Primary:To evaluate the efficacy of 100mg mepolizumab compared to placebo.Secondary:The impact on actual nasal surgery. Further efficacy assessment. Quality of life.
ID
Source
Brief title
Condition
- Other condition
- Upper respiratory tract disorders (excl infections)
Synonym
Health condition
neuspoliepen
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Total endoscopic NP score (week 52). Nasal obstruction VAS score (week 49-52).
Secondary outcome
Time to first nasal surgery. Overall VAS symptom score. SNOT-22 total score.
Number of milligrams per year of oral corticosteroid dose.
Background summary
Mepolizumab is a fully humanized IgG antibody (IgG1, kappa) which binds to and
inhibits the ability of IL-5 to bind to the IL-5 receptor. IL-5 receptors are
primarily expressed on eosinophils. IL-5, through binding to the IL-5 receptor
is a major regulator of eosinophils resulting in accumulation in tissues and
modulation of eosinophil behavior at every stage from maturation to survival.
Mepolizumab reduces eosinophils in the periphery and in tissues.
Mepolizumab is being developed for a number of eosinophilic diseases, including
nasal polyps (NP), and has been registered as add-on treatment for severe
refractory eosinophilic asthma in adults.
This new study has been designed to assess the efficacy of mepolizumab compared
to placebo in adult participants with recurrent severe bilateral nasal polyps.
Participants must also have a history of at least one prior surgery for NP and
in need for NP surgery.
Study objective
Primary:
To evaluate the efficacy of 100mg mepolizumab compared to placebo.
Secondary:
The impact on actual nasal surgery. Further efficacy assessment. Quality of
life.
Study design
Randomized, double-blind, parallel group Phase III study. Add-on of mepolizumab
100 mg s.c. or placebo to standard of care therapy for NP. Treatment period 52
weeks. For the first 200 subjects an additional follow-up of 16 weeks is
planned.
Estimation 570 subjects screened, 400 enrolled.
Intervention
Treatment with mepolizumab or placebo.
Study burden and risks
Risk: Adverse events of mepolizumab.
Burden:
16 visits in 52 weeks. For the first 200 subjects an additional follow-up
period of 16 weeks is planned (2 additional visits).
13 SC injections with mepolizumab (approx. 1 ml).
Full physical examination: once.
Peak nasal inspiratory flow measurement: every treatment visit.
University of Pennsylvania Smell Identification Test: every treatment visit.
Nasal endoscopy: 14 visits.
Blood draws: every visit (5-15 ml blood).
Pregnancy test: every treatment visit.
ECG: 4 times.
Questionnaires: symptoms (VAS), QoL (SNOT-22), asthma symptoms (ACQ-5), health
(SF-36), work and activity (WPAI): every visit.
Electronic diary.
Optional pharmacogenetic blood test.
Huis ter Heideweg 62
Zeist 3705 LZ
NL
Huis ter Heideweg 62
Zeist 3705 LZ
NL
Listed location countries
Age
Inclusion criteria
• 18 years and above.
• Body weight >=40kg.
• Male or female participants with appropriate contraceptive methods, see protocol page 43 for details.
• >=1 previous surgery in the previous 10 years for the removal of nasal polyps (NP), see protocol page 43 for details.
• Bilateral severe NP with symptoms and a need for surgery, see protocol page 43 for details.
• Treatment with intranasal corticosteroids (including intranasal liquid steroid wash/douching) for >=8 weeks prior to screening.
Exclusion criteria
• Cystic fibrosis.
• Churg Strauss, 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.
• Intranasal and/or sinus surgery within the last 6 months.
• NP surgery is contraindicated.
• Known HIV infection.
• . Not willing to be removed from a waiting list for NP surgery or have pre-planned surgery date cancelled if randomized
• Participants that have taken part in previous mepolizumab, reslizumab, dupilumab or benralizumab studies.
• Concomitant or previous medications as mentioned on protocol page 46.
• Pregnancy or breastfeeding.
• Participants who currently smoke or have smoked in the last 6 months.
• Other diseases as mentioned on protocol page 46.
• Unstable liver disease as mentioned on protocol page 46-47.
QTc prolongation (>450 msec or QTc > 480 msec in participants with bundle branch block).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-004255-70-NL |
| CCMO | NL62289.018.17 |
| Other | www.gskclinicalstudyregister.com (reg_nr 205687), www.clinicaltrials.gov (reg_nr n.n.b.) |