Effect of Mepolizumab in Severe Bilateral Nasal Polyps
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)
2 other identifiers
interventional
414
11 countries
101
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 Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started May 2017
Typical duration for phase_3
101 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 15, 2017
CompletedFirst Posted
Study publicly available on registry
March 21, 2017
CompletedStudy Start
First participant enrolled
May 25, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 11, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
December 11, 2019
CompletedResults Posted
Study results publicly available
December 17, 2020
CompletedAugust 3, 2021
August 1, 2021
2.5 years
March 15, 2017
November 20, 2020
August 2, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Change From Baseline in Total Endoscopic Nasal Polyps Score at Week 52
Independent reviewers, blinded to treatment, reviewed image recordings of nasal endoscopies to determine total endoscopic NP score based on NP size. The right and left nostrils were scored from 0 to 4 (0 = No polyps; 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle concha; 2 = Polyps reaching below the lower border of the middle turbinate; 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle concha; and 4 = Large polyps causing complete obstruction/congestion of the inferior meatus). The total score is the sum of the right and left nostril scores and ranges from 0 to 8, higher scores indicate greater disease severity. Data up to Week 52, including from participants who remained in the study after early discontinuation from IP, were included in analysis. Baseline was defined as Day 1 value. Change from Baseline = Post-baseline value minus Baseline value.
Baseline (Day 1) and Week 52
Change From Baseline in Nasal Obstruction Visual Analog Scale (VAS) Score During the 4 Weeks Prior to Week 52
Participants rated individual (nasal obstruction, nasal discharge, mucus in the throat, loss of smell, facial pain) and overall symptoms on a visual analog scale (VAS) using an electronic diary (eDiary). Captured scores ranged between 0 (none) and 100 (as bad as you can imagine), final scores derived from the electronically captured scores by dividing by 10. The final nasal obstruction VAS score ranged between 0 and 10, with higher scores indicating greater disease severity. Data up to Week 52, including from participants who remained in the study after early discontinuation from IP, were included in analysis. The average of daily scores in 4-weekly intervals were calculated and data is presented for Weeks 49-52. Baseline was defined as the average score from the 7 days of eDiary data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value.
Baseline and Weeks 49 to 52
Secondary Outcomes (6)
Percentage of Participants With Nasal Surgery Over Time
Weeks 8, 16, 24, 32, 40, 48 and 52
Change From Baseline in Overall VAS Score During the 4 Weeks Prior to Week 52
Baseline and Weeks 49 to 52
Change From Baseline in Sino-nasal Outcome Test (SNOT)-22 Total Score at Week 52
Baseline (Day 1) and Week 52
Percentage of Participants Requiring at Least One Course of Systemic Steroids for Nasal Polyps up to Week 52
Up to Week 52
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
Baseline and Weeks 49 to 52
- +1 more secondary outcomes
Study Arms (2)
Mepolizumab 100 mg SC + MF
EXPERIMENTALParticipants 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 SC + MF
PLACEBO COMPARATORParticipants 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.
Interventions
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 is a clear to opalescent, colorless sterile solution for SC injection in a single-use, safety syringe.
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
You may qualify if:
- 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 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:
- Participants with an overall VAS symptom score \>7,
- 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.
You may not qualify if:
- 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.
- +19 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GlaxoSmithKlinelead
- CRF Healthcollaborator
- Bristol-Myers Squibbcollaborator
Study Sites (101)
GSK Investigational Site
Birmingham, Alabama, 35209, United States
GSK Investigational Site
Riverside, California, 92506, United States
GSK Investigational Site
Roseville, California, 95661, United States
GSK Investigational Site
San Diego, California, 92103, United States
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Colorado Springs, Colorado, 80907, United States
GSK Investigational Site
Lake Mary, Florida, 32746, United States
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Boise, Idaho, 83706, United States
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Chicago, Illinois, 60657, United States
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Des Moines, Iowa, 50312, United States
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West Des Moines, Iowa, 50265, United States
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Louisville, Kentucky, 40205, United States
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Marrero, Louisiana, 70072, United States
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White Marsh, Maryland, 21162, United States
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Columbia, Missouri, 65201, United States
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St Louis, Missouri, 63141, United States
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Piscataway, New Jersey, 08854, United States
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New York, New York, 10016, United States
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Matthews, North Carolina, 28105, United States
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Raleigh, North Carolina, 27607, United States
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Winston-Salem, North Carolina, 27103, United States
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Oklahoma City, Oklahoma, 73120, United States
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Medford, Oregon, 97504, United States
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Bethlehem, Pennsylvania, 18017, United States
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Pittsburgh, Pennsylvania, 15213, United States
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Charleston, South Carolina, 29425, United States
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Orangeburg, South Carolina, 29118, United States
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Dallas, Texas, 75235, United States
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McKinney, Texas, 75070, United States
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San Antonio, Texas, 78258, United States
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North Logan, Utah, 84341, United States
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Salt Lake City, Utah, 84102, United States
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Lynchburg, Virginia, 24501, United States
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Norfolk, Virginia, 23507, United States
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Richmond, Virginia, 23235, United States
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Ciudad Autonoma de Buenos Aires, Buenos Aires, C1414AIF, Argentina
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Florida, Buenos Aires, 1602, Argentina
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La Plata, Buenos Aires, 1900, Argentina
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Mar del Plata, Buenos Aires, 7600, Argentina
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Rosario, Santa Fe Province, S2000DBS, Argentina
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Buenos Aires, C1121ABE, Argentina
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Buenos Aires, C1425BEN, Argentina
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Buenos Aires, C1426ABP, Argentina
GSK Investigational Site
Mendoza, 5500, Argentina
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Mendoza, M5500CCG, Argentina
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San Miguel de Tucumán, 4000, Argentina
GSK Investigational Site
Darlinghurst, New South Wales, 2010, Australia
GSK Investigational Site
Westmead, New South Wales, 2145, Australia
GSK Investigational Site
Clayton, Victoria, 3169, Australia
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Melbourne, Victoria, 3004, Australia
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Murdoch, Western Australia, 6150, Australia
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Vancouver, British Columbia, V5Z 1M9, Canada
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Hamilton, Ontario, L8L 2X2, Canada
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London, Ontario, N6A 4V2, Canada
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Ottawa, Ontario, K1G 6C6, Canada
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Montreal, Quebec, H2X 1P1, Canada
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Montreal, Quebec, H3G 1L5, Canada
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Saskatoon, Saskatchewan, S7K 1N4, Canada
GSK Investigational Site
Québec, G1S 4L8, Canada
GSK Investigational Site
Tübingen, Baden-Wurttemberg, 72076, Germany
GSK Investigational Site
Munich, Bavaria, 81377, Germany
GSK Investigational Site
Munich, Bavaria, 81675, Germany
GSK Investigational Site
Wiesbaden, Hesse, 65183, Germany
GSK Investigational Site
Düsseldorf, North Rhine-Westphalia, 40225, Germany
GSK Investigational Site
Münster, North Rhine-Westphalia, 48149, Germany
GSK Investigational Site
Dresden, Saxony, 01139, Germany
GSK Investigational Site
Dresden, Saxony, 01307, Germany
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Lübeck, Schleswig-Holstein, 23538, Germany
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Berlin, 13353, Germany
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Amsterdam, 1105 AZ, Netherlands
GSK Investigational Site
Brasov, 500091, Romania
GSK Investigational Site
Brasov, 500283, Romania
GSK Investigational Site
Bucharest, 014452, Romania
GSK Investigational Site
Cluj-Napoca, 400015, Romania
GSK Investigational Site
Târgu Mureş, 540098, Romania
GSK Investigational Site
Moscow, 119991, Russia
GSK Investigational Site
Moscow, 123095, Russia
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Moscow, 123182, Russia
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Moscow, 127473, Russia
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Moscow, 142190, Russia
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Saint Petersburg, 190013, Russia
GSK Investigational Site
Saint Petersburg, 194356, Russia
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Saint-Peterburgh, 197022, Russia
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Yaroslavl, 150003, Russia
GSK Investigational Site
Incheon, 21565, South Korea
GSK Investigational Site
Seongnam-si Gyeonggi-do, 463-707, South Korea
GSK Investigational Site
Seoul, 03722, South Korea
GSK Investigational Site
Seoul, 06351, South Korea
GSK Investigational Site
Seoul, 06591, South Korea
GSK Investigational Site
Gothenburg, SE-413 45, Sweden
GSK Investigational Site
Helsingborg, SE-251 87, Sweden
GSK Investigational Site
Lund, SE-221 85, Sweden
GSK Investigational Site
Stockholm, SE-114 86, Sweden
GSK Investigational Site
Stockholm, SE-171 76, Sweden
GSK Investigational Site
Darlington, Durham, DL3 6HX, United Kingdom
GSK Investigational Site
Liverpool, Merseyside, L9 7AL, United Kingdom
GSK Investigational Site
London, SE1 9RT, United Kingdom
GSK Investigational Site
London, SW3 6HP, United Kingdom
GSK Investigational Site
London, WC1X 8DA, United Kingdom
GSK Investigational Site
Manchester, M23 9QZ, United Kingdom
GSK Investigational Site
Newcastle upon Tyne, NE7 7DN, United Kingdom
GSK Investigational Site
Rotherham, S60 2UD, United Kingdom
Related Publications (7)
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.
PMID: 33872587BACKGROUNDChupp 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.
PMID: 37586475DERIVEDFokkens 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.
PMID: 36662344DERIVEDFokkens 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.
PMID: 35822924DERIVEDBachert 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.
PMID: 35007624DERIVEDChong 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.
PMID: 33710614DERIVEDKeene 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.
PMID: 30370691DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- GSK Response Center
- Organization
- GlaxoSmithKline
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 15, 2017
First Posted
March 21, 2017
Study Start
May 25, 2017
Primary Completion
December 11, 2019
Study Completion
December 11, 2019
Last Updated
August 3, 2021
Results First Posted
December 17, 2020
Record last verified: 2021-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
- Access Criteria
- Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
IPD for this study is available via the Clinical Study Data Request site