Clinical trial NCT01362244
Conditions: Nasal Polyps
Keywords: Quality of Life Intranasal Steroids Severe Nasal Polyposis Polyp Relapse Endoscopic Polyp Score Surgery
Sponsor: GlaxoSmithKline
Start date: 2009-05-12; Completion date: 2014-12-05
Enrollment: 109 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
A two-part, randomised, double-blind, placebo controlled, multi-centre study to investigate the use of mepolizumab (SB-240563) in reducing the need for surgery in subjects with severe bilateral nasal polyposis.

Detailed description:
Nasal polyposis 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. These symptoms can impact greatly upon a patient's quality of life.The etiology of nasal polyposis is currently unknown.

The aim of this present study is to investigate the use of mepolizumab in reducing the potential need for surgery in subjects with severe bilateral nasal polyposis. The study is split into two parts: Part A is the treatment phase and focuses on the reduction of the need for surgery by exploring the efficacy of six doses of mepolizumab (one dose every four weeks) on nasal polyposis. This dosing regime will build upon the previous PoC study by exploring the potential for increased clinical efficacy as assessed by the potential need for surgery, and also and increased duration of action as assessed by time to relapse. Part B is the follow-up phase and will assess post-treatment nasal polyposis dynamics with a focus on time to relapse. All subjects participating in this study will undergo a run-in period on a low dose of intranasal steroids (INS) prior to first dosing. INS will be continued throughout the study up until study exit. This is to reflect the real life circumstances in which mepolizumab is intended to be used as a therapy. The overall aim of the study design is to further assess the impact in the potential need for surgery and explore an appropriate mepolizumab therapeutic regimen strategy for the treatment of nasal polyposis.

In this study, the assessment of nasal polyposis will be performed by means of combining endoscopic polyp score with subject reported symptoms. This approach reflects real-life clinical assessment of nasal polyposis. Also, this study incorporates condition specific and general medical questionnaires in order to obtain a better understanding of the impact of severe nasal polyposis of the subject's quality of life (QOL). This is in line with increasing focus in the medical field on the effects of medical conditions and treatments on the quality of life of patients (Fokkens et al 2007).

Arms: arm 1: Part A comprises eight outpatient visits (Visits 1 - 8). For six of these visits, subjects will receive a dose of either 750 mg mepolizumab or placebo. Dosing occurs in four week intervals. Assessment for entry into Part B will take place at the last visit in Part A (Visit 8). Subjects not eligible for Part B will have study exit procedures performed and be discontinued. arm 2: 10-14 day run in period to assess the patients suitability for entry into Part A of the trial. arm 3: Subjects eligible for Part B will attend the clinic for up to 5 more outpatient visits (Visits 9 - 13) for assessments. Visits occur every four weeks. There is no dosing in Part B. At the point when each subject meets Study Exit criteria, study exit procedures will be performed and the subject will exit the study.
Interventions: intervention 1: Mepolizumab intervention 2: Placebo intervention 3: Run In Medication
Intervention descriptions: intervention 1: 750 mg of mepolizumab by IV infusion intervention 2: Placebo by IV infusion intervention 3: subjects will undergo a run-in period of 10 - 14 days on a low dose of Intranasal Steroids (INS).

Protocol documents: