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

August 27, 2018 updated by: Marek Lommatzsch, University of Rostock
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.

Study Overview

Status

Unknown

Intervention / Treatment

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

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • Mecklenburg-Vorpommern
      • Rostock, Mecklenburg-Vorpommern, Germany, 18057

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Benralizumab
Patients will be treated with Benralizumab 30 mg s.c. every 4 weeks (three times).
Treatment with Benralizumab 30 mg s.c. every 4 weeks (three times)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dendritic cell concentrations and phenotypes
Time Frame: 5 months
Dendritic cell concentrations and phenotypes
5 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
T-cell concentrations and phenotypes
Time Frame: 5 months
T-cell concentrations and phenotypes
5 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Marek Lommatzsch, MD, University of Rostock

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

September 1, 2018

Primary Completion (ANTICIPATED)

May 1, 2019

Study Completion (ANTICIPATED)

December 31, 2019

Study Registration Dates

First Submitted

August 26, 2018

First Submitted That Met QC Criteria

August 27, 2018

First Posted (ACTUAL)

August 29, 2018

Study Record Updates

Last Update Posted (ACTUAL)

August 29, 2018

Last Update Submitted That Met QC Criteria

August 27, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

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.

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