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Consistency & Immunogenicity Study of 3 Lots of GSK's Hib Conjugate Vaccine Versus ActHIB & Pentacel in Healthy Infants

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01000974
First Posted: October 23, 2009
Last Update Posted: September 26, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose
The purpose of this study is to evaluate safety, to demonstrate lot-to-lot consistency of the vaccine, to address the relevant concomitant vaccine administrations and to provide a comparison between GSK Biologicals' Hib conjugate vaccine and the licensed monovalent Hib vaccine ActHIB as well as the licensed combination product Pentacel in infants at 2, 4, 6 and 15-18 months of age. This study is designed with a primary and a booster phase.

Condition Intervention Phase
Haemophilus Influenzae Type b Biological: GSK Biologicals' Haemophilus influenzae type b vaccine (GSK 208108) Biological: ActHIB™ Biological: Pentacel™ Biological: Pediarix™ Biological: Prevnar 13™ Biological: Rotarix™ Biological: Engerix™-B Biological: Infanrix™ Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Prevention
Official Title: Phase III, Partially Double-blind Study to Evaluate Consistency and Immunogenicity of 3 Lots of GSK Biologicals' Hib Conjugate Vaccine 208108 Versus ActHIB and Pentacel at 2, 4, 6 and 15-18 Months of Age in Healthy Infants

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations Greater Than or Equal to (≥) 0.15 Microgram Per Milliliter (µg/mL) and ≥ 1.0 µg/mL [ Time Frame: At 1 month after last dose of primary vaccination ]
    Non-inferiority of Hiberix to ActHIB, each co-administered with Pediarix, Prevnar13 and Rotarix following 3 primary doses in terms of immune response to PRP (Anti-PRP≥ 0.15 µ g/ml and ≥1.0 µg/mL).

  • Number of Subjects With Anti-Protein-D (Anti-D) and Anti-Protein-T (Anti-T) Antibody Concentrations ≥ 0.1 International Units Per Milliliter (IU/mL) [ Time Frame: At 1 month after last dose of primary vaccination ]
    Non-inferiority of Pediarix co-administered with Hiberix, Prevnar13 and Rotarix compared to Pediarix co-administered with ActHIB, Prevnar13 and Rotarix following 3 primary vaccine doses in terms of immune response to Diphtheria, Tetanus.

  • Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations [ Time Frame: At 1 month after last dose of primary vaccination ]
    Antibody concentrations were given as Geometric Mean Concentrations (GMCs) expressed in micrograms per milliliter (µg/mL).

  • Anti-pertussis Toxoid (Anti-PT), Anti-pertactin (Anti-PRN) and Anti-filamentous Hemagglutinin (Anti-FHA) Antibody Concentrations [ Time Frame: At 1 month after last dose of primary vaccination ]
    Antibody concentrations were given as geometric mean concentrations (GMCs) expressed as enzyme-linked immuno-sorbent assay (ELISA) units per milliliter i.e. EL.U/mL.

  • Anti-Streptococcus Pneumoniae (S.Pneumoniae) Antibody Concentrations [ Time Frame: At 1 month after last dose of primary vaccination ]
    Antibody concentrations against S.pneumoniae were given as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL).

  • Number of Subjects With Seroresponse (95%) to Anti-pertussis Toxoid (Anti-PT), Anti-pertactin (Anti-PRN) and Anti-filamentous Hemagglutinin (Anti-FHA) [ Time Frame: At 1 month after last dose of primary vaccination ]
    Seroresponse (95%) was defined as the number of subjects showing a concentration above a threshold that leads to 95% seroresponse in the ActHIB group.

  • Number of Subjects With Anti-Polio 1,2,3 Antibody Titres Greater Than or Equal to Cut-off Value [ Time Frame: At 1 month after last dose of primary vaccination ]

    The cut-off value was defined as a concentration ≥ 8 ED50 (ED50 is the concentration at which the protein exhibits 50% of its maximum activity).

    The polio testing which started at the Biomnis laboratory was stopped because the polio virus micro-neutralization assays were found to be not in line with the quality standards defined in GSK Biologicals' SOPs. As a result, polio testing was restarted at the GSK laboratory and the results were uploaded into the clinical database.


  • Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations ≥ 1.0 µg/mL [ Time Frame: At 1 month after booster vaccination ]
    Non-inferiority of a booster dose of Hiberix co-administered with Infanrix in subjects 15-18 months of age who received 3 primary vaccine doses of Hiberix to a booster dose of ActHIB co-administered with Infanrix in subjects of 15-18 months of age who received 3 primary vaccine doses of ActHIB in terms of immune response to PRP


Secondary Outcome Measures:
  • Anti-protein-D (Anti-D) and Anti-protein-T (Anti-T) Antibody Concentrations [ Time Frame: At 1 month after last dose of primary vaccination ]
    Antibody concentrations were given as geometric mean concentrations (GMCs) and expressed as International Units per milliliter (IU/mL).

  • Number of Subjects With Any Solicited Local Symptoms [ Time Frame: During a 4-day follow-up period (Days 0-3) following any vaccination ]
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any symptom regardless of intensity grade.

  • Number of Subjects With Any Solicited General Symptoms [ Time Frame: During a 4-day follow-up period (Days 0-3) following any vaccination ]
    Assessed solicited general symptoms were drowsiness, irritability, fever and loss of appetite. Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination. Any fever= Rectal temperature equal to or above (≥) 38 degrees Celsius (°C).

  • Number of Subjects With Any Unsolicited Adverse Events (AEs). [ Time Frame: During the 31-day (Day 0-Day 30) follow-up period after primary vaccination ]
    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.

  • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: From Day 0 until 6 months following the last primary dose ]
    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.

  • Number of Subjects With AEs of Specific Interest (AESIs) [ Time Frame: From Day 0 until 6 months following the last primary dose or the receipt of the booster vaccination, whichever comes first ]
    An AESI was defined as an AE including autoimmune diseases and other mediated inflammatory disorders and assessed by the investigator as specific to the treatment administration.

  • Number of Subjects With Seroresponse (90%) to Anti-PT, Anti-PRN and Anti-FHA [ Time Frame: At 1 month after last dose of primary vaccination ]
    Seroresponse (90%) was defined as the number of subjects showing a concentration above a threshold that leads to 90% seroresponse in the ActHIB group.

  • Number of Subjects With Anti-PT, Anti-PRN and Anti-FHA Antibody Concentrations ≥ 5 EL.U/mL [ Time Frame: At 1 month after last dose of primary vaccination ]
    Seroresponse was defined as the number of subjects showing a concentration above a threshold that leads to 90% seroresponse in the ActHIB group.

  • Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations ≥ 0.15 µg/mL and ≥ 1.0 µg/mL [ Time Frame: Prior to the booster vaccination and 1 month after the booster vaccination ]
    Evaluation of persistence of anti-PRP antibodies induced by three primary vaccine doses of Hiberix, and ActHIB, each co-administered with Pediarix, Prevnar 13 and Rotarix, or Pentacel co-administered with Engerix-B, Rotarix and Prevnar 13 prior to the booster dose of Hiberix, ActHIB or Pentacel at 15-18 months of age and evaluation of immunogenicity of a booster dose of Hiberix co-administered with Infanrix, ActHIB co-administered with Infanrix and Pentacel in terms of the percentage of subjects with anti-PRP concentrations ≥0.15 µg/mL, ≥1.0 µg/mL and GMCs one month after the booster dose.

  • Anti-Hepatitis B (Anti-HBs) Antibody Concentrations [ Time Frame: At 1 month after last dose of primary vaccination ]
    Antibody concentrations were tabulated as geometric mean concentrations (GMCs) and expressedas milli-international units per milliliter (mIU/mL).

  • Number of Subjects With S.Pneumoniae Antibody Concentrations ≥ 0.05 µg/mL, ≥ 0.2 µg/mL and ≥1.0 µg/mL [ Time Frame: At 1 month after the last dose of primary vaccination ]
    Evaluation of immunogenicity of a 3-dose primary vaccination course of Prevnar 13 co-administered with Hiberix, Rotarix and Pediarix, of Prevnar 13 co-administered with ActHIB, Rotarix and Pediarix and of Prevnar 13 co-administered with Pentacel, Rotarix and Engerix-B in terms of S.pneumoniae GMCs and antibody concentrations ≥ 0.05µg/mL, ≥ 0.2 µg/mL, ≥ 1.0 µg/mL at one month after the last dose of primary vaccination.

  • Antibody Titers for Poliovirus Types 1, 2 and 3 [ Time Frame: At 1 month after last dose of primary vaccination ]
    Antibody titers were given as geometric mean titers(GMTs).

  • Number of Subjects With Anti-HBs Antibody Concentrations Greater Than or Equal to Cut-off Values [ Time Frame: At 1 month after last dose of primary vaccination ]
    The cut-off values were defined as a concentration≥ 3.3 mIU/mL (seropositivity) and ≥ 10 mIU/mL (seroprotection).

  • Anti-polyribosylribitol Phosphate (PRP) Antibody Concentrations [ Time Frame: Prior to the booster vaccination and 1 month after the booster vaccination ]
    Antibody concentrations were given as Geometric Mean Concentrations (GMCs) expressed in micrograms per milliliter (µg/mL).

  • Anti-Hepatitis B (Anti-HBs) Antibody Concentrations ≥10.0 mIU/mL and ≥6.2 mIU/mL [ Time Frame: Prior to the booster vaccination ]
    Antibody concentrations were expressed as geometric mean concentrations (GMCs) and expressed as milli-international units per milliliter (mIU/mL).

  • Number of Subjects With Anti-HB Antibody Concentrations ≥10.0 mlU/mL and ≥6.2mLU/mL [ Time Frame: Prior to booster vaccination ]
    The cut-off values were defined as a concentration≥ 6.2 mIU/mL (seropositivity) and ≥ 10 mIU/mL (seroprotection).

  • Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Concentrations ≥ 5 EL.U/mL [ Time Frame: Prior to the booster vaccination and 1 month after the booster vaccination ]
    Evaluation of persistence of anti-PT, anti-FHA and anti-PRN antibodies induced by Pediarix or Pentacel and Engerix-B prior to the administration of a booster dose of Hib vaccine at 15-18 months of age and evaluation of immunogenicity of a booster dose of Infanrix co-administered with Hiberix, a booster dose of Infanrix co-administered with ActHIB and a booster dose of Pentacel with respect to anti-PT, anti-FHA and anti- PRN antibodies.

  • Anti-poliovirus Types 1, 2, and 3 Antibody Titres and Titres ≥ 8 [ Time Frame: Prior to the booster vaccination ]
    Antibody concentrations were tabulated as geometric mean titers (GMTs) and expressed as titers.

  • Number of Subjects With Anti-Polio-1,2,3 Antibody Titers ≥ 8 [ Time Frame: Prior to booster vaccination ]
    Anti-polio 1,2,3 antibody titers greater or equal to the cut off value were calculated.

  • Number of Subjects With Anti-D and Anti-T Antibody Concentrations ≥ 0.1 IU/mL and ≥1.0 IU/mL, Respectively. [ Time Frame: Prior to the booster vaccination and 1 month after the booster vaccination ]
    Evaluation of persistence of anti-D, anti-T antibodies induced by Pediarix or Pentacel and Engerix-B prior to the administration of a booster dose of Hib vaccine at 15-18 months of age and evaluation of immunogenicity of a booster dose of Infanrix co-administered with Hiberix, a booster dose of Infanrix co-administered with ActHIB and a booster dose of Pentacel with respect to anti-D and anti-T antibodies.

  • Number of Subjects With Any Solicited Local Symptoms [ Time Frame: Within 4 days (Days 0-3) following the booster dose ]
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any symptom regardless of intensity grade.

  • Number of Subjects With Any Solicited General Symptoms [ Time Frame: Within 4 days (Days 0-3) following the booster dose ]
    Assessed solicited general symptoms were drowsiness, irritability, fever and loss of appetite. Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination. Any fever= Axillary temperature equal to or above (≥) 38 degrees Celsius (°C).

  • Number of Subjects With AEs of Specific Interest (AESIs) [ Time Frame: From booster dose until 6 months following receipt of the booster dose ]
    An AESI was defined as an AE including autoimmune diseases and other mediated inflammatory disorders and assessed by the investigator as specific to the treatment administration.

  • Number of Subjects With Any Unsolicited Adverse Events (AEs). [ Time Frame: Within 31 days (Day 0 to Day 30) following the booster dose ]
    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.

  • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: From the booster dose until 6 months following receipt of the booster dose ]
    SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

  • Anti-FHA, Anti-PRN and Anti-PT Antibody Concentrations [ Time Frame: pre-booster and one month after booster vaccination ]
    Antibody concentrations were given as geometric mean concentrations (GMCs) expressed as enzyme-linked immuno-sorbent assay (ELISA) units per milliliter i.e. EL.U/mL.


Enrollment: 4003
Study Start Date: June 18, 2010
Study Completion Date: July 17, 2013
Primary Completion Date: November 18, 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hiberix Group
Pooled group of subjects, male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination, who received 3 doses of 3 different lots of Hiberix® vaccine co-administered with 3 doses of Pediarix® and Prevnar13® vaccines at 2, 4 and 6 months of age and 2 doses of Rotarix® vaccine at 2 and 4 months of age The Hiberix® vaccine was administered intramuscularly in the right thigh. Pediarix® vaccine was administered intramuscularly in the left thigh. The Prevnar13® vaccine was administered intramuscularly in the left thigh or deltoid. The Rotarix® vaccine was administered orally.
Biological: GSK Biologicals' Haemophilus influenzae type b vaccine (GSK 208108)
Three doses of 3 different manufacturing lots in primary study at 2, 4 and 6 months of age as intramuscular injection and one dose as booster vaccination.
Other Name: Hiberix®
Biological: Pediarix™
Three doses in primary epoch at 2, 4 and 6 months of age as intramuscular injection
Biological: Prevnar 13™
Three doses in primary epoch at 2, 4 and 6 months of age as intramuscular injection
Biological: Rotarix™
Two oral doses in primary epoch at 2 and 4 months of age
Biological: Infanrix™
One dose in the booster epoch at 15-18 months of age as intramuscular injection
Active Comparator: ActHIB Group
Subjects, male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination, who received 3 doses of ActHIB® vaccine co-administered with 3 doses of Pediarix® and Prevnar13® vaccines at 2, 4 and 6 months of age and 2 doses of Rotarix® vaccine at 2 and 4 months of age. The ActHIB® vaccine was administered intramuscularly in the right thigh. The Pediarix® vaccine was administered intramuscularly in the left thigh. The Prevnar13® vaccine was administered intramuscularly in the left thigh or deltoid. The Rotarix® vaccine was administered orally.
Biological: ActHIB™
Three doses in primary epoch at 2, 4 and 6 months of age as intramuscular injection and one dose as a booster vaccination
Biological: Pediarix™
Three doses in primary epoch at 2, 4 and 6 months of age as intramuscular injection
Biological: Prevnar 13™
Three doses in primary epoch at 2, 4 and 6 months of age as intramuscular injection
Biological: Rotarix™
Two oral doses in primary epoch at 2 and 4 months of age
Biological: Infanrix™
One dose in the booster epoch at 15-18 months of age as intramuscular injection
Active Comparator: Pentacel Group
Subjects, male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination, who received 3 doses of Pentacel® vaccine co-administered with 3 doses of Prevnar13® vaccine, 2 or 3 doses of Engerix™-B vaccine at 2, 4 and 6 months of age and 2 doses of Rotarix® vaccine at 2 and 4 months of age. The Pentacel® vaccine was administered intramuscularly in the right thigh. The Engerix™-B vaccine was administered intramuscularly in the left thigh. The Prevnar13® vaccine was administered intramuscularly in the left thigh or deltoid. The Rotarix® vaccine was administered orally. If subjects in the Pentacel Group had received a birth dose of Hepatitis B vaccine then they were to receive Engerix™-B vaccine only at 2 and 6 months of age.
Biological: Pentacel™
Three doses in primary epoch at 2, 4 and 6 months of age as intramuscular injection and one dose as a booster vaccination
Biological: Prevnar 13™
Three doses in primary epoch at 2, 4 and 6 months of age as intramuscular injection
Biological: Rotarix™
Two oral doses in primary epoch at 2 and 4 months of age
Biological: Engerix™-B
Two or three doses in primary epoch at 2,( 4) and 6 months of age as intramuscular injection

Detailed Description:
This protocol posting has been updated following protocol amendment 3, dated 12 April 2011. The impacted section is: Eligibility Criteria (Exclusion criteria).
  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   6 Weeks to 12 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects for whom the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR[s]) can and will comply with the requirements of the protocol (e.g., completion of the diary card, return for follow-up visits).
  • A male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination.
  • Written informed consent obtained from the subject's parent/LAR.
  • Healthy subjects as established by medical history and clinical examination before entering into the study.
  • Born after a gestation period of minimum 36 weeks.
  • Infants who have not received a previous dose of hepatitis B vaccine or those who have received only 1 dose of hepatitis B vaccine administered at least 30 days prior to enrollment.

Exclusion Criteria:

  • Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
  • Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth.
  • Planned administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of study vaccine and until 30 days after the booster dose.
  • Previous vaccination against Haemophilus influenzae type b, diphtheria, tetanus, pertussis, Pneumococcus, rotavirus and/or poliovirus; more than one previous dose of hepatitis B vaccine.
  • History of Haemophilus influenzae type b, diphtheria, tetanus, pertussis, pneumococcal, rotavirus, poliovirus, and hepatitis B diseases.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, including dry natural latex rubber.
  • Major congenital defects or serious chronic illness.
  • History of any neurologic disorders or seizures.
  • Acute disease at time of enrollment. All vaccines can be administered to persons with a minor illness.
  • Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
  • Concurrent participation in another clinical study, up to 30 days prior to study entry or 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 (pharmaceutical product or device).
  • Child in care.
  • History of intussusception.
  • History of uncorrected congenital malformation of the gastrointestinal tract that would predispose the infant to intussusception.
  • History of Severe Combined Immunodeficiency Disease.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01000974


  Show 63 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01000974     History of Changes
Other Study ID Numbers: 112957
First Submitted: October 22, 2009
First Posted: October 23, 2009
Results First Submitted: April 11, 2013
Results First Posted: August 19, 2013
Last Update Posted: September 26, 2017
Last Verified: August 2017

Keywords provided by GlaxoSmithKline:
primary vaccination course
Haemophilus influenzae type b
infants, children
booster vaccination
immunogenicity
safety
Gram-negative bacterial infections
vaccines, conjugate

Additional relevant MeSH terms:
Vaccines
Heptavalent Pneumococcal Conjugate Vaccine
Immunologic Factors
Physiological Effects of Drugs