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Trial record 1 of 1 for:    NCT03207750
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This Study Will Evaluate the Immunogenicity, Reactogenicity and Safety of the Routine Infant Vaccines Pediarix®, Hiberix® and Prevenar 13® When Co-administered With GlaxoSmithKline (GSK) Biologicals' Liquid Human Rotavirus Vaccine (HRV) as Compared to GSK's Licensed Lyophilized Vaccine

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ClinicalTrials.gov Identifier: NCT03207750
Recruitment Status : Completed
First Posted : July 5, 2017
Results First Posted : October 31, 2019
Last Update Posted : December 29, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE June 16, 2017
First Posted Date  ICMJE July 5, 2017
Results First Submitted Date  ICMJE October 8, 2019
Results First Posted Date  ICMJE October 31, 2019
Last Update Posted Date December 29, 2020
Actual Study Start Date  ICMJE September 14, 2017
Actual Primary Completion Date October 9, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 8, 2019)
  • Number of Seroprotected Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations Above or Equal to Cut-off Value. [ Time Frame: At Month 5 (One month after Dose 3 of co-administered vaccines) ]
    Immunogenicity was assessed using Enzyme Linked Immunosorbent Assay (ELISA) in terms of seroprotection rates against diphtheria toxoid. A seroprotected subject is a subject whose antibody concentration is greater than or equal to (≥) the level defining clinical protection. The following seroprotection thresholds were applicable:anti-D antibody concentrations ≥ 0.1 International Units/milliliter (IU/mL), anti-T antibody concentrations ≥ 0.1 IU/mL.
  • Number of Seroprotected Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentrations Above or Equal to Cut-off Value. [ Time Frame: At Month 5 (One month after Dose 3 of co-administered vaccines) ]
    Immunogenicity was assessed using ChemiLuminescence ImmunoAssay (CLIA) in terms of seroprotection rates against Hepatitis B. A seroprotected subject is a subject whose antibody concentration is ≥ the level defining clinical protection. The following seroprotection thresholds were applicable:anti-HB antibody concentrations ≥ 10 milli International Units/milliliter (mIU/mL).
  • Number of Seroprotected Subjects With Anti-polio Virus Types 1, 2 and 3 Antibody Titers Above or Equal to Cut-off Value. [ Time Frame: At Month 5 (One month after Dose 3 of co-administered vaccines) ]
    Immunogenicity was assessed using virus micro-neutralization test in terms of seroprotection rates against polio virus types 1, 2 and 3. A seroprotected subject is a subject whose antibody concentration is ≥ the level defining clinical protection. The following seroprotection thresholds were applicable:anti-polio virus types 1, 2 and 3 types antibody titers ≥ 8 Estimated Dose 50% (ED50).
  • Immunogenicity in Terms of Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations. [ Time Frame: At Month 5 (One month after Dose 3 of co-administered vaccines) ]
    Antibody concentrations against PT, FHA and PRN were determined and expressed as Geometric Mean Concentrations (GMCs).The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations.
  • Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. [ Time Frame: At Month 5 (One month after Dose 3 of co-administered vaccines) ]
    Antibody concentrations against pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) were determined and expressed as GMCs in micrograms per milliliter (µg/mL).The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations.
  • Number of Seroprotected Subjects With Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations Above or Equal to Cut-off Value of 0.15 µg/mL. [ Time Frame: At Month 5 (One month after Dose 3 of co-administered vaccines) ]
    Immunogenicity was assessed in terms of seroprotection rates against PRP antibodies. A seroprotected subject is a subject whose antibody concentration is ≥ the level defining clinical protection. The following seroprotection thresholds were applicable:anti-PRP antibody concentrations ≥ 0.15 µg/mL.
  • Number of Seroprotected Subjects With Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations Above or Equal to Cut-off Value of 1.0 µg/mL. [ Time Frame: At Month 5 (One month after Dose 3 of co-administered vaccines) ]
    Immunogenicity was assessed in terms of seroprotection rates against PRP antibodies. A seroprotected subject is a subject whose antibody concentration is ≥ the level defining clinical protection. The following seroprotection thresholds were applicable:anti-PRP antibody concentrations ≥ 1.0 µg/mL.
  • Number of Subjects With Seroresponse to Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies. [ Time Frame: At Month 5 (One month after Dose 3 of co-administered vaccines) ]
    Seroresponse is defined as the percentage of subjects showing an antibody concentration above a threshold that leads to 95% seroresponse in the HRV lyophilized Group. The cut-offs used were as follows: anti-PT (18.566 IU/mL), anti-FHA (35.711 IU/mL) and anti-PRN (11.034 IU/mL).
Original Primary Outcome Measures  ICMJE
 (submitted: June 30, 2017)
  • Evaluation of immunogenicity with respect to components of the routine infant vaccines (Pediarix®, Hiberix® and Prevenar 13®). [ Time Frame: One month after Dose 3 of routine infant vaccines (Visit 4; Month 5) ]
    Immunogenicity will be evaluated for the following components of the routine vaccination:
    • Anti Diphtheria (Anti-D) antibody concentration ≥0.1 IU/mL
    • Anti-Tetanus (Anti-T) antibody concentration ≥0.1 IU/mL.
    • Anti-Hepatitis B surface antigen (Anti-HBs) antibody concentrations ≥10 mIU/mL Anti-poliovirus types 1, 2 and 3 antibody titers ≥8 ED50.
    • Anti-pertussis toxoid (Anti-PT), Anti-filamentous hemagglutinin (Anti-FHA) and anti-pertactin (Anti-PRN) antibody concentrations expressed as Geometric Mean Concentrations (GMCs).
    • Anti-pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) antibody concentrations expressed as GMCs.
    • Anti-Polyribosyl-Ribitol-Phosphate (Anti-PRP) antibody concentrations ≥0.15 µg/mL.
    • Anti-PRP antibody concentrations ≥1.0 µg/mL.
  • Percentage of subjects with difference in seroresponse with respect to PT, FHA and PRN antigen components. [ Time Frame: One month after Dose 3 of routine infant vaccines (Visit 4; Month 5) ]
    Seroresponse to anti-PT, anti-FHA and anti-PRN.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2019)
  • Number of Seropositive Subjects With Anti-Rota Virus Immunoglobulin A (Anti-RV IgA) Antibody Concentrations Above or Equal to Cut-off Value of 20 Units/Milliliter (U/mL). [ Time Frame: At Month 5 (Three months after Dose 2 of HRV vaccine) ]
    Immunogenicity was assessed in terms of seropositivity against Rota virus IgA antibodies. The cut off used was ≥ 20 U/mL.
  • Number of Seropositive Subjects With Anti-RV IgA Antibody Concentrations Above or Equal to Cut-off Value of 90 U/mL. [ Time Frame: At Month 5 (Three months after Dose 2 of HRV vaccine) ]
    Immunogenicity was assessed in terms of seropositivity against Rota virus IgA antibodies. The cut off used was ≥ 90 U/mL.
  • Number of Seropositive Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations Above or Equal to Cut-off Value. [ Time Frame: At Month 5 (One month after Dose 3 of co-administered vaccines) ]
    Immunogenicity was assessed using ELISA technique in terms of seropositivity against PT, FHA and PRN antibodies. The cut-offs for antibodies were the Lower Limit Of Quantification (LLOQ) of the assays which were ≥ 2.693 IU/mL (anti-PT), ≥ 2.046 IU/mL (anti-FHA) and ≥ 2.187 IU/mL (anti-PRN). The Limit of Quantification is the lowest analyte concentration that can be quantitatively detected with a stated accuracy and precision, and LLOQ is the lowest standard curve point obtained by extrapolation, that can still be used for quantification.
  • Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. [ Time Frame: At Month 5 (One month after Dose 3 of co-administered vaccines) ]
    Immunogenicity was assessed using ELISA technique in terms of seropositivity against Pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) antibodies. The cut-off used was ≥ 0.35 µg/mL.
  • Immunogenicity in Terms of Anti-D and Anti-T Antibody Concentrations. [ Time Frame: At Month 5 (One month after Dose 3 of co-administered vaccines) ]
    Antibody concentrations against diphtheria and tetanus were determined and expressed as GMCs. The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations.
  • Immunogenicity in Terms of Anti-PRP Antibody Concentrations. [ Time Frame: At Month 5 (One month after Dose 3 of co-administered vaccines) ]
    Antibody concentrations against PRP were determined and expressed as GMCs. The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations.
  • Immunogenicity in Terms of Anti-HBs Antibody Concentrations. [ Time Frame: At Month 5 (One month after Dose 3 of co-administered vaccines) ]
    Antibody concentrations against Hepatitis B were determined and expressed as GMCs. The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations.
  • Immunogenicity in Terms of Anti-poliovirus Types 1, 2 and 3 Antibody Titers. [ Time Frame: At Month 5 (One month after Dose 3 of co-administered vaccines) ]
    Antibody concentrations against Poliovirus types 1, 2 and 3 were determined and expressed as Geometric Mean Titers (GMTs).
  • Number of Subjects With Any Solicited General Adverse Events (AEs). [ Time Frame: During the 8-day (Days 1-8) follow-up period after each HRV vaccination. ]
    Assessed solicited general AEs were cough/runny nose; diarrhoea; fever measured by 3 routes which were oral, axillary and rectal, defined as temperature ≥ 38.0 degrees Celsius (°C); irritability; loss of appetite and vomiting. Any = any solicited general AE irrespective of its intensity grade and relationship to vaccination
  • Number of Subjects With Any Unsolicited AEs. [ Time Frame: During the 31-day (Days 1-31) follow-up period after each HRV vaccination. ]
    Unsolicited AEs assessed include any AE reported in addition to those solicited during the clinical study. Also any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms were reported as an unsolicited AE. Any= Any unsolicited AE irrespective of its intensity grade and relationship to vaccination.
  • Number of Subjects With Any Serious Adverse Events (SAEs). [ Time Frame: During the entire study period (Day 1 to Month 10) ]
    SAEs assessed include any untoward medical occurrence that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization or resulted in disability/incapacity.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 30, 2017)
  • Evaluation of serum anti-rotavirus IgA antibody seropositivity. [ Time Frame: 3 months after Dose 2 of HRV vaccine (Visit 4; Month 5) ]
    Serum anti-RV IgA antibody concentrations ≥20 U/mL and ≥90 U/mL.
  • Evaluation of immunogenicity with respect to components of the routine infant vaccines. [ Time Frame: One month after Dose 3 of routine infant vaccines (Visit 4; Month 5) ]
    Immunogenicity will be evaluated for the following components of the routine vaccination:
    • PT, anti-FHA and anti-PRN antibody concentrations ≥2.693 IU/mL, ≥2.046 IU/mL and ≥2.187 IU/mL, respectively.
    • Anti-pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) antibody concentrations ≥0.35 µg/mL for the ELISA.
    • Anti-D, anti-T, anti-PRP and anti-HBs antibody concentrations expressed as GMCs and anti-poliovirus types 1, 2 and 3 antibody concentrations expressed as Geometric Mean Titers (GMTs).
  • Occurrence of any general solicited Adverse Events (AEs). [ Time Frame: During the 8-day (Day 1- Day 8) follow-up period after each dose of HRV vaccine ]
    The following general AEs will be solicited:
    • Fever*,
    • Irritability/Fussiness,
    • Diarrhea#,
    • Vomiting**,
    • Loss of appetite,
    • Cough/runny nose.
      • Fever is defined as temperature ≥38.0°C/100.4°F. The preferred location for measuring temperature in this study will be the oral cavity, the axilla and the rectum.
        • Diarrhea is defined as passage of three or more, looser than normal stools within a day.
          • Vomiting is defined as one or more episodes of forceful emptying of partially digested stomach contents ≥1 hour after feeding within a day.
    The AEs will be categorized depending on their intensity into the following grades:
    • 1 (mild) = An AE which is easily tolerated by the subject, causing minimal discomfort and not interfering with everyday activities.
    • 2 (moderate) = An AE which is sufficiently discomforting to interfere with normal everyday activities.
    • 3 (severe) = An AE which prevents normal, everyday activities.
  • Occurrence of any unsolicited AEs, according to the Medical Dictionary for Regulatory Activities (MedDRA) classification. [ Time Frame: Within 31 days (Day 1-Day 31) after any dose of HRV vaccine ]
    Unsolicited AE covers any AE 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 unsolicited AE, unsolicited AEs rated as grade 3, with causal relationship to vaccination, rated as grade 3 with causal relationship to vaccination and those that resulted in a medically attended visit will be assessed. Any unsolicited AE is defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.
  • Occurrence of Serious Adverse Events (SAEs). [ Time Frame: From Dose 1 of study vaccines up to study end (approximately 10 months) ]
    SAEs to be assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of existing hospitalization or result in disability/incapacity.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE This Study Will Evaluate the Immunogenicity, Reactogenicity and Safety of the Routine Infant Vaccines Pediarix®, Hiberix® and Prevenar 13® When Co-administered With GlaxoSmithKline (GSK) Biologicals' Liquid Human Rotavirus Vaccine (HRV) as Compared to GSK's Licensed Lyophilized Vaccine
Official Title  ICMJE Immunogenicity, Reactogenicity and Safety Study of Pediarix®, Hiberix® and Prevenar 13® Co-administered With Two Different Formulations of GSK Biologicals' HRV Vaccine (444563) in Healthy Infants 6-12 Weeks of Age
Brief Summary The purpose of this study is to assess if there is any immune interference between the Porcine circovirus free (PCV-free) liquid Human rotavirus (HRV) vaccine and routine infant vaccinations currently in use in the US, namely Pediarix®, Hiberix® and Prevenar 13® as compared to the currently licensed lyophilized formulation of the HRV vaccine when co-administered with the same routine vaccinations in healthy infants 6-12 weeks of age
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Prevention
Condition  ICMJE
  • Rotavirus Infection
  • Rotavirus Vaccines
Intervention  ICMJE
  • Biological: Rotarix
    Two doses administered orally according to a 0, 2 month schedule as per the immunization schedule for HRV vaccine administration in the US.
    Other Names:
    • GSK Biologicals' PCV-free liquid formulation of oral live attenuated HRV vaccine.
    • GSK Biologicals' lyophilized formulation of oral live attenuated HRV vaccine.
  • Biological: Pediarix
    Three doses administered intramuscularly according to a 0, 2, 4 month schedule.
    Other Names:
    • GSK Biologicals' Diphtheria and tetanus toxoids and acellular pertussis adsorbed
    • hepatitis B (recombinant) and inactivated poliovirus vaccine.
  • Biological: Hiberix
    Three doses administered intramuscularly according to a 0, 2, 4 month schedule.
    Other Name: GSK Biologicals' Haemophilus b conjugate vaccine (tetanus toxoid conjugate)
  • Biological: Prevenar 13
    Three doses administered intramuscularly according to a 0, 2, 4 month schedule.
    Other Name: Pfizer's Pneumococcal 13-valent conjugate vaccine (diphtheria CRM197 Protein)
Study Arms  ICMJE
  • Experimental: HRV PCV-free Liq Group
    Healthy female or male subjects, between and including 6 and 12 weeks (42-90 days) of age at the time of the first study vaccination who received two doses of oral live-attenuated human rotavirus (HRV) vaccine in PCV-free liquid formulation, according to a 0, 2-month schedule, co-administered with one dose of each Pediarix, Hiberix and Prevnar-13 at three timepoints (day 1, month 2 and month 4). PCV-free implies no detection of PCV-1 and PCV-2 according to the limit of detection of the tests used.
    Interventions:
    • Biological: Rotarix
    • Biological: Pediarix
    • Biological: Hiberix
    • Biological: Prevenar 13
  • Active Comparator: HRV Lyo Group
    Healthy female or male subjects, between and including 6 and 12 weeks (42-90 days) of age at the time of the first study vaccination who received two doses of oral live-attenuated human rotavirus (HRV) vaccine in lyophilized formulation, according to a 0, 2-month schedule, co-administered with one dose of each Pediarix, Hiberix and Prevnar-13 at three timepoints (day 1, month 2 and month 4).
    Interventions:
    • Biological: Rotarix
    • Biological: Pediarix
    • Biological: Hiberix
    • Biological: Prevenar 13
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 30, 2017)
1280
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 1, 2019
Actual Primary Completion Date October 9, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects' parent(s)/[LAR(s)] who, in the opinion of the investigator can and will comply with the requirements of the protocol.
  • A male or female between, and including, 6 and 12 weeks (42-90 days) of age at the time of the first study vaccination.
  • Written or witnessed/thumb printed informed consent obtained from the parent(s)/LAR(s) of the subject prior to performing any study specific procedure.
  • Healthy subjects as established by medical history and clinical examination before entering into the study.

Exclusion Criteria:

  • Child in care.
  • Use of any investigational or non-registered product other than the study vaccines during the period starting 30 days before the first dose of study vaccines (Day-29 to Day 1), or planned use during the study period.
  • Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs since birth. For corticosteroids, this will mean prednisone (≥0.5 mg/kg/day, or equivalent). Inhaled and topical steroids are allowed.
  • Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
  • Administration of long-acting immune-modifying drugs at any time during the study period.
  • Planned administration/administration of a vaccine not foreseen by the study protocol within the period starting 30 days before the first dose of vaccine administration and ending at Visit 4, with the exception of the inactivated influenza vaccine, which is allowed at any time during the study, if administered at a site which is different from the sites used to administer the co-administered vaccines.
  • 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 vaccine/product.
  • Uncorrected congenital malformation of the gastrointestinal tract that would predispose for Intussusception (IS).
  • History of IS.
  • Very prematurely born infants (born ≤28 weeks of gestation).
  • Family history of congenital or hereditary immunodeficiency.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
  • Major congenital defects or serious chronic illness.
  • Previous vaccination against Haemophilus type b (Hib), diphtheria, tetanus, pertussis, pneumococcus, RV and/or poliovirus.
  • Previous confirmed occurrence of RV GE, Hib, diphtheria, tetanus, pertussis, pneumococcus, hepatitis B and/or polio disease.
  • Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
  • GE within 7 days preceding the study vaccine administration.
  • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
  • Hypersensitivity to latex.
  • History of any neurological disorders or seizures.
  • History of Severe combined immunodeficiency (SCID).
  • Acute disease and/or fever at the time of enrolment.

    • Fever is defined as temperature ≥38.0°C/100.4°F. The preferred location for measuring temperature in this study will be the oral cavity, the axilla and the rectum.
    • Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Weeks to 12 Weeks   (Child)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03207750
Other Study ID Numbers  ICMJE 201663
2016-003210-27 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study is available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: https://www.clinicalstudydatarequest.com/Posting.aspx?ID=20750
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP