- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02559791
Anti-Interleukin-5 (IL5) Monoclonal Antibody (MAb) in Prednisone-dependent Eosinophilic Asthma
Route of Administration of Anti-IL5 Monoclonal Antibody in Prednisone-dependent Eosinophilic Asthma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study design
Blinded placebo-controlled sequential clinical trial of 4 monthly doses of intravenously administered reslizumab.
The study will include two periods:
Period 1: After establishing the minimum dose of prednisone to observe sputum eosinophils ≥3% and blood eosinophils ≥300/µL, all subjects will receive 2 infusions (once monthly) of matching placebo.
Period 2: All subjects will then receive 4 infusions (once monthly) of reslizumab 3mg/kg.
Methods
15 patients (all of whom had sputum eosinophils ≥3% and blood eosinophils ≥300/µL) who were previously treated with S/C100 mg mepolizumab for at least 6 months, with the last dose at least 4 months before entering the study, will be invited to participate in the study.
Since discontinuing mepolizumab, these patients would have been re-established on their maintenance dose of daily prednisone + high doses of inhaled corticosteroids (ICS) and long acting beta agonist (LABA).
Baseline measurements of blood and sputum eosinophils, spirometry, symptoms (ACQ), and immune cells in blood and sputum (ILC2 cells, CD4 + cells, CD8+ cells, CD34+ Eo/B progenitor cells) will be enumerated by flow cytometry, and measures of local autoimmunity, using our established protocols at the start of Period 1 (baseline measurement).
They will then receive 2 infusions of placebo at monthly intervals, and measurements will be repeated at the end of Period 1 (post-placebo measurement).
The subjects will then receive by 4 infusions of 3 mg/kg reslizumab at monthly intervals. At the end of the 4 months, these measurements will be repeated (post-reslizumab measurement).
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
-
-
Ontario
-
Hamilton, Ontario, Canada, L8N 4A6
- Firestone Institute for Respiratory Health, St. Joseph's Healthcare
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Informed consent Prior to the beginning of the study, patients must be willing and fully capable to provide written informed consent.
Prednisone-dependent eosinophilic asthma
- Documented evidence of asthma: FEV1 reversibility of 12% and 200 ml after 200-400 micrograms of SABA. Or Methacholine challenge test <8mg/ml.
- Documented history of persistent eosinophilia (sputum eosinophils ≥3% and/or blood eosinophils ≥300/µL) despite maintenance treatment with systemic glucocorticoids (5 to 35 mg per day of prednisone or its equivalent) before entering the study.
- Previous treatment with 100 mg mepolizumab administered subcutaneously for at least 6 months, with the last dose at least 4 months before entering the study
- Sputum eosinophils ≥3% and blood eosinophil ≥300/µL on visit 1 (screening visit).
- Age between 18 and 75 years.
Male or eligible female subjects:
To be eligible for entry into the study, females of childbearing potential (premenopausal women who are not permanently sterilized by means of hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) must commit to consistent and correct use of a highly effective method of birth control (true sexual abstinence, a vasectomized sexual partner, Implanon, female tubal occlusion, Intrauterine device (IUD), Depo provera injections, oral contraceptive pills or Nuvaring) for the duration of the trial and for 3 months after the last study drug administration. A serum pregnancy test is required of all females at the initial Baseline Visit (Visit 1). In addition, a urine pregnancy test will be performed for all females prior to enrollment, during each scheduled study visit prior to the injection of investigational product, and during the Follow-up Visit.
- Male subjects who are sexually active must agree to use a double barrier method of contraception (condom with spermicide) from the first dose of study drug and for 3 months after the last dose of study drug.
Exclusion Criteria:
- Currently receiving another monoclonal antibody
- Currently receiving other investigational drug or immunosuppressive medication
- Known hypersensitivity to Reslizumab product or any of its excipients.
- Intolerance, hypersensitivity, insensitivity or neutralizing antibody to mepolizumab.
- Malignancy within the last 2 years
- Any co-morbidity that the investigator believes is a contraindication. This includes but is not limited to any respiratory (eg. COPD, pulmonary fibrosis, EGPA, ABPA), cardiovascular, gastrointestinal, hematological, neurological, immunological, musculoskeletal, renal, infectious, neoplastic or inflammatory condition that may place the safety of the subject at risk during the duration of the study, influence the results of the study or their interpretation, or prevent the patient from completing the entire duration of the study.
- Current pregnancy or lactation
- Current smoker or ex-smoker with a smoking history greater than 20 pack years.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Study participants
All study participants will receive 2 monthly doses of placebo followed by 4 monthly doses of IV reslizumab 3mg/kg
|
Reslizumab 3ml/kg once monthly for 4 months
Other Names:
Matching placebo once monthly for 2 months
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Sputum eosinophil percentage
Time Frame: Measured before the placebo phase (week 2), after 2 infusions of placebo (week 10), and after 4 infusions (week 26) of reslizumab 3mg/kg
|
Change in sputum eosinophil %
|
Measured before the placebo phase (week 2), after 2 infusions of placebo (week 10), and after 4 infusions (week 26) of reslizumab 3mg/kg
|
Blood eosinophil absolute number
Time Frame: Measured before the placebo phase (week 2), after 2 infusions of placebo (week 10), and after 4 infusions/4 months (week 26) of reslizumab 3mg/kg
|
Change in blood eosinophil absolute number
|
Measured before the placebo phase (week 2), after 2 infusions of placebo (week 10), and after 4 infusions/4 months (week 26) of reslizumab 3mg/kg
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Sputum and blood blood Innate lymphoid cell-2 (ILC2) cells, cluster of differentiation 4 (CD4+) cells, cluster of differentiation-8 (CD8+) cells, cluster of differentiation-34 (CD34+), Eosinophil-Basophil cluster cells (Eo/B progenitor cells),
Time Frame: Measured before the placebo phase (week 2), after 2 infusions of placebo (week 10), and after 4 infusions (week 26)of reslizumab 3mg/kg
|
Change in absolute number of both sputum and blood blood Innate lymphoid cell-2 (ILC2) cells.
Change in absolute number of different T-lymphocyte populations in cluster of differentiation 4 (CD4+) cells, cluster of differentiation-8 (CD8+) cells, cluster of differentiation-34 (CD34+) and Eosinophil-Basophil cluster cells (Eo/B progenitor cells),
|
Measured before the placebo phase (week 2), after 2 infusions of placebo (week 10), and after 4 infusions (week 26)of reslizumab 3mg/kg
|
Forced Expiratory Volume in 1 second (FEV1)
Time Frame: Measured before the placebo phase (week 2), after 2 infusions of placebo (week 10), and after 4 infusions (week 26) of reslizumab 3mg/kg
|
Change in Forced Expiratory Volume in 1 second (FEV1)
|
Measured before the placebo phase (week 2), after 2 infusions of placebo (week 10), and after 4 infusions (week 26) of reslizumab 3mg/kg
|
Asthma Control Questionnaire (ACQ)
Time Frame: Measured before the placebo phase (week 2), after 2 infusions of placebo (week 10), and after 4 infusions (week 26) of reslizumab 3mg/kg
|
Change in ACQ
|
Measured before the placebo phase (week 2), after 2 infusions of placebo (week 10), and after 4 infusions (week 26) of reslizumab 3mg/kg
|
Number of eosinophilic exacerbations
Time Frame: During the placebo phase (2 months/weeks 2-10) and during the Reslizumab phase (weeks 10-26) 4 months)
|
During the placebo phase (2 months/weeks 2-10) and during the Reslizumab phase (weeks 10-26) 4 months)
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Parameswaran Nair, MD, PhD, McMaster University
Publications and helpful links
General Publications
- D'silva L, Cook RJ, Allen CJ, Hargreave FE, Parameswaran K. Changing pattern of sputum cell counts during successive exacerbations of airway disease. Respir Med. 2007 Oct;101(10):2217-20. doi: 10.1016/j.rmed.2007.05.010. Epub 2007 Jul 2.
- Nair P, Dasgupta A, Brightling CE, Chung KF. How to diagnose and phenotype asthma. Clin Chest Med. 2012 Sep;33(3):445-57. doi: 10.1016/j.ccm.2012.05.003. Epub 2012 Jul 7.
- Bousquet J, Mantzouranis E, Cruz AA, Ait-Khaled N, Baena-Cagnani CE, Bleecker ER, Brightling CE, Burney P, Bush A, Busse WW, Casale TB, Chan-Yeung M, Chen R, Chowdhury B, Chung KF, Dahl R, Drazen JM, Fabbri LM, Holgate ST, Kauffmann F, Haahtela T, Khaltaev N, Kiley JP, Masjedi MR, Mohammad Y, O'Byrne P, Partridge MR, Rabe KF, Togias A, van Weel C, Wenzel S, Zhong N, Zuberbier T. Uniform definition of asthma severity, control, and exacerbations: document presented for the World Health Organization Consultation on Severe Asthma. J Allergy Clin Immunol. 2010 Nov;126(5):926-38. doi: 10.1016/j.jaci.2010.07.019.
- Green RH, Brightling CE, McKenna S, Hargadon B, Parker D, Bradding P, Wardlaw AJ, Pavord ID. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet. 2002 Nov 30;360(9347):1715-21. doi: 10.1016/S0140-6736(02)11679-5.
- Jayaram L, Pizzichini MM, Cook RJ, Boulet LP, Lemiere C, Pizzichini E, Cartier A, Hussack P, Goldsmith CH, Laviolette M, Parameswaran K, Hargreave FE. Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations. Eur Respir J. 2006 Mar;27(3):483-94. doi: 10.1183/09031936.06.00137704.
- Nissim Ben Efraim AH, Levi-Schaffer F. Tissue remodeling and angiogenesis in asthma: the role of the eosinophil. Ther Adv Respir Dis. 2008 Jun;2(3):163-71. doi: 10.1177/1753465808092281.
- Zhang J, Kuvelkar R, Murgolo NJ, Taremi SS, Chou CC, Wang P, Billah MM, Egan RW. Mapping and characterization of the epitope(s) of Sch 55700, a humanized mAb, that inhibits human IL-5. Int Immunol. 1999 Dec;11(12):1935-44. doi: 10.1093/intimm/11.12.1935.
- Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, Marshall RP, Bradding P, Green RH, Wardlaw AJ, Pavord ID. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med. 2009 Mar 5;360(10):973-84. doi: 10.1056/NEJMoa0808991. Erratum In: N Engl J Med. 2011 Feb 10;364(6):588.
- Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, Ortega H, Chanez P. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012 Aug 18;380(9842):651-9. doi: 10.1016/S0140-6736(12)60988-X.
- Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, Humbert M, Katz LE, Keene ON, Yancey SW, Chanez P; MENSA Investigators. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014 Sep 25;371(13):1198-207. doi: 10.1056/NEJMoa1403290. Epub 2014 Sep 8. Erratum In: N Engl J Med. 2015 Apr 30;372(18):1777.
- Castro M, Mathur S, Hargreave F, Boulet LP, Xie F, Young J, Wilkins HJ, Henkel T, Nair P; Res-5-0010 Study Group. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med. 2011 Nov 15;184(10):1125-32. doi: 10.1164/rccm.201103-0396OC. Epub 2011 Aug 18.
- Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, Ortega HG, Pavord ID; SIRIUS Investigators. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014 Sep 25;371(13):1189-97. doi: 10.1056/NEJMoa1403291. Epub 2014 Sep 8.
- Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, Hargreave FE, O'Byrne PM. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med. 2009 Mar 5;360(10):985-93. doi: 10.1056/NEJMoa0805435.
- Nair P. Anti-interleukin-5 monoclonal antibody to treat severe eosinophilic asthma. N Engl J Med. 2014 Sep 25;371(13):1249-51. doi: 10.1056/NEJMe1408614. Epub 2014 Sep 8. No abstract available.
- McKenzie AN. Type-2 innate lymphoid cells in asthma and allergy. Ann Am Thorac Soc. 2014 Dec;11 Suppl 5(Suppl 5):S263-70. doi: 10.1513/AnnalsATS.201403-097AW.
- Hogan SP, Rosenberg HF, Moqbel R, Phipps S, Foster PS, Lacy P, Kay AB, Rothenberg ME. Eosinophils: biological properties and role in health and disease. Clin Exp Allergy. 2008 May;38(5):709-50. doi: 10.1111/j.1365-2222.2008.02958.x. Epub 2008 Apr 1.
- Smith SG, Chen R, Kjarsgaard M, Huang C, Oliveria JP, O'Byrne PM, Gauvreau GM, Boulet LP, Lemiere C, Martin J, Nair P, Sehmi R. Increased numbers of activated group 2 innate lymphoid cells in the airways of patients with severe asthma and persistent airway eosinophilia. J Allergy Clin Immunol. 2016 Jan;137(1):75-86.e8. doi: 10.1016/j.jaci.2015.05.037. Epub 2015 Jul 17.
- Kabata H, Moro K, Fukunaga K, Suzuki Y, Miyata J, Masaki K, Betsuyaku T, Koyasu S, Asano K. Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation. Nat Commun. 2013;4:2675. doi: 10.1038/ncomms3675.
- Mukherjee M, Aleman Paramo F, Kjarsgaard M, Salter B, Nair G, LaVigne N, Radford K, Sehmi R, Nair P. Weight-adjusted Intravenous Reslizumab in Severe Asthma with Inadequate Response to Fixed-Dose Subcutaneous Mepolizumab. Am J Respir Crit Care Med. 2018 Jan 1;197(1):38-46. doi: 10.1164/rccm.201707-1323OC.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Immune System Diseases
- Lung Diseases
- Hypersensitivity, Immediate
- Hematologic Diseases
- Bronchial Diseases
- Lung Diseases, Obstructive
- Respiratory Hypersensitivity
- Hypersensitivity
- Leukocyte Disorders
- Eosinophilia
- Hypereosinophilic Syndrome
- Asthma
- Pulmonary Eosinophilia
- Bronchitis
- Anti-Asthmatic Agents
- Respiratory System Agents
- Reslizumab
Other Study ID Numbers
- RES-38072
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Severe Persistent Asthma
-
Lu Yuan LeeNational Institute of Allergy and Infectious Diseases (NIAID)WithdrawnPulmonary Atelectasis | Severe Persistent Asthma | Moderate Persistent Asthma | Nodule Solitary PulmonaryUnited States
-
University of PennsylvaniaCentocor, Inc.Withdrawn
-
Wake Forest UniversityNational Heart, Lung, and Blood Institute (NHLBI)CompletedAsthma | Severe Persistent AsthmaUnited States
-
Arcispedale Santa Maria Nuova-IRCCSUnknownSevere Persistent AsthmaItaly
-
University of ChicagoWithdrawnSevere Persistent Asthma
-
University of AlbertaWithdrawnSevere Persistent AsthmaCanada
-
University of PisaUniversity Of Perugia; National Research Council, Institute of Clinical Physiology... and other collaboratorsNot yet recruitingAsthma | Asthma Severe Persistent UncontrolledItaly
-
Medical Centre LeeuwardenGlaxoSmithKlineCompleted
-
Sally E. Wenzel MDCompletedAsthma | Severe Persistent AsthmaUnited States
-
Rush University Medical CenterGenentech, Inc.CompletedSevere Persistent AsthmaUnited States
Clinical Trials on Reslizumab
-
Teva Branded Pharmaceutical Products R&D, Inc.Completed
-
Teva Branded Pharmaceutical Products R&D, Inc.TerminatedEosinophils, AsthmaUnited States, Belgium, Canada, Czechia, France, Germany, Hungary, Israel, Poland, Romania, Russian Federation, Spain, Ukraine
-
Ception TherapeuticsCephalonCompletedEosinophilic EsophagitisUnited States, Canada
-
McMaster UniversityTeva CanadaCompleted
-
National Institute of Allergy and Infectious Diseases...CompletedHypereosinophilic SyndromeUnited States
-
University of RochesterWithdrawnAsthma | Chronic Rhinosinusitis (Diagnosis) | Nasal PolypsUnited States
-
Teva Branded Pharmaceutical Products R&D, Inc.PPDCompletedAsthmaUnited States, Argentina, Australia, Belgium, Canada, Czechia, France, Germany, Hungary, Israel, Japan, Korea, Republic of, Mexico, New Zealand, Poland, Romania, Russian Federation, South Africa, Spain, Turkey, Ukraine
-
Food and Drug Administration (FDA)Spaulding Clinical Research LLCCompletedHealthy Subjects | Pharmacokinetics | PharmacodynamicsUnited States
-
National Jewish HealthTeva Pharmaceuticals USAUnknown