Biologic treatment of rhinosinusitis with nasal polyposis in real-world Danish patients - a direct comparison of dupilumab and mepolizumab

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Rigshospitalet

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Otorhinolaryngologic Diseases [C09], Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

13 Apr 2023 → ongoing

Decision date (initial)

2023-03-22

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Mauritzen La Fontaine Family Foundation

External identifiers

EU CT number

2022-502250-14-00

ClinicalTrials.gov

NCT05942222

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To compare the efficacy of mepolizumab versus dupilumab on objective and subjective symptoms of CRSwNP and related comorbidities in an attempt to determine non-inferiority between the two, or possibly; superiority of dupilumab over mepolizumab.

Secondary objectives 1

1. The secondary objective is to explore any other relevant differences between mepolizumab and dupilumab in terms of frequency of AEs, need for rescue treatments, diversity in outcome based on endotype or comorbidity or other factors, that can lead to a patient-centreed approach, when choosing treatment for CRSwNP

Conditions and MedDRA coding

Chronic rhinosinusitis with nasal polyposis

Regulatory references

Plan to share IPD

Yes

IPD plan description

Will individual participant data (IPD) be shared? Yes, upon reasonable request. What data will be shared? Only anonymized individual participant data relevant to the study's outcomes. When will data be available? Starting 3 months after the primary results are published and for up to 5 years thereafter. With whom will data be shared? Only academic researchers affiliated with recognized research institutions. For what types of analyses? For non-commercial scientific research purposes, such as meta-analyses or validation of study results. How can the data be accessed? Researchers should submit a data request to the sponsor, including a research proposal and data use agreement. Access will be reviewed and granted at the sponsor's discretion.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Chronic Rhinosinusitis with bilateral nasal polyposis
2. Evidence of type 2 inflammation as measured by either eosinophilia in blood or tissue (in accordance with EPOS2020), or late-onset eosinophilic asthma
3. At least one endoscopic sinus surgery within the previous seven years (or not being fit to undergo sinus surgery)
4. Adherence to nasal steroid spray and nasal douches twice a day for a period of at least three months until start of treatment
5. Additionally: at least three of the following five: 1) need for systemic corticosteroids (OCS), at least two/year or one long term treatment lasting more than three months, or having contraindications to OCSs
6. 2) Sino-nasal outcome test 22 (SNOT-22) score of at least 50
7. 3) Reduced sense of smell (Defined as Sniffin Sticks-Evaluation Identification Test 16 (UPSIT-16) score 0-8
8. 4) Nasal polyp score (NPS) of minimum 2 on both sides, and a minimum score of 5 in total
9. 5) Asthma requiring inhaled corticosteroids
10. Age above 18 years
11. Able to read and/or speak Danish

Exclusion criteria 10

1. Systemic corticosteroid treatment within the last three months
2. Endoscopic sinus surgery (ESS) within the last six months
3. Non-adherent to medicine regimens
4. Hypersensitivity to the active substance or any of the excipients in the two IMPs
5. Not able to understand spoken and/or written Danish
6. Prior treatment with any biologic drug aimed at type II disease within the previous six months
7. Prior treatment failure with one of the two IMPs for any indication
8. Eosinophilic blood cell count of ≥1.5x109cells/L (at baseline, i.e. before first injection)
9. Pronounced fear of needles
10. Pregnant or breastfeeding patients.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Co-primary endpoint 1: Change in nasal polyp score (NPS) at 24 weeks
2. Co-primary endpoint 2: Change in SNOT-22 score at 24 weeks

Secondary endpoints 14

1. Change in loss of smell (Proportion with SSIT-16 improved to >8)
2. Improvement in asthma (measured by proportion with ACQ>0.5)
3. Improvement on visual analog scale measuring impact on quality of life of CRSwNP
4. Tympanometry - proportion with change from B-curve to A or C curve.
5. Expired Nitrous oxide (FeNO) - proportion with less than 25 ppb
6. Improvement in subjective smell function by visual analog scale
7. Improvement in aspirin-exacerbated-respiratory-intolerance (AERD) measured by visual analog scale.
8. Improvement in NPS at 52 weeks
9. Improvement in SNOT-22 at 52 weeks
10. Proportion meeting the response criteria set by the Danish Medicines council
11. Proportion of subjects needing rescue treatment (systemic corticosteroids or sinus surgery)
12. Change in Nasal Congestion Score (NCS)
13. Chang in radiologic sinus opacification (Lund-Mackey score)
14. Change in FEV1

Investigational products

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

Test 2

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rigshospitalet

Sponsor organisation

Rigshospitalet

Address

Blegdamsvej 9

City

Copenhagen Oe

Postcode

2100

Country

Denmark

Scientific contact point

Organisation

Rigshospitalet

Contact name

Christian von Buchwald

Public contact point

Organisation

Rigshospitalet

Contact name

Christian von Buchwald

Third parties 1

Locations

1 EU/EEA country · 9 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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