Efficacy of Reslizumab Dose Escalation in Patients With Severe Asthma

NCT04710134 | Completed Phase 4

• 1 other identifier: RES-2020-20
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma; Eosinophilic

Keywords

Asthma; Eosinophilic bronchitis; Reslizumab

Outcome Measures

Primary Outcomes (1)

• Change in Sputum eosinophilia

  Absolute difference between the mean sputum eosinophil percent

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

Secondary Outcomes (8)

• 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

• 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

• 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

• Change in FEV1

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

• 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

Study Arms (3)

Reslizumab 3 mg/kg

ACTIVE COMPARATOR

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

Biological: Reslizumab

Reslizumab 4 mg/kg

ACTIVE COMPARATOR

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 5 mg/kg

ACTIVE COMPARATOR

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

Interventions

Reslizumab BIOLOGICAL

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

Reslizumab 3 mg/kg; Reslizumab 4 mg/kg; Reslizumab 5 mg/kg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• McMaster University: lead
• Teva Canada: collaborator

Study Sites (1)

Firestone Institute of Respiratory Health, St Joseph's Hospital

Hamilton, Ontario, L8N 4A6, Canada

Location

Related Publications (4)

• Mukherjee M, Lim HF, Thomas S, Miller D, Kjarsgaard M, Tan B, Sehmi R, Khalidi N, Nair P. Airway autoimmune responses in severe eosinophilic asthma following low-dose Mepolizumab therapy. Allergy Asthma Clin Immunol. 2017 Jan 6;13:2. doi: 10.1186/s13223-016-0174-5. eCollection 2017.

  PMID: 28070196 BACKGROUND

• Mukherjee M, Forero DF, Tran S, Boulay ME, Bertrand M, Bhalla A, Cherukat J, Al-Hayyan H, Ayoub A, Revill SD, Javkar T, Radford K, Kjarsgaard M, Huang C, Dvorkin-Gheva A, Ask K, Olivenstein R, Dendukuri N, Lemiere C, Boulet LP, Martin JG, Nair P. Suboptimal treatment response to anti-IL-5 monoclonal antibodies in severe eosinophilic asthmatics with airway autoimmune phenomena. Eur Respir J. 2020 Oct 8;56(4):2000117. doi: 10.1183/13993003.00117-2020. Print 2020 Oct.

  PMID: 32444405 BACKGROUND

• Mukherjee M, Bulir DC, Radford K, Kjarsgaard M, Huang CM, Jacobsen EA, Ochkur SI, Catuneanu A, Lamothe-Kipnes H, Mahony J, Lee JJ, Lacy P, Nair PK. Sputum autoantibodies in patients with severe eosinophilic asthma. J Allergy Clin Immunol. 2018 Apr;141(4):1269-1279. doi: 10.1016/j.jaci.2017.06.033. Epub 2017 Jul 24.

  PMID: 28751233 BACKGROUND

• Passarell J, Jaworowicz D, Ludwig E, Rabinovich-Guilatt L, Cox DS, Levi M, Garin M, Fiedler-Kelly J, Bond M. Population Pharmacokinetic and Pharmacokinetic/Pharmacodynamic Modeling of Weight-Based Intravenous Reslizumab Dosing. J Clin Pharmacol. 2020 Aug;60(8):1039-1050. doi: 10.1002/jcph.1609. Epub 2020 Apr 25.

  PMID: 32333684 BACKGROUND

MeSH Terms

Conditions

Pulmonary Eosinophilia; Asthma

Interventions

reslizumab

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Parameswaran Nair, MD, PhD

  McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: January 8, 2021
• First Posted: January 14, 2021
• Study Start: February 10, 2021
• Primary Completion: January 9, 2024
• Study Completion: January 9, 2024
• Last Updated: January 25, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)