Clinical trial NCT02377349: Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Boostrix™ Vaccine in Pregnant Women
Official title: Immunogenicity and Safety Study of GSK Biologicals' dTpa Vaccine, Boostrix™ (263855) in Pregnant Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diphtheria-Tetanus-acellular Pertussis Vaccines
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2015-03-03
Enrollment: 688
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria for study subjects:

* 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.

Inclusion criteria for household contacts in Spain:

* 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 for study subjects:

* 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.

Exclusion criteria for household contacts in Spain:

* 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.

Primary outcomes:
measure: Antibody Concentrations Against Pertussis Toxoid Antigen (Anti-PT), Filamentous Haemagglutinin Antigen (Anti-FHA) and Pertactin Antigen (Anti-PRN) in Cord Blood Samples
timeFrame: At delivery - Visit 3 (anytime after 28 weeks of gestation)
Secondary outcomes:
measure: Percentage of Subjects by Pregnancy Outcomes
timeFrame: From Day 0 (Visit 1) to Month 2 (Visit 4, end of the study).
measure: Percentage of Subjects With Listed Pregnancy/Neonate Related Adverse Events of Interest
timeFrame: From Day 0 (Visit 1) to Month 2 post-delivery (Visit 4, end of the study).
measure: 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
timeFrame: One month post vaccination (Day 30) during pregnancy
measure: Anti-D, Anti-T, Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations
timeFrame: One month post vaccination (Day 30) during pregnancy
measure: Percentage of Subjects With Vaccine Response to Anti-D and Anti-T
timeFrame: One month post vaccination (Day 30) during pregnancy
measure: Percentage of Subjects With Vaccine Response to Anti-PT, Anti-FHA and Anti-PRN
timeFrame: One month post vaccination (Day 30) during pregnancy
measure: Percentage of Seropositive Subjects Against Anti-PT, Anti-FHA and Anti-PRN in the Cord Blood Samples
timeFrame: At delivery - Visit 3 (anytime after 27 eligible weeks of gestation)
measure: Percentage of Subjects With Solicited Local Adverse Events (AEs)
timeFrame: During the 8-day (Day 0-Day 7) follow-up period after vaccination during pregnancy
measure: Percentage of Subjects With Solicited General AEs
timeFrame: During the 8-day (Day 0-Day 7) follow-up period after vaccination during pregnancy
measure: Percentage of Subjects With Unsolicited AEs
timeFrame: Within 31 days (Day 0 - Day 30) after each vaccination
measure: Percentage of Infants With Unsolicited AEs
timeFrame: From delivery to Month 2 post delivery (Visit 4, end of the study).
measure: Number of Subjects With Serious AEs (SAEs)
timeFrame: From Day 0 (Visit 1) to Month 2 (Visit 4, end of the study).
measure: Percentage of Household Contacts of the Infants Born to Pregnant Women Vaccinated in Spain
timeFrame: From Day 0 (Visit 1) to Month 2 (Visit 4, end of the study).
measure: Percentage of Household Contacts With SAEs
timeFrame: During the 31-day (Days 0-30) follow-up period post-vaccination (Boostrix administered preferably 2 weeks before the birth of the infant, Visit 3).
Other outcomes:
Locations:
city: Carlton
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Fitzroy
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Parkville
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Calgary
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Halifax
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: Sudbury
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Mount Royal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Brno
country: Czechia
facility: GSK Investigational Site
city: Hradec Kralove
country: Czechia
facility: GSK Investigational Site
city: Ostrava - Vitkovice
country: Czechia
facility: GSK Investigational Site
city: Praha 4
country: Czechia
facility: GSK Investigational Site
city: Praha
country: Czechia
facility: GSK Investigational Site
city: Kokkola
country: Finland
facility: GSK Investigational Site
city: Oulu
country: Finland
facility: GSK Investigational Site
city: Seinajoki
country: Finland
facility: GSK Investigational Site
city: Tampere
country: Finland
facility: GSK Investigational Site
city: Turku
country: Finland
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Novara
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Torino
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Malaga
country: Spain
facility: GSK Investigational Site
state: Andalucia
city: Antequera/Málaga
country: Spain
facility: GSK Investigational Site
city: Aravaca
country: Spain
facility: GSK Investigational Site
city: Boadilla del Monte
country: Spain
facility: GSK Investigational Site
city: Burgos
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Majadahonda (Madrid)
country: Spain
facility: GSK Investigational Site
city: Móstoles
country: Spain
facility: GSK Investigational Site
city: Santiago de Compostela
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.