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Efficacy of Reslizumab Dose Escalation in Patients With Severe Asthma

Primary Purpose

Asthma; Eosinophilic

Status

Active

Phase

Phase 4

Locations

Canada

Study Type

Interventional

Intervention

Reslizumab

About this trial

This is an interventional treatment trial for Asthma; Eosinophilic focused on measuring Asthma, Eosinophilic bronchitis, Reslizumab

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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
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

Sites / Locations

Firestone Institute of Respiratory Health, St Joseph's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Arm Label

Reslizumab 3 mg/kg

Reslizumab 4 mg/kg

Reslizumab 5 mg/kg

Arm Description

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

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.

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).

Outcomes

Primary Outcome Measures

Change in Sputum eosinophilia

Absolute difference between the mean sputum eosinophil percent

Secondary Outcome Measures

Change in Proportion of patients with sputum eosinophils ≤3%

Number of patients with sputum eosinophils ≤3%

Change in Blood eosinophil count

Absolute blood eosinophil count

Change in ACQ5 score

Mean of 5-question Asthma Control Questionnaire

Change in FEV1

Forced expired volume in 1 second measured in litres

Change in Number of asthma exacerbations

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)

Type of exacerbation shown by: neutrophilic, eosinophilic or mixed neutrophilic/eosinophilic bronchitis

Change in Proportion of patients requiring daily oral corticosteroid therapy

Number of patients that require daily oral corticosteroids

Change in Cumulative systemic corticosteroid dose

The total daily dose of oral corticosteroids

Full Information

NCT ID

NCT04710134

First Posted

January 8, 2021

Last Updated

January 18, 2023

Sponsor

McMaster University

Collaborators

Teva Canada

1. Study Identification

Unique Protocol Identification Number

NCT04710134

Brief Title

Efficacy of Reslizumab Dose Escalation in Patients With Severe Asthma

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

February 10, 2021 (Actual)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

February 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

McMaster University

Collaborators

Teva Canada

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Asthma; Eosinophilic

Keywords

Asthma, Eosinophilic bronchitis, Reslizumab

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Sequential Assignment

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).

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Reslizumab 3 mg/kg

Arm Type

Active Comparator

Arm Description

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

Arm Title

Reslizumab 4 mg/kg

Arm Type

Active Comparator

Arm Description

Arm Title

Reslizumab 5 mg/kg

Arm Type

Active Comparator

Arm Description

Intervention Type

Biological

Intervention Name(s)

Reslizumab

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in Sputum eosinophilia

Description

Absolute difference between the mean sputum eosinophil percent

Time Frame

At baseline and at the end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks.

Secondary Outcome Measure Information:

Title

Change in Proportion of patients with sputum eosinophils ≤3%

Description

Number of patients with sputum eosinophils ≤3%

Time Frame