Asthma; EosinophilicPhase 4NCT04710134
Efficacy of Reslizumab Dose Escalation in Patients With Severe Asthma
A Phase 4 study testing Reslizumab in people with Asthma; Eosinophilic, run by McMaster University at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Asthma; Eosinophilic
- What is being tested?
- Reslizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteCanada
- Study dates
- 10 Feb 2021to 9 Jan 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Asthma confirmed within the past 2 years by:
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site
Firestone Institute of Respiratory Health, St Joseph's Hospital
Hamilton, Ontario, L8N 4A6
About this study
Official title: Efficacy of Reslizumab Dose Escalation in Patients With Severe Asthma and Persistent Sputum Eosinophilia Despite Standard Dose Therapy
Dose escalation of reslizumab can ameliorate sputum eosinophilia in severe asthmatics who have persistent sputum eosinophilia despite treatment with reslizumab at the standard dose.
Read the 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.
- Conditions
- Asthma; Eosinophilic
- Being tested
- Reslizumab
- Keywords
- Asthma, Eosinophilic bronchitis, Reslizumab
- Medical subject headings
- Pulmonary Eosinophilia, Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ReslizumabBiological
Reslizumab 3,4, or 5 mg/kg IV q4 weeks
| Study group | Role | What they receive |
|---|---|---|
| Reslizumab 3 mg/kg | Active comparator | All patients will initially receive reslizumab 3 mg/kg for at least 16 weeks. Receives: 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. Receives: 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). Receives: Biological: Reslizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Sputum eosinophilia
Absolute difference between the mean sputum eosinophil percent
Measured: 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%
Number of patients with sputum eosinophils ≤3%
Measured: 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
Absolute blood eosinophil count
Measured: 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
Mean of 5-question Asthma Control Questionnaire
Measured: At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks
Change in FEV1
Forced expired volume in 1 second measured in litres
Measured: 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
Number of asthma event that are defined as exacerbation (requiring increase in corticosteroids)
Measured: At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks
Change in Type of asthma exacerbations (as determined by quantitative sputum cytometry)
Type of exacerbation shown by: neutrophilic, eosinophilic or mixed neutrophilic/eosinophilic bronchitis
Measured: At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks
Change in Proportion of patients requiring daily oral corticosteroid therapy
Number of patients that require daily oral corticosteroids
Measured: At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks
Change in Cumulative systemic corticosteroid dose
The total daily dose of oral corticosteroids
Measured: At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2021
- Study start10 Feb 2021
- Primary completion9 Jan 2024
- Study completion9 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Asthma; EosinophilicStudies of the same condition, open and under way.
- More trials run by McMaster UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- 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)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Collaborators
- Teva Canada
- Responsible party
- Sponsor
- Investigators
- Parameswaran Nair, MD, PhD, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04710134
- Sponsor's protocol ID
- RES-2020-20
- Status last verified
- Jan 2024
- First submitted
- 8 Jan 2021
- Last updated
- 25 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 28070196Mukherjee 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.
PubMed 32444405Mukherjee 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.
PubMed 28751233Passarell 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.
PubMed 32333684
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Reslizumab Dose Escalation in Patients With Severe Asthma and Persistent Sputum Eosinophilia Despite Standard Dose Therapy
- ClinicalTrials.gov ID
- NCT04710134
- Acronym / sponsor ID
- RES-2020-20
- Conditions
- Asthma; Eosinophilic
- Keywords
- Asthma, Eosinophilic bronchitis, Reslizumab
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Collaborators
- Teva Canada
- Study start
- 10 Feb 2021 (actual)
- Primary completion
- 9 Jan 2024 (actual)
- Study completion
- 9 Jan 2024 (actual)
- First posted
- 14 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- 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).
| Arm | Type | Receives |
|---|---|---|
| Reslizumab 3 mg/kg | Active comparator | Biological: ReslizumabAll patients will initially receive reslizumab 3 mg/kg for at least 16 weeks. |
| Reslizumab 4 mg/kg | Active comparator | Biological: ReslizumabPatients 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. |
| Reslizumab 5 mg/kg | Active comparator | Biological: ReslizumabPatients 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). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Asthma confirmed within the past 2 years by:
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ReslizumabReslizumab 3,4, or 5 mg/kg IV q4 weeks | Biological | Reslizumab 3 mg/kg, Reslizumab 4 mg/kg, Reslizumab 5 mg/kg |
Primary outcome
Change in Sputum eosinophilia
Time frame: At baseline and at the end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks.
Absolute difference between the mean sputum eosinophil percent
8 secondary outcomes
Change in Proportion of patients with sputum eosinophils ≤3%
Time frame: 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
Time frame: 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
Time frame: At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks
Change in FEV1
Time frame: 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
Time frame: At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks
Change in Type of asthma exacerbations (as determined by quantitative sputum cytometry)
Time frame: At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks
Change in Proportion of patients requiring daily oral corticosteroid therapy
Time frame: At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks
Change in Cumulative systemic corticosteroid dose
Time frame: At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2024.
- Background: PubMed 28070196Mukherjee 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.
- Background: PubMed 32444405Mukherjee 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.
- Background: PubMed 28751233Mukherjee 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.
- Background: PubMed 32333684Passarell 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Parameswaran Nair, MD, PhD principal investigator
McMaster University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Reslizumab in people with Asthma; Eosinophilic, run by McMaster University at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Sputum eosinophilia (time frame: At baseline and at the end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04710134, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2024.