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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
3/08/2021

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 Nasal Polyps Score at Week 52
Timepoint [1] 0 0
Baseline (Day 1) and Week 52
Primary outcome [2] 0 0
Change From Baseline in Nasal Obstruction Visual Analog Scale (VAS) Score During the 4 Weeks Prior to Week 52
Timepoint [2] 0 0
Baseline and Weeks 49 to 52
Secondary outcome [1] 0 0
Percentage of Participants With Nasal Surgery Over Time
Timepoint [1] 0 0
Weeks 8, 16, 24, 32, 40, 48 and 52
Secondary outcome [2] 0 0
Change From Baseline in Overall VAS Score During the 4 Weeks Prior to Week 52
Timepoint [2] 0 0
Baseline and Weeks 49 to 52
Secondary outcome [3] 0 0
Change From Baseline in Sino-nasal Outcome Test (SNOT)-22 Total Score at Week 52
Timepoint [3] 0 0
Baseline (Day 1) and Week 52
Secondary outcome [4] 0 0
Percentage of Participants Requiring at Least One Course of Systemic Steroids for Nasal Polyps up to Week 52
Timepoint [4] 0 0
Up to Week 52
Secondary outcome [5] 0 0
Change From Baseline in the Composite VAS Score (Combining VAS Scores for Nasal Obstruction, Nasal Discharge, Mucus in the Throat and Loss of Smell) During the 4 Weeks Prior to Week 52
Timepoint [5] 0 0
Baseline and Weeks 49 to 52
Secondary outcome [6] 0 0
Change From Baseline in Individual VAS Symptom Score: Loss of Smell During the 4 Weeks Prior to Week 52
Timepoint [6] 0 0
Baseline and Weeks 49 to 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
Sex
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
25/05/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
11/12/2019
Sample size
Target
Accrual to date
Final
414
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
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
State/province [2] 0 0
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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United States of America
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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 Jersey
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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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Pennsylvania
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South Carolina
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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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Argentina
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Santa Fe
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Argentina
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Ciudad Autonoma de Buenos Aires
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Argentina
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Ciudad Autónoma de Buenos Aires
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Argentina
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Mendoza
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Argentina
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San Miguel de Tucumán
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Canada
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British Columbia
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Canada
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Ontario
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Canada
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Quebec
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Canada
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Saskatchewan
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Canada
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Québec
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Germany
State/province [33] 0 0
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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Germany
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Nordrhein-Westfalen
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Germany
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Sachsen
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Germany
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Schleswig-Holstein
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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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Korea, Republic of
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Seongnam-si Gyeonggi-do
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Korea, Republic of
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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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Russian Federation
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Saint-Petersburg
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Russian Federation
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St. Petersburg
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Russian Federation
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Yaroslavl
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Sweden
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Göteborg
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Sweden
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Helsingborg
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Sweden
State/province [55] 0 0
Lund
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Sweden
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Stockholm
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United Kingdom
State/province [57] 0 0
Durham
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United Kingdom
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Merseyside
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United Kingdom
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London
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United Kingdom
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Manchester
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United Kingdom
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Newcastle upon Tyne
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United Kingdom
State/province [62] 0 0
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/study/NCT03085797
Trial related presentations / publications
Han JK, Bachert C, Fokkens W, Desrosiers M, Wagenmann M, Lee SE, Smith SG, Martin N, Mayer B, Yancey SW, Sousa AR, Chan R, Hopkins C; SYNAPSE study investigators. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2021 Oct;9(10):1141-1153. doi: 10.1016/S2213-2600(21)00097-7. Epub 2021 Apr 16.
Bachert C, Sousa AR, Han JK, Schlosser RJ, Sowerby LJ, Hopkins C, Maspero JF, Smith SG, Kante O, Karidi-Andrioti DE, Mayer B, Chan RH, Yancey SW, Chaker AM. Mepolizumab for chronic rhinosinusitis with nasal polyps: Treatment efficacy by comorbidity and blood eosinophil count. J Allergy Clin Immunol. 2022 May;149(5):1711-1721.e6. doi: 10.1016/j.jaci.2021.10.040. Epub 2022 Jan 7.
Chong LY, Piromchai P, Sharp S, Snidvongs K, Webster KE, Philpott C, Hopkins C, Burton MJ. Biologics for chronic rhinosinusitis. Cochrane Database Syst Rev. 2021 Mar 12;3(3):CD013513. doi: 10.1002/14651858.CD013513.pub3.
Keene ON. Strategies for composite estimands in confirmatory clinical trials: Examples from trials in nasal polyps and steroid reduction. Pharm Stat. 2019 Jan;18(1):78-84. doi: 10.1002/pst.1909. Epub 2018 Oct 29.
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03085797

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
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Address 33 0
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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
[email protected]
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
[email protected]