Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Boostrix™ Vaccine in Pregnant Women

NCT02377349 | Completed Phase 4 Results

• 2 other identifiers: 1169452014-001119-38
• Study Type: interventional
• Target: 688
• Locations: 6 countries
• Sites: 35

Brief Summary

The purpose of this study is to assess the immunogenicity and safety of Boostrix™ when compared to a placebo given during 27-36 weeks of gestation in healthy women aged 18-45 years. Infants born to mothers enrolled in this study will be followed-up in two separate clinical studies: 201330 \[DTPA (BOOSTRIX)-048 PRI\] and 201334 \[DTPA (BOOSTRIX)-049 BST: 048\].

Conditions

Diphtheria-Tetanus-acellular Pertussis Vaccines

Outcome Measures

Primary Outcomes (1)

• Antibody Concentrations Against Pertussis Toxoid Antigen (Anti-PT), Filamentous Haemagglutinin Antigen (Anti-FHA) and Pertactin Antigen (Anti-PRN) in Cord Blood Samples

  Antibody concentrations were assessed by Enzyme-linked immunosorbent assay (ELISA), tabulated as Geometric Mean Concentrations (GMCs) and expressed in International units per mililiter (IU/mL) for the following assay cut-offs: 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA and 2.187 IU/mL for anti-PRN.

  At delivery - Visit 3 (anytime after 28 weeks of gestation)

Secondary Outcomes (14)

• Percentage of Subjects by Pregnancy Outcomes

  From Day 0 (Visit 1) to Month 2 (Visit 4, end of the study).

• Percentage of Subjects With Listed Pregnancy/Neonate Related Adverse Events of Interest

  From Day 0 (Visit 1) to Month 2 post-delivery (Visit 4, end of the study).

• Percentage of Seroprotected Subjects Against Diphteria Antigen (Anti-D), Tetanus Antigen (Anti-T) and of Seropositive Subjects Against Anti-PT, Anti-FHA and Anti-PRN

  One month post vaccination (Day 30) during pregnancy

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

  One month post vaccination (Day 30) during pregnancy

• Percentage of Subjects With Vaccine Response to Anti-D and Anti-T

  One month post vaccination (Day 30) during pregnancy

Study Arms (2)

dTpa Group

EXPERIMENTAL

This group will consist of pregnant women who will receive a single dose of Boostrix™ at 27-36 weeks (i.e. completed 27 weeks until 36 weeks) of gestation (Visit 1) and will receive a dose of the placebo post-delivery (within 72 hours).

Biological: Boostrix™; Drug: Saline placebo

Control Group

PLACEBO COMPARATOR

This group will consist of pregnant women who will receive a single dose of placebo at 27-36 weeks (i.e. completed 27 weeks until 36 weeks) of gestation (Visit 1) and will receive a dose of Boostrix™ post-delivery (within 72 hours).

Biological: Boostrix™; Drug: Saline placebo

Interventions

Boostrix™ BIOLOGICAL

One dose administered intramuscularly in the deltoid muscle of the non-dominant arm.

Control Group; dTpa Group

Saline placebo DRUG

One dose administered intramuscularly in the deltoid muscle of the non-dominant arm.

Control Group; dTpa Group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Written informed consent obtained from the subject prior to performing any study specific procedure, as per local regulations.
• A healthy pregnant woman between, and including, 18 and 45 years of age at the time of screening.
• Pregnant subjects at 27 0/7-36 6/7 weeks (completed 27 weeks but not 37 weeks) of gestation at the time of vaccination (Visit 1), as established by ultrasound examination.
• Not at high risk for complications, as determined by the obstetrical algorithm for identification of eligible subjects and the Obstetrical Risk Assessment Form.
• No significant foetal abnormalities, as observed by the level II ultrasound testing conducted after 18 weeks of gestation.
• Nuchal translucency scan, serum testing and any other prenatal tests, if conducted, should suggest normal pregnancy.
• Willing to have the infant born immunised with Infanrix hexa and Prevenar 13, as per national recommendations, in the follow-up clinical studies DTPA (BOOSTRIX)-048 PRI and DTPA (BOOSTRIX)-049 BST: 048.
• Subjects who do not plan to give their child for adoption or place the child in care.
• Household contacts living in the same house as that of the infant.
• Household contacts or parent(s)/LAR(s) of the household contacts who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. reporting of SAEs).
• Written informed consent obtained from the household contacts or the parent(s)/LAR(s) prior to vaccination, as per local regulations.
• Household contacts who are eligible to receive a booster dose of DTP-containing vaccine according to the Summary of Product Characteristics (SmPC) of Boostrix and according to the local governmental recommendations in Spain.
• Female household contacts of non-childbearing potential may be enrolled in the study.
• \- Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.

You may not qualify if:

• Subjects diagnosed with multiple pregnancies (twins, triplets etc.).
• Previous vaccination containing diphtheria, tetanus or pertussis antigens or diphtheria and tetanus toxoids at any time during the current pregnancy.
• Women with co-morbid medical or obstetric conditions that in the opinion of the investigator have the potential to complicate the pregnancy course and outcomes.
• Gestational diabetes as determined by glucose tolerance test conducted after 20 weeks of gestation, as per local recommendations of the country.
• History of early onset (\<34 weeks of gestation) of eclampsia/pre-eclampsia in previous pregnancy.
• History of major congenital anomalies in previous pregnancies.
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine anytime during the current pregnancy or planned use during the study period.
• Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
• Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine. For corticosteroids, this will mean prednisone ≥20 mg/day, or equivalent. Inhaled and topical steroids are allowed.
• 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 in the period within the period starting 30 days before and 30 days after the dose of vaccine with the exception of seasonal influenza vaccine that can be administered anytime during the study period.
• 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).
• Serious underlying medical condition \[e.g., immunosuppressive disease or therapy, human immunodeficiency virus infection, collagen vascular disease, epilepsy, diabetes mellitus, chronic hypertension, moderate to severe asthma, lung/heart disease, liver/kidney disease, infections including TORCHES (toxoplasmosis, rubella, cytomegalovirus, herpes simplex, syphilis) infections\].
• History of an encephalopathy of unknown aetiology, occurring within 7 days following previous vaccination with pertussis-containing vaccine.
• History of transient thrombocytopenia or neurological complications (for convulsions or hypotonic-hyporesponsive episodes) following an earlier immunisation against diphtheria and/or tetanus

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (35)

GSK Investigational Site

Carlton, Victoria, 3053, Australia

Location

GSK Investigational Site

Fitzroy, Victoria, 3065, Australia

Location

GSK Investigational Site

Parkville, Victoria, 3052, Australia

Location

GSK Investigational Site

Calgary, Alberta, T3B 6A8, Canada

Location

GSK Investigational Site

Halifax, Nova Scotia, B3K 6R8, Canada

Location

GSK Investigational Site

Greater Sudbury, Ontario, P3A 1W8, Canada

Location

GSK Investigational Site

Montreal, Quebec, H3T 1C5, Canada

Location

GSK Investigational Site

Mount Royal, Quebec, H3P 3W3, 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, 14059, 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

Boadilla del Monte, 28660, 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

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, 41013, Spain

Location

GSK Investigational Site

Seville, 41940, Spain

Location

Related Publications (1)

• Perrett KP, Halperin SA, Nolan T, Martinez Pancorbo C, Tapiero B, Martinon-Torres F, Stranak Z, Virta M, Vanderkooi OG, Kosina P, Encinas Pardilla MB, Cristobal Garcia I, Zuccotti GV, Kostanyan L, Meyer N, Ceregido MA, Cheuvart B, Kuriyakose SO, Marcos Fernandez M, Rodriguez Zambrano MA, Martin Garcia A, Asenjo de la Fuente JE, Camacho Marin MD, de la Calle Fernandez-Miranda M, Romero Espinar Y, Marchisio PG, Manzoni P, Mesaros N. Immunogenicity, transplacental transfer of pertussis antibodies and safety following pertussis immunization during pregnancy: Evidence from a randomized, placebo-controlled trial. Vaccine. 2020 Feb 18;38(8):2095-2104. doi: 10.1016/j.vaccine.2019.10.105. Epub 2019 Nov 24.

  PMID: 31776029 BACKGROUND

MeSH Terms

Interventions

Boostrix

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

en736091@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: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2015
• First Posted: March 3, 2015
• Study Start: October 14, 2015
• Primary Completion: August 14, 2017
• Study Completion: October 24, 2017
• Last Updated: January 28, 2020
• Results First Posted: January 28, 2019

Record last verified: 2020-01

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); IT (5); ES (12); AU (3); CZ (5); CA (5)