Study Assessing the Effect of Medications to Prevent Fever on Prevenar 13®

Phase 4

Completed

Conditions: Pneumococcal Vaccines

Interventions: Biological: 13-valent pneumococcal conjugate vaccine
Biological: INFANRIX hexa
Drug: Paracetamol
Drug: Ibuprofen

Registration Number: NCT01392378

Lead Sponsor: Pfizer

Brief Summary: The purposes of this study are assess the immunological response (measure the amount of antibodies, i.e. proteins that fight off germs) produced by children after they have been given the 13-valent pneumococcal vaccine (13vPnC) and INFANRIX hexa at 2, 3, 4 and 12 months of age when medications to prevent fever are given on the same day as the vaccination. Also to evaluate the safety of 13-valent pneumococcal conjugate vaccine (13vPnC) in children who receive medications to prevent fever on the day of vaccination.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 908

Inclusion Criteria

Aged 2 months (56 to 98 days) at time of enrollment.
Healthy infant as determined by medical history, physical examination, and judgment of the investigator.

Exclusion Criteria

Previous vaccination with licensed or investigational pneumococcal, diphtheria, tetanus, pertussis, polio, or Hib conjugate vaccines.
A previous anaphylactic reaction to any vaccine or vaccine-related component.
Allergy or contraindication to paracetamol or ibuprofen administration.
Contraindication to vaccination with pneumococcal conjugate, diphtheria, tetanus, pertussis, polio, Hib, or HBV vaccines.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1	13-valent pneumococcal conjugate vaccine	Subjects will receive 13-valent pneumococcal vaccine and INFANRIX hexa at 2, 3, 4 and 12 months of age. They will also receive 2 doses of paracetamol on the day of each vaccination.
Group 2	INFANRIX hexa	Subjects will receive 13-valent pneumococcal vaccine and INFANRIX hexa at 2, 3, 4 and 12 months of age. They will also receive 2 doses of ibuprofen on the day of each vaccination.the first dose.
Group 2	13-valent pneumococcal conjugate vaccine	Subjects will receive 13-valent pneumococcal vaccine and INFANRIX hexa at 2, 3, 4 and 12 months of age. They will also receive 2 doses of ibuprofen on the day of each vaccination.the first dose.
Group 4	13-valent pneumococcal conjugate vaccine	Subjects will receive 13-valent pneumococcal vaccine and INFANRIX hexa at 2, 3, 4 and 12 months of age. They will also receive 3 doses of ibuprofen on the day of each vaccination.
Group 5	13-valent pneumococcal conjugate vaccine	Subjects will receive 13-valent pneumococcal vaccine and INFANRIX hexa at 2, 3, 4 and 12 months of age. This group does not receive any antipyretic medication as part of the study.
Group 5	INFANRIX hexa	Subjects will receive 13-valent pneumococcal vaccine and INFANRIX hexa at 2, 3, 4 and 12 months of age. This group does not receive any antipyretic medication as part of the study.
Group 1	INFANRIX hexa	Subjects will receive 13-valent pneumococcal vaccine and INFANRIX hexa at 2, 3, 4 and 12 months of age. They will also receive 2 doses of paracetamol on the day of each vaccination.
Group 3	13-valent pneumococcal conjugate vaccine	Subjects will receive 13-valent pneumococcal vaccine and INFANRIX hexa at 2, 3, 4 and 12 months of age. They will also receive 3 doses of paracetamol on the day of each vaccination.
Group 3	INFANRIX hexa	Subjects will receive 13-valent pneumococcal vaccine and INFANRIX hexa at 2, 3, 4 and 12 months of age. They will also receive 3 doses of paracetamol on the day of each vaccination.
Group 4	INFANRIX hexa	Subjects will receive 13-valent pneumococcal vaccine and INFANRIX hexa at 2, 3, 4 and 12 months of age. They will also receive 3 doses of ibuprofen on the day of each vaccination.
Group 1	Paracetamol	Subjects will receive 13-valent pneumococcal vaccine and INFANRIX hexa at 2, 3, 4 and 12 months of age. They will also receive 2 doses of paracetamol on the day of each vaccination.
Group 2	Ibuprofen	Subjects will receive 13-valent pneumococcal vaccine and INFANRIX hexa at 2, 3, 4 and 12 months of age. They will also receive 2 doses of ibuprofen on the day of each vaccination.the first dose.
Group 3	Paracetamol	Subjects will receive 13-valent pneumococcal vaccine and INFANRIX hexa at 2, 3, 4 and 12 months of age. They will also receive 3 doses of paracetamol on the day of each vaccination.
Group 4	Ibuprofen	Subjects will receive 13-valent pneumococcal vaccine and INFANRIX hexa at 2, 3, 4 and 12 months of age. They will also receive 3 doses of ibuprofen on the day of each vaccination.

Primary Outcome Measures

Name	Time	Method
Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After the Infant Series	1 month after the infant series	Antibody geometric least squares (LS) mean concentrations (GMCs) for 13 pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, 1, 3, 5, 6A, 7F and 19A) are presented. GMC (13vPnC) and corresponding 2-sided 95 percent (%) confidence interval (CI) were evaluated. Geometric means (GMs) were calculated using all participants with available data for the specified blood draw. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies participants with a determinate IgG concentration to the given serotype for each arm, respectively.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody Level Greater Than or Equal to (>=)0.35 Microgram Per Milliliter (Mcg/mL) 1 Month After the Infant Series	1 month after the infant series	Percentage of participants achieving predefined antibody threshold \>=0.35 mcg/mL along with the corresponding 95% confidence interval (CI) for 13 pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, 1, 3, 5, 6A, 7F and 19A) are presented. Exact 2-sided CI based on the observed proportion of participants.
Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After the Toddler Dose	1 month after the toddler dose	Antibody geometric LS mean concentrations (GMCs) for 13 pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, 1, 3, 5, 6A, 7F and 19A) are presented. GMC (13vPnC) and corresponding 2-sided 95% CI were evaluated. Geometric means (GMs) were calculated using all participants with available data for the specified blood draw. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies participants with a determinate IgG concentration to the given serotype for each arm respectively.
Geometric Mean Concentration (GMC) for Antigen-specific Pertussis Toxin (PT), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) Antibody 1 Month After the Infant Series	1 month after the infant series	Geometric LS mean concentration (GMCs) were measured in Enzyme-linked Immunosorbent Assay (ELISA) units/mL (EU/mL) and corresponding 2-sided 95% CIs were evaluated for pertussis (pertussis toxin \[PT\], filamentous hemagglutinin \[FHA\] and pertactin \[PRN\]) antibodies.
Percentage of Participants Achieving Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Titers Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) 1 Month After the Infant Series	1 month after the infant series	Percentage of participants achieving serotype-specific pneumococcal OPA titer \>= LLOQ, along with the corresponding 95% CIs for 13 pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, 1, 3, 5, 6A, 7F and 19A) are presented. Exact 2-sided CI based on the observed proportion of participants. The OPA LLOQ in titers for each serotype: 1 = 1:18; 3 = 1:12; 4 = 1:21; 5 = 1:29; 6A = 1:37; 6B = 1:43; 7F = 1:210; 9V = 1:345; 14 = 1:35; 18C = 1:31; 19A = 1:18; 19F = 1:48; 23F = 1:13.
Geometric Mean Titer (GMT) for Serotype-specific Pneumococcal Opsonophagocytic Activity (OPA) 1 Month After the Infant Series	1 month after the infant series	Antibody-mediated serum OPA against the 13 pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, 1, 3, 5, 6A, 7F and 19A) was measured centrally using a pneumococcal OPA assay. Results were expressed as OPA titers. OPA titers were logarithmically transformed for analysis; geometric means calculated and expressed as geometric mean titers (GMTs).
Geometric Mean Concentration (GMC) for Antigen-specific Haemophilus Influenzae Type b (Hib) Polyribosylribitol Phosphate (PRP) Antibody 1 Month After the Infant Series	1 month after the infant series	Geometric LS mean concentrations (GMCs) and corresponding 2-sided 95% CIs were evaluated for Hib PRP antibody.
Geometric Mean Titer (GMT) for Antigen-specific Poliomyelitis Type 1, 2 and 3 Antibodies 1 Month After the Infant Series	1 month after the infant series	Geometric LS mean concentrations (GMCs) were measured as titers and corresponding 2-sided 95% CIs were evaluated for poliomyelitis type 1, 2 and 3 antibodies.
Geometric Mean Concentration (GMC) for Antigen-specific Haemophilus Influenzae Type b (Hib) Polyribosylribitol Phosphate (PRP) Antibody 1 Month After the Toddler Dose	1 month after the toddler dose	Geometric LS mean concentration (GMCs) were measured in mcg/mL and corresponding 2-sided 95% CIs were evaluated for Hib PRP antibody.
Geometric Mean Concentration (GMC) for Antigen-specific Tetanus and Diphtheria Antibody 1 Month After the Infant Series	1 month after the infant series	Geometric LS mean concentration (GMCs) were measured in International Units/mL (IU/mL) and corresponding 2-sided 95% CIs were evaluated for tetanus and diphtheria antibodies.
Geometric Mean Concentration (GMC) for Antigen-specific Pertussis Toxin (PT), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) Antibodies 1 Month After the Toddler Dose	1 month after the toddler dose	Geometric LS mean concentration (GMCs) were measured in EU/mL and corresponding 2-sided 95% CIs were evaluated for pertussis (pertussis toxin \[PT\], filamentous hemagglutinin \[FHA\] and pertactin \[PRN\]) antibodies.
Geometric Mean Concentration (GMC) for Antigen-specific Hepatitis B Virus (HBV) Antibody 1 Month After the Toddler Dose	1 month after the toddler dose	Geometric LS mean concentration (GMCs) were measured in mIU/mL and corresponding 2-sided 95% CIs were evaluated for hepatitis B virus (HBV) antibody.
Percentage of Participants Achieving Pre-specified Criteria for the Concomitant Antigens Contained in INFANRIX Hexa 1 Month After the Toddler Dose	1 month after the toddler dose	Percentage of participants achieving pre-specified criteria for concomitant antigens contained in INFANRIX hexa (Hib polyribosylribitol phosphate \[PRP\] \>=0.15 mcg/mL; Hib PRP \>=1 mcg/mL; Pertussis PT \>=14.8 EU/mL, FHA \>=46.5 EU/mL, PRN \>=43.5 EU/mL; Tetanus \>=0.1 IU/mL; Diphtheria \>=0.1 IU/mL; HBV \>=10 mIU/mL; Poliomyelitis Type 1, 2, 3 \>=1:8 titer) along with the corresponding 95% CIs were presented. Exact 2-sided CI based on the observed proportion of participants. Pre-specified criteria for pertussis was the level that 95% of the participants achieved in 13vPnC + INFANRIX hexa group.
Percentage of Participants Reporting Fever Within 4 Days: Infant Series Dose 2	Within 4 days after infant series Dose 2	Participants' rectal temperature was collected for 4 days after each vaccination using an electronic diary. Participants' temperature was collected at 6 to 8 hours after vaccination, 6 to 8 hours following that and coincidentally with antipyretic administration for groups receiving antipyretics. Temperature was recorded at bedtime daily for 3 following days (Day 2 to Day 4) and at any time during the 3 days when fever was suspected. The highest temperature for each day was recorded in the e-diary. Incidences of fever were presented in following categories: \>=38 but \<=39 degree C, \>39 but \<=40 degree C and \>40 degree C.
Number of Participants With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs): Infant Series	Baseline up to 1 Month (28 to 42 days) after infant series	An AE was any untoward medical occurrence in a participant who received vaccine without regard to possibility of causal relationship. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent events for infant series were events between infant series Dose 1 and up to 1 month (28 to 42 days) after infant series that were absent before treatment or that worsened relative to pre-treatment state. Reported non-SAEs included AEs other than SAEs collected using electronic diary (fever, systematic assessment) and events spontaneously collected on case report form at each visit (non-systematic assessment).
Geometric Mean Concentration (GMC) for Antigen-specific Hepatitis B Virus (HBV) Antibody 1 Month After the Infant Series	1 month after the infant series	Geometric LS mean concentration (GMCs) were measured in milli international units/mL (mIU/mL) and corresponding 2-sided 95% CIs were evaluated for hepatitis B virus (HBV) antibody.
Geometric Mean Concentration (GMC) for Antigen-specific Tetanus and Diphtheria Antibodies 1 Month After the Toddler Dose	1 month after the toddler dose	Geometric LS mean concentration (GMCs) were measured in IU/mL and corresponding 2-sided 95% CIs were evaluated for tetanus and diphtheria antibodies.
Geometric Mean Titer (GMT) for Antigen-specific Poliomyelitis Type 1, 2 and 3 Antibodies 1 Month After the Toddler Dose	1 month after the toddler dose	Geometric LS mean concentration (GMCs) were measured as titers and corresponding 2-sided 95% CIs were evaluated for poliomyelitis type 1, 2 and 3 antibodies.
Percentage of Participants Reporting Fever Within 4 Days: Infant Series Dose 3	Within 4 days after infant series Dose 3	Participants' rectal temperature was collected for 4 days after each vaccination using an electronic diary. Participants' temperature was collected at 6 to 8 hours after vaccination, 6 to 8 hours following that and coincidentally with antipyretic administration for groups receiving antipyretics. Temperature was recorded at bedtime daily for 3 following days (Day 2 to Day 4) and at any time during the 3 days when fever was suspected. The highest temperature for each day was recorded in the e-diary. Incidences of fever were presented in following categories: \>=38 but \<=39 degree C, \>39 but \<=40 degree C and \>40 degree C. Report of fever \>40 degrees C after 13vPnC Infant Series Dose 3 was confirmed as data entry error.
Number of Participants With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs): After the Infant Series	1 Month (28 to 42 days) after infant series Dose 3 up to toddler dose	An AE was any untoward medical occurrence in a participant who received vaccine without regard to possibility of causal relationship. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent events after the infant series were events between 1 month (28 to 42 days) after infant series to toddler dose that were absent before treatment or that worsened relative to pre-treatment state. Reported non-SAEs included AEs other than SAEs spontaneously collected on case report form (non-systematic assessment).
Number of Participants With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs): Toddler Dose	Toddler dose up to 1 Month (28 to 42 days) after toddler dose	An AE was any untoward medical occurrence in a participant who received vaccine without regard to possibility of causal relationship. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent events for toddler dose were events between toddler dose and up to 1 month (28 to 42 days) after toddler dose that were absent before treatment or that worsened relative to pre-treatment state. Reported non-SAEs included AEs other than SAEs collected using electronic diary (fever, systematic assessment) and events spontaneously collected on case report form at each visit (non-systematic assessment).
Percentage of Participants Achieving Pre-specified Criteria for the Concomitant Antigens Contained in INFANRIX Hexa 1 Month After the Infant Series	1 month after the infant series	Percentage of participants achieving pre-specified criteria for concomitant antigens contained in INFANRIX hexa (Hib polyribosylribitol phosphate \[PRP\] \>=0.15 mcg/mL; Hib PRP \>=1 mcg/mL; Pertussis PT \>=14.6 EU/mL, FHA \>=16.1 EU/mL, PRN \>=24.0 EU/mL; Tetanus \>=0.1 IU/mL; Diphtheria \>=0.1 IU/mL; HBV \>=10 mIU/mL; Poliomyelitis Type 1, 2, 3 \>=1:8 titer) along with the corresponding 95% CIs were presented. Exact 2-sided CI based on the observed proportion of participants. Pre-specified criteria for pertussis was the level that 95% of the participants achieved in 13vPnC + INFANRIX hexa group.
Percentage of Participants Reporting Fever Within 4 Days: Infant Series Dose 1	Within 4 days after infant series Dose 1	Participants' core (rectal) temperature was collected for 4 days after each vaccination using an electronic diary. Participants' temperature was collected at 6 to 8 hours after vaccination, 6 to 8 hours following that and coincidentally with antipyretic administration for groups receiving antipyretics. Temperature was recorded at bedtime daily for 3 following days (Day 2 to Day 4) and at any time during the 3 days when fever was suspected. The highest temperature for each day was recorded in the e-diary. Incidences of fever were presented in following categories: \>=38 but \<=39 degree Celsius (degree C), greater than (\>) 39 but \<=40 degree C and \>40 degree C.
Percentage of Participants Reporting Fever Within 4 Days: Toddler Dose	Within 4 days after toddler dose	Participants' rectal temperature was collected for 4 days after each vaccination using an electronic diary. Participants' temperature was collected at 6 to 8 hours after vaccination, 6 to 8 hours following that and coincidentally with antipyretic administration for groups receiving antipyretics. Temperature was recorded at bedtime daily for 3 following days (Day 2 to Day 4) and at any time during the 3 days when fever was suspected. The highest temperature for each day was recorded in the e-diary. Incidences of fever were presented in following categories: \>=38 but \<=39 degree C, \>39 but \<=40 degree C and \>40 degree C.

Trial Locations

Locations (14): NZOZ Praktyka Lekarza Rodzinnego Eskulap
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Lublin, Poland
NZOZ Nasz Lekarz
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Torun, Poland
DEN-MED Gabinet Lekarsko-Stomatologiczny Joanna i Jacek Witwiccy
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Warszawa, Poland
Samodzielny Publiczny Szpital Kliniczny nr 1 we Wroclawiu
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Wroclaw, Poland
Gabinet Lekarski
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Debica, Poland
Hanna Czajka Indywidualna Praktyka Lekarska
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Krakow, Poland
NZOZ "Praktimed" sp. z o.o.
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Krakow, Poland
Specjalistyczna Praktyka Lekarska Gravita
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Lodz, Poland
NZLA Michalkowice Jarosz i Partnerzy
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Siemianowice Slaskie, Poland
NZOZ Praktyka Lekarza Rodzinnego Alina Grocka-Wlazlak
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Oborniki Slaskie, Poland
Szpital im. Sw. Jadwigi Slaskiej, Oddzia Pediatryczny
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Trzebnica, Poland
SP ZOZ Lubartow
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Lubartow, Poland
NZOZ Salmed
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Leczna, Poland
Specjalistyczny ZOZ nad Matka i Dzieckiem, Oddzial Obserwacyjno Zakazny A, Szpital Dzieciecy
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Poznan, Poland