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Impact of Benralizumab Treatment on Circulating Dendritic Cells in Patients With Eosinophilic Asthma

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ClinicalTrials.gov Identifier: NCT03652376
Recruitment Status : Not yet recruiting
First Posted : August 29, 2018
Last Update Posted : August 29, 2018
Sponsor:
Information provided by (Responsible Party):
Marek Lommatzsch, University of Rostock

Brief Summary:
This study investigates the effect of removing eosinophils from peripheral blood (using treatment with Benralizumab, which is approved for the treatment of severe eosoniphilic asthma) on circulating dendritic cells in patients with severe eosinophilic asthma.

Condition or disease Intervention/treatment Phase
Severe Eosinophilic Asthma Drug: Benralizumab Phase 4

Detailed Description:
Phase III clinical trials demonstrated that benralizumab treatment results in a significant decrease in exacerbations and a significant increase in lung function and quality of life in patients with severe eosinophilic asthma. However, the precise underlying mechanisms leading to this clinical benefit of benralizumab treatment are not completely understood. Dendritic cells are key regulators of the adaptive and innate immune system. There is evidence that eosinophils have a direct influence on the function of dendritic cells. In addition, there are multiple indirect interactions between eosinophils and dendritic cells in asthma. However, there is currently no information on the impact of benralizumab treatment and a complete removal of circulating eosinophils on the number and phenotype of human dendritic cells. Benralizumab is chosen for this study because it is the only anti-IL-5 biologic which results in a complete removal of eosinophils from peripheral blood.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Patients with severe eosinophilic asthma (n=20) will be treated with benralizumab 3 times every 4 weeks, and the effect of this treatment on dendritic cell concentrations and dendritic cell characteristics will be investigated 4 weeks after the last benralizumab dose and after a follow-up of 3 months. There will be a separate control group of subjects (not a treatment or placebo arm) without asthma not treated with benralizumab (to study dendritic cell concentrations and dendritic cell characteristics in patients without asthma and without benralizumab treatment).
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Impact of Benralizumab Treatment on Circulating Dendritic Cells in Patients With Eosinophilic Asthma
Estimated Study Start Date : September 1, 2018
Estimated Primary Completion Date : May 1, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Experimental: Benralizumab
Patients will be treated with Benralizumab 30 mg s.c. every 4 weeks (three times).
Drug: Benralizumab
Treatment with Benralizumab 30 mg s.c. every 4 weeks (three times)




Primary Outcome Measures :
  1. Dendritic cell concentrations and phenotypes [ Time Frame: 5 months ]
    Dendritic cell concentrations and phenotypes


Secondary Outcome Measures :
  1. T-cell concentrations and phenotypes [ Time Frame: 5 months ]
    T-cell concentrations and phenotypes



Information from the National Library of Medicine

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

Inclusion Criteria:

  1. Age between 18 and 75 years
  2. Patients with severe eosinophilic asthma inadequately controlled despite high-dose inhaled corticosteroids plus long-acting β-agonists.
  3. Documented reversibility of airway obstruction (FEV1 increase ≥ 200 ml and ≥ 15 % after inhalation of a short-acting beta agonist) or bronchial hyperresponsiveness to methacholine or histamine
  4. Documented concentration of blood eosinophils ≥ 300 / µl blood on the day of study inclusion or in the previous 4 weeks before study inclusion
  5. Documented current treatment with high daily doses of ICS plus at least one other asthma controller for at least 3 months at Visit 1.
  6. Disease history: asthma exacerbations while on ICS plus another controller.
  7. ACQ-6 score ≥ 1.5 at Visit 1.
  8. Weight of ≥ 40 kg.
  9. Screening pre-bronchodilator (pre-BD) FEV1 of < 80% predicted
  10. Women of childbearing potential (WOCBP)(Definition: WOCBP are those women who have not been surgically sterilized or have not been free from menses for > 2 years) and male study participants have to use adequate contraception methods.

Exclusion Criteria:

  1. Smoking history of > 10 Pack years
  2. Current smoking
  3. Presence of other chronic pulmonary diseases including COPD
  4. Presence of other chronic inflammatory diseases
  5. Treatment with any systemic immunosuppressive drug including prednisolone or biologics
  6. Current pregnancy, breast feeding
  7. Known helminth infections
  8. Acute upper or lower respiratory infections within 30 days prior to the date informed consent is obtained or during the screening/run-in period.
  9. Any disorder, including, but not limited to, cardiovascular, gastrontestinal, hepatic, renal, neurological, musculosceletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could:

    • affect the safety of the patient throughout the study
    • influence the findings of the studies or their interpretations
    • impede the patient´s ability to complete the entire duration of study
  10. Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of the SmPC.
  11. A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with, or has failed to respond to, standard of care therapy.
  12. Any clinically significant abnormal findings in physical examination, vital signs, hematology, or clinical chemistry during screening period, which in the opinion of the investigator may put the patient at risk of his/her participation in the study, or may influence the results of the study, or the patient´s ability to complete entire duration of the study.
  13. Any clinically significant cardiac disease or any electrocardiogram (ECG) abnormality which in the opinion of the Investigator may put the the patient at risk or interfere with study assessments.
  14. A history of known immunodeficiency disorder including a positive human immunodeciency virus (HIV) test.
  15. Current malignancy, or history of malignancy, except for: Patients who have had non-melanoma skin cancer or in situ carcinoma of the cervix are eligible provided that the patient is in remission and curative therapy was completed at least 12 months prior to the date informed consent is obtained. Patients who have had other malignancies are eligible provided that the patient is in remission and curative therapy was completed at least 5 years prior to the date informed consent is obtained.
  16. Concurrent biologics for asthma are not allowed except for stable allergen immunotherapy (defined as a stable dose and regimen at the time of Visit 1). Acceptable washout periods or other asthma biologics:

    • Other eosinophil lowering products indicated for asthma (including reslizumab or mepolizumab): at least 4 months.
    • Prior omalizumab use: 1 month.
  17. Any immunosuppressant systemic medication (including systemic glucocorticoids) or treatment with antibodies targeting the immune system.
  18. Receipt of any investigational medication as part of a research study within approximately 5 half-lives prior to randomization
  19. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level > 3 times of the upper limit of normal (ULN) confirmed during screening period.
  20. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained.
  21. Receipt of live attenuated vaccines 30 days prior to the date of randomization; other types of vaccines are allowed.
  22. Planned surgical procedures during the conduct of the study.
  23. Concurrent enrolment in another interventional or post-authorization safety study.

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): NCT03652376


Contacts
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Contact: Marek Lommatzsch, MD +49-381-494-0 ext 7461 marek.lommatzsch@med.uni-rostock.de
Contact: Johann C. Virchow, MD +49-381-494-0 ext 7461 j.c.virchow@med.uni-rostock.de

Locations
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Germany
University of Rostock Not yet recruiting
Rostock, Mecklenburg-Vorpommern, Germany, 18057
Contact: Marek Lommatzsch, Prof.    +49-381-494-0 ext 7461    marek.lommatzsch@med.uni-rostock.de   
Sponsors and Collaborators
University of Rostock
Investigators
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Principal Investigator: Marek Lommatzsch, MD University of Rostock

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Responsible Party: Marek Lommatzsch, Prof. Dr. Marek Lommatzsch, University of Rostock
ClinicalTrials.gov Identifier: NCT03652376     History of Changes
Other Study ID Numbers: Rostock-Benralizumab-2018-1
First Posted: August 29, 2018    Key Record Dates
Last Update Posted: August 29, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Benralizumab
Asthma
Pulmonary Eosinophilia
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Hypereosinophilic Syndrome
Eosinophilia
Leukocyte Disorders
Hematologic Diseases
Anti-Asthmatic Agents
Respiratory System Agents