Tapering of Biologics in Chronic Rhinosinusitis With Nasal Polyps

NCT ID: NCT07187583

Last Updated: 2025-09-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 135 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-05
• Study Completion Date: 2028-03-01

Brief Summary

The purpose of this study is to investigate the feasibility of extending the dosing intervals of biological therapies while maintaining optimal treatment effects in chronic rhinosinusitis with nasal polyps (CRSwNP).

Detailed Description

This is an investigator-initiated, independent, national multicenter study with a real-world design and Good Clinical Practice (GCP) monitoring. The study is a randomized controlled drug trial investigating the non-inferiority of extended dosing intervals compared with standard treatment for patients with CRSwNP receiving mepolizumab (100 mg) or dupilumab (300 mg) every 4 weeks. Approximately 135 patients will be enrolled from ear, nose and throat departments in all five regions of Denmark. The study duration is approximately 2.5 years, with each patient followed for 52 weeks.

Randomization At inclusion, patients are randomized 1:1 to the intervention or control group. Randomization is computer-based (REDCap).

Control group Continues dosing of mepolizumab or dupilumab every 4 weeks.

Intervention group Increases to a 6-week dosing interval at baseline, and if response to the biological therapy is maintained, increases to 8-week dosing intervals at the follow-up visit at week 26. Thereafter, dosing every 8 weeks is maintained until the patient completes the trial at week 52. In case of worsening of CRSwNP-related symptoms, the patient reverts to the last effective dosing interval.

Clinical visits Clinical follow-ups are conducted at weeks 0, 12, 26, 38, and 52. The visits at weeks 0, 26, and 52 are already planned as a standard part of biological treatment outside the protocol and include endoscopic rhinoscopy, smell testing, and questionnaires: Sinonasal Outcome Test 22 (SNOT-22), Work Productivity and Activity Impairment (WPAI), and Asthma Control Questionnaire (ACQ). The visits at weeks 12 and 38 are study-specific and include patient-reported symptom severity on a Visual Analogue Scale (VAS), endoscopic rhinoscopy, and completion of questionnaires (SNOT-22, WPAI).

Conditions

Chronic Rhinosinusitis With Nasal Polyps

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard dosing of biological therapy

Continues dosing of mepolizumab (100 mg via injection pen, subcutaneous injection) or dupilumab (300 mg via injection pen, subcutaneous injection) every 4 weeks.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Increased dosing interval of biological therapy

Increases to a 6-week dosing interval at baseline - of mepolizumab (100 mg via injection pen, subcutaneous injection) or dupilumab (300 mg via injection pen, subcutaneous injection) - and if response to therapy is maintained, increases to 8-week dosing intervals at the follow-up visit in week 26. Thereafter, dosing every 8 weeks is maintained until the patient completes the trial at week 52.

Group Type: ACTIVE_COMPARATOR

increased dosing interval of biological therapy

Intervention Type: DRUG

Increasing dosing interval of biological therapy for CRSwNP from every 4 weeks to every 6 weeks and if continued satisfactory response then to every 8 weeks.

Interventions

increased dosing interval of biological therapy

Increasing dosing interval of biological therapy for CRSwNP from every 4 weeks to every 6 weeks and if continued satisfactory response then to every 8 weeks.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• ≥18 years of age.
• Currently receiving treatment with either dupilumab (300 mg) or mepolizumab (100 mg) every four weeks.
• Having received the biologic at unchanged dosing interval for at least three months.
• For at least one year during treatment with biologics, the patients' CRSwNP must be categorized as "partly controlled" as defined by presence of 1-2 of the following seven items (also available in EPOS 2020 table in protocol):

1. Nasal blockage: present on most days of the week

2. Rhinorrhoea/postnasal drip: mucopurulent on most days of the week

3. Facial pain/pressure: present on most days of the week

4. Sense of smell: impaired

5. Sleep disturbance or fatigue: present

6. Nasal endoscopy: diseased mucosa

7. Rescue treatment (systemic corticosteroids, ESS, antibiotics): need of 1 course of rescue treatment

of which 1-5 will be scored by the patient using VAS (0-10) and noted above 5.

Exclusion Criteria

• Patients with excellent response to biologics (0 of the above-mentioned 7 items for partly controlled disease)
• Patients with no or limited response to biologics (>2 of the above-mentioned 7 items for partly controlled disease)
• Patients with a cancer diagnosis deemed by the investigator to preclude participation in the trial
• Patients who, because of language barriers, are not able to understand Danish written information and, thus, are not able to answer questionnaires
• Patients who currently receive biologics for any other disease (asthma not included)
• Patients who are not able to give informed consent (i.e., patients who are permanently incapable)
• Patients who are not eligible because of the investigator's judgement
• Patients who experience pregnancy during the study will be excluded after an unscheduled visit - active IVF treatment (please see below)
• Unwillingness to follow the study procedure

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rigshospitalet, Denmark

OTHER

Sponsor Role: lead

Responsible Party

Elizabeth M. Stevens

national coordinating investigator, and sub-investigator at Rigshospitalet

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christian von Buchwald, MD, DMSc, prof.

Role: STUDY_DIRECTOR

Rigshospitalet, Dept. of Otorhinolaryngology, Head and Neck Surgery & Audiology

Locations

Dept of otorhinolaryngology, Aalborg University Hospital

Aalborg, , Denmark

Site Status: NOT_YET_RECRUITING

Dept of otorhinolaryngology, head and neck surgery, Aarhus University Hospital

Aarhus, , Denmark

Site Status: NOT_YET_RECRUITING

Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Copenhagen University, Rigshospitalet

Copenhagen, , Denmark

Site Status: RECRUITING

Esbjerg Og Grindsted Sygehus

Esbjerg, , Denmark

Site Status: NOT_YET_RECRUITING

Dept of otorhinolaryngology, Gødstrup Regional Hospital

Herning, , Denmark

Site Status: NOT_YET_RECRUITING

Dept of otorhinolaryngology, Nordsjaellands Hospital

Hillerød, , Denmark

Site Status: RECRUITING

Dept of otorhinolaryngology, Sjællands Universitetshospital

Køge, , Denmark

Site Status: RECRUITING

Dept of otorhinolaryngology, Odense University Hospital

Odense, , Denmark

Site Status: NOT_YET_RECRUITING

Dept of otorhinolaryngology, Lillebaelt Hospital

Vejle, , Denmark

Site Status: NOT_YET_RECRUITING

Countries

Denmark

Central Contacts

Elizabeth M. Stevens Saporito, MD

Role: CONTACT

este0027@regionh.dk

+4535452370

Facility Contacts

Søren Pauli, MD

Role: primary

sbro@rn.dk

004597660000

Kristian B Petersen, MD

Role: primary

krispete@rm.dk

004578450000

Christian M. von Buchwald, MD, DMSc, prof.

Role: primary

christian.von.buchwald@regionh.dk

+4535452370

Role: backup

christian.von.buchwald@regionh.dk

Jonas H Andersen, MD

Role: primary

jonas.hjelm.andersen2@rsyd.dk

004579182774

Adnan Madzak, MD

Role: primary

adnan.madzak@auh.rm.dk

004578439744

Grethe B Samuelsen, MD, PhD

Role: primary

grethe.badsberg.samuelsen@regionh.dk

004548293825

Bent Ivan Larsen, MD

Role: primary

bele@regionsjaelland.dk

004547321401

Anette Kjeldsen, MD, prof.

Role: primary

anette.kjeldsen@rsyd.dk

004565414314

Lars Christian Meyer, MD

Role: primary

lars.christian.meyer@rsyd.dk

004579405000

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2024-519758-35-01

Identifier Type: -

Identifier Source: org_study_id