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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01392378
First received: July 8, 2011
Last updated: January 10, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Pneumococcal Vaccines
Biological: 13-valent pneumococcal conjugate vaccine
Biological: INFANRIX hexa
Drug: Paracetamol
Drug: Ibuprofen
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase 4, Randomized, Open-Label Trial To Assess The Impact Of Prophylactic Antipyretic Medication On The Immunogenicity Of 13-Valent Pneumococcal Conjugate Vaccine Given With Routine Pediatric Vaccinations In Healthy Infants

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After the Infant Series [ Time Frame: 1 month after the infant series ] [ Designated as safety issue: No ]
    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:
  • 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 [ Time Frame: 1 month after the infant series ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 month after the toddler dose ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: 1 month after the infant series ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 month after the infant series ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 month after the infant series ] [ Designated as safety issue: No ]
    Geometric LS mean concentrations (GMCs) and corresponding 2-sided 95% CIs were evaluated for Hib PRP antibody.

  • Geometric Mean Concentration (GMC) for Antigen-specific Pertussis Toxin (PT), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) Antibody 1 Month After the Infant Series [ Time Frame: 1 month after the infant series ] [ Designated as safety issue: No ]
    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.

  • Geometric Mean Concentration (GMC) for Antigen-specific Tetanus and Diphtheria Antibody 1 Month After the Infant Series [ Time Frame: 1 month after the infant series ] [ Designated as safety issue: No ]
    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 Hepatitis B Virus (HBV) Antibody 1 Month After the Infant Series [ Time Frame: 1 month after the infant series ] [ Designated as safety issue: No ]
    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 Titer (GMT) for Antigen-specific Poliomyelitis Type 1, 2 and 3 Antibodies 1 Month After the Infant Series [ Time Frame: 1 month after the infant series ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 month after the toddler dose ] [ Designated as safety issue: No ]
    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 Pertussis Toxin (PT), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) Antibodies 1 Month After the Toddler Dose [ Time Frame: 1 month after the toddler dose ] [ Designated as safety issue: No ]
    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 Tetanus and Diphtheria Antibodies 1 Month After the Toddler Dose [ Time Frame: 1 month after the toddler dose ] [ Designated as safety issue: No ]
    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 Concentration (GMC) for Antigen-specific Hepatitis B Virus (HBV) Antibody 1 Month After the Toddler Dose [ Time Frame: 1 month after the toddler dose ] [ Designated as safety issue: No ]
    Geometric LS mean concentration (GMCs) were measured in mIU/mL and corresponding 2-sided 95% CIs were evaluated for hepatitis B virus (HBV) antibody.

  • Geometric Mean Titer (GMT) for Antigen-specific Poliomyelitis Type 1, 2 and 3 Antibodies 1 Month After the Toddler Dose [ Time Frame: 1 month after the toddler dose ] [ Designated as safety issue: No ]
    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 Achieving Pre-specified Criteria for the Concomitant Antigens Contained in INFANRIX Hexa 1 Month After the Infant Series [ Time Frame: 1 month after the infant series ] [ Designated as safety issue: No ]
    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 Achieving Pre-specified Criteria for the Concomitant Antigens Contained in INFANRIX Hexa 1 Month After the Toddler Dose [ Time Frame: 1 month after the toddler dose ] [ Designated as safety issue: No ]
    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 1 [ Time Frame: Within 4 days after infant series Dose 1 ] [ Designated as safety issue: Yes ]
    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: Infant Series Dose 2 [ Time Frame: Within 4 days after infant series Dose 2 ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants Reporting Fever Within 4 Days: Infant Series Dose 3 [ Time Frame: Within 4 days after infant series Dose 3 ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants Reporting Fever Within 4 Days: Toddler Dose [ Time Frame: Within 4 days after toddler dose ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline up to 1 Month (28 to 42 days) after infant series ] [ Designated as safety issue: Yes ]
    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).

  • Number of Participants With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs): After the Infant Series [ Time Frame: 1 Month (28 to 42 days) after infant series Dose 3 up to toddler dose ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Toddler dose up to 1 Month (28 to 42 days) after toddler dose ] [ Designated as safety issue: Yes ]
    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).


Enrollment: 908
Study Start Date: August 2011
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
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.
Biological: 13-valent pneumococcal conjugate vaccine
13vPnC will be administered by intramuscular injection at 2, 3, 4 and 12 months of age.
Biological: INFANRIX hexa
INFANRIX hexa will be administered by intramuscular injection at 2, 3, 4 and 12 months of age.
Drug: Paracetamol
Paracetamol suspension for oral administration will be given at a weight adjusted dose of 15mg/kg/dose. The first dose will be given 6-8 hours after each vaccination, the second dose to be given 6-8 hours after the first.
Experimental: Group 2
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.
Biological: 13-valent pneumococcal conjugate vaccine
13vPnC will be administered by intramuscular injection at 2, 3, 4 and 12 months of age.
Biological: INFANRIX hexa
INFANRIX hexa will be administered by intramuscular injection at 2, 3, 4 and 12 months of age.
Drug: Ibuprofen
Ibuprofen suspension for oral administration will be given at a weight adjusted dose of 10mg/kg/dose. The first dose will be given 6-8 hours after each vaccination, the second dose to be given 6-8 hours after the first.
Experimental: Group 3
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.
Biological: 13-valent pneumococcal conjugate vaccine
13vPnC will be administered by intramuscular injection at 2, 3, 4 and 12 months of age.
Biological: INFANRIX hexa
INFANRIX hexa will be administered by intramuscular injection at 2, 3, 4 and 12 months of age.
Drug: Paracetamol
Paracetamol suspension for oral administration will be given at a weight adjusted dose of 15mg/kg/dose. The first dose will be given at the time of each vaccination, the second dose to be given 6-8 hours after the first, and the third dose to be given 6-8 hours after the second.
Experimental: Group 4
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.
Biological: 13-valent pneumococcal conjugate vaccine
13vPnC will be administered by intramuscular injection at 2, 3, 4 and 12 months of age.
Biological: INFANRIX hexa
INFANRIX hexa will be administered by intramuscular injection at 2, 3, 4 and 12 months of age.
Drug: Ibuprofen
Ibuprofen suspension for oral administration will be given at a weight adjusted dose of 10mg/kg/dose. The first dose will be given at the time of each vaccination, the second dose to be given 6-8 hours after the first, and the third dose to be given 6-8 hours after the second.
Experimental: Group 5
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.
Biological: 13-valent pneumococcal conjugate vaccine
13vPnC will be administered by intramuscular injection at 2, 3, 4 and 12 months of age.
Biological: INFANRIX hexa
INFANRIX hexa will be administered by intramuscular injection at 2, 3, 4 and 12 months of age.

  Eligibility

Ages Eligible for Study:   56 Days to 98 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01392378

Locations
Poland
Gabinet Lekarski
Debica, Poland, 39-200
Hanna Czajka Indywidualna Praktyka Lekarska
Krakow, Poland, 31-302
NZOZ "Praktimed" sp. z o.o.
Krakow, Poland, 31-422
NZOZ Salmed
Leczna, Poland, 21-010
Specjalistyczna Praktyka Lekarska Gravita
Lodz, Poland, 91-347
SP ZOZ Lubartow
Lubartow, Poland, 21-100
NZOZ Praktyka Lekarza Rodzinnego Eskulap
Lublin, Poland, 20-044
NZOZ Praktyka Lekarza Rodzinnego Alina Grocka-Wlazlak
Oborniki Slaskie, Poland, 55-120
Specjalistyczny ZOZ nad Matka i Dzieckiem, Oddzial Obserwacyjno Zakazny A, Szpital Dzieciecy
Poznan, Poland, 61-734
NZLA Michalkowice Jarosz i Partnerzy
Siemianowice Slaskie, Poland, 41-103
NZOZ Nasz Lekarz
Torun, Poland, 87-100
Szpital im. Sw. Jadwigi Slaskiej, Oddzia Pediatryczny
Trzebnica, Poland, 55-100
DEN-MED Gabinet Lekarsko-Stomatologiczny Joanna i Jacek Witwiccy
Warszawa, Poland, 02-127
Samodzielny Publiczny Szpital Kliniczny nr 1 we Wroclawiu
Wroclaw, Poland, 50-345
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01392378     History of Changes
Other Study ID Numbers: B1851047, 6096A1-4027
Study First Received: July 8, 2011
Results First Received: January 10, 2014
Last Updated: January 10, 2014
Health Authority: Poland: Ministry of Health and Social Welfare. Poland: Research Ethics Committee.

Keywords provided by Pfizer:
Prevenar 13
13vPnC
Antipyretic medication
Healthy subjects

Additional relevant MeSH terms:
Acetaminophen
Antipyretics
Ibuprofen
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 23, 2014