We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02853929




Registration number
NCT02853929
Ethics application status
Date submitted
14/07/2016
Date registered
3/08/2016
Date last updated
14/01/2020

Titles & IDs
Public title
Evaluation of Immunogenicity and Safety of a Booster Dose of Infanrix Hexa™ in Healthy Infants Born to Mothers Vaccinated With Boostrix™ During Pregnancy or Immediately Post-delivery
Scientific title
Immunogenicity and Safety Study of a Booster Dose of GSK Biologicals' Infanrix Hexa™ (217744) in Healthy Infants Born to Mothers Vaccinated With Boostrix™ During Pregnancy or Immediately Post-delivery
Secondary ID [1] 0 0
2014-001120-30
Secondary ID [2] 0 0
201334
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diphtheria 0 0
Hepatitis B 0 0
Acellular Pertussis 0 0
Haemophilus Influenzae Type b 0 0
Tetanus 0 0
Poliomyelitis 0 0
Diphtheria-Tetanus-aPertussis-Hepatitis B-Poliomyelitis-Haemophilus Influenzae Type b Vaccines 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Neurological 0 0 0 0
Other neurological disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Infanrix hexa

Experimental: dTpa Group - This group will consist of healthy male or female infants, aged 9 months at the time of enrollment, born to mothers who received a single dose of Boostrix during pregnancy and a dose of placebo immediately post-delivery. All enrolled subjects in this group who will come back for subsequent visit will receive a booster dose of Infanrix hexa co-administered with Prevenar 13 according to the routine national/local immunization or study procedure

Active Comparator: Control Group - This group will consist of healthy male or female infants, aged 9 months at the time of enrollment, born to mothers who received a dose of placebo during pregnancy and single dose of Boostrix immediately post-delivery. All enrolled subjects in this group who will come back for subsequent visit will receive a booster dose of Infanrix hexa co-administered with Prevenar 13 according to the routine national/local immunization or study procedure


Other interventions: Infanrix hexa
All subjects will receive Infanrix hexa co-administered with Prevenar13 as a booster dose.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Seroprotected Subjects Against Anti-diphtheria (Anti-D), Anti-tetanus (Anti-T), Anti-hepatitis B (Anti-HBs), Anti-poliovirus Type 1, Anti-poliovirus Type 2, Anti-poliovirus Type 3 and Anti-polyribosyl-ribitol Phosphate (Anti-PRP) - Seroprotected subjects were defined as subjects with antibody concentrations/titres above or equal (=) the assay cut-offs that are accepted immunological correlates of protection.
0.1 International units per milliliter (IU/ml) for anti-D and anti-T, 10 milli-International units per milliliter (mIU/mL) for anti-HB's, 8 Effective Dose 50 (ED50) for anti-polio virus (type 1,2,3) and 0.15 microgram/milliliter (µg/mL) for anti-PRP were considered as immunological correlates of protection.
Timepoint [1] 0 0
At one month after the booster dose (Day 30)
Primary outcome [2] 0 0
Number of Subjects With a Booster Response to Pertussis Antigens (Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN)) - Booster response to PT, FHA and PRN antigens was defined as:
for subjects with pre-vaccination antibody concentration below the assay cut-off, post-vaccination antibody 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, 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, post-vaccination antibody concentration = 2 times the pre-vaccination antibody concentration
Seronegative (S-) subjects are those who have antibody concentration less than (<) assay cut-off.
Seropositive (S+) subjects are those who have antibody concentration = assay cut-off prior to vaccination.
Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti- FHA and 2.187 IU/mL for anti-PRN
Timepoint [2] 0 0
At one month after the booster dose (Day 30)
Secondary outcome [1] 0 0
Number of Seroprotected Subjects Against Anti-diphtheria, Anti-tetanus, Anti-poliovirus Type 1, Anti-poliovirus Type 2, Anti-poliovirus Type 3, Anti-HBs and Anti-PRP. - Seroprotected subjects were defined as subjects with antibody concentrations/titers above or equal (=) the assay cut-offs that are accepted immunological correlates of protection.
0.1 IU/mL for anti-D and anti-T, 10 mIU/mL for anti-HB's, 8 ED50 for anti-polio virus (type 1,2,3) and 0.15 µg/mL for anti-PRP were considered as immunological correlates of protection.
Timepoint [1] 0 0
Before the booster dose (Day 0)
Secondary outcome [2] 0 0
Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN - Seropositive subjects were defined as subjects whose antibody concentration/titre was greater than or equal to the assay cut-off.
Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA and 2.187 IU/mL for anti-PRN
Timepoint [2] 0 0
Before the booster dose (Day 0)
Secondary outcome [3] 0 0
Number of Seropositive Subjects for Anti-pneumococcal Serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) - Seropositive subjects were defined as subjects whose antibody concentration/titre was greater than or equal to the assay cut-off.
Assay cut-off's for anti-pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) are 0.080 µg/mL, 0.075 µg/mL, 0.061 µg/mL, 0.198 µg/mL, 0.111 µg/mL, 0.102 µg/mL, 0.063 µg/mL, 0.66 µg/mL, 0.160 µg/mL, 0.111 µg/mL, 0.199 µg/mL, 0.163 µg/mL, 0.073 µg/mL respectively.
Timepoint [3] 0 0
Before the booster dose (Day 0)
Secondary outcome [4] 0 0
Anti-D, Anti-T, Anti-PT, Anti-FHA, Anti-PRN Antibody Concentrations - Antibody concentrations are presented as Geometric Mean Concentrations (GMCs) and expressed in IU/mL.
Timepoint [4] 0 0
Before the booster dose (Day 0) and One month after the booster dose (Day 30)
Secondary outcome [5] 0 0
Anti-poliovirus Type 1, 2, 3 Antibody Titres - Anti-Poliovirus type 1, 2 and 3 antibody titers were expressed as Geometric Mean Titers (GMT).
Timepoint [5] 0 0
Before the booster dose (Day 0) and One month after the booster dose (Day 30)
Secondary outcome [6] 0 0
Anti-HBs Antibody Concentrations - Antibody concentrations are presented as Geometric Mean Concentrations (GMCs) and expressed in mIU/mL.
Timepoint [6] 0 0
Before the booster dose (Day 0) and One month after the booster dose (Day 30)
Secondary outcome [7] 0 0
Anti-pneumococcal Serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) and Anti-PRP Antibody Concentrations - Antibody concentrations are presented as Geometric Mean Concentrations (GMCs) and expressed in µg/mL.
Timepoint [7] 0 0
Before the booster dose (Day 0) and One month after the booster dose (Day 30)
Secondary outcome [8] 0 0
Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN. - Seropositive subjects were defined as subjects whose antibody concentration/titre was greater than or equal to the assay cut-off.
Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti- FHA and 2.187 IU/mL for anti-PRN
Timepoint [8] 0 0
At one month after the booster dose (Day 30)
Secondary outcome [9] 0 0
Number of Subjects With Solicited Local Symptoms - Assessed solicited local symptoms were pain, redness, swelling. Any redness, swelling is defined as a symptom with a surface diameter greater than 0 millimeter
Timepoint [9] 0 0
During the 4-day (Day 0-Day 3) follow-up period after booster vaccination of two vaccines (Infanrix hexa and Prevenar 13)
Secondary outcome [10] 0 0
Number of Subjects With Solicited General Symptoms - Assessed solicited general symptoms were Drowsiness, Fever, Irritability/Fussiness and Loss of appetite.
Fever was defined as temperature =37.5 degree Celsius (°C) /99.5 degree Fahrenheit (°F) for oral, axillary or tympanic route, or =38.0°C/100.4°F on rectal route.
Timepoint [10] 0 0
During the 4-day (Day 0-Day 3) follow-up period after booster vaccination
Secondary outcome [11] 0 0
Number of Subjects With Unsolicited Adverse Events (AEs) - An AE was any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Timepoint [11] 0 0
During the 31-day (Day 0-Day 30) follow-up period after booster vaccination
Secondary outcome [12] 0 0
Number of Subjects With Serious Adverse Events (SAEs) - SAE is any untoward medical occurrence that results in death, is life threatening, requires hospitalisation or prolongation of existing hospitalisation, resulting in disability/incapacity
Timepoint [12] 0 0
From booster dose up to study end (approximately 6 or 7 months, per subject)
Secondary outcome [13] 0 0
Number of Subjects With an ASQ-3 Score (Ages & Stages Questionnaires, Third Edition) in the Black Zone - Neurodevelopmental status was measured by ASQ-3 score scale [ASQ-3, 2016] in the black zone. The ASQ-3 included a series of questions designed to assess 5 areas of development (communication, gross motor, fine motor, problem solving, and personal-social). Any subject who scored below the cut-off i.e., a score more than 2 Standard Deviations (SDs) below the mean score for the U.S. reference group (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was to be referred to a developmental specialist for a formal neurodevelopmental assessment (using the Bayley Scale for Infant Development, Version III [BSID-III])
Timepoint [13] 0 0
At 9 months of age, 18 months of age, and 9 or 18 months of age
Secondary outcome [14] 0 0
Number of Subjects Referred for Formal Neurodevelopmental Evaluation Using BSID-III (Bayley Scale for Infant Development, Version III) - Any subject who scored below the cut-off i.e., a score more than 2 Standard Deviations (SDs) below the mean score for the U.S. reference group (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was referred to a developmental specialist for a formal neurodevelopmental assessment (using the Bayley Scale for Infant Development, Version III BSID-III)
Timepoint [14] 0 0
At 9 months of age, 18 months of age, and 9 or 18 months of age
Secondary outcome [15] 0 0
Estimated Proportion of Infants With at Least One of the Indicators of Neurodevelopmental Impairment Using BSID-III (Bayley Scale for Infant Development, Version III) - The estimated proportion (expressed in percentage) of infants with a BSID-III indicator of neurodevelopmental delay was based on ASQ-3 black zone indicator and subsequent BSID-III assessment using the following formula: 100 * (Number of subjects with ASQ-3 below cut off / Number of enrolled subjects with available results) * (Number of subjects with at least one indicator of neurodevelopmental delay using BSID III / Number of subjects referred for BSID III evaluation)
Timepoint [15] 0 0
At 9 months of age, 18 months of age, and 9 or 18 months of age

Eligibility
Key inclusion criteria
- Subjects' parent(s)/Legally acceptable representatives (LAR(s)) who, in the opinion of
the investigator, can and will comply, with the requirements of the protocol (e.g.
completion of the diary cards, return for follow-up visits).

- Written informed consent obtained from the parent(s)/LAR(s) of the subject prior to
performing any study specific procedure.

- A male or female child 9 months of age at the time of enrolment.

- Healthy subjects as established by medical history and clinical examination before
entering into the study.

- Subjects born to mothers who were vaccinated in 116945 [DTPA (BOOSTRIX)-047] study and
having completed their primary vaccination series as per protocol requirement in study
201330 [DTPA (BOOSTRIX)-048 PRI].
Minimum age
9 Months
Maximum age
19 Months
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Child in care

- Concurrently participating in another clinical study, within three months prior to the
booster vaccine dose and at any time during the present booster study, in which the
subject has been or will be exposed to an investigational or a non-investigational
vaccine/product (pharmaceutical product or device).

- Chronic administration (defined as more than 14 days in total) of immunosuppressants
or other immune-modifying drugs during the period within six months prior to the
booster vaccine dose. For corticosteroids, this will mean prednisone =0.5mg/kg/day, or
equivalent. Inhaled and topical steroids are allowed.

- Administration of long-acting immune-modifying drugs at any time during the study
period (e.g. infliximab).

- A vaccine not foreseen by the study protocol administered during the period starting
from 30 days before the booster dose of study vaccine and ending 30 days after*, with
the exception of inactivated influenza vaccine and other vaccines given as a part of
the national/regional immunization schedule, that are allowed at any time during the
study period.

- In case an emergency mass vaccination for an unforeseen public health threat
(e.g.: a pandemic) is organised by the public health authorities, outside the
routine immunization program, the time period described above can be reduced if
necessary for that vaccine provided it is licensed and used according to its SPC
or Product Information (PI) and according to the local governmental
recommendations and provided a written approval of the Sponsor is obtained.

- Any confirmed or suspected immunosuppressive or immunodeficient condition, based on
medical history and physical examination (no laboratory testing required).

- Major congenital defects.

- Serious chronic illness.

- Administration of immunoglobulins and/or any blood products during the period within
three months before the booster dose of study vaccines or planned administration
during the study period.

- Encephalopathy defined as an acute, severe central nervous system disorder occurring
within 7 days following vaccination with Infanrix hexa and generally consisting of
major alterations in consciousness, unresponsiveness, generalised or focal seizures
that persist more than a few hours, with failure to recover within 24 hours.

- History of Hib, diphtheria, tetanus, pertussis, pneumococcal, poliovirus and hepatitis
B diseases since the conclusion visit of study 201330 [DTPA (BOOSTRIX)-048 PRI].

- Previous booster vaccination against Hib, diphtheria, tetanus, pertussis,
pneumococcus, hepatitis B and/or poliovirus since the conclusion visit of study 201330
[DTPA (BOOSTRIX)-048 PRI].

- History of any reaction or hypersensitivity likely to be exacerbated by any component
of the vaccines (e.g: antigen, excipients).

- Hypersensitivity to latex.

- History of any neurological disorders or seizures.

- Any condition that in the judgment of the investigator would make intramuscular
injection unsafe.

- Acute disease and/or fever at the time of vaccination.

- 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.

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
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 postcode(s) [1] 0 0
3053 - Carlton
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
Quebec
Country [4] 0 0
Czechia
State/province [4] 0 0
Brno
Country [5] 0 0
Czechia
State/province [5] 0 0
Hradec Kralove
Country [6] 0 0
Czechia
State/province [6] 0 0
Ostrava - Vitkovice
Country [7] 0 0
Czechia
State/province [7] 0 0
Praha 4
Country [8] 0 0
Czechia
State/province [8] 0 0
Praha
Country [9] 0 0
Finland
State/province [9] 0 0
Kokkola
Country [10] 0 0
Finland
State/province [10] 0 0
Oulu
Country [11] 0 0
Finland
State/province [11] 0 0
Seinajoki
Country [12] 0 0
Finland
State/province [12] 0 0
Tampere
Country [13] 0 0
Finland
State/province [13] 0 0
Turku
Country [14] 0 0
Italy
State/province [14] 0 0
Lombardia
Country [15] 0 0
Italy
State/province [15] 0 0
Piemonte
Country [16] 0 0
Spain
State/province [16] 0 0
Andalucia
Country [17] 0 0
Spain
State/province [17] 0 0
Antequera/Málaga
Country [18] 0 0
Spain
State/province [18] 0 0
Aravaca
Country [19] 0 0
Spain
State/province [19] 0 0
Burgos
Country [20] 0 0
Spain
State/province [20] 0 0
Madrid
Country [21] 0 0
Spain
State/province [21] 0 0
Majadahonda (Madrid)
Country [22] 0 0
Spain
State/province [22] 0 0
Móstoles
Country [23] 0 0
Spain
State/province [23] 0 0
Santiago de Compostela
Country [24] 0 0
Spain
State/province [24] 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 the Infanrix hexa
booster dose given at 11-18 months of age to infants who received primary vaccination at 6-14
weeks. All infants in this booster study were born to pregnant women who participated in the
study 116945 [DTPA (BOOSTRIX)-047] and having received the full primary vaccination series as
per protocol requirement in study 201330 [DTPA (BOOSTRIX)-048.
Trial website
https://clinicaltrials.gov/show/NCT02853929
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