Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE August 26, 2018
First Posted Date  ICMJE August 29, 2018
Last Update Posted Date August 29, 2018
Estimated Study Start Date  ICMJE September 1, 2018
Estimated Primary Completion Date May 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 27, 2018)
Dendritic cell concentrations and phenotypes [ Time Frame: 5 months ]
Dendritic cell concentrations and phenotypes
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: August 27, 2018)
T-cell concentrations and phenotypes [ Time Frame: 5 months ]
T-cell concentrations and phenotypes
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Impact of Benralizumab Treatment on Circulating Dendritic Cells in Patients With Eosinophilic Asthma
Official Title  ICMJE Impact of Benralizumab Treatment on Circulating Dendritic Cells in Patients With Eosinophilic Asthma
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
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
Condition  ICMJE Severe Eosinophilic Asthma
Intervention  ICMJE Drug: Benralizumab
Treatment with Benralizumab 30 mg s.c. every 4 weeks (three times)
Study Arms  ICMJE Experimental: Benralizumab
Patients will be treated with Benralizumab 30 mg s.c. every 4 weeks (three times).
Intervention: Drug: Benralizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: August 27, 2018)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2019
Estimated Primary Completion Date May 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03652376
Other Study ID Numbers  ICMJE Rostock-Benralizumab-2018-1
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Marek Lommatzsch, University of Rostock
Study Sponsor  ICMJE University of Rostock
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Marek Lommatzsch, MD University of Rostock
PRS Account University of Rostock
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP