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

Regeneron Pharmaceuticals1 site in 1 country62 target enrollmentSeptember 15, 2020

ConditionsAllergic Bronchopulmonary Aspergillosis

Interventionsdupilumab Placebo

Drugsdupilumab Placebo

Overview

Phase: Phase 2
Intervention: dupilumab
Conditions: Allergic Bronchopulmonary Aspergillosis
Sponsor: Regeneron Pharmaceuticals
Enrollment: 62
Locations: 1
Primary Endpoint: Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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

Registry

clinicaltrials.gov

Start Date

September 15, 2020

End Date

February 9, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Regeneron Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

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

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.

Arms & Interventions

dupilumab

Loading subcutaneous (SC) dose on day 1, followed by SC dose, every two weeks (Q2W)

Intervention: dupilumab

Placebo

Matching dupilumab without active substance

Intervention: Placebo

Outcomes

Primary Outcomes

Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo

Time Frame: At Week 24

Secondary Outcomes

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)
Annualized Rate of ABPA-related Exacerbations(Over the 24 to 52 Week Treatment Period)
Percentage of Participants Achieving a Reduction in the SGRQ Total Score of 4 Points or Greater From Baseline(Up to 52 Weeks)
Absolute Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO)(Over the 24 to 52 Week Treatment Period)
Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score(Over the 24 to 52 Week Treatment Period)
Annualized Rate of Severe Respiratory Exacerbations(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 Score(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)
Number of Participants With 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)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) From Baseline(Through the end of the 52 Week Treatment Period)