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

NCT02853929 | Completed Phase 4 Results

• 2 other identifiers: 2013342014-001120-30
• Study Type: interventional
• Target: 551
• Locations: 6 countries
• Sites: 29

Brief Summary

The purpose of this study is to assess the immunogenicity and safety of the Infanrix hexa booster dose given at 11-18 months of age to infants who received primary vaccination at 6-14 weeks. All infants in this booster study were born to pregnant women who participated in the study 116945 \[DTPA (BOOSTRIX)-047\] and having received the full primary vaccination series as per protocol requirement in study 201330 \[DTPA (BOOSTRIX)-048.

Conditions

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

Keywords

Pertussis; Immunogenicity; Poliomyelitis; Tetanus; Hepatitis B; Diptheria

Outcome Measures

Primary Outcomes (2)

• Number of Seroprotected Subjects Against Anti-diphtheria (Anti-D), Anti-tetanus (Anti-T), Anti-hepatitis B (Anti-HBs), Anti-poliovirus Type 1, Anti-poliovirus Type 2, Anti-poliovirus Type 3 and Anti-polyribosyl-ribitol Phosphate (Anti-PRP)

  Seroprotected subjects were defined as subjects with antibody concentrations/titres above or equal (≥) the assay cut-offs that are accepted immunological correlates of protection. 0.1 International units per milliliter (IU/ml) for anti-D and anti-T, 10 milli-International units per milliliter (mIU/mL) for anti-HB's, 8 Effective Dose 50 (ED50) for anti-polio virus (type 1,2,3) and 0.15 microgram/milliliter (µg/mL) for anti-PRP were considered as immunological correlates of protection.

  At one month after the booster dose (Day 30)

• Number of Subjects With a Booster Response to Pertussis Antigens (Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN))

  Booster response to PT, FHA and PRN antigens was defined as: * for subjects with pre-vaccination antibody concentration below the assay cut-off, post-vaccination antibody concentration ≥ 4 times the assay cut-off, * for subjects with pre-vaccination antibody concentration between the assay cut-off and below 4 times the assay cut-off, post-vaccination antibody concentration ≥ 4 times the pre-vaccination antibody concentration, and * for subjects with pre-vaccination antibody concentration ≥ 4 times the assay cut-off, post-vaccination antibody concentration ≥ 2 times the pre-vaccination antibody concentration Seronegative (S-) subjects are those who have antibody concentration less than (\<) assay cut-off. Seropositive (S+) subjects are those who have antibody concentration ≥ assay cut-off prior to vaccination. Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti- FHA and 2.187 IU/mL for anti-PRN

  At one month after the booster dose (Day 30)

Secondary Outcomes (15)

• Number of Seroprotected Subjects Against Anti-diphtheria, Anti-tetanus, Anti-poliovirus Type 1, Anti-poliovirus Type 2, Anti-poliovirus Type 3, Anti-HBs and Anti-PRP.

  Before the booster dose (Day 0)

• Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN

  Before the booster dose (Day 0)

• Number of Seropositive Subjects for Anti-pneumococcal Serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F)

  Before the booster dose (Day 0)

• Anti-D, Anti-T, Anti-PT, Anti-FHA, Anti-PRN Antibody Concentrations

  Before the booster dose (Day 0) and One month after the booster dose (Day 30)

• Anti-poliovirus Type 1, 2, 3 Antibody Titres

  Before the booster dose (Day 0) and One month after the booster dose (Day 30)

Study Arms (2)

dTpa Group

EXPERIMENTAL

This group will consist of healthy male or female infants, aged 9 months at the time of enrollment, born to mothers who received a single dose of Boostrix during pregnancy and a dose of placebo immediately post-delivery. All enrolled subjects in this group who will come back for subsequent visit will receive a booster dose of Infanrix hexa co-administered with Prevenar 13 according to the routine national/local immunization or study procedure

Biological: Infanrix hexa

Control Group

ACTIVE COMPARATOR

This group will consist of healthy male or female infants, aged 9 months at the time of enrollment, born to mothers who received a dose of placebo during pregnancy and single dose of Boostrix immediately post-delivery. All enrolled subjects in this group who will come back for subsequent visit will receive a booster dose of Infanrix hexa co-administered with Prevenar 13 according to the routine national/local immunization or study procedure

Biological: Infanrix hexa

Interventions

Infanrix hexa BIOLOGICAL

All subjects will receive Infanrix hexa co-administered with Prevenar13 as a booster dose.

Control Group; dTpa Group

Eligibility Criteria

• Age: 9 Months - 19 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Subjects' parent(s)/Legally acceptable representatives (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 child 9 months of age at the time of enrolment.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• Subjects born to mothers who were vaccinated in 116945 \[DTPA (BOOSTRIX)-047\] study and having completed their primary vaccination series as per protocol requirement in study 201330 \[DTPA (BOOSTRIX)-048 PRI\].

You may not qualify if:

• Child in care
• Concurrently participating in another clinical study, within three months prior to the booster vaccine dose and at any time during the present booster study, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product (pharmaceutical product or device).
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period within six months prior to the booster 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).
• A vaccine not foreseen by the study protocol administered during the period starting from 30 days before the booster dose of study vaccine and ending 30 days after\*, with the exception of inactivated influenza vaccine and other vaccines given as a part of the national/regional immunization 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 immunization 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 Product Information (PI) and according to the local governmental recommendations and provided a written approval of the Sponsor is obtained.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• Major congenital defects.
• Serious chronic illness.
• Administration of immunoglobulins and/or any blood products during the period within three months before the booster dose of study vaccines or planned administration during the study period.
• Encephalopathy defined as an acute, severe central nervous system disorder occurring within 7 days following vaccination with Infanrix hexa and generally consisting of major alterations in consciousness, unresponsiveness, generalised or focal seizures that persist more than a few hours, with failure to recover within 24 hours.
• History of Hib, diphtheria, tetanus, pertussis, pneumococcal, poliovirus and hepatitis B diseases since the conclusion visit of study 201330 \[DTPA (BOOSTRIX)-048 PRI\].
• Previous booster vaccination against Hib, diphtheria, tetanus, pertussis, pneumococcus, hepatitis B and/or poliovirus since the conclusion visit of study 201330 \[DTPA (BOOSTRIX)-048 PRI\].
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines (e.g: antigen, excipients).
• Hypersensitivity to latex.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (29)

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

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)

• Martinon-Torres F, Halperin SA, Nolan T, Tapiero B, Perrett KP, de la Cueva IS, Garcia-Sicilia J, Stranak Z, Vanderkooi OG, Kosina P, Rumlarova S, Virta M, Arribas JMM, Miranda-Valdivieso M, Novas BA, Bozensky J, Ortega MJC, Amador JTR, Baca M, Palomino EE, Zuccotti GV, Janota J, Marchisio PG, Kostanyan L, Meyer N, Ceregido MA, Cheuvart B, Kuriyakose SO, Mesaros N. Impact of maternal diphtheria-tetanus-acellular pertussis vaccination on pertussis booster immune responses in toddlers: Follow-up of a randomized trial. Vaccine. 2021 Mar 12;39(11):1598-1608. doi: 10.1016/j.vaccine.2021.02.001. Epub 2021 Feb 19.

  PMID: 33612341 DERIVED

MeSH Terms

Conditions

Diphtheria; Hepatitis B; Haemophilus Infections; Tetanus; Poliomyelitis; Whooping Cough

Interventions

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

Condition Hierarchy (Ancestors)

Corynebacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Blood-Borne Infections; Communicable Diseases; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Pasteurellaceae Infections; Gram-Negative Bacterial Infections; Clostridium Infections; Myelitis; Central Nervous System Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Neuroinflammatory Diseases; Neuromuscular Diseases; Bordetella Infections; Respiratory Tract Infections; Respiratory Tract Diseases

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: July 14, 2016
• First Posted: August 3, 2016
• Study Start: September 19, 2016
• Primary Completion: March 19, 2019
• Study Completion: March 19, 2019
• Last Updated: January 14, 2020
• Results First Posted: January 14, 2020

Record last verified: 2019-12

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

CZ (5); IT (4); CA (3); AU (1); ES (11); FI (5)