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Anti-Interleukin-5 (IL5) Monoclonal Antibody (MAb) in Prednisone-dependent Eosinophilic Asthma

This study is enrolling participants by invitation only.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02559791
First Posted: September 24, 2015
Last Update Posted: February 10, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Teva Pharmaceuticals USA
St. Joseph's Healthcare Hamilton
Information provided by (Responsible Party):
Parameswaran Nair, McMaster University
  Purpose
The steroid sparing effect of anti interleukin (IL-5) monoclonal antibody has been proven, but the effectiveness of subcutaneous (SC) compared to intravenous (IV) administration of these drugs to suppress airway eosinophilia is still under debate. As part of a previous study, 100mg of mepolizumab were administered subcutaneously to a group of subjects with prednisone-dependent eosinophilic asthma. Despite this intervention, 50% of the subjects (15 patients participated in this study) had persistently elevated sputum eosinophil counts. The same 15 patients will be invited to participate in the current study, and if they provide their informed consent, will receive 2 monthly doses of placebo, followed by 4 monthly doses of IV reslizumab. The primary outcomes are blood and sputum eosinophils, and the secondary outcomes include sputum and 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), forced expired volume in 1 second (FEV1), asthma control questionnaire (ACQ) and number of eosinophilic exacerbations. Measurements of the outcomes will be done before placebo, after placebo and after IV reslizumab. This study design will determine whether IV reslizumab is effective in suppressing airway eosinophilia in prednisone-dependent patients.

Condition Intervention Phase
Severe Persistent Asthma Eosinophilic Bronchitis Biological: Reslizumab Drug: Placebo Phase 2 Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Route of Administration of Anti-IL5 Monoclonal Antibody in Prednisone-dependent Eosinophilic Asthma

Resource links provided by NLM:


Further study details as provided by Parameswaran Nair, McMaster University:

Primary Outcome Measures:
  • 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 %

  • 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


Secondary Outcome Measures:
  • 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),

  • 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)

  • 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

  • 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) ]

Estimated Enrollment: 15
Study Start Date: October 2015
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Study participants
All study participants will receive 2 monthly doses of placebo followed by 4 monthly doses of IV reslizumab 3mg/kg
Biological: Reslizumab
Reslizumab 3ml/kg once monthly for 4 months
Other Name: Anti Il 5 monoclonal antibody
Drug: Placebo
Matching placebo once monthly for 2 months
Other Name: 0.9% normal saline

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).

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Informed consent Prior to the beginning of the study, patients must be willing and fully capable to provide written informed consent.
  2. 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.
  3. 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
  4. Sputum eosinophils ≥3% and blood eosinophil ≥300/µL on visit 1 (screening visit).
  5. Age between 18 and 75 years.
  6. 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.

  7. 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:

  1. Currently receiving another monoclonal antibody
  2. Currently receiving other investigational drug or immunosuppressive medication
  3. Known hypersensitivity to Reslizumab product or any of its excipients.
  4. Intolerance, hypersensitivity, insensitivity or neutralizing antibody to mepolizumab.
  5. Malignancy within the last 2 years
  6. 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.
  7. Current pregnancy or lactation
  8. Current smoker or ex-smoker with a smoking history greater than 20 pack years.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02559791


Locations
Canada, Ontario
Firestone Institute for Respiratory Health, St. Joseph's Healthcare
Hamilton, Ontario, Canada, L8N 4A6
Sponsors and Collaborators
McMaster University
Teva Pharmaceuticals USA
St. Joseph's Healthcare Hamilton
Investigators
Principal Investigator: Parameswaran Nair, MD, PhD McMaster University
  More Information

Additional Information:
Publications:

Responsible Party: Parameswaran Nair, MD PhD, McMaster University
ClinicalTrials.gov Identifier: NCT02559791     History of Changes
Other Study ID Numbers: RES-38072
First Submitted: September 22, 2015
First Posted: September 24, 2015
Last Update Posted: February 10, 2016
Last Verified: February 2016

Keywords provided by Parameswaran Nair, McMaster University:
Reslizumab
Eosinophils
Asthma
Airway inflammation
Prednisone

Additional relevant MeSH terms:
Asthma
Bronchitis
Pulmonary Eosinophilia
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Respiratory Tract Infections
Hypereosinophilic Syndrome
Eosinophilia
Leukocyte Disorders
Hematologic Diseases
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Prednisone
Immunologic Factors
Physiological Effects of Drugs
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents