Infections, StreptococcalPhase 3NCT00496015
Prophylactic Antipyretic Treatment in Children Receiving Booster Dose of Pneumococcal Conjugate Vaccine GSK1024850A
A Phase 3 study testing Pneumococcal conjugate vaccine GSK1024850A., Infanrix hexa. and Meningococcal vaccine GSK134612. in people with Infections, Streptococcal, run by GlaxoSmithKline at 10 sites in Czechia.
Trial summary
The purpose of this trial is to assess if the rate of febrile reactions following the co-administration of a booster dose of pneumococcal conjugate vaccines with standard infant vaccines is lowered when paracetamol is given prophylactically and to assess the impact of pneumococcal conjugate vaccine on pneumococcal and… Read more about this study
- Who is it for?
- Ages 12 to 15 monthsHealthy volunteers can take part
- Conditions the study is for
- Infections, Streptococcal
- What is being tested?
- Pneumococcal conjugate vaccine GSK1024850A., Infanrix hexa. and Meningococcal vaccine GSK134612.
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 750 participants
- Where
- 10 sitesCzechia
- Study dates
- 2 Jul 2007to 17 Feb 2009
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 15 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study.
- A male or female between, and including, 12-15 months of age at the time of the vaccination.
- Written informed consent obtained from the parent or guardian of the subject.
- Free of obvious health problems as established by medical history and clinical examination before entering into the study.
- Subjects in the unprimed group
- A male or female who previously participated in study 107017 and received 3 doses of pneumococcal conjugate vaccine GSK1024850A.
Who cannot join
- For all subjects:
- 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 antipyretic treatment.
- Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within one month preceding the dose of study vaccines, or planned use during the entire study period.
- Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the dose of study vaccines.
- Planned administration/administration of a vaccine not foreseen by the study protocol, during the period starting one month before the dose of study vaccines and up to one month after the dose of study vaccines.
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- History of, or intercurrent, diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b disease.
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
- History of seizures (this criterion does not apply to subjects who have had a single, uncomplicated febrile convulsion in the past) or progressive neurological disease.
- Acute disease at the time of enrolment.
- 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 within three months preceding administration of the dose of study vaccines or planned administration during the study period.
- Subjects of which both parents have a history of atopia.
- Subject has received systemic antibiotic therapy for acute illness within 24 hours prior to the vaccination.
- Subject is likely to receive antipyretic treatment as a result of a concomitant illness or has been treated with paracetamol within the past 24 hours.
- DTPa-HBV-IPV/Hib vaccine:
- Known hypersensitivity after previous administration of diphtheria, tetanus, pertussis, polio, hepatitis B and Hib vaccines or to any component of the vaccines.
- Encephalopathy.
- As with other vaccines, administration of DTPa-HBV-IPV/Hib should be postponed in subjects suffering from acute mild, moderate or severe illness.
- For subjects in the AP-AP, AP-NAP and NAP groups:
- Administration of any pneumococcal, diphtheria, tetanus, pertussis, polio, hepatitis B and/or Haemophilus influenzae type b vaccines other than allowed and used in study 107017.
- For subjects in the AP-AP group:
- Subject with any contraindication to treatment with paracetamol.
- For subjects in the unprimed group:
- Previous vaccination with meningococcal polysaccharide vaccine of serogroup A, C, W-135 and/or Y.
- Previous vaccination with meningococcal polysaccharide conjugate vaccine of serogroups A, C, W-135 and/or Y.
- Planned administration of a hepatitis B vaccine not foreseen by the study protocol during the period starting one month after the dose of study vaccines and up to study end.
- Previous vaccination with tetanus toxoid containing vaccines including T, DTP, DT, DTP-IPV, DTP-HBV-IPV and Hib-TT vaccines six months prior to study entry.
- History of meningococcal disease due to serogroup A, C, W, or Y.
- Administration of any pneumococcal vaccine since birth.
- Full vaccination history since birth not available.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Czechia10 sites
GSK Investigational Site
Brno, 628 00
GSK Investigational Site
Hradec Králové, 500 01
GSK Investigational Site
Jindřichův Hradec, 377 01
GSK Investigational Site
Náchod, 547 01
GSK Investigational Site
Ostrava, 728 92
GSK Investigational Site
Pardubice, 532 03
GSK Investigational Site
Prague, 150 00
GSK Investigational Site
Prague, 1600
GSK Investigational Site
Prague, 190 00
GSK Investigational Site
Znojmo, 669 00
About this study
Official title: Prophylactic Antipyretic Treatment in Children Receiving Booster Dose of Pneumococcal Vaccine GSK1024850A and DTPa-HBV-IPV/Hib Vaccine (Infanrix Hexa) and Assessment of Impact of Pneumococcal Vaccination on Nasopharyngeal Carriage
The purpose of this trial is to assess if the rate of febrile reactions following the co-administration of a booster dose of pneumococcal conjugate vaccines with standard infant vaccines is lowered when paracetamol is given prophylactically and to assess the impact of pneumococcal conjugate vaccine on pneumococcal and H. influenzae nasopharyngeal carriage compared to control group receiving meningococcal conjugate vaccine (GSK134612).
This protocol posting deals with objectives \& outcome measures of the booster phase. The objectives \& outcome measures of the primary phase are presented in a separate protocol posting (NCT number = NCT00370318).
Read the detailed description
The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
- Conditions
- Infections, Streptococcal
- Being tested
- Pneumococcal conjugate vaccine GSK1024850A., Infanrix hexa., Meningococcal vaccine GSK134612., Paracetamol.
- Keywords
- Streptococcus Pneumoniae Vaccines, Meningococcal disease, Carriage, Prophylactic antipyretic, Safety, Pneumococcal vaccine, Fever, Pneumococcal disease, Immunogenicity, Meningococcal vaccine, Booster vaccination
- Medical subject headings
- Streptococcal Infections, Meningococcal Infections, Fever, Pneumococcal Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pneumococcal conjugate vaccine GSK1024850A.Biological
1 intramuscular injection.
Infanrix hexa.Biological
Also called DTPa-HBV-IPV/Hib
1 intramuscular injection.
Meningococcal vaccine GSK134612.Biological
Also called Mencevax™
1 intramuscular injection.
Paracetamol.Drug
Body weight of < 7 kg: none; Body weight of ≥ 7 kg to < 9 kg : 3 suppositories of 125 mg to be administered at 8h intervals after vaccination. Body weight of ≥ 9 kg: 4 suppositories of 125 mg to be administered at 6h intervals after vaccination.
| Study group | Role | What they receive |
|---|---|---|
| Synflorix I Group | Experimental | Subjects were vaccinated with 3 primary vaccination doses of Synflorix™ vaccine with prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa along with prophylactic antipyretic treatment. Receives: Biological: Pneumococcal conjugate vaccine GSK1024850A.; Biological: Infanrix hexa.; Drug: Paracetamol. |
| Synflorix II Group | Experimental | Subjects were vaccinated with 3 primary vaccination doses of Synforix™ vaccine without prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment Receives: Biological: Pneumococcal conjugate vaccine GSK1024850A.; Biological: Infanrix hexa. |
| Synflorix PRE Group | Experimental | Subjects were vaccinated with 3 primary vaccination doses of Synforix™ vaccine without prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study (before the implementation of the protocol amendment) at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment. Receives: Biological: Pneumococcal conjugate vaccine GSK1024850A.; Biological: Infanrix hexa. |
| Synflorix POST Group | Experimental | Subjects were vaccinated with 3 primary vaccination doses of Synforix™ vaccine without prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study (after the implementation of the protocol amendment) at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment. Receives: Biological: Pneumococcal conjugate vaccine GSK1024850A.; Biological: Infanrix hexa. |
| Mencevax + Infanrix Hexa Group | Active comparator | Age-matched pneumococcal vaccine unprimed group receiving a single dose of Mencevax™ vaccine co-administered with Infanrix™ hexa vaccine. Receives: Biological: Infanrix hexa.; Biological: Meningococcal vaccine GSK134612. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects Reported With Core Fever (Rectal Temperature) Greater Than or Equal to (≥) the Cut-off
The cut-off for core fever was 38.0 degrees Celsius (ºC).
Measured: Within 4 days (Day 0-3) after primary vaccine dose.
Secondary outcomes (32)
Number of Subjects Reported With Core Fever (Rectal Temperature) Greater Than (>) the Cut-off
The cut-off value for core fever (rectal temperature) was 39.0ºC.
Measured: Within 4 days (Day 0-3) after primary vaccination dose
Number of Subjects Reported With Any and Grade 3 Solicited Local Symptoms.
Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any occurrence of the specified symptom regardless of intensity. Grade 3 pain was defined as cried when limb was moved/spontaneously painful. Grade 3 redness/swelling was defined as redness/swelling > 30 millimeters (mm) from injection site.
Measured: During the 4-day (Days 0-3) post-primary vaccination period
Number of Subjects Reported With Any, Grade 3 and Related Solicited General Symptoms
Solicited general symptoms assessed were drowsiness, fever (rectal temperature ≥ 38.5°C), irritability and loss of appetite. Any was defined as any occurrence of the specified symptom regardless of intensity and relation to vaccination. Grade 3 drowsiness was defined as drowsiness that prevented normal activity. Grade 3 fever was defined as rectal temperature >40.0°C. Grade 3 irritability was defined as crying that could not be comforted/ prevented normal activity. Grade 3 loss of appetite was defined as not eating at all. Related was defined as solicited symptoms assessed by the investigator as causally related to the study vaccination.
Measured: During the 4-day (Day 0-3) post-vaccination period
Number of Subjects Reported With Unsolicited Adverse Events (AEs)
The outcome measure was not reporting statistics for all the arms in the baseline period. Results were tabulated on baseline groups except for the Synforix PRE and Synforix POST groups, for which results were presented for the Pooled Synforix PRE and POST Group.
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.
Measured: Within 31 days (Days 0-30) after primary vaccine dose.
Number of Subjects Reported With Serious Adverse Events (SAEs)
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.
Measured: Throughout the entire study period (Month 0-Month 12)
Number of Subjects Reported With AEs Resulting in Rash, New Onset of Chronic Illness (NOCI), Emergency Room (ER) Visits and Non-routine Physician Office Visits.
Results were tabulated only on Mencevax + Infanrix Hexa Group, according to the outcome measure specification of the protocol.
Measured: Up to 6 months after vaccination with Mencevax™
Number of Subjects With Antibody Concentrations Against Certain Pneumococcal Serotypes ≥ the Cut Off
Certain pneumococcal serotypes includes 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). Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations were measured by 22F-inhibition Enzyme-Linked ImmunoSorbent Assay (ELISA).
The seroprotection cut-off for the assay was ≥ 0.2 microgram per milliliter (μg/mL).
Measured: Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination
Antibody Concentrations Against Certain Pneumococcal Serotypes ≥ the Cut Off.
Certain pneumococcal serotypes included 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).
Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations were measured by 22F-inhibition Enzyme-Linked ImmunoSorbent Assay (ELISA).
Seropositivity cut-off for the assay was ≥ 0.05 microgram per milliliter (μg/mL).
Measured: Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F
OPA titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) were calculated, expressed as geometric mean titers (GMTs) and tabulated. The seropositivity cut-off for the assay was ≥ 8.
Measured: Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination
Concentrations of Antibodies Against Protein D (Anti-PD)
The seropositivity cut-off for the assay was ≥ 100 Enzyme-Linked ImmunoSorbent Assay (ELISA) units per milliliter (EL.U/mL).
Measured: Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination
Antibody Concentrations Against Pneumococcal Serotypes 6A and 19A (Anti-6A and 19A)
Anti-6A and 19A antibody concentrations were measured by 22F-inhibition Enzyme-Linked ImmunoSorbent Assay (ELISA).
Measured: Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A
OPA titers against pneumococcal serotypes 6A and 19A (Opsono-6A and 19A) were calculated, expressed as geometric mean titers (GMTs) and tabulated. The seropositivity cut-off for the assay was ≥ 8.
Measured: Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination
Number of Subjects With Serum Bactericidal Antibodies, Using Baby Rabbit Complement for Assay (rSBA) Titres ≥ the Cut-off Values
The cut-off values assessed were 1:8 and 1:128 for meningococcal polysaccharides A , C, W-135 and Y serum bactericidal antibodies, using baby rabbit complement for assay (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY).
Results were only tabulated for subjects who received a vaccine including the respective antigens (Mencevax + Infanrix Hexa Group).
Measured: Prior to vaccination (PRE), 1 month (M1) and 12 months (M12) post-vaccination
rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers in the Mencevax + Infanrix Hexa Group
Results were only tabulated for subjects who received a vaccine including the respective antigens (Mencevax + Infanrix Hexa Group).
Measured: Prior to vaccination(PRE), 1 month (M1) and 12 months (M12) post- vaccination.
Number of Subjects With Anti-polysaccharide N (Anti-PS) Concentrations ≥ the Cut-off Values
Anti-PS assessed were anti-PS meningitidis serogroup A (anti-PSA), C (anti-PSC), W (anti-PSW-135) and Y (anti-PSY). The cut-offs for anti-PS concentrations were 0.3 μg/mL and 2.0 μg/mL, tabulated for subjects who received a vaccine including the respective antigens (Mencevax + Infanrix Hexa Group).
Measured: Prior to vaccination(PRE), 1 month (M1) and 12 months (M12) post-vaccination
Geometric Mean Antibody Concentration (GMCs) for Anti-polysaccharide N (Anti-PS) Antibody Concentrations
Anti-PS assessed were Anti-PSA, anti-PSC, anti-PSW-135 and anti-PSY. Results were only tabulated for subjects who received a vaccine including the respective antigens (Mencevax + Infanrix Hexa Group).
Measured: Prior to vaccination(PRE), 1 month (M1) and 12 months (M12) post- vaccination.
Anti-tetanus Toxoids (Anti-T) Antibody Concentrations in the Mencevax + Infanrix Hexa Group
The seroprotection cut-off for the assay was ≥ 0.1 international units per milliliter (IU/mL).
Measured: Prior to vaccination (Pre)
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations in the Mencevax + Infanrix Hexa Group
The seroprotection cut-off for the assay was ≥ 10 milli international units per milliliter (mIU/mL). Results were only tabulated for subjects who received a vaccine including the respective antigens (Mencevax + Infanrix Hexa Group). Dummy lower limit (LL) (0.0) and upper limit UL (99999.9) were entered when number of subjects analysed = 1.
Measured: Prior to vaccination (Pre)
Concentrations of Antibodies Against Diphtheria and Tetanus Toxoids (Anti-D and T).
The seroprotection cut-off for the assay was ≥ 0.1 international units per milliliter (IU/mL).
Measured: 1 month post-vaccination (M1)
Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations
The seropositivity cut-off for the assay was ≥ 5 Enzyme-Linked ImmunoSorbent Assay (ELISA) units per millimiter (EL.U/mL).
Measured: 1 month post-vaccination (M1)
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations
The seroprotection cut-off for the assay was ≥ 10 mIU/mL.
Measured: 1 month post-vaccination (M1)
Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations
The seroprotection cut-off for the assay was ≥ 0.15 μg/mL.
Measured: 1 month post-vaccination (M1)
Anti-poliovirus (Anti-Polio) Types 1, 2 and 3 Titers
The seroprotection cut-off for the assay was ≥ 8.
Measured: 1 month post-vaccination (M1)
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations
The seroprotection cut-off for the assay was ≥ 10 mIU/mL.
Measured: 12 month post-vaccination (M12)
Anti-poliovirus (Anti-Polio) Type 1, 2 and 3 Titers
The seroprotection cut-off for the assay was ≥ 8.
Measured: 12 month post-vaccination (M12)
Number of Nasopharyngeal Swabs With S.Pneumoniae (Vaccine Serotypes)
Results were tabulated on Pooled Synflorix Group and on Mencevax + Infanrix Hexa Group.
Measured: Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall)
Number of Nasopharyngeal Swabs With S.Pneumoniae (Cross-reactive Serotypes)
Results were tabulated on Pooled Synflorix Group and on Mencevax + Infanrix Hexa Group.
Measured: Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall)
Number of Nasopharyngeal Swabs With S.Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes)
Results were tabulated on Mencevax + Infanrix Hexa Group and on Pooled Synflorix Group.
Measured: Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall)
Number of Nasopharyngeal Swabs With H. Influenzae
Results were tabulated on Mencevax + Infanrix Hexa Group and on Pooled Synflorix Group.
Measured: Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall)
Number of Nasopharyngeal Swabs With S. Pneumoniae and H. Influenzae
Results were tabulated on Mencevax + Infanrix Hexa Group and on Pooled Synflorix Group.
Measured: Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall)
Number of Subjects With New Acquisition Associated to S. Pneumoniae Detected in Nasopharyngeal Swabs
Results were tabulated on Mencevax + Infanrix Hexa Group and on Pooled Synflorix Group.
Measured: 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall)
Number of Subjects With New Acquisition Associated to H. Influentzae Detected in Nasopharyngeal Swabs.
Results were tabulated on Mencevax + Infanrix Hexa Group and on Pooled Synflorix Group.
Measured: 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2007 (estimated)
- Study start2 Jul 2007
- Primary completion25 Mar 2008
- Study completion17 Feb 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Infections, StreptococcalStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 750 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00496015
- Sponsor's protocol ID
- 107137
- Status last verified
- May 2017
- First submitted
- 3 Jul 2007
- Last updated
- 18 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Publications
Prymula R, Siegrist CA, Chlibek R, Zemlickova H, Vackova M, Smetana J, Lommel P, Kaliskova E, Borys D, Schuerman L. Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials. Lancet. 2009 Oct 17;374(9698):1339-50. doi: 10.1016/S0140-6736(09)61208-3.
PubMed 19837254Prymula R, Hanovcova I, Splino M, Kriz P, Motlova J, Lebedova V, Lommel P, Kaliskova E, Pascal T, Borys D, Schuerman L. Impact of the 10-valent pneumococcal non-typeable Haemophilus influenzae Protein D conjugate vaccine (PHiD-CV) on bacterial nasopharyngeal carriage. Vaccine. 2011 Feb 24;29(10):1959-67. doi: 10.1016/j.vaccine.2010.12.086. Epub 2011 Jan 6.
PubMed 21215830Prymula R et al. Does prophylactic paracetamol influence the effect of 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) on pneumococcal nasopharyngeal carriage? Abstract presented at the 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD). Tel Aviv, Israel, 14-18 March 2010.
Prymula R et al. Effects on serotype 6A and 6B nasopharyngeal carriage following immunization with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine. Abstract presented at the 28th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID). Nice, France, 4-8 May 2010.
Prymula R et al. Limited clinical benefit but reduced antibody responses to paediatric vaccines following prophylactic paracetamol administration. Abstract presented at the 4th Europaediatrics, Moscow, Russia, 03-06 July 2009.
Prymula R et al. The 10-valent pneumococcal vaccine conjugated to protein-D (PHiD-CV) reduces nasopharyngeal carriage of Streptococcus pneumoniae (SP) vaccine serotypes in Czech children. Abstract presented at the 6th World Congress of the World Society for Pediatric Infectious Diseases (WSPID). Buenos Aires, Argentina, 19-22 November 2009.
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prophylactic Antipyretic Treatment in Children Receiving Booster Dose of Pneumococcal Vaccine GSK1024850A and DTPa-HBV-IPV/Hib Vaccine (Infanrix Hexa) and Assessment of Impact of Pneumococcal Vaccination on Nasopharyngeal Carriage
- ClinicalTrials.gov ID
- NCT00496015
- Acronym / sponsor ID
- 107137
- Conditions
- Infections, Streptococcal
- Keywords
- Streptococcus Pneumoniae Vaccines, Meningococcal disease, Carriage, Prophylactic antipyretic, Safety, Pneumococcal vaccine, Fever, Pneumococcal disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 750 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 2 Jul 2007 (actual)
- Primary completion
- 25 Mar 2008 (actual)
- Study completion
- 17 Feb 2009 (actual)
- First posted
- 4 Jul 2007 (estimated)
- Results
- Posted 18 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this trial is to assess if the rate of febrile reactions following the co-administration of a booster dose of pneumococcal conjugate vaccines with standard infant vaccines is lowered when paracetamol is given prophylactically and to assess the impact of pneumococcal conjugate vaccine on pneumococcal and H. influenzae nasopharyngeal carriage compared to control group receiving meningococcal conjugate vaccine (GSK134612).
This protocol posting deals with objectives \& outcome measures of the booster phase. The objectives \& outcome measures of the primary phase are presented in a separate protocol posting (NCT number = NCT00370318).
Detailed description
The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Synflorix I Group | Experimental | Biological: Pneumococcal conjugate vaccine GSK1024850A., Biological: Infanrix hexa., Drug: Paracetamol.Subjects were vaccinated with 3 primary vaccination doses of Synflorix™ vaccine with prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa along with prophylactic antipyretic treatment. |
| Synflorix II Group | Experimental | Biological: Pneumococcal conjugate vaccine GSK1024850A., Biological: Infanrix hexa.Subjects were vaccinated with 3 primary vaccination doses of Synforix™ vaccine without prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment |
| Synflorix PRE Group | Experimental | Biological: Pneumococcal conjugate vaccine GSK1024850A., Biological: Infanrix hexa.Subjects were vaccinated with 3 primary vaccination doses of Synforix™ vaccine without prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study (before the implementation of the protocol amendment) at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment. |
| Synflorix POST Group | Experimental | Biological: Pneumococcal conjugate vaccine GSK1024850A., Biological: Infanrix hexa.Subjects were vaccinated with 3 primary vaccination doses of Synforix™ vaccine without prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study (after the implementation of the protocol amendment) at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment. |
| Mencevax + Infanrix Hexa Group | Active comparator | Biological: Infanrix hexa., Biological: Meningococcal vaccine GSK134612.Age-matched pneumococcal vaccine unprimed group receiving a single dose of Mencevax™ vaccine co-administered with Infanrix™ hexa vaccine. |
Who may qualify
- Ages
- 12 to 15 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study.
- A male or female between, and including, 12-15 months of age at the time of the vaccination.
- Written informed consent obtained from the parent or guardian of the subject.
- Free of obvious health problems as established by medical history and clinical examination before entering into the study.
- Subjects in the unprimed group
Key exclusion criteria (33 listed)
- 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 antipyretic treatment.
- Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within one month preceding the dose of study vaccines, or planned use during the entire study period.
- Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the dose of study vaccines.
- Planned administration/administration of a vaccine not foreseen by the study protocol, during the period starting one month before the dose of study vaccines and up to one month after the dose of study vaccines.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pneumococcal conjugate vaccine GSK1024850A.1 intramuscular injection. | Biological | Synflorix I Group, Synflorix II Group, Synflorix POST Group, Synflorix PRE Group |
| Infanrix hexa.Also: DTPa-HBV-IPV/Hib1 intramuscular injection. | Biological | Mencevax + Infanrix Hexa Group, Synflorix I Group, Synflorix II Group, Synflorix POST Group, Synflorix PRE Group |
| Meningococcal vaccine GSK134612.Also: Mencevax™1 intramuscular injection. | Biological | Mencevax + Infanrix Hexa Group |
| Paracetamol.Body weight of < 7 kg: none; Body weight of ≥ 7 kg to < 9 kg : 3 suppositories of 125 mg to be administered at 8h intervals after vaccination. Body weight of ≥ 9 kg: 4 suppositories of 125 mg to be administered at 6h intervals after vaccination. | Drug | Synflorix I Group |
Primary outcome
Number of Subjects Reported With Core Fever (Rectal Temperature) Greater Than or Equal to (≥) the Cut-off
Time frame: Within 4 days (Day 0-3) after primary vaccine dose.
The cut-off for core fever was 38.0 degrees Celsius (ºC).
32 secondary outcomes
Number of Subjects Reported With Core Fever (Rectal Temperature) Greater Than (>) the Cut-off
Time frame: Within 4 days (Day 0-3) after primary vaccination dose
Number of Subjects Reported With Any and Grade 3 Solicited Local Symptoms.
Time frame: During the 4-day (Days 0-3) post-primary vaccination period
Number of Subjects Reported With Any, Grade 3 and Related Solicited General Symptoms
Time frame: During the 4-day (Day 0-3) post-vaccination period
Number of Subjects Reported With Unsolicited Adverse Events (AEs)
Time frame: Within 31 days (Days 0-30) after primary vaccine dose.
Number of Subjects Reported With Serious Adverse Events (SAEs)
Time frame: Throughout the entire study period (Month 0-Month 12)
Number of Subjects Reported With AEs Resulting in Rash, New Onset of Chronic Illness (NOCI), Emergency Room (ER) Visits and Non-routine Physician Office Visits.
Time frame: Up to 6 months after vaccination with Mencevax™
Number of Subjects With Antibody Concentrations Against Certain Pneumococcal Serotypes ≥ the Cut Off
Time frame: Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination
Antibody Concentrations Against Certain Pneumococcal Serotypes ≥ the Cut Off.
Time frame: Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F
Time frame: Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination
Concentrations of Antibodies Against Protein D (Anti-PD)
Time frame: Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination
Antibody Concentrations Against Pneumococcal Serotypes 6A and 19A (Anti-6A and 19A)
Time frame: Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A
Time frame: Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination
Number of Subjects With Serum Bactericidal Antibodies, Using Baby Rabbit Complement for Assay (rSBA) Titres ≥ the Cut-off Values
Time frame: Prior to vaccination (PRE), 1 month (M1) and 12 months (M12) post-vaccination
rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers in the Mencevax + Infanrix Hexa Group
Time frame: Prior to vaccination(PRE), 1 month (M1) and 12 months (M12) post- vaccination.
Number of Subjects With Anti-polysaccharide N (Anti-PS) Concentrations ≥ the Cut-off Values
Time frame: Prior to vaccination(PRE), 1 month (M1) and 12 months (M12) post-vaccination
Geometric Mean Antibody Concentration (GMCs) for Anti-polysaccharide N (Anti-PS) Antibody Concentrations
Time frame: Prior to vaccination(PRE), 1 month (M1) and 12 months (M12) post- vaccination.
Anti-tetanus Toxoids (Anti-T) Antibody Concentrations in the Mencevax + Infanrix Hexa Group
Time frame: Prior to vaccination (Pre)
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations in the Mencevax + Infanrix Hexa Group
Time frame: Prior to vaccination (Pre)
Concentrations of Antibodies Against Diphtheria and Tetanus Toxoids (Anti-D and T).
Time frame: 1 month post-vaccination (M1)
Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations
Time frame: 1 month post-vaccination (M1)
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations
Time frame: 1 month post-vaccination (M1)
Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations
Time frame: 1 month post-vaccination (M1)
Anti-poliovirus (Anti-Polio) Types 1, 2 and 3 Titers
Time frame: 1 month post-vaccination (M1)
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations
Time frame: 12 month post-vaccination (M12)
Anti-poliovirus (Anti-Polio) Type 1, 2 and 3 Titers
Time frame: 12 month post-vaccination (M12)
Number of Nasopharyngeal Swabs With S.Pneumoniae (Vaccine Serotypes)
Time frame: Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall)
Number of Nasopharyngeal Swabs With S.Pneumoniae (Cross-reactive Serotypes)
Time frame: Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall)
Number of Nasopharyngeal Swabs With S.Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes)
Time frame: Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall)
Number of Nasopharyngeal Swabs With H. Influenzae
Time frame: Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall)
Number of Nasopharyngeal Swabs With S. Pneumoniae and H. Influenzae
Time frame: Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall)
Number of Subjects With New Acquisition Associated to S. Pneumoniae Detected in Nasopharyngeal Swabs
Time frame: 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall)
Number of Subjects With New Acquisition Associated to H. Influentzae Detected in Nasopharyngeal Swabs.
Time frame: 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19837254Prymula R, Siegrist CA, Chlibek R, Zemlickova H, Vackova M, Smetana J, Lommel P, Kaliskova E, Borys D, Schuerman L. Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials. Lancet. 2009 Oct 17;374(9698):1339-50. doi: 10.1016/S0140-6736(09)61208-3.
- Background: PubMed 21215830Prymula R, Hanovcova I, Splino M, Kriz P, Motlova J, Lebedova V, Lommel P, Kaliskova E, Pascal T, Borys D, Schuerman L. Impact of the 10-valent pneumococcal non-typeable Haemophilus influenzae Protein D conjugate vaccine (PHiD-CV) on bacterial nasopharyngeal carriage. Vaccine. 2011 Feb 24;29(10):1959-67. doi: 10.1016/j.vaccine.2010.12.086. Epub 2011 Jan 6.
- BackgroundPrymula R et al. Does prophylactic paracetamol influence the effect of 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) on pneumococcal nasopharyngeal carriage? Abstract presented at the 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD). Tel Aviv, Israel, 14-18 March 2010.
- BackgroundPrymula R et al. Effects on serotype 6A and 6B nasopharyngeal carriage following immunization with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine. Abstract presented at the 28th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID). Nice, France, 4-8 May 2010.
- BackgroundPrymula R et al. Limited clinical benefit but reduced antibody responses to paediatric vaccines following prophylactic paracetamol administration. Abstract presented at the 4th Europaediatrics, Moscow, Russia, 03-06 July 2009.
- BackgroundPrymula R et al. The 10-valent pneumococcal vaccine conjugated to protein-D (PHiD-CV) reduces nasopharyngeal carriage of Streptococcus pneumoniae (SP) vaccine serotypes in Czech children. Abstract presented at the 6th World Congress of the World Society for Pediatric Infectious Diseases (WSPID). Buenos Aires, Argentina, 19-22 November 2009.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pneumococcal conjugate vaccine GSK1024850A., Infanrix hexa. and Meningococcal vaccine GSK134612. in people with Infections, Streptococcal, run by GlaxoSmithKline at 10 sites in Czechia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects Reported With Core Fever (Rectal Temperature) Greater Than or Equal to (≥) the Cut-off (time frame: Within 4 days (Day 0-3) after primary vaccine dose.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00496015, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2019.