Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
414 participants
INTERVENTIONAL
2017-05-25
2019-12-11
Brief Summary
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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.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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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.
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.
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).
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.
Placebo
Placebo is a clear to opalescent, colorless sterile solution for SC injection in a single-use, safety syringe.
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).
Interventions
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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.
Placebo
Placebo is a clear to opalescent, colorless sterile solution for SC injection in a single-use, safety syringe.
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).
Eligibility Criteria
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Inclusion Criteria
* 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.
Exclusion Criteria
* 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.
18 Years
ALL
No
Sponsors
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CRF Health
INDUSTRY
Bristol-Myers Squibb
INDUSTRY
GlaxoSmithKline
INDUSTRY
Responsible Party
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Principal Investigators
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GSK Clinical Trials
Role: STUDY_DIRECTOR
GlaxoSmithKline
Locations
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GSK Investigational Site
Birmingham, Alabama, United States
GSK Investigational Site
Riverside, California, United States
GSK Investigational Site
Roseville, California, United States
GSK Investigational Site
San Diego, California, United States
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Colorado Springs, Colorado, United States
GSK Investigational Site
Lake Mary, Florida, United States
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Boise, Idaho, United States
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Chicago, Illinois, United States
GSK Investigational Site
Des Moines, Iowa, United States
GSK Investigational Site
West Des Moines, Iowa, United States
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Louisville, Kentucky, United States
GSK Investigational Site
Marrero, Louisiana, United States
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White Marsh, Maryland, United States
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Columbia, Missouri, United States
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St Louis, Missouri, United States
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Piscataway, New Jersey, United States
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New York, New York, United States
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Matthews, North Carolina, United States
GSK Investigational Site
Raleigh, North Carolina, United States
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Winston-Salem, North Carolina, United States
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Oklahoma City, Oklahoma, United States
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Medford, Oregon, United States
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Bethlehem, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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Charleston, South Carolina, United States
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Orangeburg, South Carolina, United States
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Dallas, Texas, United States
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McKinney, Texas, United States
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San Antonio, Texas, United States
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North Logan, Utah, United States
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Salt Lake City, Utah, United States
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Lynchburg, Virginia, United States
GSK Investigational Site
Norfolk, Virginia, United States
GSK Investigational Site
Richmond, Virginia, United States
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
GSK Investigational Site
Florida, Buenos Aires, Argentina
GSK Investigational Site
La Plata, Buenos Aires, Argentina
GSK Investigational Site
Mar del Plata, Buenos Aires, Argentina
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Rosario, Santa Fe Province, Argentina
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Buenos Aires, , Argentina
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Buenos Aires, , Argentina
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Buenos Aires, , Argentina
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Mendoza, , Argentina
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Mendoza, , Argentina
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San Miguel de Tucumán, , Argentina
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Darlinghurst, New South Wales, Australia
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Westmead, New South Wales, Australia
GSK Investigational Site
Clayton, Victoria, Australia
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Melbourne, Victoria, Australia
GSK Investigational Site
Murdoch, Western Australia, Australia
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Vancouver, British Columbia, Canada
GSK Investigational Site
Hamilton, Ontario, Canada
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London, Ontario, Canada
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Ottawa, Ontario, Canada
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Montreal, Quebec, Canada
GSK Investigational Site
Montreal, Quebec, Canada
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Saskatoon, Saskatchewan, Canada
GSK Investigational Site
Québec, , Canada
GSK Investigational Site
Tübingen, Baden-Wurttemberg, Germany
GSK Investigational Site
Munich, Bavaria, Germany
GSK Investigational Site
Munich, Bavaria, Germany
GSK Investigational Site
Wiesbaden, Hesse, Germany
GSK Investigational Site
Düsseldorf, North Rhine-Westphalia, Germany
GSK Investigational Site
Münster, North Rhine-Westphalia, Germany
GSK Investigational Site
Dresden, Saxony, Germany
GSK Investigational Site
Dresden, Saxony, Germany
GSK Investigational Site
Lübeck, Schleswig-Holstein, Germany
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Berlin, , Germany
GSK Investigational Site
Amsterdam, , Netherlands
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Brasov, , Romania
GSK Investigational Site
Brasov, , Romania
GSK Investigational Site
Bucharest, , Romania
GSK Investigational Site
Cluj-Napoca, , Romania
GSK Investigational Site
Târgu Mureş, , Romania
GSK Investigational Site
Moscow, , Russia
GSK Investigational Site
Moscow, , Russia
GSK Investigational Site
Moscow, , Russia
GSK Investigational Site
Moscow, , Russia
GSK Investigational Site
Moscow, , Russia
GSK Investigational Site
Saint Petersburg, , Russia
GSK Investigational Site
Saint Petersburg, , Russia
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Saint-Peterburgh, , Russia
GSK Investigational Site
Yaroslavl, , Russia
GSK Investigational Site
Incheon, , South Korea
GSK Investigational Site
Seongnam-si Gyeonggi-do, , South Korea
GSK Investigational Site
Seoul, , South Korea
GSK Investigational Site
Seoul, , South Korea
GSK Investigational Site
Seoul, , South Korea
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Gothenburg, , Sweden
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Helsingborg, , Sweden
GSK Investigational Site
Lund, , Sweden
GSK Investigational Site
Stockholm, , Sweden
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Stockholm, , Sweden
GSK Investigational Site
Darlington, Durham, United Kingdom
GSK Investigational Site
Liverpool, Merseyside, United Kingdom
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London, , United Kingdom
GSK Investigational Site
London, , United Kingdom
GSK Investigational Site
London, , United Kingdom
GSK Investigational Site
Manchester, , United Kingdom
GSK Investigational Site
Newcastle upon Tyne, , United Kingdom
GSK Investigational Site
Rotherham, , United Kingdom
Countries
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References
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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.
Chupp G, Alobid I, Lugogo NL, Kariyawasam HH, Bourdin A, Chaker AM, Smith SG, Sousa AR, Mayer B, Chan RH, Matucci A. Mepolizumab Reduces Systemic Corticosteroid Use in Chronic Rhinosinusitis With Nasal Polyps. J Allergy Clin Immunol Pract. 2023 Nov;11(11):3504-3512.e2. doi: 10.1016/j.jaip.2023.08.015. Epub 2023 Aug 14.
Fokkens W, Trigg A, Lee SE, Chan RH, Diamant Z, Hopkins C, Howarth P, Lund V, Mayer B, Sousa AR, Yancey S, Tabberer M; SYNAPSE study group. Mepolizumab improvements in health-related quality of life and disease symptoms in a patient population with very severe chronic rhinosinusitis with nasal polyps: psychometric and efficacy analyses from the SYNAPSE study. J Patient Rep Outcomes. 2023 Jan 20;7(1):4. doi: 10.1186/s41687-023-00543-5.
Fokkens WJ, Mullol J, Kennedy D, Philpott C, Seccia V, Kern RC, Coste A, Sousa AR, Howarth PH, Benson VS, Mayer B, Yancey SW, Chan R, Gane SB. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): In-depth sinus surgery analysis. Allergy. 2023 Mar;78(3):812-821. doi: 10.1111/all.15434. Epub 2022 Jul 27.
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.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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2016-004255-70
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
205687
Identifier Type: -
Identifier Source: org_study_id
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