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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03085797


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT03085797
Ethics application status
Date submitted
15/03/2017
Date registered
21/03/2017
Date last updated
13/01/2020

Titles & IDs
Public title
Effect of Mepolizumab in Severe Bilateral Nasal Polyps
Scientific title
A Randomised, Double-blind, Parallel Group PhIII Study to Assess the Clinical Efficacy and Safety of 100 mg SC Mepolizumab as an Add on to Maintenance Treatment in Adults With Severe Bilateral Nasal Polyps - SYNAPSE (StudY in NAsal Polyps Patients to Assess the Safety and Efficacy of Mepolizumab)
Secondary ID [1] 0 0
2016-004255-70
Secondary ID [2] 0 0
205687
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Nasal Polyps 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Mepolizumab
Treatment: Drugs - Placebo
Treatment: Drugs - Mometasone furoate

Experimental: Mepolizumab 100 mg SC + MF - Participants will receive total thirteen doses of 100 mg SC of mepolizumab in thigh, abdomen or upper arm every 4 weeks for 52 weeks on top of SoC which includes daily nasal spray of mometasone furoate.

Placebo Comparator: Placebo SC + MF - Participants will receive total thirteen doses of SC matching placebo in thigh, abdomen or upper arm every 4 weeks for 52 weeks on top of SoC which includes daily nasal spray of mometasone furoate.


Treatment: Drugs: Mepolizumab
Mepolizumab injection 100 mg/millilitre (mL) is a clear to opalescent, colorless to pale yellow to pale brown sterile solution for SC injection in a single-use, safety syringe.

Treatment: Drugs: Placebo
Placebo is a clear to opalescent, colorless sterile solution for SC injection in a single-use, safety syringe.

Treatment: Drugs: Mometasone furoate
All participants will receive mometasone furoate usually 400 micrograms (mcg), 2 actuations (50 mcg/actuation) in each nostril twice daily. Intolerant participants will use 200g (2 actuations [50 g/actuation] in each nostril once daily).

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from Baseline in total endoscopic NP score at Week 52 - Each nostril was assessed for polyps and graded at Week 0, 4, 8, 12, 16, 20, 24, 28, 32, 36 and 52. The grading was based on NP size and recorded as the sum of the right and left nostril scores. Total score ranges from 0 to 8; higher scores indicate worse status. Individual score ranges from 0 (no polyps) to 4 (large polyps causing almost complete congestion/ obstruction of the inferior meatus).
Timepoint [1] 0 0
Baseline and Week 52
Primary outcome [2] 0 0
Change from Baseline in mean nasal obstruction visual analogue scale (VAS) score during the 4 weeks prior to Week 52 - VAS is an instrument that measures a characteristic or attitude that is believed to range across a continuum of values and cannot easily be directly measured. The participant will be asked to indicate on a VAS (0 to 100 units on an electronic device which corresponds to 0 to 10 score) the severity of 5 nasal polyposis symptoms, one VAS for each symptom (1. nasal obstruction; 2. nasal discharge; 3. mucus in the throat; 4. loss of smell; 5. facial pain) and overall VAS symptoms score. The left hand side of the scale (0) represents "None" and the right hand side of the scale (100) represents "As bad as you can imagine". VAS will be collected daily in morning from screening up to Week 52.
Timepoint [2] 0 0
Baseline and up to Week 52
Secondary outcome [1] 0 0
Time to first nasal surgery up to Week 52 - NP surgery is defined as any procedure involving instruments resulting in incision and removal of tissue (polypectomy) or dilatation of the air passages (e.g. balloon sinuplasty) in the nasal cavity. Time to first nasal surgery up to Week 52 will be assessed.
Timepoint [1] 0 0
Up to Week 52
Secondary outcome [2] 0 0
Change from Baseline in mean overall VAS symptom score during the 4 weeks prior to Week 52 - The mean VAS score over the last 7 days before Visit 2 (Week 0) will be used to determine the Baseline value. The participant will be asked to indicate on a VAS (0 to 100 units on an electronic device which corresponds to 0 to 10 score) the severity of 5 nasal polyposis symptoms, one VAS for each symptom (1. nasal obstruction; 2. nasal discharge; 3. mucus in the throat; 4. loss of smell; 5. facial pain) and overall VAS symptoms score. The left hand side of the scale (0) represents "None" and the right hand side of the scale (100) represents "As bad as you can imagine". VAS will be collected daily in morning from screening up to Week 52.
Timepoint [2] 0 0
Baseline and up to Week 52
Secondary outcome [3] 0 0
Change from Baseline in sino-nasal outcome test (SNOT)-22 total score at Week 52 - The SNOT-22 is a health related quality of life questionnaire and has been shown to be a reliable outcome measure for successful septal surgery and in chronic rhinosinusitis (CRS) management. It is also a tool to evaluate outcomes in nasal polyposis. Participants will be asked to rate the severity of their condition on each of the 22 items over the previous 2 weeks using a 6-point rating scale of 0-5 including: 0 = Not present/no problem; 1 = Very mild problem; 2 = Mild or slight problem; 3 = Moderate problem; 4 = Severe problem; 5 = Problem as "bad as it can be". The theoretical total score range for the SNOT-22 is 0-110, where lower scores imply less severe symptoms and higher scores representing a worse quality of life. The SNOT-22 questionnaire will be completed by participants at Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36 and 52.
Timepoint [3] 0 0
Baseline and Week 52
Secondary outcome [4] 0 0
Number of mgs per year of prednisolone-equivalent OCS dose up to Week 52 - The number of courses of systemic steroids and OCS as well as the dose and duration of the courses will be recorded. The dose for a course of OCS will be according to the participants SoC for OCS use for its NP condition. A course of systemic corticosteroid is considered continuous if treatment is separated by less than 7 days. Various doses of intravenous and oral steroids will be converted to prednisolone-equivalent OCS.
Timepoint [4] 0 0
Up to Week 52

Eligibility
Key inclusion criteria
Inclusion Criteria

- 18 years of age and older inclusive, at the time of signing the informed consent.

- Body weight greater or equal to 40 kilogram (kg).

- Male or female participants (with appropriate contraceptive methods) to be eligible
for entry into the study. To be eligible for entry into the study, woman of
childbearing potential (WOCBP) must commit to consistent and correct use of an
acceptable method of birth control from the time of consent, for the duration of the
trial, and for 105 days after last study drug administration.

- Participants who have had at least one previous surgery in the previous 10 years for
the removal of NP. NP Surgery is defined as any procedure involving instruments with
resulting incision (cutting open) and removal of polyp tissue from the nasal cavity
(polypectomy). For the purpose of inclusion into this study, any procedure involving
instrumentation in the nasal cavity resulting in dilatation of the nasal passage such
as balloon sinuplasty, insertion of coated stents or direct injection of steroids or
other medication without any removal of NP tissue is not accepted.

- Participants with bilateral NP as diagnosed by endoscopy or computed tomography (CT)
scan.

- Presence of at least two of the following symptoms one of which should be either nasal
blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip) and
either nasal discharge (anterior/posterior nasal drip); facial pain/pressure;
reduction or loss of smell for at least 12 weeks prior to screening.

- Participants with severe NP symptoms defined as an obstruction VAS symptom score of
>5.

- Severity consistent with a need for surgery as described by:

1. Participants with an overall VAS symptom score >7,

2. Participants with an endoscopic bilateral NP score of at least 5 out of a maximum
score of 8 (with a minimum score of 2 in each nasal cavity).

- Treatment with intranasal corticosteroids (INCS) for at least 8 weeks prior to
screening.

- Capable of giving signed informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

- As a result of medical interview, physical examination, or screening investigation,
the physician responsible considers the participant unfit for the study.

- Cystic fibrosis

- Eosinophilic granulomatosis with polyangiitis (also known as churg strauss syndrome),
young's, kartagener's or dyskinetic ciliary syndromes.

- Antrochoanal polyps

- Nasal septal deviation occluding one nostril

- Acute sinusitis or upper respiratory track infection (URTI) at screening or in 2 weeks
prior to screening

- Ongoing rhinitis medicamentosa (rebound or chemical induced rhinitis)

- Participants who have had an asthma exacerbation requiring admission to hospital
within 4 weeks of Screening.

- Participants who have undergone any intranasal and/or sinus surgery (for example
polypectomy, balloon dilatation or nasal stent insertion) within 6 months prior Visit
1.

- Participants where NP surgery is contraindicated in the opinion of the Investigator.

- Participants with a known medical history of human immunodeficiency virus (HIV)
infection.

- Participants with a known, pre-existing parasitic infestation within 6 months prior to
Visit 1.

- Participants who are currently receiving, or have received within 3 months (or 5 half
lives - whatever is the longest) prior to first mepolizumab dose, chemotherapy,
radiotherapy or investigational medications/therapies.

- Participants with a history of sensitivity to any of the study medications, or
components thereof or a history of drug or other allergy that, in the opinion of the
investigator or GSK medical monitor, contraindicates their participation.
Aspirin-sensitive participants are acceptable.

- Participants with a history of allergic reaction to anti-IL-5 or other monoclonal
antibody therapy.

- Participants on a waiting list for NP surgery while at screening

- Participants that have taken part in previous mepolizumab, reslizumab, dupilumab or
benralizumab studies.

- Use of systemic corticosteroids (including oral corticosteroids) or corticosteroid
nasal solution (intranasal corticosteroid is accepted) within 4 weeks prior to
Screening or planned use of such medications during the double-blind period.

- INCS dose changes within 1 month prior to screening.

- Treatments with biological or immunosuppressive treatment (other than omalizumab)
treatment within 5 terminal phase half lives of Visit 1.

- Omalizumab treatment in the 130 days prior to Visit 1.

- Commencement of leukotriene antagonist treatment less than 30 days prior to Visit 1.

- Allergen immunotherapy within the previous 3 months.

- Women who are pregnant or lactating or are planning on becoming pregnant during the
study.

- Participants who currently smoke or have smoked in the last 6 months.

- Any participant who is considered unlikely to survive the duration of the study period
or has any rapidly progressing disease or immediate life-threatening illness (e.g.
cancer). In addition, any participant who has any other condition (e.g. neurological
condition) that is likely to affect respiratory function should not be included in the
study.

- Participants who have known, pre-existing, clinically significant endocrine,
autoimmune, cardiovascular, metabolic, neurological, renal, gastrointestinal, hepatic,
hematological or any other system abnormalities that are uncontrolled with standard
treatment.

- Immunocompromized, other than that explained by the use of corticosteroids taken as
therapy.

- A current malignancy or previous history of cancer in remission for less than 12
months prior to Screening. Participants with successfully treated basal cell
carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ, with no
evidence of recurrence may participate in the study.

- Current active liver or biliary disease (with the exception of gilbert's syndrome or
asymptomatic gallstones or otherwise stable chronic liver disease per investigator
assessment).

- Corrected QT interval (QTc) >450 milliseconds (msec) or QTc >480 msec in participants
with bundle branch block at visit 1.

- A known or suspected history of alcohol or drug abuse within 2 years prior to
Screening (Visit 1) that in the opinion of the investigator would prevent the
participant from completing the study procedures.

- An investigator, sub-investigator, study coordinator, employee of a participating
investigator or study site, or immediate family member of the aforementioned that is
involved in this study.

- In the opinion of the investigator, any participant who is unable to read and/or would
not be able to complete a questionnaire.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
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)
NSW,VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Darlinghurst
Recruitment hospital [2] 0 0
GSK Investigational Site - Westmead
Recruitment hospital [3] 0 0
GSK Investigational Site - Clayton
Recruitment hospital [4] 0 0
GSK Investigational Site - Melbourne
Recruitment hospital [5] 0 0
GSK Investigational Site - Murdoch
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
3169 - Clayton
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
6150 - Murdoch
Recruitment outside Australia
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United States of America
State/province [1] 0 0
Alabama
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California
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Colorado
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Florida
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Idaho
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Illinois
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Iowa
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Kentucky
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Louisiana
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Maryland
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Missouri
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New York
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North Carolina
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Oklahoma
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Oregon
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Texas
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Utah
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Virginia
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Argentina
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Buenos Aires
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Santa Fe
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Argentina
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Ciudad Autónoma de Buenos Aires
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Mendoza
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Argentina
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San Miguel de Tucumán
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Ontario
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Saskatchewan
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Canada
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Québec
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Germany
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Baden-Wuerttemberg
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Germany
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Bayern
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Germany
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Hessen
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Nordrhein-Westfalen
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Germany
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Germany
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Berlin
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Korea, Republic of
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Incheon
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Seongnam-si, Gyeonggi-do
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Seoul
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Netherlands
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Amsterdam
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Romania
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Brasov
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Romania
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Bucuresti
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Romania
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Cluj Napoca
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Romania
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Targu Mures
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Russian Federation
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Moscow
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Russian Federation
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Saint-Peterburgh
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St. Petersburg
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Yaroslavl
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Göteborg
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Helsingborg
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Lund
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Sweden
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Stockholm
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United Kingdom
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Durham
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United Kingdom
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Merseyside
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London
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Manchester
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Newcastle upon Tyne
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United Kingdom
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Rotherham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
CRF health
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Bristol-Myers Squibb
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Nasal polyps (NP) has long been known as chronic inflammatory disease of the nasal mucosa.
This disease is characterized by the presence of polyps in the upper nasal cavity,
originating from within the ostiomeatal complex. The presence of polyps can cause long-term
symptoms such as prominent nasal obstruction, post-nasal drip, loss of smell, and discharge.

Mepolizumab (SB240563) is an Immunoglobulin G 1 [IgG1], kappa humanized monoclonal antibody
(mAB) that blocks human interleukin-5 (hIL-5) from binding to the interleukin-5 (IL-5)
receptor complex expressed on the eosinophil cell surface and thus inhibits signaling.
Neutralization of IL-5 with mepolizumab has been shown to reduce blood, sputum and tissue
eosinophils and hence is assumed to be a treatment option in a number of eosinophilic
diseases including NP.

The aim of this randomized, double-blind, parallel group, phase 3 (PhIII) study is to assess
the clinical efficacy and safety of 100 milligram (mg) subcutaneous (SC) mepolizumab as an
add on to maintenance treatment in adults with severe bilateral NP. The study will include a
4-week run in period followed by randomization to a 52-week treatment period. Participants
will receive mepolizumab 100 mg or placebo SC by the investigator or delegate via a
pre-filled safety syringe every 4 weeks for 52 weeks. Throughout the entire study period (run
in + treatment period + follow up), participants will receive a standard of care (SoC) for NP
which consists of daily mometasone furorate (MF) nasal spray, and if required, saline nasal
douching, occasional short courses of high dose oral corticosteroids (OCS) and/or
antibiotics. The treatment period will consist of thirteen, 4-weekly doses of mepolizumab or
placebo. In addition, up to the first 200 randomized participants will be followed up every
other month for up to a further 6 months after the Visit 15 (7 months post last dose) in
order to assess maintenance of response and to validate a physiological model derived from
the previous Phase 2 study. Approximately 400 participants will be randomized (200
participants per treatment arm) in to the study. Total duration of the study will be 76 weeks
for first 200 randomized participants and 52 weeks for remainder of participants who are not
participating in the 6 months no treatment follow up.
Trial website
https://clinicaltrials.gov/show/NCT03085797
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

Additional trial details provided through ANZCTR
Accrual to date
Recruiting in Australia
Recruitment state(s)
NSW,WA,VIC
Funding & Sponsors
Primary sponsor
Commercial sector/Industry
Primary sponsor name
GlaxoSmithKline
Primary sponsor address
Primary sponsor country
Australia
Ethics approval
Ethics application status
Approved
 
Public notes
Australian Investigators:
Chady Sader, TrialsWest, Western Australia, Murdoch, Australia, 6150
Andrew Gillman, Alfred Hospital, Victoria, Melbourne, Australia, 3004
Richard Harvey, Sydney Ear Nose and Throat Clinic, New South Wales, Darlinghurst, Australia, 2010
Sara Barnes, Monash Medical Centre, Victoria, Clayton, Australia, 3169
Narinder Singh, Westmead Hospital, New South Wales, Westmead, Australia, 2145

Contacts
Principal investigator
Title 33 0
Name 33 0
Address 33 0
Country 33 0
Phone 33 0
Fax 33 0
Email 33 0
Contact person for public queries
Title 34 0
Name 34 0
Address 34 0
Country 34 0
Phone 34 0
Fax 34 0
Email 34 0
GSKClinicalSupportHD@gsk.com
Contact person for scientific queries
Title 35 0
Name 35 0
Address 35 0
Country 35 0
Phone 35 0
Fax 35 0
Email 35 0
GSKClinicalSupportHD@gsk.com