Azithromycin Treatment for the Airway Microbiome in Asthma

NCT03736629 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: IRB17-1287
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study to determine whether the bacteria inside the lungs of people with asthma can be modified (changed) if they are given an antibiotic and if this change is associated with an improvement in asthma symptoms.

Conditions

Asthma Chronic

Keywords

Asthma; Azithromycin; Microbiome; Sputum

Outcome Measures

Primary Outcomes (1)

• Asthma Control Test (ACT) Score Change From Baseline Over 8 Weeks

  Score ranging from 0 to 40 indicating the degree of asthma symptoms. Lower score indicating worse asthma symptoms.

  Baseline and 8 weeks

Secondary Outcomes (7)

• Forced Expiratory Volume (FEV1) Change From Baseline Over 8 Weeks

  8 weeks

• Sputum Eosinophils Change From Baseline Over 8 Weeks

  Baseline and 8 weeks

• Sputum Neutrophils Change From Baseline Over 8 Weeks

  Baseline and 8 weeks

• Number of Participants With Diary Event or Serious Asthma Exacerbation Over 8 Weeks

  8 weeks

• Microbiome Shannon Alpha-diversity Score Change From Baseline to 8 Weeks

  8 weeks

Study Arms (3)

Placebo

PLACEBO COMPARATOR

8 weeks of placebo capsule once daily by mouth

Drug: Placebo

Azithromycin

ACTIVE COMPARATOR

8 weeks of Azithromycin (250 mg) capsule once daily by mouth

Drug: Azithromycin

Non-asthmatic controls

NO INTERVENTION

Non-asthmatic controls to assess variability of microbiome composition and diversity over time in a normal population. No intervention given.

Interventions

Azithromycin DRUG

8 weeks of Azithromycin (250 mg) once daily by mouth

Also known as: Zithromax

Azithromycin

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 - 55 years
• Able to provide informed consent
• Smoking history \< 10 pack-years
• Methacholine PC20 \< 16 mg/ml or PD 20 \< 400 mcg/ml or albuterol response \> 12% on FEV1 after 4 puffs of albuterol
• Currently prescribed ICS + LABA
• Meet definition for Th2-low asthma: peripheral blood eosinophil count \< 300 and exhaled nitric oxide level \< 30 ppb.

You may not qualify if:

• History of allergy or intolerance to any medications used in this study
• Current use of medications that prolong QTc interval
• Current use of omalizumab or other ant-IgE therapies
• Current use of anti-IL 5 therapies
• Current use of anticoagulants
• Prednsione or other oral steroids within past 3 months
• Pregnancy or lactation, or plans to become pregnant
• Other respiratory or inflammatory disorders (e.g., sarcoidosis, emphysema)
• Pre-existing liver disease by history
• Smoking within the last 6 months
• Exacerbation of asthma in past 3 months
• Affected by a hearing disorder
• Clinically significant medical condition (e.g., heart failure, seizure disorder) which may in-crease risk as determined by study investigator
• Corrected QT interval \> 450 msec. Patients with known cardiac history or prolonged QT interval on a screening EKG are excluded given the small but real potential for macrolide-related side effects

Sponsors & Collaborators

• University of Chicago: lead
• Northwestern University: collaborator

Study Sites (2)

Northwestern University

Chicago, Illinois, 60201, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Related Publications (1)

• Vogelmeier CF, Fuhlbrigge A, Jauhiainen A, Scheepers LEJM, Bengtsson T, Peterson S, Karlsson N, Sethi T, Locantore N, Tal-Singer R, Rennard S, Fageras M, Da Silva CA. COPDCompEx: A novel composite endpoint for COPD exacerbations to enable faster clinical development. Respir Med. 2020 Nov;173:106175. doi: 10.1016/j.rmed.2020.106175. Epub 2020 Sep 28.

  PMID: 33032168 RESULT

MeSH Terms

Conditions

Asthma

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Theodore Karrison (Research Professor)
• Organization: University of Chicago

tkarrison@health.bsd.uchicago.edu

773-702-9326

Study Officials

• Steve White, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2018
• First Posted: November 9, 2018
• Study Start: February 1, 2019
• Primary Completion: March 1, 2021
• Study Completion: June 1, 2022
• Last Updated: August 23, 2023
• Results First Posted: August 23, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Upon publication of the major manuscript to be generated from this study. Data will be deposited in an appropriate major database (e.g., sequencing information will be deposited in a genetics bio-bank).
• Access Criteria: All qualified investigators who sign appropriate data use agreements and material transfer agreements with the University of Chicago and Northwestern University

Locations

US (2)