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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04710134
Other study ID # RES-2020-20
Secondary ID
Status Completed
Phase Phase 4
First received
Last updated
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
Health authority
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

Study Design


Related Conditions & MeSH terms


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
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