Immunogenicity and Safety Study of Infanrix Hexa in Healthy Infants Born to Mothers Vaccinated With Boostrix™ During Pregnancy or Immediately Post-delivery

NCT02422264 | Completed Phase 4 Results

• 2 other identifiers: 2013302014-001117-41
• Study Type: interventional
• Target: 601
• Locations: 6 countries
• Sites: 30

Brief Summary

The purpose of this study is to evaluate the immunogenicity and safety of GSK Biologicals' Infanrix hexa, given in the primary vaccination schedule to infants born to pregnant women who participated in study 116945 \[DTPA (BOOSTRIX)-047\]. This study will help us evaluate if the presence of transplacentally transferred maternal antibodies interfere with the immune response to primary vaccination with Infanrix hexa and a co-administered pneumococcal conjugate vaccine given as a part of this study in infants.

Conditions

Acellular Pertussis; Tetanus; Poliomyelitis; Diphtheria; Diphtheria-Tetanus-aPertussis-Hepatitis B-Poliomyelitis-Haemophilus Influenzae Type b Vaccines

Outcome Measures

Primary Outcomes (5)

• Number of Subjects With Vaccine Response Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens

  Vaccine response to the PT, FHA and PRN antigens, is defined as the appearance of antibodies in subjects who were initially seronegative (i.e., with concentrations lower than (\<) the cut-off value of the assay), or at least maintenance of pre-vaccination antibody concentrations in subjects who were initially seropositive (i.e., with concentrations greater than or equal to (≥) the cut-off value of the assay). Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA, 2.187 IU/mL for anti-PRN.

  1 month after the last dose of the primary vaccination

• Number of Seroprotected Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentration Above or Equal to the Assay Cut-off

  A seroprotected subject is a subject whose antibody concentration/titre was ≥ the level defining clinical protection, of 0.1 International Units per milliliter (IU/mL).

  1 month after the last dose of the primary vaccination

• Number of Seroprotected Subjects With Anti Hepatitis B (Anti-HBs) Antibody Concentration Above or Equal to the Assay Cut-off

  A seroprotected subject is a subject whose antibody concentration/titre was ≥ to the level defining clinical protection, of 10 micro International Units per milliliter (mIU/mL).

  1 month after the last dose of the primary vaccination

• Number of Seroprotected Subjects With Anti-poliovirus Type 1, 2 and 3 Antibody Concentration Above or Equal to 8

  A seroprotected subject is a subject whose antibody titre was ≥ the level defining clinical protection, of 8 ED50.

  1 month after the last dose of the primary vaccination

• Number of Seroprotected Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Above or Equal to the Assay Cut-off

  A seroprotected subject is a subject whose antibody concentration/titre was ≥ the level defining clinical protection, of 0.15 micrograms per milliliter (µg/mL).

  1 month after the last dose of the primary vaccination

Secondary Outcomes (15)

• Number of Seroprotected Subjects Against Diphtheria (Anti-D) and Tetanus (Anti-T) Antibody Concentration Above or Equal to the Assay Cut-off.

  Before the first dose of Infanrix hexa

• Anti-D and Anti-T Antibody Concentrations

  Before the first dose of Infanrix hexa

• Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off.

  Before the first dose of Infanrix hexa

• Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations

  Before the first dose of Infanrix hexa

• Anti-D and Anti-T Antibody Concentrations

  1 month after the last dose of the primary vaccination

Study Arms (2)

dTpa Group

EXPERIMENTAL

This group will consist of infants born to mothers belonging to the dTpa Group in study 116945 \[DTPA (BOOSTRIX)-047\] i.e. who received a single dose of BoostrixTM during pregnancy and a dose of placebo immediately post-delivery. All infants in this group will receive Infanrix hexaTM co-administered with Prevenar 13®.

Biological: Infanrix hexa; Drug: Prevnar13

Control Group

ACTIVE COMPARATOR

This group will consist of infants born to mothers belonging to the Control group in study 116945 \[DTPA (BOOSTRIX)-047\], i.e. who received a single dose of placebo during pregnancy and a dose of BoostrixTM immediately post-delivery. All infants in this group will receive Infanrix hexaTM co-administered with Prevenar 13®.

Biological: Infanrix hexa; Drug: Prevnar13

Interventions

Infanrix hexa BIOLOGICAL

• All subjects will receive Infanrix hexa at 2 and 4, at 3 and 5, at 2, 4 and 6 months or at 2, 3 and 4 months, depending on the immunisation schedule of the country. Infanrix hexa is administered intramuscularly to the right thigh.

Control Group; dTpa Group

Prevnar13 DRUG

• All subjects will receive Infanrix hexa co-administered with Prevenar13\* at 2 and 4, at 3 and 5, at 2, 4 and 6 months or at 2, 3 and 4 months, depending on the immunisation schedule of the country. \*In some countries/regions with an Infanrix hexa 3-dose vaccination schedule, Prevenar 13 could be administered as 2-doses or 3-doses primary vaccination schedule (according to the routine national immunisation schedule). Prevnar13 is administered intramuscularly to the left thigh.

Control Group; dTpa Group

Eligibility Criteria

• Age: 6 Weeks - 14 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Subjects' parent(s)/Legally Acceptable Representative(s) \[LAR(s)\] who, in the opinion of the investigator, can and will comply, with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits).
• Written informed consent obtained from the parent(s)/LAR(s) of the subject prior to performing any study specific procedure.
• A male or female between, 6 and 14 weeks of age (including 6 weeks and up to and including 14 weeks and 6 days of age) at the time of the first vaccination.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• Born to a mother enrolled in study 116945 \[DTPA (BOOSTRIX)-047\].
• Medically stable\* prematurely born infants, born after a gestation period of 27-36 weeks may be enrolled in the study at the discretion of the investigator.
• Medically stable refers to the condition of premature infants who do not require significant medical support or ongoing management for debilitating disease and who have demonstrated a clinical course of sustained recovery by the time they receive the first dose of study vaccine.

You may not qualify if:

• Child in care
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting at birth prior to the first vaccine dose. For corticosteroids, this will mean prednisone ≥0.5mg/kg/day, or equivalent. Inhaled and topical steroids are allowed.
• Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
• Administration of any chronic drug therapy to be continued during the study period.
• A vaccine not foreseen by the study protocol administered during the period starting from 30 days before each dose of vaccine and ending 30 days after\*, with the exception of inactivated influenza vaccine and other vaccines given as a part of the national/regional immunisation schedule, that are allowed at any time during the study period.
• In case an emergency mass vaccination for an unforeseen public health threat (e.g.: a pandemic) is organised by the public health authorities, outside the routine immunisation program, the time period described above can be reduced if necessary for that vaccine provided it is licensed and used according to its SPC or package insert (PI) and according to the local governmental recommendations and provided a written approval of the Sponsor is obtained.
• 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 (pharmaceutical product or device).
• Previous vaccination against Hib, diphtheria, tetanus, pertussis, pneumococcus, and/or poliovirus since birth.
• History of Hib, diphtheria, tetanus, pertussis, pneumococcal, poliovirus and hepatitis B diseases.
• Any confirmed or suspected immunosuppressive or immunodeficient condition including severe combined immunodeficiency disease (SCID), based on medical history and physical examination (no laboratory testing required).
• Family history of congenital or hereditary immunodeficiency.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
• Major congenital defects
• Serious chronic illness.
• History of any neurological disorders or seizures.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (30)

GSK Investigational Site

Carlton, Victoria, 3053, Australia

Location

GSK Investigational Site

Calgary, Alberta, T3B 6A8, Canada

Location

GSK Investigational Site

Halifax, Nova Scotia, B3K 6R8, Canada

Location

GSK Investigational Site

Montreal, Quebec, H3T 1C5, Canada

Location

GSK Investigational Site

Brno, 613 00, Czechia

Location

GSK Investigational Site

Hradec Králové, 500 02, Czechia

Location

GSK Investigational Site

Ostrava - Vitkovice, 703 84, Czechia

Location

GSK Investigational Site

Prague, 140 59, Czechia

Location

GSK Investigational Site

Prague, 14700, Czechia

Location

GSK Investigational Site

Kokkola, 67100, Finland

Location

GSK Investigational Site

Oulu, 90220, Finland

Location

GSK Investigational Site

Seinäjoki, 60100, Finland

Location

GSK Investigational Site

Tampere, 33100, Finland

Location

GSK Investigational Site

Turku, 20520, Finland

Location

GSK Investigational Site

Milan, Lombardy, 20122, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20142, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20154, Italy

Location

GSK Investigational Site

Novara, Piedmont, 28100, Italy

Location

GSK Investigational Site

Turin, Piedmont, 10126, Italy

Location

GSK Investigational Site

Málaga, Andalusia, 29004, Spain

Location

GSK Investigational Site

Antequera/Málaga, 29200, Spain

Location

GSK Investigational Site

Aravaca, 28023, Spain

Location

GSK Investigational Site

Burgos, 09006, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Madrid, 28050, Spain

Location

GSK Investigational Site

Majadahonda (Madrid), 28222, Spain

Location

GSK Investigational Site

Móstoles, 28938, Spain

Location

GSK Investigational Site

Santiago de Compostela, 15706, Spain

Location

GSK Investigational Site

Seville, 41014, Spain

Location

Related Publications (1)

• Perrett KP, Halperin SA, Nolan T, Carmona Martinez A, Martinon-Torres F, Garcia-Sicilia J, Virta M, Vanderkooi OG, Zuccotti GV, Manzoni P, Kostanyan L, Meyer N, Ceregido MA, Cheuvart B, Kuriyakose SO, Stranak Z, Merino Arribas JM, Cilleruelo Ortega MJ, Miranda-Valdivieso M, Arias Novas B, Ramos Amador JT, Omenaca F, Baca M, Marchisio PG, Mesaros N. Impact of tetanus-diphtheria-acellular pertussis immunization during pregnancy on subsequent infant immunization seroresponses: follow-up from a large randomized placebo-controlled trial. Vaccine. 2020 Feb 18;38(8):2105-2114. doi: 10.1016/j.vaccine.2019.10.104. Epub 2019 Nov 24.

  PMID: 31776027 DERIVED

MeSH Terms

Conditions

Tetanus; Poliomyelitis; Diphtheria

Interventions

diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine

Condition Hierarchy (Ancestors)

Clostridium Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Myelitis; Central Nervous System Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Virus Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Neuroinflammatory Diseases; Neuromuscular Diseases; Corynebacterium Infections; Actinomycetales Infections

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 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2015
• First Posted: April 21, 2015
• Study Start: January 22, 2016
• Primary Completion: March 7, 2018
• Study Completion: March 7, 2018
• Last Updated: July 9, 2019
• Results First Posted: June 10, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• 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

FI (5); AU (1); CA (3); CZ (5); IT (5); ES (11)