Biomarkers for the prediction of individual CRSwNP patients' responses to mepolizumab

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC

Participant type

Patients, Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Otorhinolaryngologic Diseases [C09]

Trial duration

5 Aug 2024 → ongoing

Decision date (initial)

2024-06-03

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

GlaxoSmithKline

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

1. Identification of easily measurable biomarkers predicting individual patient’s response to mepolizumab
2. Correlation of patient-derived cell responses to mepolizumab with individual clinical responses to mepolizumab in ex vivo mucosal immunity model
3. Characterization of immune mechanisms behind immune responses of CRSwNP patients to mepolizumab
4. Characterization of immune mechanisms behind immune cell responses derived from CRSsNP patients to mepolizumab in ex vivo model

Conditions and MedDRA coding

Chronic rhinosinusitis with nasal polyps (CRSwNP)

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. For CRSwNP group: adult patients (≥18 years) with CRSwNP and fulfilling the EPOS2020 criteria for treatment with a biological who will be treated with mepolizumab
2. For CRSsNP group: ≥18 years of age AND ENT physician diagnosis of CRSsNP AND Ongoing symptoms for at least 8 weeks prior to study entry, including nasal congestion, blockage, or obstruction with moderate or severe symptom scores
3. For healthy control group: ≥18 years of age AND Good general health AND No abnormalities in nasal endoscopy

Exclusion criteria 3

1. For CRSwNP group: age ≤ 17 years OR previous participation in mepolizumab (and/or anti IL-5 treatment) study OR a patient is not able to complete the SNOT 22 questionnaire OR a strong indication for surgical treatment (e.g.: mucoceles) OR systemic diseases affecting the nose (e.g.: GPA, EGPA, sarcoid, primary ciliary dyskinesia, cystic fibrosis) OR antrochoanal polyps (isolated benign polyps originating from the mucosa of the maxillary sinus with a distinctive small stalk) OR inverted papilloma and malignant polyps OR acute upper or lower respiratory tract infections within 2 weeks before the inclusion visit OR use of systemic corticosteroids within 4 weeks before the inclusion visit OR need for continuous systemic corticosteroid treatment for another disease than CRSwNP OR systemic diseases preventing participation in the study (all comorbidities that have a higher impact on quality of life than CRSwNP and/or making the patient at risk during the study period) OR other systemic medical treatments influencing disease or primary and secondary study outcome measurements such as (non-)selective immunosuppressants (e.g.: azathioprine, methotrexate) and other monoclonal antibodies other than mepolizumab
2. For CRSsNP group: age ≤ 17 years OR previous participation in mepolizumab study OR systemic diseases affecting the nose (e.g.: GPA, EGPA, sarcoid, primary ciliary dyskinesia, cystic fibrosis) OR antrochoanal polyps (isolated benign polyps originating from the mucosa of the maxillary sinus with a distinctive small stalk) OR inverted papilloma and malignant polyps OR acute upper or lower respiratory tract infections within 2 weeks before the inclusion visit OR use of systemic corticosteroids within 4 weeks before the inclusion visit OR need for continuous systemic corticosteroid treatment of systemic diseases preventing participation in the study OR other systemical medical treatments influencing disease or primary and secondary study outcome measurements such as (non-)selective immunosuppressants (e.g.: azathioprine, methotrexate) and other monoclonal antibodies
3. For healthy control group: age ≤ 17 years OR previous participation in mepolizumab study OR nasal surgery at least six months prior to the study visit OR presence of any (chronic) or acute pathologies of the upper and lower airways at least six weeks prior to the inclusion OR need for any medications at least three weeks prior to the inclusion OR other systemical medical treatments influencing disease or primary and secondary study outcome measurements such as (non-)selective and other monoclonal antibodies

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Identification of cell/molecular biomarkers correlated with individual patients’ responses. These could be: frequencies of cell (sub)populations, gene expression pattern, cell activation statues/phenotype, expression/production pattern of cell products
2. Identification of immunological mechanisms behind responses to mepolizumab
3. Evidence for the effectiveness in in vitro setting of mepolizumab in certain CRSsNP patients / endotypes

Secondary endpoints 1

1. For CRSwNP group: Change in SNOT-22 from baseline to 6 months post-treatment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC

Sponsor organisation

Amsterdam UMC

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC

Contact name

Dr. Sietze Reitsma

Public contact point

Organisation

Amsterdam UMC

Contact name

Dr. Sietze Reitsma

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications