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Completed

NCT Number: NCT04442269

Investigating Treatment With Dupilumab in Patients With Allergic Bronchopulmonary Aspergillosis (ABPA) (LIBERTY ABPA AIRED)

The primary objective of the study is to evaluate the efficacy of dupilumab on lung function in participants with Allergic Bronchopulmonary Aspergillosis (ABPA).

The secondary objectives of the study are:

* To evaluate the effects of dupilumab on exacerbations in participants with ABPA * To evaluate the effects of dupilumab on ABPA-related exacerbations * To evaluate the effects of dupilumab on hospitalization/emergency department (ED)/urgent care visits in participants with ABPA * To evaluate the effects of dupilumab on asthma control in participants with ABPA * To evaluate the effects of dupilumab on health-related quality of life (HRQoL) in participants with ABPA * To evaluate the effects of dupilumab on serum total immunoglobulin E (IgE) and Aspergillus-specific IgE concentrations * To evaluate the effects of dupilumab on Fractional exhaled Nitric Oxide (FeNO) levels * To evaluate safety and tolerability of dupilumab in participants with ABPA * To evaluate dupilumab concentrations in serum and the incidence of anti-dupilumab antibodies in participants with ABPA

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Key information

Age range

12 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Regeneron Study Site, Haskovo, Bulgaria

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Who can participate

Healthy volunteers accepted: No

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

Key Inclusion Criteria:

  • Diagnosis of both ABPA and asthma
  • On a maintenance therapy for their asthma with controller medication which must include inhaled corticosteroids (ICS) and may include 1 or more additional controller medications including a long-acting beta agonist (LABA), leukotriene receptor antagonist (LTRA), and/or long-acting muscarinic receptor antagonist (LAMA), etc for at least 12 weeks, with a stable dose and regimen with no change in the dose or frequency of administration for at least 4 weeks prior to the screening visit and between the screening and baseline/randomization visits
  • For participants on OCS (oral corticosteroid): must be on a chronic stable dose (no change in the dose) of OCS of up to 10 mg/day (for participants taking daily corticosteroids) or up to 30 mg every alternate day (for participants taking alternate day corticosteroids) (prednisone/prednisolone or the equivalent) for at least 4 weeks prior to the screening visit and between the screening and the baseline/randomization visit
  • Must have experienced ≥1 severe respiratory exacerbation requiring treatment with systemic corticosteroids or hospitalization or treatment in ED/urgent care within 12 months prior to the screening visit or must be receiving chronic stable low-dose OCS per above criteria

Key Exclusion Criteria:

  • Weight less than 30.0 kilograms
  • Current smoker or e-cigarette user, cessation of smoking or e-cigarette use within 6 months prior to randomization, or >=10 pack-years smoking history
  • Post-bronchodilator FEV1 <30% predicted normal at screening
  • Respiratory exacerbation requiring systemic corticosteroids within 4 weeks prior to screening and between screening and baseline visit (for patients on daily or alternate day OCS, exacerbation requiring at least double the maintenance dose of corticosteroids)
  • Upper or lower respiratory tract infection within the 4 weeks prior to screening (visit 1) or between the screening and randomization visits
  • Significant chronic pulmonary disease other than asthma complicated with ABPA (eg, physician-diagnosed bronchiectasis due to a condition other than ABPA; cystic fibrosis; sarcoidosis; interstitial lung disease not due to ABPA; chronic obstructive pulmonary disease [COPD] not due to ABPA; hypereosinophilic syndrome; etc), a diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts
  • Diagnosis or suspected diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) (also called Churg-Strauss Syndrome)

NOTE: Other protocol defined inclusion / exclusion criteria applies.

Treatment and study plan

Dupilumab

Drug

Single-use prefilled glass syringe administered by subcutaneous (SC) injection.

Other names: • DUPIXENT, • REGN668, • SAR231893

Placebo

Drug

Matching placebo

Primary outcomes

  1. Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo

    Time frame: At Week 24

Secondary outcomes

  1. Annualized Rate of ABPA-related Exacerbations

    Time frame: Over the 24 to 52 Week Treatment Period

    Defined as severe respiratory exacerbations that are associated with a doubling of serum total Immunoglobulin E (IgE) from the prior pre-exacerbation value.

    Adjusted Rate: Negative Binomial Regression Model Unadjusted Rate: (Number of events)/(number of participant years)

  2. Annualized Rate of Severe Respiratory Exacerbations

    Time frame: Over the 24 to 52 Week Treatment Period

    Defined as new onset of symptoms or clinical worsening of respiratory symptoms requiring systemic corticosteroid treatment for ≥3 consecutive days; for participants who are on maintenance systemic corticosteroids, at least double the dose of maintenance systemic corticosteroids for ≥3 consecutive days (with or without antibiotic therapy if indicated)

    Adjusted Rate: Negative Binomial Regression Model Unadjusted Rate: (Number of events)/(number of participant years)

  3. Annualized Rate of Severe Respiratory Exacerbations Requiring Either Hospitalization or Observation for >24 Hours in an ED/Urgent Care Facility

    Time frame: Over the 24 to 52 Week Treatment Period

    Annualized rate of severe respiratory exacerbations requiring either hospitalization or observation for >24 hours in an emergency department/urgent care facility (events per person-year)

    Adjusted Rate: Negative Binomial Regression Model Unadjusted Rate: (Number of events)/(number of participant years)

  4. Change From Baseline in Asthma Control Questionnaire (ACQ)-5 Score

    Time frame: Over the 24 to 52 Week Treatment Period

    ACQ is completed by patient to measure both the adequacy of asthma control and change in asthma control, which occurs either spontaneously or as a result of treatment. The ACQ-5 score is the mean of the first 5 questions, between 0 (totally controlled) and 6 (severely uncontrolled). A higher score indicates lower asthma control. Participants with a score below 1.0 reflect adequately controlled asthma and participants with scores above 1.0 reflect inadequately controlled asthma. The optimal cut-point score of 1.50 should be used to be confident that a patient has inadequately controlled asthma.

  5. Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score

    Time frame: Over the 24 to 52 Week Treatment Period

    SGRQ will be completed by the patient to measure and quantify health status in adult participants with chronic airflow limitation. Total score ranges from 0 to 100. Scores by dimension are calculated for three domains: Symptoms, Activity, and Impacts (Psychosocial). Lower score indicates better Quality of Life (QoL).

  6. Percentage of Participants Achieving a Reduction in the SGRQ Total Score of 4 Points or Greater From Baseline

    Time frame: Up to 52 Weeks

    SGRQ will be completed by the patient to measure and quantify health status in adult participants with chronic airflow limitation. Total score ranges from 0 to 100. Scores by dimension are calculated for three domains: Symptoms, Activity, and Impacts (Psychosocial). Lower score indicates better Quality of Life (QoL).

  7. Percent Change From Baseline in Total IgE in Serum

    Time frame: Over the 24 to 52 Week Treatment Period

  8. Percent Change From Baseline in A Fumigatus-specific IgE in Serum

    Time frame: Over the 24 to 52 Week Treatment Period

  9. Absolute Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO)

    Time frame: Over the 24 to 52 Week Treatment Period

  10. Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO)

    Time frame: Over the 24 to 52 Week Treatment Period

  11. Number of Participants With Treatment-emergent Adverse Events (TEAEs) From Baseline

    Time frame: Through the end of the 52 Week Treatment Period

  12. Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) Responses and Titer Over Time

    Time frame: Up to 64 Weeks

  13. Concentrations of Functional Dupilumab in Serum by Treatment Regimen

    Time frame: Up to 64 Weeks

Sponsors and collaborators

Lead sponsor

Regeneron Pharmaceuticals

Industry

Collaborators

  • Sanofi

Registry information

Official study title

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Dupilumab in Patients With Allergic Bronchopulmonary Aspergillosis

Important dates

Study start
2020
Primary completion
2023
Study completion
2024
First posted
Jun 22, 2020
Registry last updated
Apr 4, 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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