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Trial record 1 of 1 for:    NCT03085797
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Effect of Mepolizumab in Severe Bilateral Nasal Polyps

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ClinicalTrials.gov Identifier: NCT03085797
Recruitment Status : Completed
First Posted : March 21, 2017
Results First Posted : December 17, 2020
Last Update Posted : August 3, 2021
Sponsor:
Collaborators:
CRF health
Bristol-Myers Squibb
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE March 15, 2017
First Posted Date  ICMJE March 21, 2017
Results First Submitted Date  ICMJE November 20, 2020
Results First Posted Date  ICMJE December 17, 2020
Last Update Posted Date August 3, 2021
Actual Study Start Date  ICMJE May 25, 2017
Actual Primary Completion Date December 11, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 20, 2020)
  • Change From Baseline in Total Endoscopic Nasal Polyps Score at Week 52 [ Time Frame: Baseline (Day 1) and 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.
  • Change From Baseline in Nasal Obstruction Visual Analog Scale (VAS) Score During the 4 Weeks Prior to Week 52 [ Time Frame: Baseline and Weeks 49 to 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 15, 2017)
  • Change from Baseline in total endoscopic NP score at Week 52 [ Time Frame: Baseline and 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).
  • Change from Baseline in mean nasal obstruction visual analogue scale (VAS) score during the 4 weeks prior to Week 52 [ Time Frame: Baseline and up 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2020)
  • Percentage of Participants With Nasal Surgery Over Time [ Time Frame: Weeks 8, 16, 24, 32, 40, 48 and 52 ]
    The percentage of participants with nasal surgery over time (by Weeks 8, 16, 24, 32, 40, 48 and 52) was derived from Kaplan-Meier time-to-event analyses for the event 'first nasal surgery'. Nasal surgery was defined as any procedure involving instruments resulting in incision and removal of tissue (polypectomy) in the nasal cavity. Time to first nasal surgery was defined as (Date of first nasal surgery - Date of first dose of study treatment) + 1. Percentage of participants with nasal surgery over time (by Weeks 8, 16, 24, 32, 40, 48 and 52) and corresponding 95% CI have been presented, calculated using the Kaplan-Meier method. Analysis included surgeries occurring up to Week 52, reported on-treatment and those reported after early discontinuation from IP by participants who remained in the study.
  • Change From Baseline in Overall VAS Score During the 4 Weeks Prior to Week 52 [ Time Frame: Baseline and Weeks 49 to 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 using an 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 overall 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.
  • Change From Baseline in Sino-nasal Outcome Test (SNOT)-22 Total Score at Week 52 [ Time Frame: Baseline (Day 1) and Week 52 ]
    The SNOT-22 is a 22-item self-reported questionnaire developed to measure symptoms and impacts related to chronic rhinosinusitis. The 22 questions are self-completed by participants based on their recall of their symptoms over the previous 2 weeks using a 6-point rating scale (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"). Scores for each question are summed to derive the total score. The SNOT-22 total score ranges from 0 to 110, with higher scores representing worse quality of life. 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.
  • Percentage of Participants Requiring at Least One Course of Systemic Steroids for Nasal Polyps up to Week 52 [ Time Frame: Up to Week 52 ]
    The number of courses of systemic steroids received by participants were recorded. For the purpose of this study, a course of systemic corticosteroid separated by less than 7 days was considered as a continuation of the same course. Percentage of participants requiring at least one course of systemic steroids for nasal polyps up to Week 52 is presented. Data up to Week 52, including from participants who remained in the study after early discontinuation from IP, were included in analysis.
  • 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 [ Time Frame: Baseline and Weeks 49 to 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 using an eDiary. Captured scores ranged between 0 (none) and 100 (as bad as you can imagine), final scores derived from electronically captured scores by dividing by 10. The composite VAS score was calculated as average of individual scores of nasal obstruction, nasal discharge, mucus in the throat and loss of smell and 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.
  • Change From Baseline in Individual VAS Symptom Score: Loss of Smell During the 4 Weeks Prior to Week 52 [ Time Frame: Baseline and Weeks 49 to 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 using an 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 loss of smell 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 15, 2017)
  • Time to first nasal surgery up to Week 52 [ Time Frame: 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.
  • Change from Baseline in mean overall VAS symptom score during the 4 weeks prior to Week 52 [ Time Frame: Baseline and up 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.
  • Change From Baseline in Sino-nasal Outcome Test (SNOT)-22 Total Score at Week 52 [ Time Frame: Baseline and 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.
  • Number of mgs per year of prednisolone-equivalent OCS dose up to Week 52 [ Time Frame: 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Mepolizumab in Severe Bilateral Nasal Polyps
Official Title  ICMJE 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)
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Nasal Polyps
Intervention  ICMJE
  • Drug: 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.
  • Drug: Placebo
    Placebo is a clear to opalescent, colorless sterile solution for SC injection in a single-use, safety syringe.
  • Drug: 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).
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Mepolizumab
    • Drug: 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.
    Interventions:
    • Drug: Placebo
    • Drug: Mometasone furoate
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 20, 2020)
414
Original Estimated Enrollment  ICMJE
 (submitted: March 15, 2017)
400
Actual Study Completion Date  ICMJE December 11, 2019
Actual Primary Completion Date December 11, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Canada,   Germany,   Korea, Republic of,   Netherlands,   Romania,   Russian Federation,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03085797
Other Study ID Numbers  ICMJE 205687
2016-004255-70 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study is available via the Clinical Study Data Request site
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (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.
URL: https://clinicalstudydatarequest.com/Posting.aspx?ID=20845
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE
  • CRF health
  • Bristol-Myers Squibb
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP