Clinical trial NCT04108962: Benralizumab in the Treatment of Patients With Severe Asthma With ABPA
Official title: Phase IV, Single-Center, Open-Label Study Evaluating the Effects of an Anti-IL5 Receptor Alpha (Benralizumab) Monoclonal Antibody in the Treatment of Severe Asthma in Patients With Allergic Bronchopulmonary Aspergillosis
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: ABPA
Severe Asthma
Allergic Bronchopulmonary Aspergillosis
Keywords: ABPA
Benralizumab
Lead sponsor: Baylor Research Institute
Sponsor class: OTHER
First posted: 2019-09-30
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase IV, open-label study will evaluate effects of Benralizumab in the treatment of severe asthma in patients with allergic bronchopulmonary aspergillosis

Detailed description: Subjects who have been identified to have severe asthma with ABPA will be consented and enrolled in the study to receive benralizumab injections administered every 4 weeks for the first 3 injections with an additional injection eight weeks to follow for a total of 16 weeks active treatment with a follow-up/termination visit eight weeks from the last injection. The termination visit will occur week 24 for subjects who complete the study treatment. Subjects who receive the first dose of benralizumab but withdraw from the study or terminate study treatment for any reason should complete all the procedures outlined for the termination visit.

Eligibility criteria: SELECT INCLUSION CRITERIA

* Female and Male patients aged 18-75 years inclusively at the time of Visit 1 with a physician diagnosis of Allergic Bronchopulmonary Aspergillosis has met the ISHAM Working Group Diagnostic Criteria for ABPA:

  * Predisposing condition: Bronchial asthma
  * Obligatory criteria (both should be present)

    * Type I aspergillus skin test positive (immediate cutaneous hypersensitivity Aspergillus antigen) or elevated IgE level against Aspergillus fumigatus (Af)
    * Aspergillus niger or Aspergillus flavus may be eligible provided antigen-specific IgE and IgG measurements are available for use.
    * Elevated total IgE levels (\>1,000IU/mL)\*
  * Other criteria (at least two of three)

    * Presence of precipitating or IgG antibodies against Af in serum
    * Radiographic pulmonary opacities consistent with ABPA
    * Total eosinophil count \>500 cells/uL in steroid naïve patients (may be historical)

      * (if the patient meets all other criteria, an IgE value \<1,000 IU/mL may be acceptable)
* Severe chronic asthma (for at least 12 months) requiring treatment with high dose ICS plus asthma controller prior to Visit 1

  * Other acceptable asthma controllers include long acting bronchodilators (e.g. a long acting beta-agonist (LABA) or long-acting muscarinic antagonists (LAMA)), a leukotriene inhibitor, theophylline preparations and/or maintenance OCS (daily or every other day OCS requirement in order to maintain asthma control
  * Documented current treatment with high daily doses of ICS ( \>500ug of FP equivalent) plus at least one other asthma controller for at least 3 months prior to Visit 1

    * For ICS/LABA combination preparation, highest-strength maintenance doses approved in the U.S. will meet this criterion
    * If the ICS and the other asthma controller therapies are given by separate inhalers, then the patient must be on a high daily ICS dose for 3 months prior to entering the study.
* History of at least 2 asthma exacerbations while on ICS plus another asthma controller (see inclusion criterion 2 for examples) that required treatment with systemic corticosteroids (IM, IV, or oral) in the 12 months prior to Visit 1. For patients receiving oral corticosteroids as a maintenance therapy, an exacerbation is defined as a temporary increase of their maintenance dose for a minimum of 3 days.
* Weight \> 40kg

SELECT EXCLUSION CRITERIA

* Clinical important pulmonary disease other than asthma with allergic bronchopulmonary aspergillosis (ie. chronic obstructive pulmonary disease (COPD), cystic fibrosis, sarcoid, and pulmonary fibrosis)
* History of anaphylaxis to any biologic therapy
* Known history of allergy or hypersensitivity reaction to benralizumab or any of its components
* Current smokers or former smokers with a smoking history of \> 10 pack years. A former smoker is defined as a patient who quit smoking at least 6 months prior to Visit 1.
* Currently pregnant, breastfeeding, or lactating women
* Concurrent enrollment in another interventional or post-authorization safety study, unless it is observational.

Primary outcomes:
measure: Number of steroid requiring exacerbations
timeFrame: 26 Weeks
Secondary outcomes:
measure: Patient-Reported Quality of Life as assessed by Saint George Respiratory Questionnaire
timeFrame: 26 Weeks
measure: Asthma Control as assessed by Asthma Control Questionnaire 6
timeFrame: 26 Weeks
measure: Lung Function (FEV1)
timeFrame: 26 Weeks
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
Study officials:
affiliation: Baylor Scott and White Health
name: Yolanda Mageto, MD
role: PRINCIPAL_INVESTIGATOR
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.