Use of DNAse in Neutrophilic Asthma

Phase 1

• Conditions: Neutrophilic Asthma
• Interventions: Drug: RhDNAse Inhalation Solution

• Registration Number: NCT03994380
• Lead Sponsor: National Jewish Health

Brief Summary

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

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 Timeline

• Study First Submitted: 2019-06-20
• Study First Submitted QC: 2019-06-20
• Study First Posted: 2019-06-21
• Status Verified: 2020-02
• Study Start: 2020-02-12
• Last Update Submitted: 2020-02-24
• Last Update Posted: 2020-02-26
• Primary Completion: 2020-03
• Study Completion: 2020-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intervention	RhDNAse Inhalation Solution	rhDNAse 2.5 mg nebulizer daily for 4 weeks

Primary Outcome Measures

Name	Time	Method
Lung Function	4 weeks	FEV1
Symptom Control	4 weeks	Asthma Control Test

Trial Locations

Locations (1)

National Jewish Health; 🇺🇸 Denver, Colorado, United States