Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)RELIBIONCT06683261
Real-life Evaluation of the Efficacy of Biologicals in Chronic Rhinosinusitis With Nasal Polyposis (CRSwNP)
An observational study of Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) and Chronic Rhinosinusitis (CRS), run by Universitaire Ziekenhuizen KU Leuven at 8 sites in Belgium.
Trial summary
The goal of this observational study is to learn more about the real-world efficacy of biologics in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). All patients who are 18 years or older, who have CRSwNP and are eligible for reimbursement of a biological for the indication of CRSwNP can be… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Rhinosinusitis With Nasal Polyps (CRSwNP), Chronic Rhinosinusitis (CRS)
- What is being tested?
- Omalizumab, Dupilumab and Mepolizumab 100 mg
- How many people
- 300 participants
- Where
- 8 sitesBelgium
- Study dates
- 23 Sep 2022to Dec 2026
- How long will I take part?
- 3 Years
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with CRSwNP that are prescribed a biological in the outpatient clinic of several ENT departments across Belgium
Who may be able to join
- Participant must be at least 18 years of age at the time of signing the informed consent.
- Capable of giving signed informed consent.
- Participants should have CRSwNP.
- Participants should fulfil the reimbursement criteria for their prescribed biological (omalizumab, mepolizumab and/or dupilumab).
Who cannot join
- 1. Patients treated with other biological therapies in the 3 months prior to the current biological (this is not applicable to patients who are in the trial and switch biological).
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
Belgium8 sites, 8 recruiting
- Recruiting
Onze Lieve Vrouw hospital Aalst
Aalst, 9300
Principal investigator Dr. Benedicte Verhaeghe, MD, +3253728524, b.verhaeghe@yahoo.com
- Recruiting
General hospital Sint-Jan Bruges
Bruges, 8000
Principal Investigator Dr. K. Speleman, MD, +3250 45 22 80, kato.speleman@azsintjan.be
- Recruiting
University hospital Saint-Luc
Brussels, 1200
Principal investigator Prof. Valérie Hox, MD-PhD, +322 764 19 42, valerie.hox@saintluc.uclouvain.be
- Recruiting
University hospital of Antwerp
Edegem, 2650
Principal investigator prof. Olivier Vanderveken, MD-PhD, +32 3 821 30 00, olivier.vanderveken@uza.be
Anneclaire Vroegop, MD-PhD
- Recruiting
Hospital Zuid-Oost Limburg
Genk, 3600
Principal Investigator Dr. W. Lemmens, MD, +3289/32.50.50, winde.lemmens@zol.be
- Recruiting
University Hospital Brussels
Jette, 1090
Principal investigator Dr. Stijn Halewyck, MD, +322 477 60 02, stijn.halewyck@uzbrussel.be
- Recruiting
University hospitals Leuven
Leuven, 3000
Elien Borgers, MSc, +3216/34.20.37, elien.borgers@uzleuven.be
Peter Hellings, MD-PhD
- Recruiting
CHU de Liège
Liège, 4000
Séverine Camby, +32474415961, s.camby@chuliege.be
Florence Rogister, MD
About this study
Official title: Real-life Evaluation of the Efficacy of Biologicals in CRSwNP
The goal of this observational study is to learn more about the real-world efficacy of biologics in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). All patients who are 18 years or older, who have CRSwNP and are eligible for reimbursement of a biological for the indication of CRSwNP can be included.
The main question is the efficacy of biologics in real life after 24 weeks. The main focus are patient reported outcomes measured via several questionnaires and the nasal polyp score, scored with nasal endoscopy.
Read the detailed description
Chronic rhinosinusitis with nasal polyps (CRSwNP) has a prevalence of 5-10% in adults. It is often associated with other comorbidities, such as asthma (30-70% of CRSwNP patients) and aspirin exacerbated respiratory disease (AERD) (16% of CRSwNP patients) leading to a significant reduced quality of life (QoL). CRSwNP is diagnosed in patients with nasal polyps who have 2 or more of the following symptoms for more than 12 weeks:
- Nasal blockage or nasal congestion
- Runny nose or postnasal drip
- Impaired sense of smell
- Facial pain/pressure. Nasal rinses, intranasal or systemic corticosteroids, long-term antibiotics, and sinus surgery are the current standard of care. However, many patients fail to achieve complete therapeutic benefit and relapse after time, even after surgery. Moreover, oral corticosteroids are associated with significant side effects, and repeated sino-nasal surgery becomes progressively more complex with higher risk of complications. Patients with CRSwNP and most patients with asthma share a common type 2 inflammatory response, characterised by elevated levels of interleukin (IL)-4, IL-5, IL-13, eosinophils, T helper 2 (Th2)cells, and type 2 innate lymphoid cells. In addition, locally produced immunoglobulin E (IgE) is able to activate mast cells and induce local inflammation in CRSwNP.
Biologicals are a specific kind of treatment with recombinant DNA-derived humanized monoclonal antibody that selectively binds specific targets in the inflammatory cascade which contributes to the pathophysiology of CRSwNP. Different biologicals have already been reimbursement for the treatment of Asthma for years, slowly these biologicals start to get their approval and reimbursement for CRSwNP. In Belgium (omalizumab (Xolair®), mepolizumab (Nucala®) and dupilumab (Dupixent ®) are reimbursed for patients with CRSwNP. Their efficacy has been demonstrated through large double-blind placebo-controlled clinical studies. However, until now only very limited reports on real-world data regarding this therapy have been published. This real-world data is important because it enables us to go beyond data gathered throughout a traditional randomised controlled trial (RCT). Traditional RCTs gather data from a controlled sample population with limited comorbidities and concomitant medications, who are likely to be compliant with the study requirements, whereas in real life patients might have poorer performance status and compliance and consist of a higher proportion of elderly patients.
Therefore, this real-world data study aims to investigate how clinical outcomes of biologic therapy in real-world application (real-world efficacy) corresponds to outcomes in clinical trials (efficacy) and to look into factors that might explain an efficacy gap.
- Being tested
- Omalizumab, Dupilumab, Mepolizumab 100 mg
- Keywords
- biologicals, CRSwNP, real-world data study, mepolizumab, omalizumab, dupilumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OmalizumabBiological
biological prescribed as add-on treatment as part of the standard of care
DupilumabBiological
biological prescribed as add-on treatment as part of the standard of care
Mepolizumab 100 mgBiological
biological prescribed as add-on treatment as part of the standard of care
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the effect of biologicals (omalizumab, mepolizumab and dupilumab) on the nasal congestion score (NCS).
Nasal congestion is scored from 0 ("No symptoms") to 3 ("Severe symptoms"). Higher scores denote greater symptom severity.
Changes from baseline in NCS will be measured at 1, 3 and 6 months and 1, 1.5, 2 and 3 years for every biological (mepolizumab, omalizumab and dupilumab).
Measured: From enrollment until 3 years of treatment
Secondary outcomes (7)
To evaluate the effect of biologicals (omalizumab, mepolizumab and dupilumab) on the nasal polyp score (NPS).
The total nasal polyp score (NPS) is an endoscopic nasal polyp scoring system to quantify nasal polyps with endoscopy. The higher the score, the more polyps are present in the nose. A unilateral score from 0 (absence of polyps) to 4 is given. The total nasal polyp score is the sum of the scores for both nostrils, thus ranging from 0 to 8, and is based on the continuous extension of nasal polyps beyond clear landmarks such as the upper and lower borders of the middle and inferior turbinate. This implies that a score can only be attributed if the criteria of the lower scores are met. E.g. a unilateral score of 3 cannot be given without nasal polyps also meeting the criteria for a score of 2, and similarly, a score of 4 cannot be given without having a score of 3.
Changes from baseline in NPS will be measured at 1, 3 and 6 months and 1, 1.5, 2 and 3 years for every biological.
Measured: From enrollment until 3 years of treatment
To evaluate the effect of biologicals (omalizumab, mepolizumab and dupilumab) on the Visual analogue scale (VAS).
The rhinosinusitis severity VAS is used to evaluate the overall severity of the rhinosinusitis. It is a recommended scale to determine the patient's disease severity and to guide the treatment for CRS. The participant is asked to answer the following question: "How troublesome are your symptoms of your rhinosinusitis" on a 10-cm VAS from 0 ('not troublesome') to 10 ('worst thinkable troublesome'). Based on their score on the VAS, the severity of rhinosinusitis can be divided into 3 categories as follows:
- Mild = VAS 0 to 3
- Moderate = VAS >3 to 7
- Severe = VAS >7 to 10
In this study, changes from baseline in VAS-scores at 1, 3 and 6 months and 1, 1.5, 2 and 3 years for every biological (mepolizumab, omalizumab and dupilumab) will be measured.
Measured: From enrollment until 3 years of treatment
To evaluate the effect of biologicals (omalizumab, mepolizumab and dupilumab) on the Sino-Nasal Outcome Test-22 items (SNOT-22).
The SNOT-22 is a questionnaire designed to assess the impact of chronic rhinosinusitis on the patients' QoL. It has 22 items covering symptoms, social/emotional impact, productivity, and sleep consequences of CRS. Each item is rated on a 6-point Likert scale response option, ranging from 0 ('No problem') to 5 ('Problem as bad as it can be'). A global score ranging from 0 to 110 is calculated by summing the responses to all items; higher score indicates greater rhinosinusitis-related health burden.
This study investigates changes from baseline in SNOT-22 at 1, 3 and 6 months and 1, 1.5, 2 and 3 years for every biological (mepolizumab, omalizumab and dupilumab).
Measured: From enrollment until 3 years of treatment
To compare the effect of biologicals (omalizumab, mepolizumab and dupilumab) on the asthma control questionnaires 5-item version(ACQ-5).
The ACQ-5 was designed to measure both the adequacy of asthma control and change in asthma control. The participants are asked to recall how their asthma has been during the previous week and to respond to 5 questions on a 7-point scale (0 = no impairment, 6 = maximum impairment).
A global score is calculated as follows: the questions are equally weighted, and the ACQ-5 score is the mean of the 5 questions and, therefore, falls between 0 (totally controlled) and 6 (severely uncontrolled). A higher score indicates lower asthma control.
This study evaluates changes from baseline in ACQ-5 at 1, 3 and 6 months and 1, 1.5, 2 and 3 years for every biological (mepolizumab, omalizumab and dupilumab).
Measured: From enrollment until 3 years of treatment
To compare the effect of biologicals (omalizumab, mepolizumab and dupilumab) on the asthma quality of life questionnaire (AQLQ).
The AQLQ is comprised of 32 items, each rated on a 7-point Likert scale from 1 to 7. A higher score indicates better quality of life.
This study evaluates changes from baseline in AQLQ at 1, 3 and 6 months and 1, 1.5, 2 and 3 years for every biological (mepolizumab, omalizumab and dupilumab).
Measured: From enrollment until 3 years of treatment
To compare the effect of omalizumab, mepolizumab and dupilumab on the sense of smell with the short questionnaire of olfactory disorders: negative statements (sQOD-NS).
sQOD-NS patient-reported outcome questionnaire includes social, eating, annoyance, and anxiety questions. Items are rated on a scale of 0-3, with higher scores reflecting the better olfactory-specific quality of life (QOL). The total score ranges from 0 (severe impact on QoL) to 21 (no impact on QoL).
This study evaluates changes from baseline in sQOD-NS at 1, 3 and 6 months and 1, 1.5, 2 and 3 years for every biological (mepolizumab, omalizumab and dupilumab).
Measured: From enrollment until 3 years of treatment
To evaluate patient's adherence to their biological add-on treatment.
Patients are asked at every consultation whether they took their biological treatment correctly according to the treatment schedule or if a problem occurred ( missed injection, problem with the injection,..)
Measured: form enrollment until 3 years of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2024
- Study start23 Sep 2022
- Primary completionJan 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)Studies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
- Target duration
- 3 Years
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Peter Hellings, Universitaire Ziekenhuizen KU Leuven
- Investigators
- Peter Hellings, MD,PhD, Principal investigator, Universitaire Ziekenhuizen KU Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06683261
- Sponsor's protocol ID
- S66646
- Acronym
- RELIBIO
- Status last verified
- Nov 2024
- First submitted
- 22 Oct 2024
- Last updated
- 12 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Kilty SJ, Lasso A. Canadian real-world study of access and clinical results using dupilumab for chronic rhinosinusitis with polyps. J Otolaryngol Head Neck Surg. 2022 Apr 25;51(1):17. doi: 10.1186/s40463-022-00570-0.
PubMed 35468866Bachert C, Corren J, Lee SE, Zhang H, Harel S, Cunoosamy D, Khan AH, Jacob-Nara JA, Siddiqui S, Nash S, Rowe PJ, Deniz Y. Dupilumab efficacy and biomarkers in chronic rhinosinusitis with nasal polyps: Association between dupilumab treatment effect on nasal polyp score and biomarkers of type 2 inflammation in patients with chronic rhinosinusitis with nasal polyps in the phase 3 SINUS-24 and SINUS-52 trials. Int Forum Allergy Rhinol. 2022 Sep;12(9):1191-1195. doi: 10.1002/alr.22964. Epub 2022 Jan 31. No abstract available.
PubMed 34970860Han JK, Bachert C, Fokkens W, Desrosiers M, Wagenmann M, Lee SE, Smith SG, Martin N, Mayer B, Yancey SW, Sousa AR, Chan R, Hopkins C; SYNAPSE study investigators. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2021 Oct;9(10):1141-1153. doi: 10.1016/S2213-2600(21)00097-7. Epub 2021 Apr 16.
PubMed 33872587Gevaert P, Omachi TA, Corren J, Mullol J, Han J, Lee SE, Kaufman D, Ligueros-Saylan M, Howard M, Zhu R, Owen R, Wong K, Islam L, Bachert C. Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials. J Allergy Clin Immunol. 2020 Sep;146(3):595-605. doi: 10.1016/j.jaci.2020.05.032. Epub 2020 Jun 7.
PubMed 32524991Zhang N, Holtappels G, Gevaert P, Patou J, Dhaliwal B, Gould H, Bachert C. Mucosal tissue polyclonal IgE is functional in response to allergen and SEB. Allergy. 2011 Jan;66(1):141-8. doi: 10.1111/j.1398-9995.2010.02448.x.
PubMed 20659077Tomassen P, Vandeplas G, Van Zele T, Cardell LO, Arebro J, Olze H, Forster-Ruhrmann U, Kowalski ML, Olszewska-Ziaber A, Holtappels G, De Ruyck N, Wang X, Van Drunen C, Mullol J, Hellings P, Hox V, Toskala E, Scadding G, Lund V, Zhang L, Fokkens W, Bachert C. Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. J Allergy Clin Immunol. 2016 May;137(5):1449-1456.e4. doi: 10.1016/j.jaci.2015.12.1324. Epub 2016 Mar 4.
PubMed 26949058Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, Cohen N, Cervin A, Douglas R, Gevaert P, Georgalas C, Goossens H, Harvey R, Hellings P, Hopkins C, Jones N, Joos G, Kalogjera L, Kern B, Kowalski M, Price D, Riechelmann H, Schlosser R, Senior B, Thomas M, Toskala E, Voegels R, Wang de Y, Wormald PJ. EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. Rhinology. 2012 Mar;50(1):1-12. doi: 10.4193/Rhino12.000.
PubMed 22469599Stevens WW, Peters AT, Hirsch AG, Nordberg CM, Schwartz BS, Mercer DG, Mahdavinia M, Grammer LC, Hulse KE, Kern RC, Avila P, Schleimer RP. Clinical Characteristics of Patients with Chronic Rhinosinusitis with Nasal Polyps, Asthma, and Aspirin-Exacerbated Respiratory Disease. J Allergy Clin Immunol Pract. 2017 Jul-Aug;5(4):1061-1070.e3. doi: 10.1016/j.jaip.2016.12.027. Epub 2017 Mar 9.
PubMed 28286156Dudvarski Z, Djukic V, Janosevic L, Tomanovic N, Soldatovic I. Influence of asthma on quality of life and clinical characteristics of patients with nasal polyposis. Eur Arch Otorhinolaryngol. 2013 Mar;270(4):1379-83. doi: 10.1007/s00405-012-2242-x. Epub 2012 Nov 8.
PubMed 23135235Kowalski ML, Agache I, Bavbek S, Bakirtas A, Blanca M, Bochenek G, Bonini M, Heffler E, Klimek L, Laidlaw TM, Mullol J, Nizankowska-Mogilnicka E, Park HS, Sanak M, Sanchez-Borges M, Sanchez-Garcia S, Scadding G, Taniguchi M, Torres MJ, White AA, Wardzynska A. Diagnosis and management of NSAID-Exacerbated Respiratory Disease (N-ERD)-a EAACI position paper. Allergy. 2019 Jan;74(1):28-39. doi: 10.1111/all.13599. Epub 2018 Oct 2.
PubMed 30216468Khan A, Vandeplas G, Huynh TMT, Joish VN, Mannent L, Tomassen P, Van Zele T, Cardell LO, Arebro J, Olze H, Foerster-Ruhrmann U, Kowalski ML, Olszewska-Ziaber A, Holtappels G, De Ruyck N, van Drunen C, Mullol J, Hellings PW, Hox V, Toskala E, Scadding G, Lund VJ, Fokkens WJ, Bachert C. The Global Allergy and Asthma European Network (GALEN rhinosinusitis cohort: a large European cross-sectional study of chronic rhinosinusitis patients with and without nasal polyps. Rhinology. 2019 Feb 1;57(1):32-42. doi: 10.4193/Rhin17.255.
PubMed 29911211Hastan D, Fokkens WJ, Bachert C, Newson RB, Bislimovska J, Bockelbrink A, Bousquet PJ, Brozek G, Bruno A, Dahlen SE, Forsberg B, Gunnbjornsdottir M, Kasper L, Kramer U, Kowalski ML, Lange B, Lundback B, Salagean E, Todo-Bom A, Tomassen P, Toskala E, van Drunen CM, Bousquet J, Zuberbier T, Jarvis D, Burney P. Chronic rhinosinusitis in Europe--an underestimated disease. A GA(2)LEN study. Allergy. 2011 Sep;66(9):1216-23. doi: 10.1111/j.1398-9995.2011.02646.x. Epub 2011 May 24.
PubMed 21605125