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

Allergic Bronchopulmonary Aspergillosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04442269
• Other study ID #: R668-ABPA-1923
• Secondary ID: 2019-002619-24
• Status: Completed
• Phase: Phase 2
• Start date: September 15, 2020
• Est. completion date: February 9, 2024

Study information

• Verified date: February 2024
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: February 9, 2024
• Est. primary completion date: July 27, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Allergic Bronchopulmonary Aspergillosis
• Aspergillosis
• Pulmonary Aspergillosis

Intervention

Drug:
• dupilumab
Single-use prefilled glass syringe administered by subcutaneous (SC) injection.
• Placebo
Matching placebo

Locations

Country	Name	City	State
Bulgaria	Regeneron Study Site	Haskovo
Bulgaria	Regeneron Study Site	Razgrad
Bulgaria	Regeneron Study Site	Smolyan
Bulgaria	Regeneron Study Site	Sofia
France	Regeneron Study Site	Brest
France	Regeneron Study Site	Lyon
France	Regeneron Study Site	Marseille
France	Regeneron Study Site	Montpellier
France	Regeneron Study Site	Paris
France	Regeneron Study Site	Rennes
France	Regeneron Study Site	Tours
Germany	Regeneron Study Site	Berlin
Germany	Regeneron Study Site	Frankfurt am Main
Germany	Regeneron Study Site	Leipzig	Saxony
Hungary	Regeneron Study Site	Budapest
Japan	Regeneron Study Site	Fukuyama
Japan	Regeneron Study Site	Kanagawa
Japan	Regeneron Study Site	Nagoya
Japan	Regeneron Study Site	Naka-gun
Japan	Regeneron Study Site	Sakai
Japan	Regeneron Study Site	Yanagawa
Japan	Regeneron Study Site	Yokohama
Netherlands	Regeneron Study Site	Amsterdam	North Holland
Netherlands	Regeneron Study Site	Arnhem
Netherlands	Regeneron Study Site	Breda
Netherlands	Regeneron Study Site	Eindhoven
Netherlands	Regeneron Study Site	Zutphen
Poland	Regeneron Study Site	Bialystok
Poland	Regeneron Study Site	Gdansk
Romania	Regeneron Study Site	Brasov
Romania	Regeneron Study Site	Oradea	Bihor
United Kingdom	Regeneron Study Site	Bradford	West Yorkshire
United Kingdom	Regeneron Study Site	Leicester	England
United Kingdom	Regeneron Study Site	Liverpool	England
United Kingdom	Regeneron Study Site	London	England
United Kingdom	Regeneron Study Site	London	England
United Kingdom	Regeneron Study Site	Wythenshawe	England
United States	Regeneron Study Site	Bakersfield	California
United States	Regeneron Study Site	Birmingham	Alabama
United States	Regeneron Study Site	Boise	Idaho
United States	Regeneron Study Site	Bronx	New York
United States	Regeneron Study Site	Columbus	Ohio
United States	Regeneron Study Site	DuBois	Pennsylvania
United States	Regeneron Study Site	Iowa City	Iowa
United States	Regeneron Study Site	La Jolla	California
United States	Regeneron Study Site	Los Angeles	California
United States	Regeneron Study Site	New York	New York
United States	Regeneron Study Site	Philadelphia	Pennsylvania
United States	Regeneron Study Site	Riverside	California
United States	Regeneron Study Site	Scottsdale	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Bulgaria,  France,  Germany,  Hungary,  Japan,  Netherlands,  Poland,  Romania,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1) compared to placebo		At Week 24
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percent change from baseline in total IgE in serum		Over the 24 to 52 Week Treatment Period
Secondary	Percent change from baseline in A fumigatus-specific IgE in serum		Over the 24 to 52 Week Treatment Period
Secondary	Percent change from baseline in fractional exhaled nitric oxide (FeNO)		Over the 24 to 52 Week Treatment Period
Secondary	Absolute change from baseline in FeNO		Over the 24 to 52 Week Treatment Period
Secondary	Incidence of treatment-emergent adverse events (TEAEs) from baseline		Through the end of the 52 Week Treatment Period
Secondary	Incidence of treatment-emergent anti-drug antibody (ADA) responses and titer over time		Up to 64 Weeks
Secondary	Concentrations of functional dupilumab in serum by treatment regimen		Up to 64 Weeks