Clinical trial NCT04442269: Investigating Treatment With Dupilumab in Patients With Allergic Bronchopulmonary Aspergillosis (ABPA) (LIBERTY ABPA AIRED)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Allergic Bronchopulmonary Aspergillosis
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2020-06-22
Enrollment: 62
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo
timeFrame: At Week 24
Secondary outcomes:
measure: Annualized Rate of ABPA-related Exacerbations
timeFrame: Over the 24 to 52 Week Treatment Period
measure: Annualized Rate of Severe Respiratory Exacerbations
timeFrame: Over the 24 to 52 Week Treatment Period
measure: Annualized Rate of Severe Respiratory Exacerbations Requiring Either Hospitalization or Observation for >24 Hours in an ED/Urgent Care Facility
timeFrame: Over the 24 to 52 Week Treatment Period
measure: Change From Baseline in Asthma Control Questionnaire (ACQ)-5 Score
timeFrame: Over the 24 to 52 Week Treatment Period
measure: Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score
timeFrame: Over the 24 to 52 Week Treatment Period
measure: Percentage of Participants Achieving a Reduction in the SGRQ Total Score of 4 Points or Greater From Baseline
timeFrame: Up to 52 Weeks
measure: Percent Change From Baseline in Total IgE in Serum
timeFrame: Over the 24 to 52 Week Treatment Period
measure: Percent Change From Baseline in A Fumigatus-specific IgE in Serum
timeFrame: Over the 24 to 52 Week Treatment Period
measure: Absolute Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO)
timeFrame: Over the 24 to 52 Week Treatment Period
measure: Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO)
timeFrame: Over the 24 to 52 Week Treatment Period
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) From Baseline
timeFrame: Through the end of the 52 Week Treatment Period
measure: Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) Responses and Titer Over Time
timeFrame: Up to 64 Weeks
measure: Concentrations of Functional Dupilumab in Serum by Treatment Regimen
timeFrame: Up to 64 Weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Regeneron Study Site
state: Alabama
city: Scottsdale
country: United States
facility: Regeneron Study Site
state: Arizona
city: Bakersfield
country: United States
facility: Regeneron Study Site
state: California
city: La Jolla
country: United States
facility: Regeneron Study Site
state: California
city: Los Angeles
country: United States
facility: Regeneron Study Site
state: California
city: Riverside
country: United States
facility: Regeneron Study Site
state: California
city: Boise
country: United States
facility: Regeneron Study Site
state: Idaho
city: Iowa City
country: United States
facility: Regeneron Study Site
state: Iowa
city: Bronx
country: United States
facility: Regeneron Study Site
state: New York
city: New York
country: United States
facility: Regeneron Study Site
state: New York
city: Columbus
country: United States
facility: Regeneron Study Site
state: Ohio
city: DuBois
country: United States
facility: Regeneron Study Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Regeneron Study Site
state: Pennsylvania
city: Haskovo
country: Bulgaria
facility: Regeneron Study Site
city: Razgrad
country: Bulgaria
facility: Regeneron Study Site
city: Smolyan
country: Bulgaria
facility: Regeneron Study Site
city: Sofia
country: Bulgaria
facility: Regeneron Study Site
city: Brest
country: France
facility: Regeneron Study Site
city: Lyon
country: France
facility: Regeneron Study Site
city: Marseille
country: France
facility: Regeneron Study Site
city: Montpellier
country: France
facility: Regeneron Study Site
city: Paris
country: France
facility: Regeneron Study Site
city: Rennes
country: France
facility: Regeneron Study Site
city: Tours
country: France
facility: Regeneron Study Site
city: Leipzig
country: Germany
facility: Regeneron Study Site
state: Saxony
city: Berlin
country: Germany
facility: Regeneron Study Site
city: Frankfurt am Main
country: Germany
facility: Regeneron Study Site
city: Budapest
country: Hungary
facility: Regeneron Study Site
city: Fukuyama
country: Japan
facility: Regeneron Study Site
city: Kanagawa
country: Japan
facility: Regeneron Study Site
city: Nagoya
country: Japan
facility: Regeneron Study Site
city: Naka-gun
country: Japan
facility: Regeneron Study Site
city: Sakai
country: Japan
facility: Regeneron Study Site
city: Yanagawa
country: Japan
facility: Regeneron Study Site
city: Yokohama
country: Japan
facility: Regeneron Study Site
city: Amsterdam
country: Netherlands
facility: Regeneron Study Site
state: North Holland
city: Arnhem
country: Netherlands
facility: Regeneron Study Site
city: Breda
country: Netherlands
facility: Regeneron Study Site
city: Eindhoven
country: Netherlands
facility: Regeneron Study Site
city: Zutphen
country: Netherlands
facility: Regeneron Study Site
city: Bialystok
country: Poland
facility: Regeneron Study Site
city: Gdansk
country: Poland
facility: Regeneron Study Site
city: Oradea
country: Romania
facility: Regeneron Study Site
state: Bihor
city: Brasov
country: Romania
facility: Regeneron Study Site
city: Leicester
country: United Kingdom
facility: Regeneron Study Site
state: England
city: Liverpool
country: United Kingdom
facility: Regeneron Study Site
state: England
city: London
country: United Kingdom
facility: Regeneron Study Site
state: England
city: London
country: United Kingdom
facility: Regeneron Study Site
state: England
city: Wythenshawe
country: United Kingdom
facility: Regeneron Study Site
state: England
city: Bradford
country: United Kingdom
facility: Regeneron Study Site
state: West Yorkshire
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: Kao CC, Hanania NA, Parulekar AD. The impact of fungal allergic sensitization on asthma. Curr Opin Pulm Med. 2021 Jan;27(1):3-8. doi: 10.1097/MCP.0000000000000740.