Anti-viral Effects of Azithromycin in Patients With Asthma and COPD

NCT04319705 | Unknown Phase 4 DMC

• 1 other identifier: 0052256
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the anti-viral effects of low-dose AZM treatment in patients with asthma and COPD with an exacerbation history. The investigators expect that long-term treatment with low dose AZM modulates the immune response to viral infections, with an increased interferon release, in patients with asthma and COPD with an exacerbation history. In addition, the investigators expect a decrease in inflammatory cells and mediators, and changes in bacteria, measured in samples from the lungs. Half of the participants will receive azithromycin on top of their regular asthma/COPD treatment, while the other half will receive placebo on top of their regular asthma/COPD treatment.

Conditions

Asthma; COPD; Exacerbation Copd; Asthma; Eosinophilic; Bronchial Diseases; Lung Diseases, Obstructive; Lung Diseases; Immune System Diseases

Keywords

Eosinophil; Smoking; COPD; Asthma; Rhinovirus; Azithromycin; Inflammation; Microbiome

Outcome Measures

Primary Outcomes (2)

• IFN-beta gene and/or protein expression

  To investigate the potential change in viral induced interferon response in HBECs from baseline and after 12 weeks of treatment with low dose azithromycin or placebo, after stimulation with viral infection mimics (RV16 or Poly (I:C)

  12 weeks

• Viral load

  To investigate the potential change in viral load response in HBECs from baseline and 12 weeks of treatment with low dose azithromycin or placebo, after stimulation with viral infection mimics (RV16 or Poly (I:C)

  12 weeks

Secondary Outcomes (5)

• INF-beta gene and/or protein expression

  12 weeks

• IL-33

  12 weeks

• TSLP

  12 weeks

• Mast cells, eosinophils, Neutrophils

  12 weeks

• Lung microbiome

  12 weeks

Study Arms (2)

Azithromycin

EXPERIMENTAL

Azithromycin, 500mg capsule, 3 times per week, during a 12-week period, administered orally

Drug: Azithromycin

Placebo

PLACEBO COMPARATOR

Apart from the active substance, the placebo is otherwise identical to IMP, capsule, 3 times per week, during a 12-week period, administered orally

Drug: Placebo oral tablet

Interventions

Azithromycin DRUG

Azithromycin, 500mg, 3 times per week, 12-week treatment period, administered orally

Azithromycin

Placebo oral tablet DRUG

capsule containing placebo, 3 times per week, 12-week treatment period, administered orally

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Asthma patients (n=40)
• Diagnosis of asthma according to GINA, with confirmed variable airflow obstruction at screening visit or previously.
• Age ≥ 18 through 75 years.
• A postbronchodilator FEV1 ≥ 50% predicted
• Maintenance treatment with ICS and ≥ 1 second controller (LABA, LAMA, LTRA or Xanthines) for at least three months prior to Visit 1.
• Non-smokers (\<10 packyears, quit \>6 months).
• ≥ 1 Systemic steroid treated exacerbation in the past one year despite maintenance treatment with inhaled corticosteroids.
• Eosinophilic (n=20, blood eosinophils ≥ 0.200x109/L) and non-eosinophilic (n=20, blood eosinophils \<0.200x109/L) phenotypes.
• COPD patients (n=40)
• Diagnosis of COPD according to GOLD
• Age ≥ 45 through 75 years.
• ≥ 10 packyears smoking history (current or ex-smokers).
• A postbronchodilator FEV1 ≥ 30% predicted.
• Maintenance treatment with long-acting bronchodilators (LABA and/or LAMA) ≥ ICS.
• ≥ 1 Systemic steroid and/or antibiotic treated exacerbation in the past one year.

You may not qualify if:

• Any of the following would exclude the subject from participation in the study:
• Previous medical history or evidence of an uncontrolled intercurrent illness that in the opinion of the investigator may compromise the safety of the subject in the study or interfere with evaluation of the investigational product or reduce the subject's ability to participate in the study. Subjects with well-controlled comorbid disease (e.g., hypertension, hyperlipidemia, gastroesophageal reflux disease) on a stable treatment regimen for 15 days prior to Visit 1 are eligible.
• Any concomitant respiratory disease that in the opinion of the investigator and/or medical monitor will interfere with the evaluation of the investigational product or interpretation of subject safety or study results (e.g., cystic fibrosis, pulmonary fibrosis, moderate-severe bronchiectasis, allergic bronchopulmonary aspergillosis, Churg-Strauss syndrome, active tuberculosis). In addition for the different groups the following:
• Patient with asthma: concomitant COPD.
• Patients with COPD: concomitant asthma (former and current)
• Healthy subjects: COPD and asthma.
• Any clinically relevant abnormal findings in hematology or clinical chemistry (laboratory results from Visit 1), physical examination, vital signs during the screening, which in the opinion of the investigator, may put the subject at risk because of his/her participation in the study, or may influence the results of the study, or the subject's ability to participate in the study.
• Evidence of active liver disease, including jaundice or aspartate transaminase, alanine transaminase, or alkaline phosphatase \>1.5 times the upper limit of normal (laboratory results from Visit 1).
• GFR \<30 ml/min.
• Acute upper or lower respiratory infections requiring antibiotics or antiviral medications within 2 weeks prior to Visit 1, during the run-in period, or at Visit 2 (randomization).
• A positive human immunodeficiency virus (HIV) test at screening or subject taking antiretroviral medications, as determined by medical history and/or subject's verbal report.
• History of sensitivity to any component of the investigational product formulation or a history of drug or other allergy that, in the opinion of the investigator or medical monitor contraindicates their participation.
• History of any known primary immunodeficiency disorder excluding asymptomatic selective immunoglobulin A or IgG subclass deficiency.
• Receipt of any of the following within 30 days prior to Visit 1:
• Immunoglobulin or blood products, or

Sponsors & Collaborators

• Bispebjerg Hospital: lead
• Lund University: collaborator
• University of Copenhagen: collaborator
• Herlev and Gentofte Hospital: collaborator

Study Sites (1)

University Hospital Bispebjerg and Frederiksberg

Copenhagen, 2400, Denmark

RECRUITING

MeSH Terms

Conditions

Asthma; Pulmonary Disease, Chronic Obstructive; Pulmonary Eosinophilia; Bronchial Diseases; Lung Diseases, Obstructive; Lung Diseases; Immune System Diseases; Smoking; Inflammation

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Behavior

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Celeste Porsbjerg, MD, PhD

  University Hospital Bispebjerg and Frederiksberg

  PRINCIPAL INVESTIGATOR

• Therese S Lapperre, MD, PhD

  University Hospital Bispebjerg and Frederiksberg

  STUDY DIRECTOR

Central Study Contacts

Muzhda Ghanizada, MD

CONTACT

+45 29 20 48 43; muzhdaghanizada@hotmail.com

Therese S Lapperre, MD, PhD

CONTACT

+45 27597822; therese.sophie.lapperre@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD, PhD

Study Record Dates

• First Submitted: March 12, 2020
• First Posted: March 24, 2020
• Study Start: March 2, 2020
• Primary Completion: March 31, 2022
• Study Completion: December 31, 2022
• Last Updated: July 26, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)