Withdrawal of Dupilumab in Severe Asthma

NCT ID: NCT06818019

Last Updated: 2025-02-10

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 205 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-02
• Study Completion Date: 2029-12-31

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.

Conditions

Severe Asthma

Study Design

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

Study Groups

Stopping dupilumab

The experimental strategy comprises stopping dupilumab with no dose-reducing or interval of time-increasing strategy from the day of inclusion/randomisation

Group Type: EXPERIMENTAL

Stopping dupilumab

Intervention Type: DRUG

Stopping dupilumab with no dose-reducing or interval of time-increasing strategy

Dupilumab continuation

Dupilumab continuation at the same dose and same interval as baseline

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Stopping dupilumab

Stopping dupilumab with no dose-reducing or interval of time-increasing strategy

Intervention Type: DRUG

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

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

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Laurent GUILLEMINAULT, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Locations

CHU de Toulouse

Toulouse, CHU de Toulouse, France

CHU Amiens-Picardie

Amiens, France, France

CHR d'Angers

Angers, France, France

CH de Bayonne

Bayonne, France, France

CHU de Besançon

Besançon, France, France

CHU de Brest

Brest, France, France

CHU de Caen

Caen, France, France

CH de Cannes

Cannes, France, France

CHU de Clermont-Ferrand

Clermont-Ferrand, France, France

CHI de Créteil

Créteil, France, France

CHU de Dijon

Dijon, France, France

CH Annecy Genevois

Epagny-Metz-Annecy, France, France

CHU Grenoble-Alpes

La Tronche, France, France

Hôpital Kremlin Bicêtre

Le Kremlin-Bicêtre, France, France

CH Le Mans

Le Mans, France, France

Institut Coeur Poumon, CHU de Lille

Lille, France, France

Hôpital Croix Rousse

Lyon, France, France

Hôpital Avicenne

Paris, France, France

Hôpital Européen Georges Pompidou

Paris, France, France

Hôpital Bichât

Paris, France, France

CHU de Bordeaux

Pessac, France, France

Hôpital Lyon Sud

Pierre-Bénite, France, France

CHU de Guadeloupe

Pointe à Pitre, France, France

CHU de Reims

Reims, France, France

CH de Roubaix

Roubaix, France, France

CHU de Nantes

Saint-Herblain, France, France

Nouvel Hôpital Civil

Strasbourg, France, France

Hôpital Foch

Suresnes, France, France

Hôpital Tarbes Lourdes

Tarbes, France, France

Countries

France

Central Contacts

Laurent GUILLEMINAULT, Md, PhD

Role: CONTACT

guilleminault.l@chu-toulouse.fr

0567771850 ext. +33

Facility Contacts

Laurent GUILLEMINAULT, MD, PhD

Role: primary

guilleminault.l@chu-toulouse.fr

0567771850 ext. +33

Claire ANDREJAK, MD, PhD

Role: primary

andrejak.claire@chu-amiens.fr

0322087893 ext. +33

Yasmina PASCAUD MANSOUR, MD

Role: primary

yasmina.mansour@chu-angers.fr

0245353461 ext. +33

Cécilia NOCENT, MD

Role: primary

cnocent@ch-cotebasque.fr

0559443852 ext. +33

Cindy BARNIG, MD, PhD

Role: primary

cbarnig@chu-besancon.fr

0647737530 ext. +33

Françis COUTURAUD, MD, PhD

Role: primary

francis.couturaud@chu-brest.fr

0298347347 ext. +33

Helen FOUQUET, MD

Role: primary

fouquet-h@chu-caen.fr

0231064677 ext. +33

Fabien ROLLAND, MD

Role: primary

f.rolland@ch-cannes.fr

0493697860 ext. +33

Camille ROLLAND-DEBORD, MD

Role: primary

crollanddebord@chu-clermontferrand.fr

0473751653 ext. +33

Amel BOUDJEMAA, MD

Role: primary

amel.boudjemaa@chicreteil.fr

0157022080 ext. +33

Philippe BONNIAUD, MD, PhD

Role: primary

philippe.bonniaud@chu-dijon.fr

0380293772 ext. +33

Toufik DIDI, MD

Role: primary

tdidi@ch-annecygenevois.fr

0450636603 ext. +33

Christel SAINT-RAYMOND, MD

Role: primary

csaint-raymond@chu-grenoble.fr

0476765522 ext. +33

Antoine BEURNIER, MD

Role: primary

antoine.beurnier@aphp.fr

0145217896 ext. +33

François GOUPIL, MD

Role: primary

fgoupil@ch-lemans.fr

0243434345 ext. +33

Stéphanie FRY, MD

Role: primary

stephanie.fry@chu-lille.fr

0320445948 ext. +33

Gille DEVOUASSOUX, MD, PhD

Role: primary

gilles.devouassoux@chu-lyon.fr

0426732947 ext. +33

Lucile SESE, MD

Role: primary

Lucile.sese@aphp.fr

06677289103 ext. +33

Thibaud SOUMAGNE, MD

Role: primary

thibaud.soumagne@live.fr

0156093462 ext. +33

Camille TAILLE, MD, PhD

Role: primary

camille.taille@aphp.fr

0140256802 ext. +33

Pierre-Olivier GIRODET, MD, PhD

Role: primary

pierre-olivier.girodet@chu-bordeaux.fr

0557623194 ext. +33

Nathalie FREYMOND, MD

Role: primary

nathalie.freymond@chu-lyon.fr

0478864401 ext. +33

Chantal RAHERISON SEMJEN, MD, PhD

Role: primary

chantal.raherison@chu-guadeloupe.fr

891360 ext. +590

Jeanne-Marie PEROTIN-COLLARD, MD, PhD

Role: primary

jmperotin-collard@chu-reims.fr

0326787614 ext. +33

Nicolas JUST, MD

Role: primary

nicolas.just@ch-roubaix.fr

0320993048 ext. +33

François-Xavier BLANC, MD, PhD

Role: primary

xavier.blanc@chu-nantes.fr

0240165710 ext. +33

Naji KHAYATH, MD

Role: primary

naji.khayath@chru-strasbourg.fr

0369550898 ext. +33

Colas TCHERAKIAN, MD, PhD

Role: primary

c.tcherakian@hopital-foch.com

0146252315 ext. +33

Joëlle COURDEAU, MD

Role: primary

jcourdeau-labourie@ch-tarbes.vic.fr

0562546060 ext. +33

Other Identifiers

2024-516789-13-00

Identifier Type: CTIS

Identifier Source: secondary_id

RC31/24/0325

Identifier Type: -

Identifier Source: org_study_id