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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02377349




Registration number
NCT02377349
Ethics application status
Date submitted
26/02/2015
Date registered
3/03/2015
Date last updated
28/01/2019

Titles & IDs
Public title
Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Boostrix™ Vaccine in Pregnant Women
Scientific title
Immunogenicity and Safety Study of GSK Biologicals' dTpa Vaccine, Boostrix™ (263855) in Pregnant Women
Secondary ID [1] 0 0
2014-001119-38
Secondary ID [2] 0 0
116945
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diphtheria-Tetanus-acellular Pertussis Vaccines 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Boostrix™
Treatment: Drugs - Saline placebo

Experimental: 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).

Placebo Comparator: 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).


Other interventions: Boostrix™
One dose administered intramuscularly in the deltoid muscle of the non-dominant arm.

Treatment: Drugs: Saline placebo
One dose administered intramuscularly in the deltoid muscle of the non-dominant arm.

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
At delivery - Visit 3 (anytime after 28 weeks of gestation)
Secondary outcome [1] 0 0
Percentage of Subjects by Pregnancy Outcomes - Pregnancy outcomes included live birth with no congenital anomalies, live birth with congenital anomalies, still birth with no congenital anomalies, still birth with congenital anomalies, elective termination with no congenital anomalies and elective termination with congenital anomalies. No subjects with still birth or elective termination of infant were reported.
Timepoint [1] 0 0
From Day 0 (Visit 1) to Month 2 (Visit 4, end of the study).
Secondary outcome [2] 0 0
Percentage of Subjects With Listed Pregnancy/Neonate Related Adverse Events of Interest - Listed pregnancy-related adverse events of interest/ neonate-related events of interest included gestational diabetes, pregnancy-related hypertension, premature rupture of mem-branes, preterm premature rupture of membranes, premature labour, premature uterine contractions, intrauterine growth restriction/poor foetal growth, pre-eclampsia, eclampsia, vaginal or intrauterine haemorrhage, maternal death, preterm birth, neonatal death, small for gestational age, neonatal hypoxic ischaemic encephalopathy and failure to thrive/growth deficiency were reported.
Timepoint [2] 0 0
From Day 0 (Visit 1) to Month 2 post-delivery (Visit 4, end of the study).
Secondary outcome [3] 0 0
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 - A seroprotected subject against diphteria and tetanus was a subject with antibody concentration = 0.1 IU/mL. A seropositive subject was a subjects with antibody concentration = 2.693 IU/mL for anti-PT, = 2.046 IU/mL for anti-FHA and = 2.187 IU/mL for anti-PRN.
Timepoint [3] 0 0
One month post vaccination (Day 30) during pregnancy
Secondary outcome [4] 0 0
Anti-D, Anti-T, Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations - Antibody concentrations were determined by ELISA, tabulated as GMCs and expressed in IU/mL.
Timepoint [4] 0 0
One month post vaccination (Day 30) during pregnancy
Secondary outcome [5] 0 0
Percentage of Subjects With Vaccine Response to Anti-D and Anti-T - Vaccine response for anti-D and anti-T was defined as:
for initially seronegative subjects (S-) with pre-vaccination concentration below cut-off: < 0.1 IU/mL) was an antibody concentration at least four times the assay cut-off (post-vaccination concentration = 0.4 IU/mL); for initially seropositive subjects (S+) with pre-vaccination concentration = 0.1 IU/mL): an increase in antibody concentrations of at least four times the pre-vaccination concentration.
Timepoint [5] 0 0
One month post vaccination (Day 30) during pregnancy
Secondary outcome [6] 0 0
Percentage of Subjects With Vaccine Response to Anti-PT, Anti-FHA and Anti-PRN - Vaccine response to PT, FHA and PRN antigens is defined as: for subjects with pre-vaccination antibody concentration below the assay cut-off (S-), post-vaccination anti-body 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 (S+), 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 (S+), post-vaccination antibody concentration =2 times the pre-vaccination antibody concentration.
Timepoint [6] 0 0
One month post vaccination (Day 30) during pregnancy
Secondary outcome [7] 0 0
Percentage of Seropositive Subjects Against Anti-PT, Anti-FHA and Anti-PRN in the Cord Blood Samples - For this assay the anti-PT, anti-FHA and anti-PRN seropositivity status was determined from the cord blood samples. The seropositivity cut-offs were the following: 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA and 2.187 IU/mL for anti-PRN.
Timepoint [7] 0 0
At delivery - Visit 3 (anytime after 27 eligible weeks of gestation)
Secondary outcome [8] 0 0
Percentage of Subjects With Solicited Local Adverse Events (AEs) - Assessed solicited local symptoms were pain, redness and swelling. "Any" = any report of the specified symptom irrespective of intensity grade. Dose 1 = pregnancy dose at Day 0 - Visit 1, Dose 2 = post-delivery dose at birth - Visit 3.
Timepoint [8] 0 0
During the 8-day (Day 0-Day 7) follow-up period after vaccination during pregnancy
Secondary outcome [9] 0 0
Percentage of Subjects With Solicited General AEs - Assessed solicited general symptoms were fatigue, gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain), headache and fever [defined as oral, axillary or tympanic temperature = 37.5 degrees Celsius (°C) or rectal temperature = 38.0 °C]. "Any" = any report of the specified symptom irrespective of intensity grade. Dose 1 = pregnancy dose at Day 0 - Visit 1, Dose 2 = post-delivery dose at birth - Visit 3.
Timepoint [9] 0 0
During the 8-day (Day 0-Day 7) follow-up period after vaccination during pregnancy
Secondary outcome [10] 0 0
Percentage of Subjects With Unsolicited AEs - An unsolicited AE was any AE that was not solicited using a subject diary and that was spontaneously communicated by the subject. Also any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event. Dose 1 = pregnancy dose at Day 0 - Visit 1, Dose 2 = post-delivery dose at birth - Visit 3.
Timepoint [10] 0 0
Within 31 days (Day 0 - Day 30) after each vaccination
Secondary outcome [11] 0 0
Percentage of Infants With Unsolicited AEs - An unsolicited AE was any AE that was not solicited using a subject diary and that was spontaneously communicated by the subject. Also any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event.
Timepoint [11] 0 0
From delivery to Month 2 post delivery (Visit 4, end of the study).
Secondary outcome [12] 0 0
Number of Subjects With Serious AEs (SAEs) - A SAE was any untoward medical occurrence that resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or a congenital anomaly/birth defect in the offspring of a study subject.
Timepoint [12] 0 0
From Day 0 (Visit 1) to Month 2 (Visit 4, end of the study).
Secondary outcome [13] 0 0
Percentage of Household Contacts of the Infants Born to Pregnant Women Vaccinated in Spain - This analysis assessed the vaccination status of the household contacts (who accepted, received or refused vaccination) and also the reasons for refusal (not coming to site, refused to be vaccinated, unspecified) as part of an assessment of cocooning among the eligible household contacts.
Timepoint [13] 0 0
From Day 0 (Visit 1) to Month 2 (Visit 4, end of the study).
Secondary outcome [14] 0 0
Percentage of Household Contacts With SAEs - SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.
Timepoint [14] 0 0
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).

Eligibility
Key inclusion 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.
Minimum age
18 Years
Maximum age
45 Years
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
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.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Carlton
Recruitment hospital [2] 0 0
GSK Investigational Site - Fitzroy
Recruitment hospital [3] 0 0
GSK Investigational Site - Parkville
Recruitment postcode(s) [1] 0 0
3053 - Carlton
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy
Recruitment postcode(s) [3] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Alberta
Country [2] 0 0
Canada
State/province [2] 0 0
Nova Scotia
Country [3] 0 0
Canada
State/province [3] 0 0
Ontario
Country [4] 0 0
Canada
State/province [4] 0 0
Quebec
Country [5] 0 0
Czechia
State/province [5] 0 0
Brno
Country [6] 0 0
Czechia
State/province [6] 0 0
Hradec Kralove
Country [7] 0 0
Czechia
State/province [7] 0 0
Ostrava - Vitkovice
Country [8] 0 0
Czechia
State/province [8] 0 0
Praha 4
Country [9] 0 0
Czechia
State/province [9] 0 0
Praha
Country [10] 0 0
Finland
State/province [10] 0 0
Kokkola
Country [11] 0 0
Finland
State/province [11] 0 0
Oulu
Country [12] 0 0
Finland
State/province [12] 0 0
Seinajoki
Country [13] 0 0
Finland
State/province [13] 0 0
Tampere
Country [14] 0 0
Finland
State/province [14] 0 0
Turku
Country [15] 0 0
Italy
State/province [15] 0 0
Lombardia
Country [16] 0 0
Italy
State/province [16] 0 0
Piemonte
Country [17] 0 0
Spain
State/province [17] 0 0
Andalucia
Country [18] 0 0
Spain
State/province [18] 0 0
Antequera/Málaga
Country [19] 0 0
Spain
State/province [19] 0 0
Aravaca
Country [20] 0 0
Spain
State/province [20] 0 0
Boadilla del Monte
Country [21] 0 0
Spain
State/province [21] 0 0
Burgos
Country [22] 0 0
Spain
State/province [22] 0 0
Madrid
Country [23] 0 0
Spain
State/province [23] 0 0
Majadahonda (Madrid)
Country [24] 0 0
Spain
State/province [24] 0 0
Móstoles
Country [25] 0 0
Spain
State/province [25] 0 0
Santiago de Compostela
Country [26] 0 0
Spain
State/province [26] 0 0
Sevilla

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
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].
Trial website
https://clinicaltrials.gov/show/NCT02377349
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications