Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ongoing, recruiting
Participants planned
75
Countries
1
Sites
11
chronic rhinosinusitis (CRS)
Primary endpoint is the improvement in quality of life, determined by sinonasal outcome test (SNOT-22) result
Key facts
- Sponsor
- Instituto De Investigacion Marques De Valdecilla
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Otorhinolaryngologic Diseases [C09]
- Trial duration
- 18 Dec 2023 → ongoing
- Decision date (initial)
- 2023-10-20
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2023-505426-34-01
- ClinicalTrials.gov
- NCT05923047
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Safety, Efficacy
Primary endpoint is the improvement in quality of life, determined by sinonasal outcome test (SNOT-22) result
Secondary objectives 6
- Change in nasal polyposis severity VAS score at V1, V6, V12.
- Change in endoscopic nasal polyp score at V1, V6, V12.
- Improvement in individual VAS symptoms (rhinorrhea, mucus in throat, nasal blockage, and sense of smell), patient-reported outcomes at V1, V6, V12
- Number of patients no longer requiring rescue systemic corticosteroid treatment throughout the first year after the first month of starting the study
- Safety of Mepolizumab and in-office nasal polypectomy
- Change from baseline in sinonasal outcome test (SNOT-22) total score at weeks 4 and 24.
Conditions and MedDRA coding
chronic rhinosinusitis (CRS)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.1 | PT | 10080060 | Chronic rhinosinusitis with nasal polyps | 100000004855 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Mepolizumab and in-office nasal polypectomy in patients with chronic rhinosinusitis (CRS). This randomized, controlled multicenter trial will recruit patients aged 18 to 70 years with recurrent nasal polyposis requiring surgery and indication for biologic treatment according to EPOS 2020 guideline. Patients will receive 100 mg of subcutaneous mepolizumab every 4 weeks for a total of 12 doses in addition to daily topical corticosteroid treatment. All study procedures will be performed in five study visits and may take approximately 30 minutes. Clinical assessments include different questionnaires and nasal endoscopy.
This trial includes three treatment arms.
1. Combined group (In-office nasal polypectomy group with mepolizumab): This group will undergone in-office nasal polypectomy and will receive Mepolizumab.
2. Medical group (mepolizumab): This group will receive Mepolizumab.
3. Surgical group (In-office nasal polypectomy): This group will undergone in-office nasal polypectomy.
The main advantage is that it allows comparison of mepolizumab versus surgery and surgery/mepolizumab versus surgery + mepolizumab, providing more information on the most effective therapeutic approach.
The presence of adverse effects will be assessed in each treatment arm.
|
Randomised Controlled | None | Combined group (In-office nasal polypectomy group with mepolizumab): This group of patients will undergo in-office nasal polypectomy before starting treatment with mepolizumab. Mepolizumab treatment will be administered at the surgical procedure visit or within 48 hours after the polypectomy. Medical group (mepolizumab): This group of patients will not undergo in-office nasal polypectomy and will start treatment with mepolizumab directly after randomization. Surgical group (polypectomy): This group of patients will undergo nasal polypectomy in the office and will not receive mepolizumab treatment. |
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2023-505426-34-00 | Mepolizumab and in-office nasal polypectomy in patients with chronic rhinosinusitis (CRS). A three arm study. | Instituto De Investigacion Marques De Valdecilla |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Participant 18 years of age or older
- Patients with a diagnosis of CRS with polyposis according to the criteria of the EPOS2020 guideline: Chronic rhinosinusitis with nasal polyps in adults is defined as presence of two or more symptoms, one of which should be either nasal blockage / obstruction / congestion or nasal discharge (anterior / posterior nasal drip); ± facial pain/pressure; ± reduction or loss of smell; for ≥12 weeks; and either endoscopic signs of nasal polyps, and/or CT changes: mucosal changes within the ostiomeatal complex and/or sinuses.
- Patients with indication for biologic treatment according to the criteria of the EPOS2020 guideline. 3. Presence of bilateral polyps in a patient who had ESS (except in cases where the patient is not fit for surgery, see bellow) and three of the following criteria are required: 3.1. Evidence of type 2 inflammation (tissue eos> 10/hpf* or blood eos>250, OR total IgE> 100). * Whenever possible histology from previous surgery should be reviewed to confirm if eosinophilic pathology. If the previous surgery was performed more than 2 years earlier, a blood eosinophil count is essential, as the previous biopsy data may not be relevant. 3.2. Need for systemic corticosteroids or contraindication to systemic steroids (≥ 2 courses per yr, OR long term (>3 months) 3.3. Significantly impaired quality of life (SNOT ≥ 40) 3.4. Significant loss of smell (≥7 VAS) 3.5. Diagnosis of comorbid asthma
- Basal eosinophil count (BEC) ≥300 cells/µL for surgical naïve patients- only those not fit for surgery (major criteria) or for those who have had surgery and have recurrence (minor criteria).
- Patients have been informed and signed consent to participate in the study.
- For those patients not suitable for surgery, the criteria of the EUFOREA guidelines for indication of biological treatment will be used (4 criteria, one of them being ≥300 cells/µL BEC).
Exclusion criteria 8
- Any serious or uncontrolled systemic or psychiatric illness that prevents a correct cognitive or endoscopic assessment or does not advise participation in the study.
- Unilateral localized secondary CRS (odontogenic, fungal ball, tumor)
- Bilateral diffuse secondary CRS (cystic fibrosis; eosinophilic granulomatosis with polyangiitis-S. de Churg-Strauss-; granulomatosis with polyangiitis-S de Wegener-; primary ciliary dyskinesia; selective immunodeficiencies.
- Pregnancy/ breast feeding.
- Hypersensitivity to mepolizumab or it’s excipients.
- Patients unable to complete the questionnaire or follow prescribed treatment.
- Patients who are participating in another clinical trial related to polyposis or asthma.
- Previously documented failure with IL-5/IL-5 receptor biologics
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- SINO-NASAL OUTCOME TEST (SNOT-22)
Secondary endpoints 6
- VAS score for nasal symptoms
- The following measurement will be assessed using a nasopharyngoscope: 1. CRSwNP: Lund-Kennedy scale 2. CRSwNP: Meltzer scale
- Need of rescue therapy with systemic corticosteroids: dose, route of administration, length of treatment, number of treatments.
- Need of rescue surgery (either in-office polypectomy or full endoscopic sinus surgery)
- The resected polyp in the polypectomy groups will be sent for histology to confirm that it is eosinophilic and to obtain evidence of type 2 inflammation (tissue eos> 10/hpf)
- The safety of the treatment will be assessed by collecting Adverse Events at each of the study visits.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Nucala 100 mg solution for injection in pre-filled syringe
PRD7486575 · Product
- Active substance
- Mepolizumab
- Substance synonyms
- SB240563
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 1200 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- R03DX09 — -
- Marketing authorisation
- EU/1/15/1043/006
- MA holder
- GLAXOSMITHKLINE TRADING SERVICES LIMITED
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Instituto De Investigacion Marques De Valdecilla
- Sponsor organisation
- Instituto De Investigacion Marques De Valdecilla
- Address
- Avenida Del Cardenal Herrera Oria S/n
- City
- Santander
- Postcode
- 39011
- Country
- Spain
Scientific contact point
- Organisation
- Instituto De Investigacion Marques De Valdecilla
- Contact name
- galo peralta
Public contact point
- Organisation
- Instituto De Investigacion Marques De Valdecilla
- Contact name
- galo peralta
Locations
1 EU/EEA country · 11 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Spain | Ongoing, recruiting | 75 | 11 |
| Rest of world | — | 0 | — |
Investigational sites
Hospital Universitario Virgen De La Macarena
ORL, Avenida Del Doctor Fedriani 3, 41009, Sevilla
Hospital De Jerez De La Frontera
ORL, Carretera De La Ronda Circunvalacion S/n, 11408, Jerez De La Frontera
Hospital Universitario Puerta De Hierro De Majadahonda
ORL, Calle De Joaquin Rodrigo 2, 28222, Majadahonda
Hospital Universitario Marques De Valdecilla
ORL, 5 Planta, Avenida Valdecilla S/n, Santander
Hospital Clinico Universitario De Valladolid
ORL, Avenida Ramon Y Cajal 3, 47003, Valladolid
Hospital Universitario De Cruces
ORL, Cruces Plaza S/n, 48903, Barakaldo
Hospital Universitario Central De Asturias
ORL, Avenida De Roma S/n, 33011, Oviedo
Hospital Universitario De Salamanca
ORL, Paseo De San Vicente 58-182, 37007, Salamanca
Hospital Universitario 12 De Octubre
ORL, Bloque D, Avenida De Cordoba S/n, Madrid
Hospital General Universitario Dr. Balmis
ORL, Avinguda Del Pintor Baeza 12, 03010, Alicante
Complexo Hospitalario Universitario De Santiago
ORL, Calle Choupana Da S/n, 15706, Santiago De Compostela
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Spain | 2023-12-18 | 2023-12-18 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 7 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2023-505426-34-00 | 1 |
| Protocol (for publication) | D1_Protocol v3_ 2023-505426-34-01_changes control | 1 |
| Protocol (for publication) | D1_Protocol v3_ 2023-505426-34-01_clean | 1 |
| Recruitment arrangements (for publication) | k1_recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC Mepolizumab | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_2023-505426-34-00 | 1 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-07-27 | Spain | Acceptable 2023-10-20
|
2023-10-20 |
| 2 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-09-17 | Spain | Acceptable 2024-11-14
|
2024-11-14 |
| 3 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-06-20 | Spain | Acceptable | 2025-07-29 |
| 4 | SUBSTANTIAL MODIFICATION | SM-6 | 2025-10-22 | Spain | Acceptable | 2025-11-14 |