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Trial registered on ANZCTR


Registration number
ACTRN12622001216707
Ethics application status
Approved
Date submitted
3/08/2022
Date registered
9/09/2022
Date last updated
9/09/2022
Date data sharing statement initially provided
9/09/2022
Date results information initially provided
9/09/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Persistence of immunity to 4 years of age following a delayed pertussis vaccine schedule in infancy
Scientific title
A follow up study of Optimising pertussis vaccination in infants: a new
approach

Response to a booster dose of DTPa-IPV at 4 years old and persistence of
immunity following a new approach to an optimised pertussis vaccination
schedule in healthy infants
Secondary ID [1] 307609 0
Nil known
Universal Trial Number (UTN)
Trial acronym
InfantDTPaBooster301015
Linked study record
This study is a follow up of the infants enrolled on study with registration record ACTRN12615000898550

Health condition
Health condition(s) or problem(s) studied:
vaccine 327078 0
pertussis 327079 0
immunity persistence 327080 0
Condition category
Condition code
Inflammatory and Immune System 324234 324234 0 0
Other inflammatory or immune system disorders
Infection 324678 324678 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Our First Phase trial examined whether a modified infant vaccination schedule for DTPaIPV-Hep B-Hib (Infanrix Hexa®) at 6 weeks, 12 weeks and 11-12 months gave similar
immune protection in the first 6 months of life in comparison to the existing vaccine
schedule (at 6 weeks, 4 months, and 6 months of age),

In this follow on study the aim is to compare surrogate measures of protection (IgG antibody) against pertussis prior to and following a DTPa-IPV booster vaccine at 4 years old in children previously recruited in the primary alternate schedule pertussis vaccine study (ACTRN12615000898550)

No additional booster vaccines were given in this study. Children enrolled on the study followed the routine immunization program at the time the study was conducted from 12 months of age onwards.
Intervention code [1] 324061 0
Prevention
Comparator / control treatment
Participants form the original study ACTRN12615000898550 will be followed up to 4 years of life and their immune responses will be measured at 18-36 months of age and pre and post the routine 4 year old DTaP-IPV booster vaccine. The immunogenicity results from children in this study will be compared to a historical control of infants from another pertussis vaccine trial (these infants received the routine schedule at the time the study was conducted 6 weeks, 4 and 6 months of age). Trial registry for this trial is ACTRN12609000905268
Control group
Historical

Outcomes
Primary outcome [1] 332053 0
To compare surrogate measures of protection (IgG antibody) against pertussis antigens prior to and following a DTPa-IPV booster vaccine at 4 years old in children previously recruited to a study of a 3 dose alternate policy relevant pertussis vaccine schedule.

The IgG antibodies to pertussis antigens will be measured on blood sera samples collected from participants in the trial
Timepoint [1] 332053 0
Serology will be measured at 4 years - prior to receipt of the DTaP-IPV booster vaccine and at 4 years and 1 month 1 month after receipt of pre-school DTPa-IPV vaccine
Secondary outcome [1] 412001 0
In children previously recruited to the 3 dose alternate pertussis vaccine schedule:
Compare surrogate measures of protection (IgG antibody) against pertussis at 18-36 months of age. The pertussis IgG antibody levels will be measured on serology/blood samples collected at the time/age points specified in the protocol
Timepoint [1] 412001 0
aged 18-36 months and post receipt of DTPa booster at 4 years of age
Secondary outcome [2] 413730 0
In children previously recruited to the 3 dose alternate pertussis vaccine schedule:
Evaluate adverse reactions following the 4 year DTPa-IPV booster vaccination.
Adverse events will be measured by the use of diary cards (routinely used in vaccine trials) that collect solicited information on local and systemic adverse events. Serious adverse events will also be collected during the study.
Timepoint [2] 413730 0
4 years - prior to receipt of the DTPa-IPV vaccine and at 4 years and 1 month (1 month after receipt of pre-school DTPa-IPV vaccine)
Secondary outcome [3] 413731 0
In children previously recruited to the 3 dose alternate pertussis vaccine schedule:
Evaluate antibodies to other concomitantly administered vaccine antigens (diphtheria and tetanus) following the 4 year DTPa-IPV booster vaccination.

IgG antibodies to diphtheria and tetanus will be measured on serology/blood samples collected prior to receipt of the 4 year old DTaP-IPV vaccine and at 4 years 1 month (1 month after receipt of pre-school DTPa-IPV vaccine)
Timepoint [3] 413731 0
4 years - prior to receipt of the DTPa-IPV vaccine and at 4 years and 1 month (1 month after receipt of pre-school DTPa-IPV vaccine)

Eligibility
Key inclusion criteria
Children who are between 18 to 36 months old and were subjects previously enrolled in the
First Phase study (ACTRN12615000898550) are eligible to participate in this study.
Eligible children must meet inclusion and exclusion criteria at the time of first visit and
parents/guardians must give written informed consent.
Minimum age
18 Months
Maximum age
36 Months
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Contraindications to vaccination as listed in the NHMRC Australian
Immunisation Handbook or as listed in the Infanrix-IPV Product
Information. DTPa-IPV vaccine will not be administered to individuals known to be
hypersensitive to any component of the vaccine or residues carried over from
manufacture (such as formaldehyde and glutaraldehyde).

Administration of immunoglobulins and any blood products within the 3 month
period prior to the first visit or planned administration during the study period; in
which case, a delay in enrolment will be considered in the absence of other excluding
criteria.
Any confirmed or suspected immunosuppressive or immunodeficient condition
.
History of serious chronic illness or condition which in the judgement of the clinical
investigator would preclude study participation.

History of neurologic disease or seizure

Must not have had the vaccination scheduled for age 4 years (ie Infanrix-IPV).

Must not have had a DTPa booster in the second year of life (prior to study
enrolment)

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
Single group
Other design features
Follow up of participants who participated in the 2+1 primary vaccine study (ACTRN12615000898550).
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Immunogenicity: Continuous (geometric mean antibody concentration) and categorical
(presumptive threshold) measures of antibodies to pertussis and other contemporaneously
administered antigens will be examined. All serum antibody concentrations will be log
transformed for statistical analysis as geometric mean concentrations (GMC) with 95%
confidence limits.

Where protective thresholds are well-established, the proportions with
95% confidence limits at or above the assay cut off will be calculated – anti-diphtheria (0.1
IU/ml)*, anti-tetanus (0.1 IU/ml). Antibody to polio serotypes 1, 2 and 3 will be measured by
microneutralisation assay and the lowest dilution tested at 1:8.

Statistical analysis will include both comparisons of GMC (with 95% confidence intervals) as a continuous variable. (Student’s t-test) and categorical analysis of relevant antibody thresholds (Chi square). The frequency of seroresponses defined as a 4-fold increase from pre-vaccination antibody level will be compared between our study group and the NHMRC Birth Pertussis Study (historical control) cohort by the Chi square test statistic.
Note: * this threshold is significantly above the known protective level of 0.01 IU/ml but is
the lower limit of assay detection.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
13/05/2016
Date of last participant enrolment
Anticipated
Actual
14/03/2017
Date of last data collection
Anticipated
Actual
22/05/2019
Sample size
Target
60
Accrual to date
Final
47
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 22848 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 38147 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 311877 0
Hospital
Name [1] 311877 0
The Sydney Children's Hospital Network
Country [1] 311877 0
Australia
Funding source category [2] 311980 0
Commercial sector/Industry
Name [2] 311980 0
GlaxoSmithKline
Country [2] 311980 0
Australia
Primary sponsor type
Hospital
Name
The Sydney Children's Hospital Network
Address
The Children's Hospital at Westmead
Locked Bag 4001
Westmead NSW 2145
Country
Australia
Secondary sponsor category [1] 313462 0
None
Name [1] 313462 0
Address [1] 313462 0
Country [1] 313462 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311312 0
The Sydney Children's Hospital Network
Ethics committee address [1] 311312 0
The Children's Hospital at Westmead
Locked Bag 4001
Westmead NSW 2145
Ethics committee country [1] 311312 0
Australia
Date submitted for ethics approval [1] 311312 0
Approval date [1] 311312 0
16/09/2015
Ethics approval number [1] 311312 0

Summary
Brief summary
Our First trial (ACTRN12615000898550) examined the immune responses to pertussis and other vaccine antigens following a modified infant vaccination schedule for DTPa-IPV-Hep B-Hib (Infanrix Hexa®) vaccine when given at 6 weeks, 12 weeks and 11-12 months of age.

The immune responses in this study following this modified vaccine schedule will be compared to immune responses in a separate historical comparison study where Infanrix Hexa® vaccine was given at 6 weeks, 4 months, and 6 months of age),

Continued study of the cohort enrolled onto ACTRN12615000898550 is a unique opportunity to examine the longer-term safety and immunogenicity at 18 to 36 months and again at 4 years old of children who followed the modified vaccine schedule and to compare their results with a historical cohort of infants who received pertussis-containing vaccines given according to the standard immunisation schedule.

The key questions of prolonged immune tolerance to pertussis antigens, negative interference on concomitantly administered antigens and increased reactogenicity to booster doses following altered timing of Pa vaccination are only able to be answered by the long term follow up of our cohort. These are essential data to inform national vaccine policy and will be of considerable interest internationally.

Antibody responses in the blood of children originally enrolled on ACTRN12615000898550, which are believed to correlate with protection, will be measured at (1) 18 to 36 months of age, at (2) 4 years of age pre-booster dose of DTPa-IPV vaccine and (3) 1 month after receipt of 4 year old DTPa-IPV booster vaccine.

In addition, differences in immune and safety responses in the study cohort after receipt of the 4 year old booster dose of DTPa-IPV compared to historical controls who have received the existing vaccine schedule (at 6 weeks, 4 months and 6 months of age).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120670 0
Dr Nicholas Wood
Address 120670 0
National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases, The Children’s Hospital at Westmead
Westmead NSW 2145
Country 120670 0
Australia
Phone 120670 0
+61 2 9845 1433
Fax 120670 0
Email 120670 0
nicholas.wood@health.nsw.gov.au
Contact person for public queries
Name 120671 0
Dr Nicholas Wood
Address 120671 0
National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases, The Children’s Hospital at Westmead
Westmead NSW 2145
Country 120671 0
Australia
Phone 120671 0
+61 2 9845 1433
Fax 120671 0
Email 120671 0
nicholas.wood@health.nsw.gov.au
Contact person for scientific queries
Name 120672 0
Dr Nicholas Wood
Address 120672 0
National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases, The Children’s Hospital at Westmead
Westmead NSW 2145
Country 120672 0
Australia
Phone 120672 0
+61 2 9845 1433
Fax 120672 0
Email 120672 0
nicholas.wood@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No ethics approval to do so.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
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Plain language summaryNo A total of 47 infants enrolled on the primary tria... [More Details]

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