Severe AsthmaPhase 4WIDUSANCT06818019
Withdrawal of Dupilumab in Severe Asthma
A Phase 4 study testing Stopping dupilumab in people with Severe Asthma, run by University Hospital, Toulouse at 29 sites in France.
Trial summary
Asthma management has been revolutionised by the development of biological therapies. Dupilumab is an anti-interleukin4 receptor marketed in 2020 for severe asthmatic patients with 2 exacerbations or more within the last 12 months. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Severe Asthma
- What is being tested?
- Stopping dupilumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 205 participants
- Where
- 29 sitesFrance
- Study dates
- 15 Dec 2025to 31 Dec 2029
- Phase
- Phase 4
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
Who may be able to join
- Adult patients ≥ 18 years old
- Treated with dupilumab for at least 36 months for severe asthma
- Well controlled asthma defined by an Asthma Control Questionnaire score ≥ 18 and 0 or 1 exacerbation within the year prior to the inclusion visit
Who cannot join
- Patients who refuse to discontinue dupilumab, for any reason
- Patients with Forced expiratory volume in one second ≤ 30% of predicted values
- Patients treated by an oral corticosteroid dose ≥ 10 mg/day (in prednisone equivalent)
- Patients who have to discontinue dupilumab for a reason other than controlled asthma, such as an adverse drug reaction, a planned or current pregnancy, or a planned switch to another biologic indicated in severe asthma
- Patients who have to continue dupilumab for the treatment of comorbidities apart from nasal polyposis
- Active smoking
- Pregnancy or breastfeeding
Trial locations and contacts
29 sites in 1 country. Contact the study team or a site near you to ask about taking part.
29 sites in 1 country
France29 sites, 28 recruiting
- Not yet recruiting
CHU Amiens-Picardie
Amiens, France, 80480
Claire ANDREJAK, MD, PhD, 0322087893 ext. +33, andrejak.claire@chu-amiens.fr
- Not yet recruiting
CHR d'Angers
Angers, France, 49100
Yasmina PASCAUD MANSOUR, MD, 0245353461 ext. +33, yasmina.mansour@chu-angers.fr
- Not yet recruiting
CH de Bayonne
Bayonne, France, 64100
Cécilia NOCENT, MD, 0559443852 ext. +33, cnocent@ch-cotebasque.fr
- Recruiting
CHU de Besançon
Besançon, France, 25000
Cindy BARNIG, MD, PhD, 0647737530 ext. +33, cbarnig@chu-besancon.fr
- Not yet recruiting
CHU de Brest
Brest, France, 29200
Françis COUTURAUD, MD, PhD, 0298347347 ext. +33, francis.couturaud@chu-brest.fr
- Not yet recruiting
CHU de Caen
Caen, France, 14000
Helen FOUQUET, MD, 0231064677 ext. +33, fouquet-h@chu-caen.fr
- Not yet recruiting
CH de Cannes
Cannes, France, 06400
Fabien ROLLAND, MD, 0493697860 ext. +33, f.rolland@ch-cannes.fr
- Not yet recruiting
CHU de Clermont-Ferrand
Clermont-Ferrand, France, 63000
Camille ROLLAND-DEBORD, MD, 0473751653 ext. +33, crollanddebord@chu-clermontferrand.fr
- Not yet recruiting
CHI de Créteil
Créteil, France, 94000
Amel BOUDJEMAA, MD, 0157022080 ext. +33, amel.boudjemaa@chicreteil.fr
- Recruiting
CHU de Dijon
Dijon, France, 21000
Philippe BONNIAUD, MD, PhD, 0380293772 ext. +33, philippe.bonniaud@chu-dijon.fr
- Not yet recruiting
CH Annecy Genevois
Epagny-Metz-Annecy, France, 74370
Toufik DIDI, MD, 0450636603 ext. +33, tdidi@ch-annecygenevois.fr
- Recruiting
CHU Grenoble-Alpes
La Tronche, France, 38700
Christel SAINT-RAYMOND, MD, 0476765522 ext. +33, csaint-raymond@chu-grenoble.fr
- Recruiting
Hôpital Kremlin Bicêtre
Le Kremlin-Bicêtre, France, 94270
Antoine BEURNIER, MD, 0145217896 ext. +33, antoine.beurnier@aphp.fr
- Not yet recruiting
CH Le Mans
Le Mans, France, 72037
François GOUPIL, MD, 0243434345 ext. +33, fgoupil@ch-lemans.fr
- Recruiting
Institut Coeur Poumon, CHU de Lille
Lille, France, 59000
Stéphanie FRY, MD, 0320445948 ext. +33, stephanie.fry@chu-lille.fr
- Recruiting
Hôpital Croix Rousse
Lyon, France, 69004
Gille DEVOUASSOUX, MD, PhD, 0426732947 ext. +33, gilles.devouassoux@chu-lyon.fr
- Not yet recruiting
Hôpital Avicenne
Paris, France, 75012
Lucile SESE, MD, 06677289103 ext. +33, Lucile.sese@aphp.fr
- Not yet recruiting
Hôpital Européen Georges Pompidou
Paris, France, 75015
Thibaud SOUMAGNE, MD, 0156093462 ext. +33, thibaud.soumagne@live.fr
- Recruiting
Hôpital Bichât
Paris, France, 75018
Camille TAILLE, MD, PhD, 0140256802 ext. +33, camille.taille@aphp.fr
- Not yet recruiting
CHU de Bordeaux
Pessac, France, 33600
Pierre-Olivier GIRODET, MD, PhD, 0557623194 ext. +33, pierre-olivier.girodet@chu-bordeaux.fr
- Not yet recruiting
Hôpital Lyon Sud
Pierre-Bénite, France, 69495
Nathalie FREYMOND, MD, 0478864401 ext. +33, nathalie.freymond@chu-lyon.fr
- Recruiting
CHU de Reims
Reims, France, 51092
Jeanne-Marie PEROTIN-COLLARD, MD, PhD, 0326787614 ext. +33, jmperotin-collard@chu-reims.fr
- Not yet recruiting
CH de Roubaix
Roubaix, France, 59100
Nicolas JUST, MD, 0320993048 ext. +33, nicolas.just@ch-roubaix.fr
- Active, not recruiting
CHU de La Réunion
Saint-Denis, France, 97400
- Recruiting
CHU de Nantes
Saint-Herblain, France, 44800
François-Xavier BLANC, MD, PhD, 0240165710 ext. +33, xavier.blanc@chu-nantes.fr
- Recruiting
Nouvel Hôpital Civil
Strasbourg, France, 67000
Naji KHAYATH, MD, 0369550898 ext. +33, naji.khayath@chru-strasbourg.fr
- Recruiting
Hôpital Foch
Suresnes, France, 92150
Colas TCHERAKIAN, MD, PhD, 0146252315 ext. +33, c.tcherakian@hopital-foch.com
- Not yet recruiting
Hôpital Tarbes Lourdes
Tarbes, France, 65000
Joëlle COURDEAU, MD, 0562546060 ext. +33, jcourdeau-labourie@ch-tarbes.vic.fr
- Recruiting
CHU de Toulouse
Toulouse, CHU de Toulouse, 31059
Laurent GUILLEMINAULT, MD, PhD, 0567771850 ext. +33, guilleminault.l@chu-toulouse.fr
About this study
Official title: WIthdrawal of DUpilumab in Severe Asthma: a Randomized Non-inferiority-controlled Trial
Asthma management has been revolutionised by the development of biological therapies. Dupilumab is an anti-interleukin4 receptor marketed in 2020 for severe asthmatic patients with 2 exacerbations or more within the last 12 months. Although data showed that safety and efficacy of dupilumab are sustained when treatment is extended up to 3 years, no study has emerged regarding dupilumab discontinuation. This study aims to demonstrate the non-inferiority regarding strategy failure at 24 months of stopping dupilumab (intervention group) compared with its continuation (control group) in controlled asthma patients receiving this drug for at least 3 years.
Read the detailed description
Although dupilumab is a very effective drug in severe asthma, the optimal duration of this drug is unknown. However, this is a crucial question given the high cost of dupilumab and the lack of data regarding the long-term inhibition of type 2 pathway. Studies on biologic discontinuation are scarce in severe asthma. Studies with other biologics have shown that discontinuation of these drugs is feasible particularly for patients with low exacerbation rate before stopping treatment. In a study with pooled asthma biologics, 1247 (25.1%) stopped the biologic among the 4958 biologic users (including 19.8% of dupilumab users). Among all stoppers, 10.2% failed discontinuation of the asthma biologic in the 6 months after stopping, defined as an increase of 50% or more in exacerbations. Among patients who continued the biologic, 9.5% had an increase of 50% or more in exacerbations during a 6-month period, showing a similar failing rate. Such data for dupilumab discontinuation are lacking.
In this study, we plan to include patients with controlled asthma treated with dupilumab for at least 3 years who will be randomised to stopping dupilumab or dupilumab continuation with a follow-up of 24 months.
In total, 5 visits will occur for each patient: the inclusion/randomisation visit (baseline), 3 follow-up visits at month 6, month 12, month 24 as usually done in severe asthma, and a phone call visit at 18 months for exacerbations, treatments and adverse events collection. At each onsite visit, asthma medications, concomitant treatments, nasal polyp score (if applicable), number of exacerbations, Asthma Control Questionnaire, Severe Asthma Questionnaire, Treatment Burden Questionnaire and Sino-Nasal Outcome Test-22 scores, Forced expiratory volume in one second, Forced vital capacity, Fraction exhaled nitric oxide (if available), blood eosinophil, neutrophil and lymphocyte counts, adverse events, hospital admissions, and unscheduled medical visits will be recorded.
- Conditions
- Severe Asthma
- Being tested
- Stopping dupilumab
- Keywords
- severe asthma, dupilumab, exacerbation, discontinuation
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stopping dupilumabDrug
Stopping dupilumab with no dose-reducing or interval of time-increasing strategy
| Study group | Role | What they receive |
|---|---|---|
| Stopping dupilumab | Experimental | The experimental strategy comprises stopping dupilumab with no dose-reducing or interval of time-increasing strategy from the day of inclusion/randomisation Receives: Drug: Stopping dupilumab |
| Dupilumab continuation | No intervention | Dupilumab continuation at the same dose and same interval as baseline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Strategy failure
Proportion of patients with strategy failure defined as patients with an annualised number of asthma exacerbations ≥ 2 and/or dupilumab resume or switch to another biologic within 24 months following randomisation
Measured: 24 months
Secondary outcomes (12)
Change in asthma control test score
Comparing the interventional group with the control group regarding the change in asthma control test score at 6, 12 and 24 months compared to baseline. The asthma control test score is a self-administered questionnaire consisting of 5 questions related to the frequency of asthma symptoms and the use of rescue treatments over the past 4 weeks. The score ranges from 5 (poorest control) to 25 (perfect control)
Measured: 6, 12 and 24 months
Resumption of dupilumab
Proportion of patients with resumption of dupilumab in the interventional group (stopping dupilumab) at 6, 12 and 24 months
Measured: 6, 12 and 24 months
Adverse events or serious adverse events
Proportion of patients with adverse events or serious adverse events in both groups
Measured: 24 months
Time to loss of control
Comparing the interventional group with the control group regarding the time between baseline to loss of control defined by a reduction of 5 points or more on asthma test control score
Measured: 24 months
First exacerbation
Comparing the interventional group with the control group regarding the time to first exacerbation
Measured: 24 months
Number of exacerbations
Comparing the interventional group with the control group regarding the number of exacerbations within 24 months
Measured: 24 months
Proportion of patients with ≥ 1 exacerbation(s)
Comparing the interventional group with the control group regarding the proportion of patients with ≥ 1 exacerbation(s) or severe exacerbation(s) at 6, 12 and 24 months. A severe exacerbation is defined as an emergency room visit or hospital admission or death related to asthma exacerbation.
Measured: 6, 12 and 24 months
Change in quality of life
Comparing the interventional group with the control group regarding the change in quality of life at 6, 12 and 24 months compared to baseline.
The change in the severe asthma questionnary quality of life score and the Burden of Treatment Questionnaire score at 6, 12 and 24 months compared to baseline.
The severe asthma questionnary is a health-related quality of life questionnaire validated for use in severe asthma. It is scored using the mean value of 16 items (severe asthma questionnary score) in addition to a single item global rating of health-related quality of life. The Burden of Treatment Questionnaire is a 15-item questionnaire that assesses the treatment burden of chronic diseases.
Measured: 6, 12 and 24 months
Change in lung function
The lung function change is a qualitative clinical criteria of failure/success of the strategy. This failure is made up of 3 components : Forced Expiratory Volume in 1 second (in L and % predicted, pre- and post-bronchodilator), Forced Vital Capacity (in L and % predicted) and forced exhaled nitric oxide (in ppb) at 6, 12 and 24 months compared to baseline
Measured: 6, 12 and 24 months
Change in the daily dose of oral corticosteroids
Comparing the interventional group with the control group regarding the change in the daily dose (mg/day) of oral corticosteroids (in prednisone equivalent) at 6, 12 and 24 months compared to baseline
Measured: 6, 12 and 24 months
Change in the daily dose of inhaled corticosteroids
Comparing the interventional group with the control group regarding the change in the daily dose (μg/day) of inhaled corticosteroids (in beclomethasone equivalent) at 6, 12 and 24 months
Measured: 6, 12 and 24 months
Effect on nasal polyposis
Comparing the interventional group with the control group regarding the change in nasal polyposis endoscopic score (if available) and Sino-Nasal Outcome Test-22 score at 6, 12 and 24 months compared to baseline.
The french version of Sino-Nasal Outcome Test-22 is a further modification of the Sino-Nasal Outcome Test-20, a fully validated and easy-to-use outcome measure in rhinology. In addition to the normal 20-item version of the Sino-Nasal Outcome Test, 2 additional items were measured, nasal blockage, and loss of sense of taste and smell. The 22-question Sino-Nasal Outcome Test-22 is scored as 0 (no problem) to 5 (problem as bad as it can be) with a total range from 0 to 110 (higher scores indicate poorer outcomes).
Measured: 6, 12 and 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2025
- Study start15 Dec 2025
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe AsthmaStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multicentre open-label non-inferiority randomised controlled trial with two parallel groups, ratio 1:1
- Masking
- None (open label)
- Enrolment
- 205 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Laurent GUILLEMINAULT, MD, PhD, Principal investigator, University Hospital, Toulouse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06818019
- Sponsor's protocol ID
- RC31/24/0325
- Other IDs
- 2024-516789-13-00
- Acronym
- WIDUSA
- Status last verified
- Oct 2026
- First submitted
- 19 Nov 2024
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No