Clinical trial NCT06818019: Withdrawal of Dupilumab in Severe Asthma
Official title: WIthdrawal of DUpilumab in Severe Asthma: a Randomized Non-inferiority-controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Severe Asthma
Keywords: severe asthma
dupilumab
exacerbation
discontinuation
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2025-02-10
Enrollment: 205
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicentre open-label non-inferiority randomised controlled trial with two parallel groups, ratio 1:1
Primary purpose: TREATMENT

Brief 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. 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Strategy failure
timeFrame: 24 months
Secondary outcomes:
measure: Change in asthma control test score
timeFrame: 6, 12 and 24 months
measure: Resumption of dupilumab
timeFrame: 6, 12 and 24 months
measure: Adverse events or serious adverse events
timeFrame: 24 months
measure: Time to loss of control
timeFrame: 24 months
measure: First exacerbation
timeFrame: 24 months
measure: Number of exacerbations
timeFrame: 24 months
measure: Proportion of patients with ≥ 1 exacerbation(s)
timeFrame: 6, 12 and 24 months
measure: Change in quality of life
timeFrame: 6, 12 and 24 months
measure: Change in lung function
timeFrame: 6, 12 and 24 months
measure: Change in the daily dose of oral corticosteroids
timeFrame: 6, 12 and 24 months
measure: Change in the daily dose of inhaled corticosteroids
timeFrame: 6, 12 and 24 months
measure: Effect on nasal polyposis
timeFrame: 6, 12 and 24 months
Other outcomes:
Locations:
city: Toulouse
country: France
facility: CHU de Toulouse
state: CHU de Toulouse
city: Amiens
country: France
facility: CHU Amiens-Picardie
city: Angers
country: France
facility: CHR d'Angers
city: Bayonne
country: France
facility: CH de Bayonne
city: Besançon
country: France
facility: CHU de Besançon
city: Brest
country: France
facility: CHU de Brest
city: Caen
country: France
facility: CHU de Caen
city: Cannes
country: France
facility: CH de Cannes
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
city: Créteil
country: France
facility: CHI de Créteil
city: Dijon
country: France
facility: CHU de Dijon
city: Epagny-Metz-Annecy
country: France
facility: CH Annecy Genevois
city: La Tronche
country: France
facility: CHU Grenoble-Alpes
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital Kremlin Bicêtre
city: Le Mans
country: France
facility: CH Le Mans
city: Lille
country: France
facility: Institut Coeur Poumon, CHU de Lille
city: Lyon
country: France
facility: Hôpital Croix Rousse
city: Paris
country: France
facility: Hôpital Avicenne
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: Hôpital Bichât
city: Pessac
country: France
facility: CHU de Bordeaux
city: Pierre-Bénite
country: France
facility: Hôpital Lyon Sud
city: Pointe-à-Pitre
country: France
facility: CHU de Guadeloupe
city: Reims
country: France
facility: CHU de Reims
city: Roubaix
country: France
facility: CH de Roubaix
city: Saint-Herblain
country: France
facility: CHU de Nantes
city: Strasbourg
country: France
facility: Nouvel Hôpital Civil
city: Suresnes
country: France
facility: Hôpital Foch
city: Tarbes
country: France
facility: Hôpital Tarbes Lourdes
Study officials:
affiliation: University Hospital, Toulouse
name: Laurent GUILLEMINAULT, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: