Efficacy of Reslizumab Dose Escalation in Patients With Severe Asthma

Asthma; Eosinophilic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04710134
• Other study ID #: RES-2020-20
• Status: Completed
• Phase: Phase 4
• Start date: February 10, 2021
• Est. completion date: January 9, 2024

Study information

• Verified date: January 2024
• Source: McMaster University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: January 9, 2024
• Est. primary completion date: January 9, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthma
• Asthma; Eosinophilic
• Pulmonary Eosinophilia

Intervention

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

Locations

Country	Name	City	State
Canada	Firestone Institute of Respiratory Health, St Joseph's Hospital	Hamilton	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
McMaster University	Teva Canada

Country where clinical trial is conducted

Canada, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

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