunization (At Month 3)
Secondary	Number of Subjects With Any and Grade 3 Solicited Local Symptoms	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).	Within the 4-day (Days 0-3) post-primary vaccination period following each dose and across doses
Secondary	Number of Subjects With Any and Grade 3 Solicited Local Symptoms	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).	Within the 4-day (Days 0-3) period following booster vaccination
Secondary	Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	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.	Within the 4-day (Days 0-3) post-primary vaccination period following each dose and across doses
Secondary	Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	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.	Within the 4-day (Days 0-3) period following booster vaccination
Secondary	Number of Subjects With Any Serious Adverse Events (SAEs)	SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity.	During the entire study period (Month 0 to 10)
Secondary	Number of Subjects With Any Unsolicited Adverse Events (AEs)	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.	Within 31-days (Day 0-30) following each primary vaccination dose
Secondary	Number of Subjects With Any Unsolicited Adverse Events (AEs)	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.	Within 31-days (Day 0-30) following booster vaccination
Secondary	Antibody Concentrations Against Vaccine Pneumococcal Serotypes	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.	Prior to (Month 9) and one month after booster vaccination (Month 10)
Secondary	Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes	OPA titers against pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (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 an antibody titer = 8.	One month after primary immunization (Month 3)
Secondary	Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes	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.	Prior to (Month 9) and one month after booster vaccination (Month 10)
Secondary	Antibody Concentrations Against Protein D (Anti-PD)	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.	Prior to (Month 9) and one month after booster vaccination (Month 10)
Secondary	Antibody Concentrations Against Diphtheria (D) and Tetanus (T) Toxoids	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.	One month after primary immunization (Month 3)
Secondary	Antibody Concentrations Against Diphteria (D) and Tetanus (T) Toxoids	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.	Prior to (Month 9) and one month after booster vaccination (Month 10)
Secondary	Antibody Concentrations Against Pertussis Toxoid (Anti-PT), Filamentous Haemagglutinin (Anti-FHA) and Pertactin (Anti-PRN)	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.	One month after primary immunization (Month 3)
Secondary	Antibody Concentrations Against Pertussis Toxoid (Anti-PT), Filamentous Haemagglutinin (Anti-FHA) and Pertactin (Anti-PRN)	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.	Prior to (Month 9) and one month after booster vaccination (Month 10)
Secondary	Antibody Concentrations Against Hepatitis B Surface Antigen (HBs)	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.	One month after primary immunization (Month 3)
Secondary	Antibody Concentrations Against Hepatitis B Surface Antigen	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.	Prior to (Month 9) and one month after booster vaccination (Month 10)
Secondary	Antibody Concentrations Against Polyribosyl-ribitol-phosphate (PRP)	Antibody concentrations assessed were presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL). The seroprotection cut-off for the assay was an antibody concentration = 0.15 µg/mL.	One month after primary immunization (Month 3)
Secondary	Antibody Concentrations Against Polyribosyl-ribitol-phosphate (PRP)	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.	Prior to (Month 9) and one month after booster vaccination (Month 10)
Secondary	Antibody Titers Against Poliovirus Type 1, 2 and 3	Antibody titers assessed were presented as geometric mean titers (GMTs). The seroprotection cut-off for the assay was a titer = the value of 8.	One month after primary immunization (Month 3)
Secondary	Antibody Titers Against Poliovirus Type 1, 2 and 3	Antibody titers assessed were presented as geometric mean titers (GMTs). The seroprotection cut-off for the assay was a titer = the value of 8.	Prior to (Month 9) and one month after booster vaccination (Month 10)

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