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

NCT03207750 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 2016632016-003210-27
• Study Type: interventional
• Target: 1,280
• Locations: 1 country
• Sites: 47

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

Conditions

Rotavirus Infection; Rotavirus Vaccines

Keywords

Immunogenicity; lyophilized formulation; United States; Reactogenicity; Safety; Porcine circovirus -free; Human rotavirus vaccine; liquid formulation; Healthy infants

Outcome Measures

Primary Outcomes (8)

• Number of Seroprotected Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations Above or Equal to Cut-off Value.

  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.

  At Month 5 (One month after Dose 3 of co-administered vaccines)

• Number of Seroprotected Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentrations Above or Equal to Cut-off Value.

  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).

  At Month 5 (One month after Dose 3 of co-administered vaccines)

• Number of Seroprotected Subjects With Anti-polio Virus Types 1, 2 and 3 Antibody Titers Above or Equal to Cut-off Value.

  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).

  At Month 5 (One month after Dose 3 of co-administered vaccines)

• Immunogenicity in Terms of Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations.

  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.

  At Month 5 (One month after Dose 3 of co-administered vaccines)

• Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations.

  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.

  At Month 5 (One month after Dose 3 of co-administered vaccines)

• 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.

  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.

  At Month 5 (One month after Dose 3 of co-administered vaccines)

• 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.

  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.

  At Month 5 (One month after Dose 3 of co-administered vaccines)

• Number of Subjects With Seroresponse to Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies.

  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).

  At Month 5 (One month after Dose 3 of co-administered vaccines)

Secondary Outcomes (11)

• 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)

• 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)

• 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)

• 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 in Terms of Anti-D and Anti-T Antibody Concentrations.

  At Month 5 (One month after Dose 3 of co-administered vaccines)

Study Arms (2)

HRV PCV-free Liq Group

EXPERIMENTAL

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.

Biological: Rotarix; Biological: Pediarix; Biological: Hiberix; Biological: Prevenar 13

HRV Lyo Group

ACTIVE COMPARATOR

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).

Biological: Rotarix; Biological: Pediarix; Biological: Hiberix; Biological: Prevenar 13

Interventions

Rotarix BIOLOGICAL

Two doses administered orally according to a 0, 2 month schedule as per the immunization schedule for HRV vaccine administration in the US.

Also known as: GSK Biologicals' PCV-free liquid formulation of oral live attenuated HRV vaccine., GSK Biologicals' lyophilized formulation of oral live attenuated HRV vaccine.

HRV Lyo Group; HRV PCV-free Liq Group

Pediarix BIOLOGICAL

Three doses administered intramuscularly according to a 0, 2, 4 month schedule.

Also known as: GSK Biologicals' Diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B (recombinant) and inactivated poliovirus vaccine.

HRV Lyo Group; HRV PCV-free Liq Group

Hiberix BIOLOGICAL

Three doses administered intramuscularly according to a 0, 2, 4 month schedule.

Also known as: GSK Biologicals' Haemophilus b conjugate vaccine (tetanus toxoid conjugate)

HRV Lyo Group; HRV PCV-free Liq Group

Prevenar 13 BIOLOGICAL

Three doses administered intramuscularly according to a 0, 2, 4 month schedule.

Also known as: Pfizer's Pneumococcal 13-valent conjugate vaccine (diphtheria CRM197 Protein)

HRV Lyo Group; HRV PCV-free Liq Group

Eligibility Criteria

• Age: 6 Weeks - 12 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (47)

GSK Investigational Site

Birmingham, Alabama, 35205, United States

Location

GSK Investigational Site

Fayetteville, Arkansas, 72703, United States

Location

GSK Investigational Site

Jonesboro, Arkansas, 72401, United States

Location

GSK Investigational Site

Daly City, California, 94015, United States

Location

GSK Investigational Site

Oakland, California, 94611, United States

Location

GSK Investigational Site

Walnut Creek, California, 94596, United States

Location

GSK Investigational Site

West Covina, California, 91790, United States

Location

GSK Investigational Site

Colorado Springs, Colorado, 80922, United States

Location

GSK Investigational Site

Altamonte Springs, Florida, 32701, United States

Location

GSK Investigational Site

Boynton Beach, Florida, 33435, United States

Location

GSK Investigational Site

Miami, Florida, 33142, United States

Location

GSK Investigational Site

Tampa, Florida, 33617, United States

Location

GSK Investigational Site

Nampa, Idaho, 83686, United States

Location

GSK Investigational Site

Bardstown, Kentucky, 40004, United States

Location

GSK Investigational Site

Louisville, Kentucky, 40202, United States

Location

GSK Investigational Site

Frederick, Maryland, 21702, United States

Location

GSK Investigational Site

Fall River, Massachusetts, 02721, United States

Location

GSK Investigational Site

Bingham Farms, Michigan, 48025, United States

Location

GSK Investigational Site

Lincoln, Nebraska, 68504, United States

Location

GSK Investigational Site

Lincoln, Nebraska, 68505, United States

Location

GSK Investigational Site

Lincoln, Nebraska, 68522, United States

Location

GSK Investigational Site

Syracuse, New York, 13202, United States

Location

GSK Investigational Site

The Bronx, New York, 10468, United States

Location

GSK Investigational Site

Boone, North Carolina, 28607, United States

Location

GSK Investigational Site

Raleigh, North Carolina, 27609, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44121, United States

Location

GSK Investigational Site

Dayton, Ohio, 45406, United States

Location

GSK Investigational Site

Dayton, Ohio, 45414, United States

Location

GSK Investigational Site

Dayton, Ohio, 45419, United States

Location

GSK Investigational Site

Grove City, Ohio, 43123, United States

Location

GSK Investigational Site

Hermitage, Pennsylvania, 16148, United States

Location

GSK Investigational Site

Charleston, South Carolina, 29407, United States

Location

GSK Investigational Site

North Charleston, South Carolina, 29406-9170, United States

Location

GSK Investigational Site

Kingsport, Tennessee, 37660, United States

Location

GSK Investigational Site

Fort Worth, Texas, 76107, United States

Location

GSK Investigational Site

Galveston, Texas, 77555, United States

Location

GSK Investigational Site

Tomball, Texas, 77375, United States

Location

GSK Investigational Site

Kaysville, Utah, 84037, United States

Location

GSK Investigational Site

Layton, Utah, 84041, United States

Location

GSK Investigational Site

Murray, Utah, 84107, United States

Location

GSK Investigational Site

Orem, Utah, 84057, United States

Location

GSK Investigational Site

Provo, Utah, 84604, United States

Location

GSK Investigational Site

Roy, Utah, 84067, United States

Location

GSK Investigational Site

South Jordan, Utah, 84095, United States

Location

GSK Investigational Site

Syracuse, Utah, 84075, United States

Location

GSK Investigational Site

Charlottesville, Virginia, 22902, United States

Location

GSK Investigational Site

Marshfield, Wisconsin, 54449, United States

Location

MeSH Terms

Conditions

Rotavirus Infections

Interventions

RIX4414 vaccine; PEDIARIX; Tetanus Toxoid; Hepatitis B Vaccines; Poliovirus Vaccine, Inactivated; Hiberix; 13-valent pneumococcal vaccine; CRM197 (non-toxic variant of diphtheria toxin)

Condition Hierarchy (Ancestors)

Reoviridae Infections; RNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Toxoids; Vaccines; Biological Products; Complex Mixtures; Viral Hepatitis Vaccines; Viral Vaccines; Vaccines, Inactivated; Poliovirus Vaccines

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2017
• First Posted: July 5, 2017
• Study Start: September 14, 2017
• Primary Completion: October 9, 2018
• Study Completion: March 1, 2019
• Last Updated: December 29, 2020
• Results First Posted: October 31, 2019

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

US (47)