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

Study Overview
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Brief Summary
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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

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

Conditions
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Allergic Bronchopulmonary Aspergillosis

Intervention / Treatment
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* Drug: dupilumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dupilumab<br>Loading subcutaneous (SC) dose on day 1, followed by SC dose, every two weeks (Q2W) | Drug: dupilumab<br>* Single-use prefilled glass syringe administered by subcutaneous (SC) injection.<br>* Other names: • SAR231893;|
| Experimental: Placebo<br>Matching dupilumab without active substance | Drug: Placebo<br>* Matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1) compared to placebo |  | At Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized rate of severe respiratory exacerbations | Defined as new onset of symptoms or clinical worsening of respiratory symptoms requiring systemic corticosteroid treatment for ≥3 consecutive days; for patients 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) | Over the 24 to 52 Week Treatment Period | 
| Annualized rate of ABPA-related exacerbations | Defined as severe respiratory exacerbations (as defined above) that are associated with a doubling of serum total Immunoglobulin E (IgE) from the prior pre-exacerbation value. | Over the 24 to 52 Week Treatment Period | 
| Annualized rate of severe respiratory exacerbations requiring either hospitalization or observation for >24 hours in an ED/urgent care facility |  | Over the 24 to 52 Week Treatment Period | 
| Change from baseline in Asthma Control Questionnaire (ACQ)-5 | 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. Patients with a score below 1.0 reflect adequately controlled asthma and patients 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. | Over the 24 to 52 Week Treatment Period | 
| Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score | SGRQ will be completed by the patient to measure and quantify health status in adult patients 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). | Over the 24 to 52 Week Treatment Period | 
| Percentage of participants achieving a reduction in the SGRQ score of 4 points or greater from baseline | SGRQ will be completed by the patient to measure and quantify health status in adult patients 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). | Up to 52 Weeks | 
| Percent change from baseline in total IgE in serum |  | Over the 24 to 52 Week Treatment Period | 
| Percent change from baseline in A fumigatus-specific IgE in serum |  | Over the 24 to 52 Week Treatment Period | 
| Percent change from baseline in fractional exhaled nitric oxide (FeNO) |  | Over the 24 to 52 Week Treatment Period | 
| Absolute change from baseline in FeNO |  | Over the 24 to 52 Week Treatment Period | 
| Incidence of treatment-emergent adverse events (TEAEs) from baseline |  | Through the end of the 52 Week Treatment Period | 
| Incidence of treatment-emergent anti-drug antibody (ADA) responses and titer over time |  | Up to 64 Weeks | 
| Concentrations of functional dupilumab in serum by treatment regimen |  | Up to 64 Weeks |