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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 4

Conditions: Infections, Streptococcal

Treatments: Drug: Ibuprofen; Biological: Infanrix hexa; Biological: Infanrix-IPV/Hib; Drug: Paracetamol; Biological: GSK1024850A (SynflorixTM)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01235949

112921

2010-019761-28 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 850 patients

Sex: All

Ages: 12 to 16 weeks old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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850 participants in 18 patient groups

Group IIBU

Experimental group

Description:

Immediate ibuprofen group: subjects receiving immediate ibuprofen treatment after each primary vaccine dose

Treatment:

Biological: Infanrix-IPV/Hib

Biological: GSK1024850A (SynflorixTM)

Drug: Ibuprofen

Biological: Infanrix hexa

Group DIBU

Active Comparator group

Description:

Delayed ibuprofen group: subjects receiving delayed ibuprofen treatment after each primary vaccine dose

Treatment:

Biological: Infanrix-IPV/Hib

Biological: GSK1024850A (SynflorixTM)

Drug: Ibuprofen

Biological: Infanrix hexa

Group NIBU

Active Comparator group

Description:

No ibuprofen group: subjects receiving no prophylactic ibuprofen treatment after each primary vaccine dose

Treatment:

Biological: Infanrix-IPV/Hib

Biological: GSK1024850A (SynflorixTM)

Biological: Infanrix hexa

Group IPARA

Experimental group

Description:

Immediate paracetamol group: subjects receiving immediate paracetamol treatment after each primary vaccine dose

Treatment:

Biological: Infanrix-IPV/Hib

Drug: Paracetamol

Biological: GSK1024850A (SynflorixTM)

Biological: Infanrix hexa

Group DPARA

Experimental group

Description:

Delayed paracetamol group: subjects receiving delayed paracetamol treatment after each primary vaccine dose

Treatment:

Biological: Infanrix-IPV/Hib

Drug: Paracetamol

Biological: GSK1024850A (SynflorixTM)

Biological: Infanrix hexa

Group NPARA

Active Comparator group

Description:

No paracetamol group: subjects receiving no prophylactic paracetamol treatment after each primary vaccine dose

Treatment:

Biological: Infanrix-IPV/Hib

Biological: GSK1024850A (SynflorixTM)

Biological: Infanrix hexa

Group IIBU-IIBU

Experimental group

Description:

1/3 of the subjects from the primary IIBU group receiving immediate ibuprofen treatment after booster vaccination

Treatment:

Biological: Infanrix-IPV/Hib

Biological: GSK1024850A (SynflorixTM)

Drug: Ibuprofen

Biological: Infanrix hexa

Group IIBU-DIBU

Experimental group

Description:

1/3 of the subjects from the primary IIBU group receiving delayed ibuprofen treatment after booster vaccination

Treatment:

Biological: Infanrix-IPV/Hib

Biological: GSK1024850A (SynflorixTM)

Biological: Infanrix hexa

Group IIBU-NIBU

Experimental group

Description:

1/3 of the subjects from the primary IIBU group receiving no prophylactic ibuprofen treatment after booster vaccination

Treatment:

Biological: Infanrix-IPV/Hib

Biological: GSK1024850A (SynflorixTM)

Drug: Ibuprofen

Biological: Infanrix hexa

Group DIBU-IIBU

Experimental group

Description:

1/3 of the subjects from the primary DIBU group receiving immediate ibuprofen treatment after booster vaccination

Treatment:

Biological: Infanrix-IPV/Hib

Biological: GSK1024850A (SynflorixTM)

Drug: Ibuprofen

Biological: Infanrix hexa

Group DIBU-DIBU

Experimental group

Description:

1/3 of the subjects from the primary DIBU group receiving delayed ibuprofen treatment after booster vaccination

Treatment:

Biological: Infanrix-IPV/Hib

Biological: GSK1024850A (SynflorixTM)

Drug: Ibuprofen

Biological: Infanrix hexa

Group DIBU-NIBU

Experimental group

Description:

1/3 of the subjects from the primary DIBU group receiving no prophylactic ibuprofen treatment after booster vaccination

Treatment:

Biological: Infanrix-IPV/Hib

Biological: GSK1024850A (SynflorixTM)

Biological: Infanrix hexa

Group NIBU-IIBU

Experimental group

Description:

1/3 of the subjects from the primary NIBU group receiving immediate ibuprofen treatment after booster vaccination

Treatment:

Biological: Infanrix-IPV/Hib

Biological: GSK1024850A (SynflorixTM)

Drug: Ibuprofen

Biological: Infanrix hexa

Group NIBU-DIBU

Experimental group

Description:

1/3 of the subjects from the primary NIBU group receiving delayed ibuprofen treatment after booster vaccination

Treatment:

Biological: Infanrix-IPV/Hib

Biological: GSK1024850A (SynflorixTM)

Drug: Ibuprofen

Biological: Infanrix hexa

Group NIBU-NIBU

Active Comparator group

Description:

1/3 of the subjects from the primary NIBU group receiving no prophylactic ibuprofen treatment after booster vaccination

Treatment:

Biological: Infanrix-IPV/Hib

Biological: GSK1024850A (SynflorixTM)

Biological: Infanrix hexa

Group IPARA-NPARA

Experimental group

Description:

subjects from the primary IPARA group receiving no paracetamol treatment after booster vaccination

Treatment:

Biological: Infanrix-IPV/Hib

Biological: GSK1024850A (SynflorixTM)

Biological: Infanrix hexa

Group DPARA-IPARA

Experimental group

Description:

subjects from the primary DPARA group receiving immediate paracetamol treatment after booster vaccination

Treatment:

Biological: Infanrix-IPV/Hib

Drug: Paracetamol

Biological: GSK1024850A (SynflorixTM)

Biological: Infanrix hexa

Group NPARA-IPARA

Experimental group

Description:

subjects from the primary NPARA group receiving immediate paracetamol treatment after booster vaccination

Treatment:

Biological: Infanrix-IPV/Hib

Drug: Paracetamol

Biological: GSK1024850A (SynflorixTM)

Biological: Infanrix hexa