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Trial registered on ANZCTR


Registration number
ACTRN12610000916044
Ethics application status
Approved
Date submitted
18/10/2010
Date registered
28/10/2010
Date last updated
27/06/2019
Date data sharing statement initially provided
27/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A Multi-Centre, Randomised, Double-Blind, Placebo-Controlled,
Parallel Group, Single-Season Study to Assess the Efficacy and
Safety of HI-164OV Oral Vaccine in Moderate to Severe chronic obstructive pulmonary disease (COPD).
Scientific title
A Multi-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group, Single-Season Study to Assess the Efficacy and Safety of HI-164OV, an Enteric-coated Oral Vaccine Tablet Containing 45 mg HI-164 Active Substance (Inactivated, Whole Cells of Non-typeable Haemophilus influenzae, isolate 164) for Reducing the Rate and Severity of Acute Exacerbations in Patients with Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD).
Secondary ID [1] 252564 0
Nil
Universal Trial Number (UTN)
U1111-1116-3615
Trial acronym
HI-H005
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease (COPD) 257876 0
Condition category
Condition code
Respiratory 258039 258039 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral vaccine tablet containing 45 mg HI-164 active product.

Participants will be asked to take the study medication on three consecutive days each month for the first three months (ie. nine doses in total). Each daily dose of HI-164OV contains 90 mg of HI-164 and will be taken orally approximately one hour prior to breakfast.
Intervention code [1] 256930 0
Treatment: Drugs
Intervention code [2] 257429 0
Prevention
Comparator / control treatment
Placebo tablets matched in appearance and weight to active product.

Participants will be asked to take the study medication on three consecutive days each month for the first three months (ie. nine doses in total). Each daily dose of HI-164OV placebo contains 0 mg of HI-164 and will be taken orally approximately one hour prior to breakfast.
Control group
Placebo

Outcomes
Primary outcome [1] 258887 0
The primary endpoint is the rate of exacerbations requiring oral/parenteral corticosteroid treatment or hospitalisation. Patients will maintain daily diaries to record severity of respiratory symptoms and the need for medications. Episodes of acute exacerbations, medication usage, and COPD-related clinic or hospital visits will be recorded at each study visit. The rate of exacerbations will be measured in number of days since study entry to start of treatment or hospitalisation.
Timepoint [1] 258887 0
End of Study
Secondary outcome [1] 265041 0
The proportion of participants per group experiencing exacerbations requiring oral/parenteral corticosteroid treatment or hospitalisation since study entry.
Timepoint [1] 265041 0
End of Study
Secondary outcome [2] 265336 0
The time to systemic corticosteroid use or hospitalisation, or time to antibiotic use (separately and collectively) as measured in number of days from study entry to start of treatment.
Timepoint [2] 265336 0
End of Study
Secondary outcome [3] 265337 0
The usage of antibiotics over the course of the study measured as total days usage, total number of courses, and number of acute exacerbation events requiring three or more course of antibiotics.
Timepoint [3] 265337 0
End of Study
Secondary outcome [4] 265338 0
Use of oral/parenteral corticosteroid therapy for COPD exacerbations as measured by total number of courses and total number of days of usage since study entry.
Timepoint [4] 265338 0
End of Study
Secondary outcome [5] 265339 0
Total number of acute COPD exacerbations defined as mild, moderate or severe. Acute COPD exacerbations are defined as sustained (2 days or more) worsening or new onset of respiratory symptoms, particularly cough, purulent sputum, and breathlessness, from steady state and beyond normal day to day variation that is acute in onset and necessitates a change in medication. Severity of exacerbations are based on the GOLD COPD classification of severity.
Timepoint [5] 265339 0
End of Study
Secondary outcome [6] 265340 0
Proportion of participants having recurrent (more than one) COPD exacerbation. Acute exacerbations will be considered distinct events if onset dates are 7 or more days after resolution of symptoms defining the previous exacerbation.
Timepoint [6] 265340 0
End of Study
Secondary outcome [7] 265341 0
Severity of acute exacerbations (mild, moderate or severe) based on the GOLD COPD classification system.
Timepoint [7] 265341 0
End of Study
Secondary outcome [8] 265342 0
Duration of acute COPD exacerbations in number of days from onset until resolution of symptoms.
Timepoint [8] 265342 0
End of Study
Secondary outcome [9] 265343 0
The duration in number of days of moderate and severe COPD exacerbations
Timepoint [9] 265343 0
End of Study
Secondary outcome [10] 265344 0
The number and duration of hospitalisations. Measured as total number of hospitalisations since study entry, total number of days per hospitalisaion and total number of days hospitalisation since study entry.
Timepoint [10] 265344 0
End of Study
Secondary outcome [11] 265345 0
Total number of unscheduled visits to a physician and to the emergency department due to a COPD exacerbation since study entry.
Timepoint [11] 265345 0
End of Study
Secondary outcome [12] 265346 0
Change in forced expiratory volume (FEV1) in one second from study entry based on spirometry (lung function test) measurement at each study visit.
Timepoint [12] 265346 0
End of Study
Secondary outcome [13] 265347 0
Change in quality of life based on the St George's Respiratory Questionnaire for COPD patients.
Timepoint [13] 265347 0
End of Study
Secondary outcome [14] 265348 0
Safety of HI-164OV based on adverse events (e.g. nausea diarrhoea), vital signs (blood pressure, pulse, respiration rate), ECG and laboratory results.
Unsolicited adverse events will be recorded at each study visit and the relationship to study medication determined by the investigator.
Timepoint [14] 265348 0
End of Study

Eligibility
Key inclusion criteria
1. 40 to 85 years of age.

2. History of 1 moderate or severe acute COPD exacerbation in the previous 12 months

3. An established diagnosis of COPD and severity status of moderate to severe defined by a post bronchodilator FEV1 <60% of predicted value and post-bronchodilator FEV1/FVC < 0.7.

4. Willingness and ability to give signed informed consent.
Minimum age
40 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Planned or previous lung transplantation, lung volume reduction surgery, or other lung surgery for emphysema.

2. A primary diagnosis of bronchiectasis.

3. Current respiratory disorders other than COPD (e.g., lung cancer, sarcoidosis, tuberculosis, restrictive lung disease/benign tumours).

4. History of asthma as primary diagnosis as an adult.

5. Unresolved acute COPD exacerbation.

6. 6. Oral/parenteral corticosteroids in excess of 10 mg/day, or antibiotics taken for all acute conditions (including acute exacerbations of COPD), within four weeks of the scheduled first dose of study medication. This does not apply to background antibiotic maintenance therapy.

7. New therapy or a change in dose of existing therapy for COPD, including, but not limited to, inhaled bronchodilators and inhaled corticosteroids, started within 4 weeks prior to the first dose of study medication.

8. Participation in a clinical trial of any other vaccine, drug, or immune stimulating agent within three months of screening and for the duration of the study.

9. History of systemic immunosuppressive therapy (including systemic corticosteroids at an equivalent prednisone dose of >10 mg/day) within 4 weeks prior to randomisation.

10. Women who are pregnant, breast-feeding, or of child-bearing potential without effective contraception.

11. Any significant medical disorder which would preclude evaluation of the participant's condition. Participants with impaired hepatic function defined as raised liver function tests greater than 2.5 times upper limit of normal range.

13. Participants with impaired renal function defined as serum creatinine > 177 umol/L.

13. Cancer within the previous five years (except for non-melanomatous skin cancer and non-invasive cervical cancer).

14. Life expectancy of less than 1 year.

15. Participants with lactose intolerance.

16. Any other medical or social reason the Investigator feels justifies exclusion of the participant, including being likely to withdraw, not comply or be able to understand the protocol requirements.

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)
Participants may be included in the study only if they meet all of the inclusion criteria and none of the exclusion criteria.

Participants will be randomly allocated to receive either active treatment with HI-164OV or matching placebo in a 1:1 ratio. Allocation will be concealed. Participants will be allocated the next sequential pack number at the study site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation sequences will be computer generated in a 1:1 ratio to either HI-164OV or matched placebo, and blocks of study medication allocated to study sites.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Not applicable.
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/11/2010
Actual
12/01/2011
Date of last participant enrolment
Anticipated
Actual
31/05/2011
Date of last data collection
Anticipated
Actual
17/02/2012
Sample size
Target
340
Accrual to date
Final
332
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 3371 0
2305
Recruitment postcode(s) [2] 3372 0
2010
Recruitment postcode(s) [3] 3373 0
2037
Recruitment postcode(s) [4] 3374 0
2031
Recruitment postcode(s) [5] 3375 0
2070
Recruitment postcode(s) [6] 3376 0
2250
Recruitment postcode(s) [7] 3377 0
2350
Recruitment postcode(s) [8] 3378 0
3084
Recruitment postcode(s) [9] 3379 0
3004
Recruitment postcode(s) [10] 3380 0
4102
Recruitment postcode(s) [11] 3381 0
4029
Recruitment postcode(s) [12] 3382 0
4032
Recruitment postcode(s) [13] 3383 0
4215
Recruitment postcode(s) [14] 3384 0
6006
Recruitment postcode(s) [15] 3385 0
6009
Recruitment postcode(s) [16] 3386 0
6160
Recruitment postcode(s) [17] 3387 0
6847
Recruitment postcode(s) [18] 3388 0
5011
Recruitment postcode(s) [19] 3389 0
5041

Funding & Sponsors
Funding source category [1] 257377 0
Commercial sector/Industry
Name [1] 257377 0
Hunter Immunology Limited
Country [1] 257377 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Hunter Immunology Limited
Address
5/8 St Andrews Street
Brighton, Victoria 3186
Country
Australia
Secondary sponsor category [1] 256619 0
None
Name [1] 256619 0
Address [1] 256619 0
Country [1] 256619 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259918 0
Ethics committee address [1] 259918 0
Ethics committee country [1] 259918 0
Australia
Date submitted for ethics approval [1] 259918 0
22/09/2010
Approval date [1] 259918 0
Ethics approval number [1] 259918 0
Ethics committee name [2] 303702 0
Hunter New England Research Ethics and Governance Unit
Ethics committee address [2] 303702 0
Ethics committee country [2] 303702 0
Australia
Date submitted for ethics approval [2] 303702 0
30/09/2010
Approval date [2] 303702 0
04/11/2010
Ethics approval number [2] 303702 0
Ethics committee name [3] 303703 0
Bellberry Human Research Ethics Committee
Ethics committee address [3] 303703 0
Ethics committee country [3] 303703 0
Australia
Date submitted for ethics approval [3] 303703 0
26/10/2010
Approval date [3] 303703 0
02/11/2010
Ethics approval number [3] 303703 0
Ethics committee name [4] 303704 0
Austin Health Human Research Ethics Committee
Ethics committee address [4] 303704 0
Ethics committee country [4] 303704 0
Australia
Date submitted for ethics approval [4] 303704 0
14/10/2010
Approval date [4] 303704 0
15/12/2010
Ethics approval number [4] 303704 0
Ethics committee name [5] 303705 0
Metro South Health Service District Human Research Ethics Committee
Ethics committee address [5] 303705 0
Ethics committee country [5] 303705 0
Australia
Date submitted for ethics approval [5] 303705 0
13/10/2010
Approval date [5] 303705 0
06/12/2010
Ethics approval number [5] 303705 0
Ethics committee name [6] 303706 0
Sir Charles Gairdner Hospital Human Research Ethics Committee
Ethics committee address [6] 303706 0
Ethics committee country [6] 303706 0
Australia
Date submitted for ethics approval [6] 303706 0
26/10/2010
Approval date [6] 303706 0
16/12/2010
Ethics approval number [6] 303706 0
Ethics committee name [7] 303707 0
Royal Perth Hospital Ethics Committee
Ethics committee address [7] 303707 0
Ethics committee country [7] 303707 0
Australia
Date submitted for ethics approval [7] 303707 0
02/11/2010
Approval date [7] 303707 0
23/11/2010
Ethics approval number [7] 303707 0
Ethics committee name [8] 303708 0
Southern Adelaide Health Service / Flinders University Human Research Ethics Committee
Ethics committee address [8] 303708 0
Ethics committee country [8] 303708 0
Australia
Date submitted for ethics approval [8] 303708 0
08/10/2010
Approval date [8] 303708 0
26/11/2010
Ethics approval number [8] 303708 0
Ethics committee name [9] 303709 0
Central Northern Adelaide Health Service Ethics of Human Research Committee (TQEH & LMH)
Ethics committee address [9] 303709 0
Ethics committee country [9] 303709 0
Australia
Date submitted for ethics approval [9] 303709 0
01/10/2010
Approval date [9] 303709 0
01/12/2010
Ethics approval number [9] 303709 0
Ethics committee name [10] 303710 0
South Metropolitan Area Health Service Human Research Ethics Committee
Ethics committee address [10] 303710 0
Ethics committee country [10] 303710 0
Australia
Date submitted for ethics approval [10] 303710 0
20/09/2010
Approval date [10] 303710 0
28/10/2010
Ethics approval number [10] 303710 0

Summary
Brief summary
The purpose of this study is to test the safety and efficacy of a new treatment for COPD, HI-164OV, in participants with moderate to severe COPD. COPD (which includes emphysema and chronic bronchitis) causes irreversible damage to the lungs and is the most common respiratory disease in Australia affecting up to 1 in 10 people over the age of 45 years. Exacerbations of symptoms often require hospitalisation and happen most often during the winter months. HI-164OV is an oral vaccine tablet that contains killed non-typeable Haemophilus influenza bacteria, which are commonly found in the sputum of COPD patients. It is hoped that HI-164OV may help reduce the severity, duration and rate of exacerbations in COPD patients.

The study is a multi-centre, placebo controlled, randomised, double blind study that will occur over 12 months. It is anticipated that 340 participants, aged 40-85 years, will be randomised in a 1:1 ratio to receive either HI-164OV or placebo. Participants will be asked to take the study medication on three consecutive days each month for the first three months (ie. nine doses in total). Each daily dose of HI-164OV contains 90 mg of HI-164 or placebo. Participants will be asked to attend seven study visits over a nine month period, approximately, for safety and efficacy assessments. Participants will be asked to keep a daily diary during the study to record COPD exacerbation details.

Safety will be assessed by collecting data on adverse events, routine clinical laboratory
measurements (haematology, biochemistry and sputum), cardio-thoracic physical examination, ECG and vital signs.

The efficacy of HI-164OV in reducing the rate and severity of exacerbations in comparison to placebo will be determined by measuring:
1. number of moderate to severe acute COPD exacerbations
2. number of days of antibiotic usage
3. duration of acute exacerbations
4. duration of moderate and severe exacerbations
5. hospitalisations
6. quality of life (using the validated St George’s Respiratory Questionnaire-C)
Trial website
Not applicable
Trial related presentations / publications
Unknown
Public notes

Contacts
Principal investigator
Name 31462 0
Address 31462 0
Country 31462 0
Phone 31462 0
Fax 31462 0
Email 31462 0
Contact person for public queries
Name 14709 0
Margaret Dunkley
Address 14709 0
Level 4 David Maddison Building
Crn King and Watts St
University of Newcastle
Callaghan
NSW 2308
Country 14709 0
Australia
Phone 14709 0
+61 2 4913 8581
Fax 14709 0
Email 14709 0
[email protected]
Contact person for scientific queries
Name 5637 0
Margaret Dunkley
Address 5637 0
Level 4 David Maddison Building
Crn King and Watts St
University of Newcastle
Callaghan
NSW 2308
Country 5637 0
Australia
Phone 5637 0
+61 2 4913 8581
Fax 5637 0
Email 5637 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


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.