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Trial registered on ANZCTR


Registration number
ACTRN12614001003662
Ethics application status
Approved
Date submitted
2/09/2014
Date registered
17/09/2014
Date last updated
14/07/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy and safety of Prevenar 13 in people with asthma
Scientific title
A single-site trial to investigate the efficacy, safety and immunogenicity of conjugated pneumococcal vaccine
(CJPV13, Prevenar) on airway inflammation in people with eosinophilic asthma
Secondary ID [1] 285235 0
Nil
Secondary ID [2] 289682 0
Nil known
Universal Trial Number (UTN)
Trial acronym
PIES (Pneumococcal vaccine In Eosinophilic asthma Study)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 292865 0
Condition category
Condition code
Respiratory 293164 293164 0 0
Asthma
Inflammatory and Immune System 293334 293334 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Prevenar 13 (Active ingredients: 30.8 mg pneumococcal purified capsular polysaccharides and 32 mg CRM197 protein)
0.5ml to be administered by intramuscular injection
given in 2 doses at monthly intervals

Parallel group to receive Pneumovax 23 (Pneumococcal vaccine polyvalent). It contains a mixture of purified capsular polysaccharides from the 23 most prevalent or invasive pneumococcal types of Streptococcus pneumoniae.
Each 0.5 ml dose of vaccine contains 25 mcg of each polysaccharide type dissolved in isotonic saline solution containing 0.25% phenol as preservative.
0.5ml to be administered by intramuscular injection
1 dose given, followed by 1 dose of saline 4 weeks later
Intervention code [1] 290109 0
Treatment: Other
Intervention code [2] 290250 0
Treatment: Drugs
Comparator / control treatment
Prevenar treatment group will be compared to parallel group who receive Pneumococcal vaccine Pneumovax23
Control group
Active

Outcomes
Primary outcome [1] 293062 0
Induced sputum eosinophils- Sputum induction will be performed with selection and dispersion of muco-cellular clumps and performance of total and differential cell counts.
Timepoint [1] 293062 0
Assessed at screening visit, during two treatment visits, at the end of treatment visit, which is 4 weeks after treatment 2, and end of study visit which is 12 months after the first treatment.
Primary outcome [2] 293063 0
Regulatory T cell numbers and functional responses-
Treg cell numbers and functional responses will be analysed in peripheral blood mononuclear cells through flow cytometry.
Timepoint [2] 293063 0
Assessed at the two treatment visits and at the end of treatment visit, which is 4 weeks after treatment 2.
Secondary outcome [1] 310273 0
Asthma symptoms- assessed using the Juniper Asthma Control Questionnaire (ACQ(6))
Timepoint [1] 310273 0
ACQ(6) will be assessed at screening visit, two treatment visits, end of treatment visit (4 weeks after treatment 2), and end of study visit (12 months after treatment 1)
Secondary outcome [2] 310274 0
Health status- assessed using the Juniper Asthma Quality of Life
Questionnaire (AQLQ).
Timepoint [2] 310274 0
AQLQ will be assessed at screening visit, two treatment visits, end of treatment visit (4 weeks after treatment 2), and end of study visit (12 months after treatment 1).

Eligibility
Key inclusion criteria
Symptomatic stable asthma [ACQ(6) > 0.75], confirmed variable airflow obstruction, maintenance therapy
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Forced expiratory volume in 1 second (FEV1) < 40% predicted.. Received pneumococcal vaccination with Pneumovax in the past 12 months, or Prevenar ever. Current smoking (or having quit within 6 months of study entry). Cold or respiratory tract infection within 4 weeks of study entry. Pregnancy, breast feeding, possibility of becoming pregnant (unwilling to use contraception during the treatment phase). Inability to attend study visits. Participation in another investigative drug study within 4 weeks of study entry.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
We will use concealed random allocation. Randomisation is done by a computer generated list. Outcomes will be assessed by staff unaware of treatment allocation.
The person assessing eligibility will not have access to the randomisation information, randomisation will be done over the phone by designated staff members who do not have any participant contact in the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation ratio is 1:1. A computer generated list was created.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Hypothesis A will be tested using analysis of covariance. A model will be fitted with sputum eosinophils at 52 weeks as the outcome of interest. The predictor variable of interest in the analysis of variance model will be treatment group (Prevenar13 or Pneumovax 23) with baseline level of sputum eosinophils included as a covariate.
Hypothesis B, health status and asthma symptom scores, will also be analysed using analysis of covariance with baseline level included as a covariate.
Baseline characteristics, change scores and end of treatment results will be summarised by treatment group. Continuous outcomes will be analysed using Student’s t test for parametric data and Wilcoxon ranksum tests for nonparametric data. Categorical data will be compared using the Chi square or Fisher’s exact test as appropriate.
Data will be analysed on an intention-to-treat basis using 2-sided tests with p values <0.05 considered statistically significant. The analysis will be repeated on the per protocol population.

Number of study participants for the study:
Alpha: 0.05; Power: 80%; Sample size required is 49 per group, as described below and allowing for dropouts.

ACQ: a clinically important difference is 0.5 units. In a previous study the response within each subject group was normally distributed with standard deviation 0.83. If the true difference in the experimental and control means is 0.5, we will need 44 experimental and 44 control subjects.

FEV1%predicted: In a prior study the response within each subject group was normally distributed with standard deviation 20.8. If the true difference in the experimental and control means is 15.5, we will need to study 29 experimental subjects and 29 control subjects.

Sputum eosinophils: In a previous study the response within each subject group was normally distributed with standard deviation of 16.28%. If the true difference in the experimental and control means is 10%, we will need to study 43 experimental subjects and 43 control subjects.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/06/2016
Actual
1/07/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 6173 0
Hunter Medical Research Institute - New Lambton Heights

Funding & Sponsors
Funding source category [1] 289880 0
Other Collaborative groups
Name [1] 289880 0
Asthma Australia
Country [1] 289880 0
Australia
Primary sponsor type
Other
Name
Hunter Medical Research Institute
Address
1/Kookaburra Circuit, New Lambton Heights NSW 2305
Country
Australia
Secondary sponsor category [1] 288534 0
None
Name [1] 288534 0
Address [1] 288534 0
Country [1] 288534 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291576 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 291576 0
Hunter New England Area Health Service Locked Bag 1, Hunter Region
Mail Centre, Newcastle NSW 2310
Ethics committee country [1] 291576 0
Australia
Date submitted for ethics approval [1] 291576 0
20/04/2016
Approval date [1] 291576 0
09/05/2016
Ethics approval number [1] 291576 0
16/04/20/3.01
Ethics committee name [2] 295480 0
Hunter New England Human Research Ethics Committee
Ethics committee address [2] 295480 0
Hunter New England Area Health Service Locked Bag 1, Hunter Region Mail Centre, Newcastle NSW 2310
Ethics committee country [2] 295480 0
Australia
Date submitted for ethics approval [2] 295480 0
20/04/2016
Approval date [2] 295480 0
09/05/2016
Ethics approval number [2] 295480 0
16/04/20/3.01

Summary
Brief summary
Asthma is a high impact, chronic inflammatory airway disease where modulation holds the promise of long term clinical benefits. Different types of cells have been involved in asthma such as eosinophils, neutrophils and a mixture of both eosinophils and neutrophils. The main purpose of this study is to see if treatment with conjugated pneumococcal vaccine (Prevenar 13) will help people with eosinophilic asthma. It is hypothesised that Prevenar 13 will attenuate eosinophilic airway inflammation and improve health status.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 50338 0
Prof Peter Gibson
Address 50338 0
Hunter Medical Research Institute
John Hunter Hospital
Department of Respiratory and Sleep Medicine
Locked Bag 1000,
New Lambton NSW 2305
Country 50338 0
Australia
Phone 50338 0
+61240420143
Fax 50338 0
Email 50338 0
[email protected]
Contact person for public queries
Name 50339 0
Catherine Delahunty
Address 50339 0
Department of Respiratory & Sleep Medicine
Hunter Medical Research Institute
Level 2 West
Locked Bag 1000
New Lambton NSW 2305
Country 50339 0
Australia
Phone 50339 0
+61240420135
Fax 50339 0
+61240420046
Email 50339 0
[email protected]
Contact person for scientific queries
Name 50340 0
Peter Gibson
Address 50340 0
Hunter Medical Research Institute
John Hunter Hospital
Department of Respiratory and Sleep Medicine
Locked Bag 1000,
New Lambton NSW 2305
Country 50340 0
Australia
Phone 50340 0
+61240420143
Fax 50340 0
Email 50340 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Current supporting documents:


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23345Study protocol    366820-(Uploaded-15-12-2020-17-12-54)-Study-related document.pdf
23346Clinical study report  [email protected]

Results publications and other study-related documents

Documents added manually
Current Study Results
No documents have been uploaded by study researchers.

Update to Study Results
Doc. No.TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
3809Basic resultsNo 366820-(Uploaded-17-12-2020-19-57-22)-Basic results summary.pdf
3977Plain language summaryNo 1. Research Question The aim of this pilot study ... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseNeutrophilic asthma features increased airway classical monocytes.2021https://dx.doi.org/10.1111/cea.13811
N.B. These documents automatically identified may not have been verified by the study sponsor.