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
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
Brief Title
Investigating Treatment With Dupilumab in Patients With Allergic Bronchopulmonary Aspergillosis (ABPA) (LIBERTY ABPA AIRED)
Categories
Completion Date
Completion Date Type
Actual
Conditions
Allergic Bronchopulmonary Aspergillosis
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.
* 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.
Inclusion 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
inclusion /
* 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
inclusion /
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
12 Years
NCT Id
NCT04442269
Org Class
Industry
Org Full Name
Regeneron Pharmaceuticals
Org Study Id
R668-ABPA-1923
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Measure
Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo
Outcome Time Frame
At Week 24
Secondary Ids
Secondary Id
2019-002619-24
Secondary Outcomes
Outcome Description
Defined as severe respiratory exacerbations that are associated with a doubling of serum total Immunoglobulin E (IgE) from the prior pre-exacerbation value.
Adjusted Rate: Negative Binomial Regression Model Unadjusted Rate: (Number of events)/(number of participant years)
Adjusted Rate: Negative Binomial Regression Model Unadjusted Rate: (Number of events)/(number of participant years)
Outcome Time Frame
Over the 24 to 52 Week Treatment Period
Outcome Measure
Annualized Rate of ABPA-related Exacerbations
Outcome Description
Defined as new onset of symptoms or clinical worsening of respiratory symptoms requiring systemic corticosteroid treatment for ≥3 consecutive days; for participants 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)
Adjusted Rate: Negative Binomial Regression Model Unadjusted Rate: (Number of events)/(number of participant years)
Adjusted Rate: Negative Binomial Regression Model Unadjusted Rate: (Number of events)/(number of participant years)
Outcome Time Frame
Over the 24 to 52 Week Treatment Period
Outcome Measure
Annualized Rate of Severe Respiratory Exacerbations
Outcome Description
Annualized rate of severe respiratory exacerbations requiring either hospitalization or observation for \>24 hours in an emergency department/urgent care facility (events per person-year)
Adjusted Rate: Negative Binomial Regression Model Unadjusted Rate: (Number of events)/(number of participant years)
Adjusted Rate: Negative Binomial Regression Model Unadjusted Rate: (Number of events)/(number of participant years)
Outcome Time Frame
Over the 24 to 52 Week Treatment Period
Outcome Measure
Annualized Rate of Severe Respiratory Exacerbations Requiring Either Hospitalization or Observation for >24 Hours in an ED/Urgent Care Facility
Outcome Description
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. Participants with a score below 1.0 reflect adequately controlled asthma and participants 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.
Outcome Time Frame
Over the 24 to 52 Week Treatment Period
Outcome Measure
Change From Baseline in Asthma Control Questionnaire (ACQ)-5 Score
Outcome Description
SGRQ will be completed by the patient to measure and quantify health status in adult participants 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).
Outcome Time Frame
Over the 24 to 52 Week Treatment Period
Outcome Measure
Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score
Outcome Description
SGRQ will be completed by the patient to measure and quantify health status in adult participants 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).
Outcome Time Frame
Up to 52 Weeks
Outcome Measure
Percentage of Participants Achieving a Reduction in the SGRQ Total Score of 4 Points or Greater From Baseline
Outcome Time Frame
Over the 24 to 52 Week Treatment Period
Outcome Measure
Percent Change From Baseline in Total IgE in Serum
Outcome Time Frame
Over the 24 to 52 Week Treatment Period
Outcome Measure
Percent Change From Baseline in A Fumigatus-specific IgE in Serum
Outcome Time Frame
Over the 24 to 52 Week Treatment Period
Outcome Measure
Absolute Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO)
Outcome Time Frame
Over the 24 to 52 Week Treatment Period
Outcome Measure
Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO)
Outcome Time Frame
Through the end of the 52 Week Treatment Period
Outcome Measure
Number of Participants With Treatment-emergent Adverse Events (TEAEs) From Baseline
Outcome Time Frame
Up to 64 Weeks
Outcome Measure
Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) Responses and Titer Over Time
Outcome Time Frame
Up to 64 Weeks
Outcome Measure
Concentrations of Functional Dupilumab in Serum by Treatment Regimen
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
12
Investigators
Investigator Type
Principal Investigator
Investigator Name
Golda Hudes
Investigator Email
ghudes@montefiore.org
Investigator Phone
646-229-9509