E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of nasal polyposis
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E.1.1.1 | Medical condition in easily understood language |
severe bilateral nasal polyps |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028756 |
E.1.2 | Term | Nasal polyps |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of 100 mg mepolizumab compared to placebo |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the impact on actual nasal surgery of 100mg mepolizumab compared to placebo
- To further evaluate the efficacy of 100mg mepolizumab compared to placebo
- To evaluate the impact on quality of life of 100mg mepolizumab
compared to placebo
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|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Participants are eligible to be included in the study only if all of the following criteria apply:
AGE
1. 18 years of age and older inclusive, at the time of signing the informed consent.
WEIGHT
2. Body weight greater or equal to 40kg.
Gender
3. 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; see Appendix 5 for definition) 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. See Appendix 5 for a listing of acceptable methods of birth control.
Previous polyps surgery
4. 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.
Current polyps diagnosis medication and need for surgery
5. Participants with bilateral NP as diagnosed by endoscopy or CT scan
6. 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
7. Participants with severe NP symptoms defined as an obstruction VAS symptom score of >5
8. Severity consistent with a need for surgery as described by:
a) Participants with an overall VAS symptom score >7
b) 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)
9. Treatment with INCS for at least 8 weeks prior to screening
INFORMED CONSENT
10. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. |
|
E.4 | Principal exclusion criteria |
Participants are excluded from the study if any of the following criteria apply:
CONCURRENT CONDITIONS/MEDICAL HISTORY
1. As a result of medical interview, physical examination, or screening investigation the physician responsible considers the participant unfit for the study.
2. Cystic fibrosis
3. Eosinophilic granulomatosis with polyangiitis (also known as Churg Strauss syndrome), Young’s, Kartagener’s or dyskinetic ciliary syndromes
4. Antrochoanal polyps
5. Nasal septal deviation occluding one nostril
6. Acute sinusitis or upper respiratory track infection (URTI) at screening or in 2 weeks prior to screening
7. Ongoing rhinitis medicamentosa (rebound or chemical induced rhinitis)
8. Participants who have had an asthma exacerbation requiring admission to hospital within 4 weeks of Screening.
9. Participants who have undergone any intranasal and/or sinus surgery (for example polypectomy, balloon dilatation or nasal stent insertion) within 6 months prior V1
10. Participants where NP surgery is contraindicated in the opinion of the Investigator
11. Participants with a known medical history of HIV infection.
12. Participants with a known, pre-existing parasitic infestation within 6 months prior to Visit 1.
13. 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.
14. 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. Aspirinsensitive
participants are acceptable.
15. Participants with a history of allergic reaction to anti-IL-5 or other monoclonal antibody therapy.
16. Participants on a waiting list for NP surgery while at screening
17. Participants that have taken part in previous mepolizumab, reslizumab, dupilumab or benralizumab studies
CONCOMITANT MEDICATIONS
18. Use of systemic corticosteroids (including oral corticosteroids) or corticosteroid nasal solution (intranasal corticosteroid is excepted) within 4 weeks prior to screening or planned use of such medications during the double-blind period
19. INCS dose changes within 1 month prior to screening.
20. Treatments with biological or immunosuppressive treatment (other than Xolair) treatment within 5 terminal phase half lives of Visit 1
21. Omalizumab (Xolair) treatment in the 130 days prior to Visit 1
22. Commencement of leukotriene antagonist treatment less than 30 days prior to Visit 1
23. Allergen immunotherapy within the previous 3 months.
Pregnancy:
24. Women who are pregnant or lactating or are planning on becoming pregnant during the study.
Smoking History:
25. Participants who currently smoke or have smoked in the last 6 months
Other Diseases/Abnormalities:
26. Any subject 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 subject who has any other condition (e.g. neurological condition) that is likely to affect respiratory function should not be included in the study.
27. Other Concurrent Medical Conditions: Participants who have known, pre-existing, clinically significant endocrine, autoimmune, cardiovascular, metabolic, neurological, renal, gastrointestinal, hepatic, haematological or any other system abnormalities that are uncontrolled with standard treatment.
28. Participants with a known, pre-existing or suspected parasitic infection within 6 months before the Screening visit.
29. Immunocompromised, other than that explained by the use of corticosteroids taken as therapy
30. A current malignancy or previous history of cancer in remission for less than 12 months prior to screening.
Note: 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.
For Exclusion criteria (point 31 to 35) please refer to the protocol P 36-37. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Change from baseline in total endoscopic NP score at Week 52
- Change from baseline in mean nasal obstruction VAS score during the 4 weeks prior to Week 52 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Time to first nasal surgery up to Week 52.
- Change from baseline in mean overall VAS symptom score during the 4 weeks prior to Week 52
- Change from baseline in SNOT-22 total score at Week 52
- Number of mgs per year of prednisolone-equivalent OCS dose up to Week 52 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Canada |
Germany |
Japan |
Korea, Republic of |
Netherlands |
Romania |
Russian Federation |
Sweden |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |