Benralizumab in the Treatment of Patients With Severe Asthma With ABPA

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

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

Study Overview

• Status: Withdrawn
• Conditions: Severe Asthma; Allergic Bronchopulmonary Aspergillosis; ABPA
• Intervention / Treatment: Drug: Fasenra, 30 Mg/mL Subcutaneous Solution

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.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Benralizumab treatment will be given by 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	Drug: Fasenra, 30 Mg/mL Subcutaneous Solution; Anti-IL5 receptor alpha monoclonal antibody; Other Names: Benralizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of steroid requiring exacerbations	Number of asthma exacerbations requiring the initiation of (or temporary increase in) systemic corticosteroids in severe asthma complicated by ABPA	26 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-Reported Quality of Life as assessed by Saint George Respiratory Questionnaire	The change from baseline score in Saint George Respiratory Questionnaire	26 Weeks
Asthma Control as assessed by Asthma Control Questionnaire 6	The change from baseline score in Asthma Control Questionnaire 6	26 Weeks
Lung Function (FEV1)	The FEV1 change from baseline to End of Treatment	26 Weeks

Collaborators and Investigators

• Sponsor: Baylor Research Institute
• Investigators: Principal Investigator: Yolanda Mageto, MD, Baylor Scott and White Health

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): December 23, 2019
• Primary Completion (Actual): September 24, 2021
• Study Completion (Actual): October 1, 2021

Study Registration Dates

• First Submitted: September 24, 2019
• First Submitted That Met QC Criteria: September 27, 2019
• First Posted (Actual): September 30, 2019

Study Record Updates

• Last Update Posted (Actual): February 1, 2022
• Last Update Submitted That Met QC Criteria: January 17, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Benralizumab; ABPA
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Bacterial Infections and Mycoses; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Mycoses; Lung Diseases, Fungal; Asthma; Aspergillosis; Pulmonary Aspergillosis; Aspergillosis, Allergic Bronchopulmonary; Anti-Asthmatic Agents; Respiratory System Agents; Benralizumab
• Other Study ID Numbers: 019-294

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: no subjects enrolled

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No