Use of DNAse in Neutrophilic Asthma

In this pilot protocol, the researchers look to determine benefits from use of nebulized rh-DNase for 4 weeks in patients with neutrophilic asthma.

Study Overview

• Status: Unknown
• Conditions: Neutrophilic Asthma
• Intervention / Treatment: Drug: RhDNAse Inhalation Solution

Detailed Description

Patients with asthma of a non-Th2 phenotype have few advanced therapeutic options if their asthma remains poorly controlled despite adherence to guideline-based therapy. Currently, no targeted biologic therapies are available for neutrophilic asthma. The role of Recombinant human deoxyriboneuclease (rhDNase) has not been investigated in refractory asthma. rhDNase cleaves extracellular DNA released by neutrophils and other granulocytes, thereby reducing the viscosity of mucus. It is known that patients with asthma have higher levels of extracellular DNA than normals; however, these levels are lower than DNA levels found in the sputum of patients with cystic fibrosis. The benefits of rhDNase in cystic fibrosis have been well described. In these patients, use of daily nebulized rhDNase has shown improvement in lung function and reduction in exacerbations. Very little is known about DNAse use in asthmatics. Case reports have shown benefit when used in acute asthma exacerbations, but there are no data on its use as a therapy for neutrophilic asthma.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80206
      • Recruiting
      • National Jewish Health
      • Contact: Laurie Manka, MD; Phone Number: 303-398-1355; Email: mankal@njhealth.org
      • Contact: Richard Martin, MD; Phone Number: 303-398-1355

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• i. Able to read and sign an Informed Consent Form (ICF)
• ii. At least Age 18
• iii. Diagnosis of Asthma with previous source documentation of PC 20 ≤ 16 mg/dl measured by FEV1 and/or reversibility with albuterol of ≥12% in FEV1
• iv. pre-bronchodilator Forced Vital Capacity (FVC) less than 85% predicted AND Serum total MMP9 ≥ 1800 (cut off determined by previous clinical investigation- Medimmune) OR serum IL-8> 20 pg/ml OR Sputum extracellular DNA ≥ 3.8 µg/mL OR Sputum Neutrophils > 40%

Exclusion Criteria:

• i. Pregnancy
• ii. Current smoker, smoking within the past year or pack/year history ≥ 10
• iii. Respiratory infection within past 6 weeks
• iv. Antibiotics within the past 4 weeks
• v. Active lung disease other than asthma
• vi. Cancer within the past 5 years (excluding basal cell skin cancer)
• vii. Chronic infection due to HIV, HBV, or HCV
• viii. Hematologic or autoimmune disease
• ix. Unable to safely undergo bronchoscopy as determined by primary or study doctor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; rhDNAse 2.5 mg nebulizer daily for 4 weeks	Drug: RhDNAse Inhalation Solution; rhDNAse 2.5 mg nebulizer daily for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung Function	FEV1	4 weeks
Symptom Control	Asthma Control Test	4 weeks

Collaborators and Investigators

• Sponsor: National Jewish Health

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2020
• Primary Completion (Anticipated): March 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: June 20, 2019
• First Submitted That Met QC Criteria: June 20, 2019
• First Posted (Actual): June 21, 2019

Study Record Updates

• Last Update Posted (Actual): February 26, 2020
• Last Update Submitted That Met QC Criteria: February 24, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 3030005151

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