Efficacy of Reslizumab Dose Escalation in Patients With Severe Asthma

Sponsor

McMaster University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04710134

Collaborator

Teva Canada (Other)

Enrollment

Location

Arms

19.6

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma; Eosinophilic	Biological: Reslizumab	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

Patients will initially all receive 3 mg/kg of reslizumab. After 16 weeks of treatment, those patients that have uncontrolled sputum eosinophilia will be escalated to 4 mg/kg; the remaining patients will continue on 3 mg/kg. After a further 16 weeks of therapy, those that still have uncontrolled sputum eosinophilia will receive 5 mg/kg; the remaining patients will continue on the dose they were receiving (i.e., either 3 or 4 mg/kg).Patients will initially all receive 3 mg/kg of reslizumab. After 16 weeks of treatment, those patients that have uncontrolled sputum eosinophilia will be escalated to 4 mg/kg; the remaining patients will continue on 3 mg/kg. After a further 16 weeks of therapy, those that still have uncontrolled sputum eosinophilia will receive 5 mg/kg; the remaining patients will continue on the dose they were receiving (i.e., either 3 or 4 mg/kg).

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Efficacy of Reslizumab Dose Escalation in Patients With Severe Asthma and Persistent Sputum Eosinophilia Despite Standard Dose Therapy

Actual Study Start Date :

Feb 10, 2021

Anticipated Primary Completion Date :

Jul 1, 2022

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Reslizumab 3 mg/kg All patients will initially receive reslizumab 3 mg/kg for at least 16 weeks.	Biological: Reslizumab Reslizumab 3,4, or 5 mg/kg IV q4 weeks
Active Comparator: Reslizumab 4 mg/kg Patients who have uncontrolled sputum eosinophilia at 16 weeks will receive an increased dose of 4 mg/kg for the next 16 weeks. The patients with controlled eosinophilia will continue to receive 3 mg/kg.	Biological: Reslizumab Reslizumab 3,4, or 5 mg/kg IV q4 weeks
Active Comparator: Reslizumab 5 mg/kg Patients who have uncontrolled sputum eosinophilia who were previously receiving reslizumab at 4 mg/kg at 32 weeks will receive an increased dose of 5 mg/kg for the next 16 weeks. The patients remaining patients will continue on the dose they were receiving (i.e., either 3 mg/kg or 4 mg/kg).	Biological: Reslizumab Reslizumab 3,4, or 5 mg/kg IV q4 weeks

Arm

Intervention/Treatment

Active Comparator: Reslizumab 3 mg/kg

All patients will initially receive reslizumab 3 mg/kg for at least 16 weeks.

Biological: Reslizumab

Reslizumab 3,4, or 5 mg/kg IV q4 weeks

Active Comparator: Reslizumab 4 mg/kg

Patients who have uncontrolled sputum eosinophilia at 16 weeks will receive an increased dose of 4 mg/kg for the next 16 weeks. The patients with controlled eosinophilia will continue to receive 3 mg/kg.

Biological: Reslizumab

Reslizumab 3,4, or 5 mg/kg IV q4 weeks

Active Comparator: Reslizumab 5 mg/kg

Patients who have uncontrolled sputum eosinophilia who were previously receiving reslizumab at 4 mg/kg at 32 weeks will receive an increased dose of 5 mg/kg for the next 16 weeks. The patients remaining patients will continue on the dose they were receiving (i.e., either 3 mg/kg or 4 mg/kg).

Biological: Reslizumab

Reslizumab 3,4, or 5 mg/kg IV q4 weeks

Outcome Measures

Primary Outcome Measures

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

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%
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 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 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 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 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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Asthma confirmed within the past 2 years by:

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

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
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
Ability to provide informed consent

Exclusion Criteria:

Current smokers, ex-smokers with greater than 20 pack-year history or ex-smokers who have smoked within the past 6 months
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
Currently treated with another biologic agent (excluding denosumab for osteoporosis)
Use of anti-IL-5 (other than reslizumab) or anti-IgE mAb use within the past one month
Use of a systemic immunosuppressive or immunomodulatory agent within 6 months prior to study entry
Suspected of abusing drugs or alcohol
Pregnancy or lactation