WIthdrawal of DUpilumab in Severe Asthma : a randomised non-inferiority-controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Toulouse

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

15 Dec 2025 → ongoing

Decision date (initial)

2025-01-30

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

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 36 months

Secondary objectives 4

1. To compare stopping dupilumab with its continuation regarding: a) the change in asthma control at 6, 12 and 24 months compared to baseline b) the time to loss of control c) the time to first exacerbation d) the number of exacerbation(s) within 24 months e) the proportion of patients with exacerbation(s) or severe exacerbation(s) at 6, 12 and 24 months f) the change in quality of life at 6, 12 and 24 months compared to baseline g) the change in lung function at 6, 12 and 24 months compared to baseline h) the change in the daily dose of oral corticosteroids in patients taking long-term oral corticosteroids at 6, 12 and 24 months compared to baseline i) the change in the daily dose of inhaled corticosteroids at 6, 12 and 24 months compared to baseline j) the effect on nasal polyposis at 6, 12 and 24 months compared to baseline
2. To determine the proportion of patients in the intervention group with resumption of dupilumab at 6, 12 and 24 months
3. To assess safety in both groups
4. Exploratory objectives are: 1/ to identify baseline factors associated to asthma loss of control at 6, 12 and 24 months for all included patients 2/ to identify biomarkers associated to asthma loss of control over the 24 months in a subset of patients included in high inclusion potential centres (≥ 10 patients) who will provide supplementary samples at baseline, 6, 12 and 24 months. Asthma loss of control is defined by either a/ number of annualised asthma exacerbations ≥ 2 or b/ resumption of dupilumab or switch to another biologic or c/ a decrease in the ACT score (at least 5 points), at 6, 12 and 24 months.

Conditions and MedDRA coding

Severe asthma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Adult patients ≥ 18 years old
2. Patients treated with dupilumab, prescribed by a pneumologist, for at least 36 months for severe asthma
3. Well controlled asthma defined by an ACT score ≥ 18 and 0 or 1 exacerbation within the year prior to randomization
4. Affiliated person or beneficiary of a social security scheme
5. Free, informed and written consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research)
6. Effective contraception for women of childbearing age

Exclusion criteria 13

1. Patients who refuse to discontinue dupilumab, for any reason
2. Patients with FEV1 ≤ 30% of predicted values
3. Patients treated by an oral corticosteroid dose ≥ 10 mg/day (in prednisolone equivalent)
4. Patients who have to discontinue dupilumab for a reason other than controlled asthma, such as an adverse drug reaction, a planned or current pregnancy, a medical condition requiring the discontinuation of dupilumab (e.g. in a context of the occurrence of helminthiasis), a planned or current vaccination with live and/or live- attenuated vaccine, or a planned switch to another biologic indicated in severe asthma
5. Patients who have to continue dupilumab for the treatment of comorbidities apart from nasal polyposis
6. Active smoking
7. Patients whose compliance to asthma treatment is considered poor or doubtful by the investigator
8. Patients participating in another interventional research study
9. Patients with any condition that would prevent participation in the study and completion of the study procedures, including language limitation
10. Alcohol and/or drug misuse as determined by the investigator
11. Pregnancy or breastfeeding
12. Patient unwilling to sign the informed consent form
13. Patient placed under juridical protection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion of patients with strategy failure defined as patients with an annualised number of asthma exacerbations ≥ 2 and/or resumption of dupilumab or switch to another biologic within 24 months following randomisation

Secondary endpoints 3

1. To compare stopping dupilumab with its continuation regarding: a) the change in the asthma control test (ACT) score at 6, 12 and 24 months compared to baseline b) the time between baseline to loss of control defined with a reduction of 5 points or more on ACT score (compared to baseline) c) the time between baseline to the first exacerbation d) the number of exacerbations within 24 months e) the proportion of patients with ≥ 1 exacerbation and ≥ 1 severe exacerbation at 6, 12 and 24 months
2. The proportion of patients with resumption of dupilumab in the interventional group (stopping dupilumab) at 6, 12 and 24 months
3. The proportion of patients with AE or SAE in both groups

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Toulouse

Sponsor organisation

Centre Hospitalier Universitaire De Toulouse

Address

2 Rue Viguerie

City

Toulouse

Postcode

31300

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

Pr Laurent GUILLEMINAULT

Public contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

Laura BOGDANOVITCH

Locations

1 EU/EEA country · 31 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications