Trial Review

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 registered on ANZCTR


Registration number
ACTRN12607000271404
Ethics application status
Approved
Date submitted
17/05/2007
Date registered
18/05/2007
Date last updated
2/06/2009
Type of registration
Retrospectively registered

Titles & IDs
Public title
Immunogenicity and safety of orally administered killed whole cell non-typeable Haemophilus influenzae (Study HI-H003)
Scientific title
A single centre, double blind, placebo controlled, prospective study to assess the immunogenicity and safety of orally administered killed whole cell non-typeable Haemophilus influenzae (NTHi) HI-1-164 in smokers at risk of recurrent bronchitis (Study HI-H003)
Secondary ID [1] 368 0
Hunter Immunology Ltd Protocol HI-H003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Smokers at risk of recurrent bronchitis 1811 0
Condition category
Condition code
Respiratory 1901 1901 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The test product was formalin-inactivated whole cell non-typeable Haemophilus influenzae formulated in enteric-coated tablets to be taken orally. Each tablet contained 45mg of active ingredient plus excipients. Three courses of tablets were taken by each participant at monthly intervals. Each course consisted of 2 tablets per day for three consecutive days. Thus treatment took place over a period of 60 days. Participants attended visits at 2-week intervals for 3 months.
Intervention code [1] 1764 0
Prevention
Comparator / control treatment
Control placebo tablets contained excipients only.
Control group
Placebo

Outcomes
Primary outcome [1] 2706 0
To compare surrogate markers of mucosal protection (NTHi-specific antibody in saliva and serum, NTHi-specific T cells in blood) and non-specific parameters (INF-gamma, lysozyme, lactoferrin and nitric oxide in saliva) between vaccine and placebo groups. NTHi-specific antibody, IFNg, lysozyme and lactoferrin were measured by ELISA assays. NTHi-specific lymphocytes were measured by in vitro proliferation of blood lymphocytes in response to antigen stimulation. Nitric oxide was measured by chemical assay.
Timepoint [1] 2706 0
Measured at baseline, at weeks 2,4,6 and 8 during intervention and at weeks 10 and 12 post-intervention.
Secondary outcome [1] 4565 0
To monitor nasal and pharyngeal colonisation with NTHi, Moraxella catarrhalis and Streptococcus pneumoniae through the study in vaccine and placebo groups. Quantitative bacteriology was performed by plating out serial dilutions of samples on selective media and performing identity tests where required.
Timepoint [1] 4565 0
Bacterial carriage was monitored at weeks 2,4,6 and 8 during intervention and at weeks 10 and 12 post-intervention.
Secondary outcome [2] 4566 0
To demonstrate safety of the product. Blood samples were collected for pathology safety testing. Pathology tests (Haematology and Biochemistry) were performed by the Hunter Area Pathology Service. Advere event information was collected via patient narrative at each visit to demonstrate safety of the product. Examples of adverse events included cough, hayfever, throat infection (these examples were not related to product).
Timepoint [2] 4566 0
Adverse event information was obtained at weeks 2,4,6,8 during intervention and weeks 10,12 post-intervention. Blood for safety profiling was obtained at baseline, week 6 during intervention, and week 12 post-intervention.
Secondary outcome [3] 4567 0
To identify episodes of acute bronchitis (defined: episode of purulent sputum)
Timepoint [3] 4567 0
Obtained at weeks 2,4,6,8 during intervention and weeks 10,12 post-intervention.

Eligibility
Key inclusion criteria
Smokers who had smoked at least 10 cigarettes per day for the past 2 years (1 pack year), with no medical or social reason for being unable to comply with requirements of the study, and willingness and ability to give signed informed consent.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Known current chronic infection (except episodes of acute bronchitis with or without chronic bronchitis); participation in a clinical trial in the past 3 months; pregnant, breast-feeding, or women with child-bearing potential without an effective method of contraception, any patient likely to withdraw or not comply with the study protocol; any other medical reason that the medical advisor feels that a patient should not be included.

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)
Potential subjects were provided with information sheets and invited to attend a first visit at which willing subjects were enrolled by the clinician. Each subject entered into the study was allocated a Randomisation/Subject number. Randomisation numbers were in sequential blocks which ensured balance between those taking the active tablets and those taking the placebo. The randomisation code was generated by the contract CRO (Novotech Pty Ltd) and kept in a sealed envelope off-site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated randomisation sequence. Randomisation occurred in blocks of eight to ensure balance between treatment groups.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
The study was double-blind with all participants blinded to the randomisation code. The code was broken when the data-base was locked and the statistician performed the statistical analysis knowing the code-break. The people involved in the study were: subjects (identified only by initials and study number) and, investigators (2 clinicians who interviewed the subjects and 2 scientists who were involved in the planning and operation of the study), study co-ordinator, study nurse (who collected samples from the subjects), Hunter Immunology Ltd laboratory staff (who performed assays on study samples), study monitor (supplied by Novotech (Aust) Pty Ltd), Hunter Area Pathology Service (HAPS) (performed Biochemistry and Haematology testing). Note that all samples for testing were identified only by subject number, initials and bar code.
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
25/07/2005
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
64
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 2047 0
Commercial sector/Industry
Name [1] 2047 0
Hunter Immunology Ltd
Country [1] 2047 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
The University of Newcastle Research Associates (TUNRA) Ltd
Address
University of Newcastle,
University Drive,
Callaghan NSW 2308
Country
Australia
Secondary sponsor category [1] 1853 0
Commercial sector/Industry
Name [1] 1853 0
Hunter Immunology Ltd
Address [1] 1853 0
18 Rodborough Road,
Frenchs Forest, NSW 2086
Country [1] 1853 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 3801 0
The University of Newcastle Human Research Ethics Committee
Ethics committee address [1] 3801 0
Research Office, The University of Newcastle, University Drive, Callaghan NSW 2308
Ethics committee country [1] 3801 0
Australia
Date submitted for ethics approval [1] 3801 0
25/05/2005
Approval date [1] 3801 0
15/06/2005
Ethics approval number [1] 3801 0
H-057-0605

Summary
Brief summary
This study monitored safety and measured specific and non-specific immunological parameters in smokers, who are a group at risk of recurrent bronchitis. This group was chosen rather than healthy non-smoking volunteers for this safety/pharmacokinetic study as it was thought possible that the immune parameters may differ in smokers to that in healthy non-smokers. This safety and immunogenicity study has been completed. It was not registered prior to initiation due to our unawareness of the registration system at that time. As it is a Phase I study and is not required to be registered it is being registered for the purpose of public information as we are now aware that post-initiation registration is possible
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 27867 0
Address 27867 0
Country 27867 0
Phone 27867 0
Fax 27867 0
Email 27867 0
Contact person for public queries
Name 10953 0
E/Prof Robert Clancy
Address 10953 0
Immunology & Microbiology, Level 4 David Maddison Building, University of Newcastle, Callaghan NSW 2308
Country 10953 0
Australia
Phone 10953 0
+61 2 4913 8195
Fax 10953 0
+61 2 4913 8998
Email 10953 0
[email protected]
Contact person for scientific queries
Name 1881 0
A/Prof Margaret Dunkley
Address 1881 0
Hunter Immunology Ltd, Level 4 David Maddison Building, University of Newcastle, Callaghan NSW 2308
Country 1881 0
Australia
Phone 1881 0
+61 2 4913 8581
Fax 1881 0
Email 1881 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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

Documents added automatically
No additional documents have been identified.