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Severe Prednisone Dependent Eosinophilic AsthmaPhase 3NCT03470311

Benralizumab in Patients With Inadequate Response to Anti-IL5 Monoclonal Antibody Therapies

A Phase 3 study testing Benralizumab in people with Severe Prednisone Dependent Eosinophilic Asthma, run by McMaster University at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

In severe prednisone-dependent eosinophilic asthma, Benralizumab would suppress airway eosinophilia that is not suppressed by either Mepolizumab or Reslizumab and this would be associated with greater asthma control Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Benralizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
20 participants
Where
1 siteCanada
Study dates
26 Apr 2018to 30 Nov 2022
Phase
Phase 3
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Informed consent Prior to the beginning of the study, patients must be willing and fully capable to provide written informed consent.
  • Diagnosed prednisone-dependent eosinophilic asthma
  • Previous treatment with 100 mg mepolizumab administered subcutaneously Q4W or reslizumab 3 mg/kg IV Q4W for at least 6 months
  • Sputum eosinophils >3%
  • ACQ ≥1.5
  • Age >18
Show all 9Show fewer
  • 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.

Who cannot join

  • Currently receiving another monoclonal antibody
  • Intolerance, hypersensitivity, insensitivity or neutralizing antibody to Mepolizumab and/or Reslizumab
  • Malignancy within the last 5 years
  • Any co-morbidity that the investigator believes is a contraindication. This includes but is not limited to any respiratory, 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.

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Firestone Institute for Respiratory Health, Research - St. Joseph's Healthcare

    Hamilton, Ontario, L8N 4A6

Other trials in Canada

About this study

In severe prednisone-dependent eosinophilic asthma, Benralizumab would suppress airway eosinophilia that is not suppressed by either Mepolizumab or Reslizumab and this would be associated with greater asthma control

Read the detailed description

Benralizumab thus targets 'eosinophil biology', by inhibiting the interleukin (IL-5) receptor signalling, and inducing apoptosis in cells with an IL-5receptor. Hence, for patients who remain 'uncontrolled' on anti-IL-5 therapy (with detectable eosinophil activity and IL5-Rα+ cells in the airways), the investigators believe would benefit from a strategy that not only reduces eosinophil proliferation/recruitment/maturation, but also depletes cells capable of inducing downstream IL-5 signalling.

Being tested
Benralizumab, Placebo
Keywords
Eosinophils, asthma, inflammation, prednisone
Medical subject headings
Asthma, Inflammation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BenralizumabBiological

    Also called MEDI-563

    30mg in 1mL pre-filled syringe

  • PlaceboBiological

    Matched placebo (1mL) in pre-filled syringe

Study groups in NCT03470311
Study groupRoleWhat they receive
BenralizumabActive comparatorBenralizumab 30mg in 1mL subcutaneously
Receives: Biological: Benralizumab
PlaceboPlacebo comparatorMatched placebo (1mL) to active Benralizumab subcutaneously
Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Sputum eosinophil percentage

    Change in Percentage of sputum eosinophils (%)

    Measured: Visit 1 (Week 2) and Visit 10 (Week 38)

Secondary outcomes (7)

  1. Blood eosinophils

    Blood eosinophil level (x10^9/L)

    Measured: Visit 1 (Week 2) and Visit 10 (Week 38)

  2. Forced Expired Volume in 1 second (FEV1)(pre and post bronchodilator)

    FEV1 in litres both pre and post bronchodilator

    Measured: Visit 1 (Week 2) and Visit 10 (Week 38)

  3. ACQ-5 (Asthma Control Questionnaire)

    Asthma Control Questionnaire score (mean answer of 5 questions on a 7-point scale (0=no impairment, 6= maximum impairment).

    Measured: Visit 1 (Week 2) and Visit 10 (Week 38)

  4. Fraction of exhaled nitric oxide (FeNO)

    Exhaled nitric oxide measurement in ppb

    Measured: Visit 1 (Week 2) and Visit 10 (Week 38)

  5. Number of Exacerbations (defined as: ER visit/hospitalization requiring prednisone burst)

    Worsening requiring increase in oral steroids/prednisone (30mg x 5 days)

    Measured: Visit 1 (Week 2) and Visit 10 (Week 38)

  6. Sputum and blood ILC2 biology

    Measurement of ILC2 biological cells in both blood and sputum

    Measured: Visit 1 (Week 2) and Visit 10 (Week 38)

  7. Sputum autoimmune responses

    Measurement of autoimmune markers in sputum: anti-eosinophil peroxidase (EPX) and anti-nuclear antibodies (ANA) - (See last reference PubMed ID: 28751233)

    Measured: Visit 1 (Week 2) and Visit 10 (Week 38)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Mar 2018
  2. Study start26 Apr 2018
  3. Primary completion14 Jun 2022
  4. Study completion30 Nov 2022

Resources

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 3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03470311
Sponsor's protocol ID
17-12992
Status last verified
Jan 2023
First submitted
1 Mar 2018
Last updated
20 Jan 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

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 28070196

  • 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.

    PubMed 26194544

  • Sehmi R, Smith SG, Kjarsgaard M, Radford K, Boulet LP, Lemiere C, Prazma CM, Ortega H, Martin JG, Nair P. Role of local eosinophilopoietic processes in the development of airway eosinophilia in prednisone-dependent severe asthma. Clin Exp Allergy. 2016 Jun;46(6):793-802. doi: 10.1111/cea.12695.

    PubMed 26685004

  • Kolbeck R, Kozhich A, Koike M, Peng L, Andersson CK, Damschroder MM, Reed JL, Woods R, Dall'acqua WW, Stephens GL, Erjefalt JS, Bjermer L, Humbles AA, Gossage D, Wu H, Kiener PA, Spitalny GL, Mackay CR, Molfino NA, Coyle AJ. MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol. 2010 Jun;125(6):1344-1353.e2. doi: 10.1016/j.jaci.2010.04.004.

    PubMed 20513525

  • 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.

    PubMed 28915080

  • Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P, Barker P, Sproule S, Ponnarambil S, Goldman M; ZONDA Trial Investigators. Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma. N Engl J Med. 2017 Jun 22;376(25):2448-2458. doi: 10.1056/NEJMoa1703501. Epub 2017 May 22.

    PubMed 28530840

  • 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.

    PubMed 28751233

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Benralizumab in people with Severe Prednisone Dependent Eosinophilic Asthma, 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 9 inclusion and 6 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 20 Jan 2023. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

Sputum eosinophil percentage (time frame: Visit 1 (Week 2) and Visit 10 (Week 38)). 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 NCT03470311, which also lists 7 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 20 Jan 2023.

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