A Randomised, Double-blind, Placebo Controlled, Parallel Group Phase III Study to Assess the Clinical Efficacy and Safety of 100 mg SC Mepolizumab in Adults With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) / Eosinophilic Chronic Rhinosinusitis (ECRS) MERIT: Mepolizumab in Eosinophilic Chronic RhinosinusITis Study
Overview
- Phase
- Phase 3
- Intervention
- Mepolizumab
- Conditions
- Nasal Polyps
- Sponsor
- GlaxoSmithKline
- Enrollment
- 169
- Locations
- 1
- Primary Endpoint
- Mean Change From Baseline in Total Endoscopic Nasal Polyps (NP) Score at Week 52 - ITT Population Excluding Medipharma Managed Sites
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a randomized, double blind, placebo controlled, parallel group phase III study designed to assess the clinical efficacy and safety of 100 milligrams (mg) subcutaneous (SC) mepolizumab treatment in adults with CRSwNP/ECRS for the purpose of registration in Japan and China. Approximately 160 participants will be randomized in a 1:1 ratio to receive either 100 mg SC mepolizumab or placebo SC. The study will include a 4-week run-in period followed by randomization to a 52-week treatment period, where participants will be administered 4-weekly doses of mepolizumab or placebo via a pre-filled safety syringe device (SSD) injection.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants of 18 years of age and older inclusive, at the time of signing the informed consent.
- •Body weight greater than or equal to 40 kilograms (kg).
- •Male or female participants (with appropriate contraceptive methods) to be eligible for entry into the study.
- •Female participant is eligible to participate if she is not pregnant or breastfeeding, one of the following conditions applies:
- •Is a woman of non- childbearing potential (WONCBP) : or
- •Is a woman of child bearing potential (WOCBP) and using a contraceptive method that is highly effective \[with a failure rate of less than (\<)1percent (%) per year\], preferably with low user dependency, during the study intervention period and for at least 105 days after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (for example \[e.g.\] noncompliance, recently initiated) in relationship to the first dose of study intervention.
- •A WOCBP must have a negative highly sensitive urine pregnancy test within 24 hours before the first dose of study intervention.
- •If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
- •The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
- •A documented blood eosinophil count of over 2% in the 12 months prior to Visit 0 or through a blood sample taken between Visit 0 and Visit
Exclusion Criteria
- •As a result of medical interview, physical examination, or screening investigation the physician responsible considers the participant unfit for the study. (e.g. symptomatic herpes zoster within 3 months prior to screening, evidence of tuberculosis \[TB\] active or latent).
- •Cystic fibrosis
- •Eosinophilic granulomatosis with polyangiitis (also known as Churg Strauss syndrome), Young's, Kartagener's or dyskinetic ciliary syndromes.
- •Antrochoanal polyps.
- •Severe nasal septal deviation preventing full assesment of nasal polyps in both nostrils.
- •Acute sinusitis or upper respiratory tract 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 to Visit
- •Participants where NP surgery is contraindicated in the opinion of the Investigator.
Arms & Interventions
Participants receiving mepolizumab + Standard of care (SoC)
Participants will receive one dose of 100 mg mepolizumab SC on top of SoC every 4 weeks during the 52-week treatment period.
Intervention: Mepolizumab
Participants receiving mepolizumab + Standard of care (SoC)
Participants will receive one dose of 100 mg mepolizumab SC on top of SoC every 4 weeks during the 52-week treatment period.
Intervention: Standard of care
Participants receiving placebo + SoC
Participants will receive one dose of placebo via SC route on top of SoC, every 4 weeks during the 52-week treatment period.
Intervention: Placebo
Participants receiving placebo + SoC
Participants will receive one dose of placebo via SC route on top of SoC, every 4 weeks during the 52-week treatment period.
Intervention: Standard of care
Outcomes
Primary Outcomes
Mean Change From Baseline in Total Endoscopic Nasal Polyps (NP) Score at Week 52 - ITT Population Excluding Medipharma Managed Sites
Time Frame: Baseline (Day 1) up to week 52
Total endoscopic nasal polyp score is collected at clinical visits. 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 (calculated by summing the scores \[0 to 4\] in each nostril), higher scores indicate worse status. Baseline was defined as Day 1 value. Change from Baseline = Post-baseline value minus Baseline value.
Mean Change From Baseline in Total Endoscopic NP Score at Week 52 - Intent-to-Treat (ITT) Population
Time Frame: Baseline (Day 1) up to Week 52
Total endoscopic nasal polyp score is collected at clinical visits. The assessments were performed by central video image recordings of nasal endoscopy (NE). 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 (calculated by summing the scores \[0 to 4\] in each nostril), "0" score represents better status while "8" represents worse status. Baseline was defined as last value prior to first dose (Day 1). Change from Baseline = Post-baseline value minus Baseline value.
Mean Change From Baseline in Mean Nasal Obstruction Visual Analogue Scale (VAS) Score During the 4 Weeks Prior to Week 52 - ITT Population Excluding Medipharma Managed Sites
Time Frame: Baseline (Day 1) up to 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 (none) and 10 (worst), with higher scores indicating greater disease severity. 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.
Mean Change From Baseline in Mean Nasal Obstruction VAS Score During the 4 Weeks Prior to Week 52 - ITT Population
Time Frame: Baseline (Day 1) up to 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 dividing by 10. The final nasal obstruction VAS score ranged between 0 and 10, with higher scores indicating greater disease severity. 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.
Secondary Outcomes
- Mean Change From Baseline in Mean Overall VAS Symptom Score During the 4 Weeks Prior to Week 52 - ITT Population Excluding Medipharma Managed Sites(Baseline (Day 1) up to 4 weeks prior to week 52)
- Mean Change From Baseline in Mean Overall VAS Symptom Score During the 4 Weeks Prior to Week 52 - ITT Population(Baseline (Day 1) up to 4 weeks prior to week 52)
- Mean Change From Baseline in Lund Mackay (LMK) Computed Tomography (CT) Score at Week 52 - ITT Population Excluding Medipharma Managed Sites(Baseline (Day 1) and Week 52)
- Mean Change From Baseline in LMK CT Score at Week 52 - ITT Population(Baseline (Day 1) and Week 52)
- Mean Change From Baseline in the Mean 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 - ITT Population Excluding Medipharma Managed Sites(Baseline (Day 1) up to 4 weeks prior to week 52)
- Mean Change From Baseline in the Mean 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 - ITT Population(Baseline (Day 1) up to 4 weeks prior to week 52)
- Mean Change From Baseline in Sino-nasal Outcome Test (SNOT)-22 Total Score at Week 52 - ITT Population Excluding Medipharma Managed Sites(Baseline (Day 1) up to Week 52)
- Mean Change From Baseline in Sino-nasal Outcome Test (SNOT)-22 Total Score at Week 52 - ITT Population(Baseline (Day 1) up to Week 52)
- Mean Change From Baseline in Mean Individual VAS Symptom Score for Loss of Smell During the 4 Weeks Prior to Week 52 - ITT Population Excluding Medipharma Managed Sites(Baseline (Day 1) up to 4 weeks prior to week 52)
- Change From Baseline in Mean Individual VAS Symptom Score for Loss of Smell During the 4 Weeks Prior to Week 52 - ITT Population(Baseline (Day 1) up to 4 weeks prior to week 52)
- Percentage of Participants With Nasal Surgery or Systemic Corticosteroids (CS) for Chronic Rhinosinusitis With Nasal Polyposis/Eosinophilic Chronic Rhinosinusitis (CRSwNP/ECRS) Over Time- ITT Population Excluding Medipharma Managed Sites(At Week 8, 16, 24, 32, 40, 48 and Week 52)
- Percentage of Participants With Nasal Surgery or Course of Systemic CS for CRSwNP/ECRS up to Week 52 - ITT Population(At Week 8, 16, 24, 32, 40, 48 and Week 52)