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NCT02377349

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

Completed Phase 4 Results posted Last updated 28 January 2020
What this trial tests

Phase 4 trial testing Boostrix™ in Diphtheria-Tetanus-acellular Pertussis Vaccines in 688 participants. Completed in 24 October 2017.

Timeline
14 October 2015
Primary endpoint
14 August 2017
24 October 2017

Quick facts

Lead sponsorGlaxoSmithKline
PhasePhase 4
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designcrossover
Maskingtriple
Primary purposeprevention
Enrollment688
Start date14 October 2015
Primary completion14 August 2017
Estimated completion24 October 2017
Sites35 locations across Italy, Finland, Canada, Australia, Spain, Czechia

Drugs / interventions tested

Conditions studied

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 18 to 45, female only, with Diphtheria-Tetanus-acellular Pertussis Vaccines. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Antibody Concentrations Against Pertussis Toxoid Antigen (Anti-PT), Filamentous Haemagglutinin Antigen (Anti-FHA) and Pertactin Antigen (Anti-PRN) in Cord Blood Samples Primary · At delivery - Visit 3 (anytime after 28 weeks of gestation)

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.

Anti-PT
GroupValue95% CI
dTpa Group - Mother46.941.2 – 53.3
Control Group - Mother5.54.8 – 6.3
Anti-FHA
GroupValue95% CI
dTpa Group - Mother366.1329 – 407.3
Control Group - Mother22.719.7 – 26.2
Anti-PRN
GroupValue95% CI
dTpa Group - Mother301.8250.9 – 362.9
Control Group - Mother14.612.1 – 17.7
Percentage of Subjects by Pregnancy Outcomes Secondary · From Day 0 (Visit 1) to Month 2 (Visit 4, end of the study).

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.

Live infant No apparent congenital anomaly
GroupValue95% CI
dTpa Group - Mother97.495 – 98.8
Control Group - Mother97.495.1 – 98.8
Live infant congenital anomaly
GroupValue95% CI
dTpa Group - Mother2.61.2 – 5
Control Group - Mother2.31 – 4.5
Lost to follow-up
GroupValue95% CI
dTpa Group - Mother00 – 1.1
Control Group - Mother0.30 – 1.6
Percentage of Subjects With Listed Pregnancy/Neonate Related Adverse Events of Interest Secondary · From Day 0 (Visit 1) to Month 2 post-delivery (Visit 4, end of the study).

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.

Intrauterine growth restriction/poor foetal growth
GroupValue95% CI
dTpa Group - Mother1.50.5 – 3.4
Control Group - Mother0.60.1 – 2.1
Pre-eclampsia
GroupValue95% CI
dTpa Group - Mother0.30 – 1.6
Control Group - Mother1.40.5 – 3.3
Pregnancy-related hypertension
GroupValue95% CI
dTpa Group - Mother1.20.3 – 3
Control Group - Mother1.40.5 – 3.3
Premature labour
GroupValue95% CI
dTpa Group - Mother3.82 – 6.4
Control Group - Mother3.21.6 – 5.6
Premature rupture of membranes
GroupValue95% CI
dTpa Group - Mother3.82 – 6.4
Control Group - Mother4.32.4 – 7
Premature uterine contractions
GroupValue95% CI
dTpa Group - Mother0.60.1 – 2.1
Control Group - Mother0.90.2 – 2.5
Preterm birth
GroupValue95% CI
dTpa Group - Mother3.21.6 – 5.7
Control Group - Mother2.61.2 – 4.9
Preterm premature rupture of membranes
GroupValue95% CI
dTpa Group - Mother1.20.3 – 3
Control Group - Mother20.8 – 4.1
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 Secondary · One month post vaccination (Day 30) during pregnancy

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.

Anti-D
GroupValue95% CI
dTpa Group - Mother97.695.1 – 99
Control Group - Mother70.665 – 75.8
Anti-T
GroupValue95% CI
dTpa Group - Mother10098.7 – 100
Control Group - Mother96.693.8 – 98.3
Anti-PT
GroupValue95% CI
dTpa Group - Mother98.696.5 – 99.6
Control Group - Mother61.355.5 – 66.9
Anti-FHA
GroupValue95% CI
dTpa Group - Mother10098.7 – 100
Control Group - Mother94.591.2 – 96.8
Anti-PRN
GroupValue95% CI
dTpa Group - Mother10098.7 – 100
Control Group - Mother84.579.9 – 88.5
Anti-D, Anti-T, Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations Secondary · One month post vaccination (Day 30) during pregnancy

Antibody concentrations were determined by ELISA, tabulated as GMCs and expressed in IU/mL.

Anti-D
GroupValue95% CI
dTpa Group - Mother2.191.87 – 2.57
Control Group - Mother0.230.19 – 0.27
Anti-T
GroupValue95% CI
dTpa Group - Mother8.437.72 – 9.2
Control Group - Mother0.980.86 – 1.11
Anti-PT
GroupValue95% CI
dTpa Group - Mother45.640.4 – 51.5
Control Group - Mother4.13.6 – 4.6
Anti-FHA
GroupValue95% CI
dTpa Group - Mother317.5285 – 353.8
Control Group - Mother1513.1 – 17.2
Anti-PRN
GroupValue95% CI
dTpa Group - Mother283.6237.1 – 339.1
Control Group - Mother10.58.7 – 12.5
Percentage of Subjects With Vaccine Response to Anti-D and Anti-T Secondary · One month post vaccination (Day 30) during pregnancy

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.

Anti-D, S-
GroupValue95% CI
dTpa Group - Mother64.154 – 73.3
Control Group - Mother00 – 4.3
Anti-D, S+
GroupValue95% CI
dTpa Group - Mother7568.1 – 81.1
Control Group - Mother00 – 1.8
Anti-D, Total
GroupValue95% CI
dTpa Group - Mother71.165.5 – 76.3
Control Group - Mother00 – 1.3
Anti-T, S-
GroupValue95% CI
dTpa Group - Mother10073.5 – 100
Control Group - Mother00 – 30.8
Anti-T, S+
GroupValue95% CI
dTpa Group - Mother67.861.9 – 73.2
Control Group - Mother00 – 1.3
Anti-T, Total
GroupValue95% CI
dTpa Group - Mother69.163.4 – 74.4
Control Group - Mother00 – 1.3
Percentage of Subjects With Vaccine Response to Anti-PT, Anti-FHA and Anti-PRN Secondary · One month post vaccination (Day 30) during pregnancy

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 a

Anti-PT, S-
GroupValue95% CI
dTpa Group - Mother82.674.7 – 88.9
Control Group - Mother0.90 – 5.1
Anti-PT, S+ (<4 cut-off)
GroupValue95% CI
dTpa Group - Mother90.783.6 – 95.5
Control Group - Mother00 – 3.1
Anti-PT, S+ (≥4 cut-off)
GroupValue95% CI
dTpa Group - Mother93.183.3 – 98.1
Control Group - Mother30.4 – 10.4
Anti-PT, Total
GroupValue95% CI
dTpa Group - Mother87.883.4 – 91.4
Control Group - Mother10.2 – 3
Anti-FHA, S-
GroupValue95% CI
dTpa Group - Mother10079.4 – 100
Control Group - Mother00 – 20.6
Anti-FHA, S+ (<4 cut-off)
GroupValue95% CI
dTpa Group - Mother10095.7 – 100
Control Group - Mother00 – 5.5
Anti-FHA, S+ (≥4 cut-off)
GroupValue95% CI
dTpa Group - Mother89.984.7 – 93.8
Control Group - Mother1.90.5 – 4.8
Anti-FHA, Total
GroupValue95% CI
dTpa Group - Mother93.489.9 – 96
Control Group - Mother1.40.4 – 3.5
Percentage of Seropositive Subjects Against Anti-PT, Anti-FHA and Anti-PRN in the Cord Blood Samples Secondary · At delivery - Visit 3 (anytime after 27 eligible weeks of gestation)

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.

Anti-PT
GroupValue95% CI
dTpa Group - Mother98.696.5 – 99.6
Control Group - Mother68.863.2 – 74.1
Anti-FHA
GroupValue95% CI
dTpa Group - Mother10098.7 – 100
Control Group - Mother96.693.8 – 98.3
Anti-PRN
GroupValue95% CI
dTpa Group - Mother99.798.1 – 100
Control Group - Mother8883.7 – 91.5
Percentage of Subjects With Solicited Local Adverse Events (AEs) Secondary · During the 8-day (Day 0-Day 7) follow-up period after vaccination during pregnancy

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.

Any Pain, Dose 1
GroupValue95% CI
dTpa Group - Mother86.382.1 – 89.8
Control Group - Mother14.611 – 18.8
Any Redness (mm), Dose 1
GroupValue95% CI
dTpa Group - Mother28.723.9 – 33.8
Control Group - Mother12.89.5 – 16.8
Any Swelling (mm), Dose 1
GroupValue95% CI
dTpa Group - Mother25.120.5 – 30.1
Control Group - Mother3.51.8 – 6
Any Pain, Dose 2
GroupValue95% CI
dTpa Group - Mother12.79.2 – 16.8
Control Group - Mother62.757.3 – 68
Any Redness (mm), Dose 2
GroupValue95% CI
dTpa Group - Mother10.57.4 – 14.4
Control Group - Mother29.724.8 – 34.9
Any Swelling (mm), Dose 2
GroupValue95% CI
dTpa Group - Mother5.23.1 – 8.3
Control Group - Mother26.421.7 – 31.5
Percentage of Subjects With Solicited General AEs Secondary · During the 8-day (Day 0-Day 7) follow-up period after vaccination during pregnancy

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.

Any Fatigue, Dose 1
GroupValue95% CI
dTpa Group - Mother43.638.2 – 49.1
Control Group - Mother36.331.2 – 41.6
Any Gastrointestinal symptom, Dose 1
GroupValue95% CI
dTpa Group - Mother17.914 – 22.4
Control Group - Mother15.211.6 – 19.5
Any Headache, Dose 1
GroupValue95% CI
dTpa Group - Mother24.820.2 – 29.8
Control Group - Mother22.818.5 – 27.6
Any Temperature/(Axillary) (°C), Dose 1
GroupValue95% CI
dTpa Group - Mother1.20.3 – 3
Control Group - Mother0.90.2 – 2.5
Any Fatigue, Dose 2
GroupValue95% CI
dTpa Group - Mother40.134.7 – 45.7
Control Group - Mother46.240.8 – 51.8
Any Gastrointestinal symptom, Dose 2
GroupValue95% CI
dTpa Group - Mother9.96.9 – 13.7
Control Group - Mother12.79.3 – 16.8
Any Headache, Dose 2
GroupValue95% CI
dTpa Group - Mother23.118.7 – 28.1
Control Group - Mother23.619.1 – 28.5
Any Temperature/(Axillary) (°C), Dose 2
GroupValue95% CI
dTpa Group - Mother4.62.6 – 7.5
Control Group - Mother9.16.2 – 12.7
Percentage of Subjects With Unsolicited AEs Secondary · Within 31 days (Day 0 - Day 30) after each vaccination

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.

Any unsolicited AE, Dose 1
GroupValue95% CI
dTpa Group - Mother38.733.5 – 44.1
Control Group - Mother35.530.5 – 40.8
Any unsolicited AE, Dose 2
GroupValue95% CI
dTpa Group - Mother30.725.8 – 35.9
Control Group - Mother32.227.2 – 37.4
Percentage of Infants With Unsolicited AEs Secondary · From delivery to Month 2 post delivery (Visit 4, end of the study).

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.

GroupValue95% CI
dTpa Group - Infant26.421.8 – 31.4
Control Group - Infnat22.318.0 – 27.0

Adverse events — posted to ClinicalTrials.gov

Time frame: For the Mothers' Groups: Solicited local and general AEs were reported during Days 0 - 7 following each dose. Unsolicited AEs were reported during Days 0 - 30 following each dose. SAEs were reported during the entire study period (Day 0 up to Month 2). For the Infants' Groups: unsolicited AEs and SAEs were reported From Day 0 (Visit 1) to Month 2 (Visit 4, end of the study). For the Household Group: SAEs were reported during the 31-day (Days 0-30) follow-up period post-vaccination.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

dTpa Group-Mother
Serious: 51/341 (15%)
Deaths: 0/341
Control Group-Mother
Serious: 52/346 (15%)
Deaths: 0/346
dTpa Group - Infant
Serious: 52/341 (15%)
Deaths: 0/341
Control Group-Infant
Serious: 45/346 (13%)
Deaths: 0/346
Household Group
Serious: 0/608 (0%)
Deaths: 0/608

Serious adverse events (93 terms)

ReactionSystemdTpa Group-MotherControl Group-MotherdTpa Group - InfantControl Group-InfantHousehold Group
Premature rupture of membranesPregnancy, puerperium and perinatal conditions
Premature babyPregnancy, puerperium and perinatal conditions
Premature labourPregnancy, puerperium and perinatal conditions
JaundiceHepatobiliary disorders
Postpartum haemorrhagePregnancy, puerperium and perinatal conditions
Pre-eclampsiaPregnancy, puerperium and perinatal conditions
Preterm premature rupture of membranesPregnancy, puerperium and perinatal conditions
Respiratory distressRespiratory, thoracic and mediastinal disorders
Gestational hypertensionPregnancy, puerperium and perinatal conditions
Premature deliveryPregnancy, puerperium and perinatal conditions
CryptorchismCongenital, familial and genetic disorders
HyperbilirubinaemiaHepatobiliary disorders
BronchiolitisInfections and infestations
Foetal growth restrictionPregnancy, puerperium and perinatal conditions
Small for dates babyPregnancy, puerperium and perinatal conditions
PolydactylyCongenital, familial and genetic disorders
VomitingGastrointestinal disorders
Amniotic cavity infectionInfections and infestations
Endometritis decidualInfections and infestations
GastroenteritisInfections and infestations
Neonatal infectionInfections and infestations
Respiratory syncytial virus bronchiolitisInfections and infestations
Sepsis neonatalInfections and infestations
Urinary tract infectionInfections and infestations
DehydrationMetabolism and nutrition disorders
Other adverse events (213 terms — click to expand)

ReactionSystemdTpa Group-MotherControl Group-MotherdTpa Group - InfantControl Group-InfantHousehold Group
Injection site painGeneral disorders
FatigueGeneral disorders
HeadacheNervous system disorders
Injection site erythemaGeneral disorders
Injection site swellingGeneral disorders
Gastrointestinal disorderGastrointestinal disorders
PyrexiaGeneral disorders
Afterbirth painPregnancy, puerperium and perinatal conditions
AnaemiaBlood and lymphatic system disorders
MastitisInfections and infestations
Back painMusculoskeletal and connective tissue disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Upper respiratory tract infectionInfections and infestations
NasopharyngitisInfections and infestations
ConstipationGastrointestinal disorders
Urinary tract infectionInfections and infestations
Abdominal painGastrointestinal disorders
ConjunctivitisInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders
DizzinessNervous system disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
HaemorrhoidsGastrointestinal disorders
GastroenteritisInfections and infestations
JaundiceHepatobiliary disorders
Breast engorgementReproductive system and breast disorders
DermatitisSkin and subcutaneous tissue disorders
DyspepsiaGastrointestinal disorders
Injection site pruritusGeneral disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
Abdominal discomfortGastrointestinal disorders
Anaemia of pregnancyBlood and lymphatic system disorders
ArthralgiaMusculoskeletal and connective tissue disorders
DiarrhoeaGastrointestinal disorders
Influenza like illnessGeneral disorders
Injection site haematomaGeneral disorders
InsomniaPsychiatric disorders
Labour painPregnancy, puerperium and perinatal conditions
MyalgiaMusculoskeletal and connective tissue disorders
Neck painMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Premature rupture of membranes, Premature baby, Premature labour, Jaundice, Postpartum haemorrhage, Pre-eclampsia, Preterm premature rupture of membranes, Respiratory distress.

Data from ClinicalTrials.gov NCT02377349 adverse events section.

Sponsor's own description

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 \[DTPA (BOOSTRIX)-049 BST: 048\].

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.

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