Efficacy of Reslizumab Dose Escalation in Patients With Severe Asthma

Phase 4

Completed

• Conditions: Asthma; Eosinophilic

• Registration Number: NCT04710134
• Lead Sponsor: McMaster University

Brief Summary

Dose escalation of reslizumab can ameliorate sputum eosinophilia in severe asthmatics who have persistent sputum eosinophilia despite treatment with reslizumab at the standard dose.

Detailed Description

Monoclonal antibody therapies targeting the interleukin-5 (IL-5) pathway, critical for maintaining eosinophil homeostasis, have been developed as adjunct therapy for severe asthma with an eosinophilic phenotype. Reslizumab/Cinqair is an approved/marketed product administered monthly by intravenous to severe eosinophilic asthmatics at 3mg/kg. However some patients do exhibit sputum eosinophilia at this dosage. We are investigating whether those that receive 3mg/kg that have persistent sputum eosinophils would benefit at a higher dose of 4mg/kg and those that still exhibit sputum eosinophils at this elevated dose would show improvement at 5mg/kg.

The overall aim of this study is to determine whether dose escalation of reslizumab can ameliorate sputum eosinophilia in severe asthmatics who have persistent sputum eosinophilia despite treatment with reslizumab at the standard dose.

Study Timeline

• Study First Submitted: 2021-01-08
• Study First Submitted QC: 2021-01-12
• Study First Posted: 2021-01-14
• Study Start: 2021-02-10
• Status Verified: 2024-01
• Primary Completion: 2024-01-09
• Study Completion: 2024-01-09
• Last Update Submitted: 2024-01-24
• Last Update Posted: 2024-01-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

1. Asthma confirmed within the past 2 years by:

   a. A ≥12% improvement in forced expiratory volume in 1 second (FEV1) after use of a beta agonist, or a methacholine challenge test showing a ≥20% reduction in FEV1 after a concentration of ≤8 mg/mL of methacholine

2. Blood eosinophils ≥400 cells/µL and/or sputum eosinophils ≥3% (or presence of moderate-to-many free eosinophil granules) at the time of study enrollment

3. Treated with an inhaled corticosteroid at a dose of ≥1500 µg of fluticasone propionate (or equivalent) and a long-acting beta agonist with or without oral corticosteroids

4. Ability to provide informed consent

Exclusion Criteria

1. Current smokers, ex-smokers with greater than 20 pack-year history or ex-smokers who have smoked within the past 6 months
2. Any comorbidity that the investigator believes is a contraindication including but not limited to any respiratory (e.g., chronic obstructive pulmonary disease, allergic bronchopulmonary aspergillosis, pulmonary fibrosis), cardiovascular (e.g., congestive cardiac failure, pulmonary hypertension), hematological, gastrointestinal, immunological, musculoskeletal, infectious, or neoplastic disease
3. Currently treated with another biologic agent (excluding denosumab for osteoporosis)
4. Use of anti-IL-5 (other than reslizumab) or anti-IgE mAb use within the past one month
5. Use of a systemic immunosuppressive or immunomodulatory agent within 6 months prior to study entry
6. Suspected of abusing drugs or alcohol
7. Pregnancy or lactation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Primary Outcome Measures

Name	Time	Method
Change in Sputum eosinophilia	At baseline and at the end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks.	Absolute difference between the mean sputum eosinophil percent

Secondary Outcome Measures

Name	Time	Method
Change in Number of asthma exacerbations	At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks	Number of asthma event that are defined as exacerbation (requiring increase in corticosteroids)
Change in Cumulative systemic corticosteroid dose	At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks	The total daily dose of oral corticosteroids
Change in Blood eosinophil count	At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks	Absolute blood eosinophil count
Change in Type of asthma exacerbations (as determined by quantitative sputum cytometry)	At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks	Type of exacerbation shown by: neutrophilic, eosinophilic or mixed neutrophilic/eosinophilic bronchitis
Change in Proportion of patients requiring daily oral corticosteroid therapy	At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks	Number of patients that require daily oral corticosteroids
Change in ACQ5 score	At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks	Mean of 5-question Asthma Control Questionnaire
Change in FEV1	At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks	Forced expired volume in 1 second measured in litres
Change in Proportion of patients with sputum eosinophils ≤3%	At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks	Number of patients with sputum eosinophils ≤3%

Trial Locations

Locations (1)

Firestone Institute of Respiratory Health, St Joseph's Hospital; 🇨🇦 Hamilton, Ontario, Canada