A Study to Evaluate the Efficacy and Safety of Dupilumab in Participants With Allergic Bronchopulmonary Aspergillosis (ABPA) (LIBERTY ABPA AIRED)

• ClinicalTrials.gov Identifier: NCT04442269
• Recruitment Status: Recruiting
• First Posted: June 22, 2020
• Last Update Posted: March 9, 2021
• Sponsor: Regeneron Pharmaceuticals
• Collaborator: Sanofi
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Study Description

Brief Summary:

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

The secondary objectives of the study are:

• To evaluate the effects of dupilumab on lung function 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

Condition or disease	Intervention/treatment	Phase
Allergic Bronchopulmonary Aspergillosis	Drug: dupilumab; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 170 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 15, 2020
• Estimated Primary Completion Date: September 7, 2023
• Estimated Study Completion Date: October 23, 2023

Arms and Interventions

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 injection.; Other Names: • DUPIXENT; • REGN668; • SAR231893
Experimental: Placebo; Matching dupilumab without active substance	Drug: Placebo; Matching placebo

Outcome Measures

Primary Outcome Measures :

1. Annualized rate of severe respiratory exacerbations [ Time Frame: Up to Week 52 ]

Secondary Outcome Measures :

1. Change in pre-bronchodilator Forced expiratory volume in 1 second (FEV1) compared to placebo [ Time Frame: At week 24 ]
2. Change from baseline in pre-bronchodilator FEV1 compared to placebo [ Time Frame: At week 52 ]
3. Annualized rate of ABPA-related exacerbations compared to placebo [ Time Frame: Up to 52 Weeks ]
4. Annualized rate of severe respiratory exacerbations requiring either hospitalization or observation for >24 hours in an ED/urgent care facility compared to compared to placebo [ Time Frame: Up to 52 Weeks ]
5. Change from baseline in Asthma Control Questionnaire (ACQ)-5 compared to placebo [ Time Frame: Up to 52 Weeks ]
   Questionnaire completed by patient to measure both the adequacy of asthma control and change in asthma control. 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.
6. Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score compared to placebo [ Time Frame: Up to 52 Weeks ]
   Questionnaire will be completed by the patient to measure and quantify health status in adult patients with chronic airflow limitation. Global score ranges from 0 to 100. Scores by dimension are calculated for three domains: Symptoms, Activity, and Impacts (Psychosocial) as well as a total score. Lower score indicates better Quality of Life (QoL).
7. Percentage of participants achieving a reduction in the SGRQ score of 4 points or greater from baseline compared to placebo [ Time Frame: Up to 52 Weeks ]
8. Percent change from baseline in total IgE in serum compared to placebo [ Time Frame: Up to 52 Weeks ]
9. Percent change from baseline in A fumigatus-specific IgE in serum compared to placebo [ Time Frame: Up to 52 Weeks ]
10. Percent and absolute change from baseline in fractional exhaled nitric oxide (FeNO) compared to placebo [ Time Frame: Up to 52 Weeks ]
11. Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 52 Weeks ]
12. Incidence of treatment-emergent anti-drug antibody (ADA) responses and titer [ Time Frame: Up to 64 Weeks ]
13. Concentrations of functional dupilumab in serum by treatment regimen [ Time Frame: Up to 64 Weeks ]

Eligibility Criteria

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

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 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 OCS, exacerbation requiring at least doubling of the daily 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.

Contacts and Locations

Contacts

Contact: Clinical Trials Administrator; 844-734-6643; clinicaltrials@regeneron.com

Locations

United States, Alabama

Regeneron Study Site; Recruiting

Birmingham, Alabama, United States, 35209

United States, California

Regeneron Study Site; Recruiting

Bakersfield, California, United States, 93301

Regeneron Study Site; Recruiting

Riverside, California, United States, 92506

Regeneron Study Site; Recruiting

Stockton, California, United States, 95207

United States, Maryland

Regeneron Study Site; Recruiting

Baltimore, Maryland, United States, 21224

United States, Minnesota

Regeneron Study Site; Recruiting

Minneapolis, Minnesota, United States, 55402

United States, New Jersey

Regeneron Study Site; Recruiting

Brick, New Jersey, United States, 08724

United States, North Carolina

Regeneron Study Site; Recruiting

Mooresville, North Carolina, United States, 28117

United States, Wisconsin

Regeneron Study Site; Recruiting

Cudahy, Wisconsin, United States, 53110

Canada

Regeneron Study Site; Recruiting

Ottawa, Canada, K1G 6C6

Germany

Regeneron Study Site; Not yet recruiting

Berlin, Germany, 10717

Hungary

Regeneron Study Site; Not yet recruiting

Debrecen, Hungary, 4031

Japan

Regeneron Study Site; Recruiting

Fukuyama, Japan, 7200001

Regeneron Study Site; Recruiting

Naka-gun, Japan, 3191113

Regeneron Study Site; Recruiting

Yanagawa, Japan, 8320059

Romania

Regeneron Study Site; Recruiting

Bragadiru, Romania, 769764

Regeneron Study Site; Recruiting

Brasov, Romania, 500051

Regeneron Study Site; Recruiting

Bucharest, Romania, 011461

Regeneron Study Site; Recruiting

Bucharest, Romania, 050159

Regeneron Study Site; Recruiting

Oradea, Romania, 410169

Sponsors and Collaborators

Regeneron Pharmaceuticals

Sanofi

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04442269
• Other Study ID Numbers: R668-ABPA-1923; 2019-002619-24 ( EudraCT Number )
• First Posted: June 22, 2020
• Last Update Posted: March 9, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• 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.
• 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).
• URL: https://vivli.org/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Aspergillosis; Pulmonary Aspergillosis; Aspergillosis, Allergic Bronchopulmonary; Mycoses; Lung Diseases, Fungal; Lung Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Respiratory Tract Infections; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases