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

NCT ID: NCT02377349

Last Updated: 2020-01-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 688 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-14
• Study Completion Date: 2017-10-24

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].

Detailed Description

The protocol was amended to include Spain in the study. The reasons for the Spain-specific amendment are listed below:

• Based on the feedback from the Spanish Ethics Committee, the evaluation related to the acceptance of cocooning was added in the protocol.
• The objectives and endpoints to include cocooning were added in the protocol.
• The eligibility criteria for participation of household contacts were defined in the protocol.
• The study procedures for household contacts were included.

Conditions

Diphtheria-Tetanus-acellular Pertussis Vaccines

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

dTpa Group

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).

Group Type: EXPERIMENTAL

Boostrix™

Intervention Type: BIOLOGICAL

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

Saline placebo

Intervention Type: DRUG

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

Control Group

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).

Group Type: PLACEBO_COMPARATOR

Boostrix™

Intervention Type: BIOLOGICAL

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

Saline placebo

Intervention Type: DRUG

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

Interventions

Boostrix™

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

Intervention Type: BIOLOGICAL

Saline placebo

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.
• Female household contacts of childbearing potential may be enrolled in the study , if the household contact

• has practiced adequate contraception for 30 days prior to vaccination,
• has a negative pregnancy test on the day of vaccination and
• has agreed to continue adequate contraception for 2 months after receiving the vaccine dose.

Exclusion Criteria

• 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
• Significant mental illness (e.g. schizophrenia, psychosis and major depression).
• Family history (first degree relatives only) of congenital anomalies, recurrent pregnancy losses (two or more consecutive losses) and unexplained neonatal death(s) in the subject.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
• History of febrile illness within the past 72 hours.
• History of physician-diagnosed or laboratory-confirmed pertussis within the past five years.
• Anything that would prevent subject from completing the study or put the subject at risk, as determined by the investigator.
• Acute disease and/or fever at the time of enrolment.

• Fever is defined as temperature ≥ 37.5°C /99.5°F for oral, axillary or tympanic route, or ≥ 38.0°C /100.4°F on rectal route.
• Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.
• Administration of immunoglobulins and/or any blood products within the 3 months preceding the dose of study vaccine, or planned administration during the study period, with the exception of anti-D (Rh)-immunoglobulin.
• History of chronic excessive alcohol consumption and/or drug abuse.

• Child in care.
• Concurrently participating in another clinical study, at any time during the study period, in which the household contact has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the dose of study vaccine, or planned use during the study period.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
• History of an encephalopathy of unknown aetiology, occurring within 7 days following previous vaccination with pertussis-containing vaccine.
• Acute disease and/or fever at the time of enrolment.

• Fever is defined as temperature ≥ 37.5°C /99.5°F for oral, axillary or tympanic route, or ≥ 38.0°C /100.4°F on rectal route. The preferred route of recording temperature will be axillary in household contacts.
• Household contacts with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.
• Anything that would put the household contact at risk, as determined by the investigator.
• Pregnant or lactating household contacts.
• Household contacts planning to become pregnant or planning to discontinue contraceptive precautions prior to 2 months post-vaccination.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Carlton, Victoria, Australia

GSK Investigational Site

Fitzroy, Victoria, Australia

GSK Investigational Site

Parkville, Victoria, Australia

GSK Investigational Site

Calgary, Alberta, Canada

GSK Investigational Site

Halifax, Nova Scotia, Canada

GSK Investigational Site

Greater Sudbury, Ontario, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Mount Royal, Quebec, Canada

GSK Investigational Site

Brno, , Czechia

GSK Investigational Site

Hradec Králové, , Czechia

GSK Investigational Site

Ostrava - Vitkovice, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Kokkola, , Finland

GSK Investigational Site

Oulu, , Finland

GSK Investigational Site

Seinäjoki, , Finland

GSK Investigational Site

Tampere, , Finland

GSK Investigational Site

Turku, , Finland

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Novara, Piedmont, Italy

GSK Investigational Site

Turin, Piedmont, Italy

GSK Investigational Site

Málaga, Andalusia, Spain

GSK Investigational Site

Antequera/Málaga, , Spain

GSK Investigational Site

Aravaca, , Spain

GSK Investigational Site

Boadilla del Monte, , Spain

GSK Investigational Site

Burgos, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Majadahonda (Madrid), , Spain

GSK Investigational Site

Móstoles, , Spain

GSK Investigational Site

Santiago de Compostela, , Spain

GSK Investigational Site

Seville, , Spain

GSK Investigational Site

Seville, , Spain

Countries

Australia; Canada; Czechia; Finland; Italy; Spain

References

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.

Reference Type: BACKGROUND

PMID: 31776029 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2014-001119-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

116945

Identifier Type: -

Identifier Source: org_study_id