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

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

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

Study Overview

• Status: Completed
• Conditions: Allergic Bronchopulmonary Aspergillosis
• Intervention / Treatment: Drug: Placebo; Drug: dupilumab

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Haskovo, Bulgaria, 6305
    • Regeneron Study Site
  • Razgrad, Bulgaria, 7200
    • Regeneron Study Site
  • Smolyan, Bulgaria, 4700
    • Regeneron Study Site
  • Sofia, Bulgaria, 1142
    • Regeneron Study Site
• France
  • Brest, France, 29609
    • Regeneron Study Site
  • Lyon, France, 69004
    • Regeneron Study Site
  • Marseille, France, 13015
    • Regeneron Study Site
  • Montpellier, France, 34295
    • Regeneron Study Site
  • Paris, France, 75018
    • Regeneron Study Site
  • Rennes, France, 35033
    • Regeneron Study Site
  • Tours, France, 37044
    • Regeneron Study Site
• Germany
  • Berlin, Germany, 10717
    • Regeneron Study Site
  • Frankfurt am Main, Germany, 60389
    • Regeneron Study Site
  • Saxony
    • Leipzig, Saxony, Germany, 4357
      • Regeneron Study Site
• Hungary
  • Budapest, Hungary, 1083
    • Regeneron Study Site
• Japan
  • Fukuyama, Japan, 7200001
    • Regeneron Study Site
  • Kanagawa, Japan, 259-1193
    • Regeneron Study Site
  • Nagoya, Japan, 454-8509
    • Regeneron Study Site
  • Naka-gun, Japan, 3191113
    • Regeneron Study Site
  • Sakai, Japan, 591-8555
    • Regeneron Study Site
  • Yanagawa, Japan, 8320059
    • Regeneron Study Site
  • Yokohama, Japan, 231-8682
    • Regeneron Study Site
• Netherlands
  • Arnhem, Netherlands, 6815
    • Regeneron Study Site
  • Breda, Netherlands, 4818 CK
    • Regeneron Study Site
  • Eindhoven, Netherlands, 5623
    • Regeneron Study Site
  • Zutphen, Netherlands, 7207
    • Regeneron Study Site
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1105AZ
      • Regeneron Study Site
• Poland
  • Bialystok, Poland, 15-044
    • Regeneron Study Site
  • Gdansk, Poland, 80402
    • Regeneron Study Site
• Romania
  • Brasov, Romania, 500051
    • Regeneron Study Site
  • Bihor
    • Oradea, Bihor, Romania, 410169
      • Regeneron Study Site
• United Kingdom
  • England
    • Leicester, England, United Kingdom, LE39QP
      • Regeneron Study Site
    • Liverpool, England, United Kingdom, L7 8XP
      • Regeneron Study Site
    • London, England, United Kingdom, E1 2EF
      • Regeneron Study Site
    • London, England, United Kingdom, SW3 6NP
      • Regeneron Study Site
    • Wythenshawe, England, United Kingdom, M23 9LT
      • Regeneron Study Site
  • West Yorkshire
    • Bradford, West Yorkshire, United Kingdom, BD96RJ
      • Regeneron Study Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Regeneron Study Site
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Regeneron Study Site
  • California
    • Bakersfield, California, United States, 93301
      • Regeneron Study Site
    • La Jolla, California, United States, 92093
      • Regeneron Study Site
    • Los Angeles, California, United States, 90025
      • Regeneron Study Site
    • Riverside, California, United States, 92506
      • Regeneron Study Site
  • Idaho
    • Boise, Idaho, United States, 83706
      • Regeneron Study Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Regeneron Study Site
  • New York
    • Bronx, New York, United States, 10461
      • Regeneron Study Site
    • New York, New York, United States, 10032
      • Regeneron Study Site
  • Ohio
    • Columbus, Ohio, United States, 43235
      • Regeneron Study Site
  • Pennsylvania
    • DuBois, Pennsylvania, United States, 15801
      • Regeneron Study Site
    • Philadelphia, Pennsylvania, United States, 19140
      • Regeneron Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dupilumab; Loading subcutaneous (SC) dose on day 1, followed by SC dose, every two weeks (Q2W)	Drug: dupilumab; Single-use prefilled glass syringe administered by subcutaneous (SC) injection.; Other Names: • DUPIXENT; • REGN668; • SAR231893
Experimental: Placebo; Matching dupilumab without active substance	Drug: Placebo; Matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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
Concentrations of functional dupilumab in serum by treatment regimen		Up to 64 Weeks
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

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Sanofi
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2020
• Primary Completion (Actual): July 27, 2023
• Study Completion (Actual): February 9, 2024

Study Registration Dates

• First Submitted: June 4, 2020
• First Submitted That Met QC Criteria: June 19, 2020
• First Posted (Actual): June 22, 2020

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bacterial Infections and Mycoses; Respiratory Hypersensitivity; Hypersensitivity; Mycoses; Lung Diseases, Fungal; Aspergillosis; Pulmonary Aspergillosis; Aspergillosis, Allergic Bronchopulmonary
• Other Study ID Numbers: R668-ABPA-1923; 2019-002619-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• IPD Sharing Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No