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NCT Number: NCT06818019

Withdrawal of Dupilumab in Severe Asthma

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.

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Key information

Conditions

Severe Asthma Asthma Bronchial Diseases Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Lung Diseases Lung Diseases, Obstructive Respiratory Hypersensitivity Respiratory Tract Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

CHU de Toulouse, Toulouse, France

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Stopping dupilumab

Drug

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

Primary outcomes

  1. Strategy failure

    Time frame: 24 months

    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

Secondary outcomes

  1. Change in asthma control test score

    Time frame: 6, 12 and 24 months

    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)

  2. Resumption of dupilumab

    Time frame: 6, 12 and 24 months

    Proportion of patients with resumption of dupilumab in the interventional group (stopping dupilumab) at 6, 12 and 24 months

  3. Adverse events or serious adverse events

    Time frame: 24 months

    Proportion of patients with adverse events or serious adverse events in both groups

  4. Time to loss of control

    Time frame: 24 months

    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

  5. First exacerbation

    Time frame: 24 months

    Comparing the interventional group with the control group regarding the time to first exacerbation

  6. Number of exacerbations

    Time frame: 24 months

    Comparing the interventional group with the control group regarding the number of exacerbations within 24 months

  7. Proportion of patients with ≥ 1 exacerbation(s)

    Time frame: 6, 12 and 24 months

    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.

  8. Change in quality of life

    Time frame: 6, 12 and 24 months

    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.

  9. Change in lung function

    Time frame: 6, 12 and 24 months

    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

  10. Change in the daily dose of oral corticosteroids

    Time frame: 6, 12 and 24 months

    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

  11. Change in the daily dose of inhaled corticosteroids

    Time frame: 6, 12 and 24 months

    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

  12. Effect on nasal polyposis

    Time frame: 6, 12 and 24 months

    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).

Study contacts

Contact information is provided by the study sponsor or research team.

Laurent GUILLEMINAULT, Md, PhD

CONTACT

[email protected]

0567771850 ext. +33

Sponsors and collaborators

Lead sponsor

University Hospital, Toulouse

Other

Registry information

Official study title

WIthdrawal of DUpilumab in Severe Asthma: a Randomized Non-inferiority-controlled Trial

Acronym: WIDUSA

Important dates

Study start
2025
Primary completion
2027
Study completion
2029
First posted
Feb 10, 2025
Registry last updated
Feb 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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