Phase 3
N=407
Effect of Mepolizumab in Severe Bilateral Nasal Polyps
Nasal Polyps
Bottom Line
View on ClinicalTrials.gov: NCT03085797 ↗Enrolled (actual)
407
Serious AEs
5.9%
Results posted
Dec 2020
Primary outcome: Primary: Change From Baseline in Total Endoscopic Nasal Polyps Score at Week 52 — 0.0; -1.0 Scores on a scale — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Mepolizumab (Drug); Placebo (Drug); Mometasone furoate (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Dec 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Total Endoscopic Nasal Polyps Score at Week 52 |
0.0; -1.0 | <0.001 sig |
| PRIMARY Change From Baseline in Nasal Obstruction Visual Analog Scale (VAS) Score During the 4 Weeks Prior to Week 52 |
-0.82; -4.41 | <0.001 sig |
| SECONDARY Percentage of Participants With Nasal Surgery Over Time |
1.0; 0.5; 3.5; 1.0; 9.1; 4.0 | 0.003 sig |
| SECONDARY Change From Baseline in Overall VAS Score During the 4 Weeks Prior to Week 52 |
-0.90; -4.48 | 0.003 sig |
| SECONDARY Change From Baseline in Sino-nasal Outcome Test (SNOT)-22 Total Score at Week 52 |
-14.0; -30.0 | 0.003 sig |
| SECONDARY Percentage of Participants Requiring at Least One Course of Systemic Steroids for Nasal Polyps up to Week 52 |
37; 25 | 0.020 sig |
| SECONDARY 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 |
-0.89; -3.96 | 0.020 sig |
| SECONDARY Change From Baseline in Individual VAS Symptom Score: Loss of Smell During the 4 Weeks Prior to Week 52 |
0.00; -0.53 | 0.020 sig |
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.
Eligibility 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:
- 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.
- 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
Data sourced from ClinicalTrials.gov (NCT03085797). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.