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

Phase 3

Completed

• Conditions: Rotavirus Vaccines; Rotavirus Infection
• Interventions: Biological: Rotarix; Biological: Pediarix; Biological: Hiberix; Biological: Prevenar 13

• Registration Number: NCT03207750
• Lead Sponsor: GlaxoSmithKline

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 available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-06-16
• Study First Submitted QC: 2017-06-30
• Study First Posted: 2017-07-05
• Study Start: 2017-09-14
• Primary Completion: 2018-10-09
• Study Completion: 2019-03-01
• Results First Submitted: 2019-10-08
• Results First Submitted QC: 2019-10-08
• Results First Posted: 2019-10-31
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-07
• Last Update Posted: 2020-12-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1280

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HRV PCV-free Liq Group	Rotarix	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.
HRV PCV-free Liq Group	Prevenar 13	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.
HRV Lyo Group	Rotarix	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).
HRV Lyo Group	Hiberix	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).
HRV PCV-free Liq Group	Pediarix	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.
HRV Lyo Group	Pediarix	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).
HRV PCV-free Liq Group	Hiberix	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.
HRV Lyo Group	Prevenar 13	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).

Primary Outcome Measures

Name	Time	Method
Number of Seroprotected Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentrations Above or Equal to Cut-off Value.	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-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations Above or Equal to Cut-off Value.	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-polio Virus Types 1, 2 and 3 Antibody Titers Above or Equal to Cut-off Value.	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.	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.	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.	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.	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.	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).

Secondary Outcome Measures

Name	Time	Method
Immunogenicity in Terms of Anti-HBs Antibody Concentrations.	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.
Number of Subjects With Any Unsolicited AEs.	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.
Immunogenicity in Terms of Anti-D and Anti-T Antibody Concentrations.	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.
Number of Subjects With Any Solicited General Adverse Events (AEs).	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 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).	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.	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.	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.	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-PRP Antibody Concentrations.	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-poliovirus Types 1, 2 and 3 Antibody Titers.	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 Serious Adverse Events (SAEs).	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.

Trial Locations

Locations (1)

GSK Investigational Site; 🇺🇸 Marshfield, Wisconsin, United States