Clinical trial NCT01235949: Primary and Booster Vaccination Study With Pneumococcal Vaccine GSK1024850A and Prophylactic Antipyretic Treatment
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Infections, Streptococcal
Keywords: Pneumococcal vaccine
Immunogenicity
Safety
Fever
Primary vaccination
Booster vaccination
Pneumococcal disease
Prophylactic antipyretic
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-11-07
Enrollment: 850
Sex: ALL
Minimum age (years): 12
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Subjects With Antibody Concentrations Against Vaccine Pneumococcal Serotypes Greater Than or Equal to (≥) the Cut-off
timeFrame: One month after primary immunization (At Month 3)
measure: Antibody Concentrations Against Vaccine Pneumococcal Serotypes
timeFrame: One month after primary immunization (At Month 3)
measure: Antibody Concentrations Against Protein D (Anti-PD)
timeFrame: One month after primary immunization (At Month 3)
Secondary outcomes:
measure: Antibody Concentrations Against Cross-reactive Pneumococcal Serotypes 6A and 19A
timeFrame: One month after primary immunization (At Month 3)
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: Within the 4-day (Days 0-3) post-primary vaccination period following each dose and across doses
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: Within the 4-day (Days 0-3) period following booster vaccination
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: Within the 4-day (Days 0-3) post-primary vaccination period following each dose and across doses
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: Within the 4-day (Days 0-3) period following booster vaccination
measure: Number of Subjects With Any Serious Adverse Events (SAEs)
timeFrame: During the entire study period (Month 0 to 10)
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: Within 31-days (Day 0-30) following each primary vaccination dose
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: Within 31-days (Day 0-30) following booster vaccination
measure: Antibody Concentrations Against Vaccine Pneumococcal Serotypes
timeFrame: Prior to (Month 9) and one month after booster vaccination (Month 10)
measure: Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes
timeFrame: One month after primary immunization (Month 3)
measure: Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes
timeFrame: Prior to (Month 9) and one month after booster vaccination (Month 10)
measure: Antibody Concentrations Against Protein D (Anti-PD)
timeFrame: Prior to (Month 9) and one month after booster vaccination (Month 10)
measure: Antibody Concentrations Against Diphtheria (D) and Tetanus (T) Toxoids
timeFrame: One month after primary immunization (Month 3)
measure: Antibody Concentrations Against Diphteria (D) and Tetanus (T) Toxoids
timeFrame: Prior to (Month 9) and one month after booster vaccination (Month 10)
measure: Antibody Concentrations Against Pertussis Toxoid (Anti-PT), Filamentous Haemagglutinin (Anti-FHA) and Pertactin (Anti-PRN)
timeFrame: One month after primary immunization (Month 3)
measure: Antibody Concentrations Against Pertussis Toxoid (Anti-PT), Filamentous Haemagglutinin (Anti-FHA) and Pertactin (Anti-PRN)
timeFrame: Prior to (Month 9) and one month after booster vaccination (Month 10)
measure: Antibody Concentrations Against Hepatitis B Surface Antigen (HBs)
timeFrame: One month after primary immunization (Month 3)
measure: Antibody Concentrations Against Hepatitis B Surface Antigen
timeFrame: Prior to (Month 9) and one month after booster vaccination (Month 10)
measure: Antibody Concentrations Against Polyribosyl-ribitol-phosphate (PRP)
timeFrame: One month after primary immunization (Month 3)
measure: Antibody Concentrations Against Polyribosyl-ribitol-phosphate (PRP)
timeFrame: Prior to (Month 9) and one month after booster vaccination (Month 10)
measure: Antibody Titers Against Poliovirus Type 1, 2 and 3
timeFrame: One month after primary immunization (Month 3)
measure: Antibody Titers Against Poliovirus Type 1, 2 and 3
timeFrame: Prior to (Month 9) and one month after booster vaccination (Month 10)
Other outcomes:
Locations:
city: Bacau
country: Romania
facility: GSK Investigational Site
city: Braila
country: Romania
facility: GSK Investigational Site
city: Braila
country: Romania
facility: GSK Investigational Site
city: Brasov
country: Romania
facility: GSK Investigational Site
city: Brasov
country: Romania
facility: GSK Investigational Site
city: Brasov
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucuresti
country: Romania
facility: GSK Investigational Site
city: Bucuresti
country: Romania
facility: GSK Investigational Site
city: Calarasi
country: Romania
facility: GSK Investigational Site
city: Cluj-Napoca
country: Romania
facility: GSK Investigational Site
city: Constanta
country: Romania
facility: GSK Investigational Site
city: Constanta
country: Romania
facility: GSK Investigational Site
city: Galati
country: Romania
facility: GSK Investigational Site
city: Galati
country: Romania
facility: GSK Investigational Site
city: Galati
country: Romania
facility: GSK Investigational Site
city: Galati
country: Romania
facility: GSK Investigational Site
city: Galati
country: Romania
facility: GSK Investigational Site
city: Iasi
country: Romania
facility: GSK Investigational Site
city: Pantelimon
country: Romania
facility: GSK Investigational Site
city: Sibiu
country: Romania
facility: GSK Investigational Site
city: Timisoara
country: Romania
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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, Francois 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.