Efficacy of Reslizumab Dose Escalation in Patients With Severe Asthma

McMaster University

Status and phase: Completed; Phase 4

Conditions: Asthma; Eosinophilic

Treatments: Biological: Reslizumab

Study type: Interventional

Funder types: Other

Identifiers

NCT04710134

RES-2020-20

Details and patient eligibility

About

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

Full 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.

Enrollment: 10 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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10 participants in 3 patient groups

Reslizumab 3 mg/kg

Active Comparator group

Description:

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

Treatment:

Biological: Reslizumab

Reslizumab 4 mg/kg

Active Comparator group

Description:

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.

Treatment:

Biological: Reslizumab

Reslizumab 5 mg/kg

Active Comparator group

Description:

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).

Treatment:

Biological: Reslizumab