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

Phase 4

Completed

• Conditions: Diphtheria-Tetanus-acellular Pertussis Vaccines
• Interventions: Biological: Boostrix™; Drug: Saline placebo

• Registration Number: NCT02377349
• Lead Sponsor: GlaxoSmithKline

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.

Study Timeline

• Study First Submitted: 2015-02-26
• Study First Submitted QC: 2015-02-26
• Study First Posted: 2015-03-03
• Study Start: 2015-10-14
• Primary Completion: 2017-08-14
• Study Completion: 2017-10-24
• Results First Submitted: 2018-08-10
• Results First Submitted QC: 2018-08-10
• Results First Posted: 2019-01-28
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-16
• Last Update Posted: 2020-01-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 688

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Control Group	Saline placebo	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).
dTpa Group	Boostrix™	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).
Control Group	Boostrix™	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).
dTpa Group	Saline placebo	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).

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Percentage of Subjects by Pregnancy Outcomes	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.
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).	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.
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	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.
Number of Subjects With Serious AEs (SAEs)	From Day 0 (Visit 1) to Month 2 (Visit 4, end of the study).	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.
Percentage of Infants With Unsolicited AEs	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.
Percentage of Seropositive Subjects Against Anti-PT, Anti-FHA and Anti-PRN in the Cord Blood Samples	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.
Percentage of Household Contacts of the Infants Born to Pregnant Women Vaccinated in Spain	From Day 0 (Visit 1) to Month 2 (Visit 4, end of the study).	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.
Anti-D, Anti-T, Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations	One month post vaccination (Day 30) during pregnancy	Antibody concentrations were determined by ELISA, tabulated as GMCs and expressed in IU/mL.
Percentage of Subjects With Unsolicited AEs	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.
Percentage of Subjects With Vaccine Response to Anti-D and Anti-T	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.
Percentage of Subjects With Vaccine Response to Anti-PT, Anti-FHA and Anti-PRN	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 antibody concentration.
Percentage of Subjects With Solicited Local Adverse Events (AEs)	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.
Percentage of Subjects With Solicited General AEs	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.
Percentage of Household Contacts With SAEs	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).	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.

Trial Locations

Locations (1)

GSK Investigational Site; 🇪🇸 Sevilla, Spain