Use of DNAse in Neutrophilic Asthma

National Jewish Health

Status and phase

Unknown

Phase 2

Phase 1

Conditions

Neutrophilic Asthma

Treatments

Drug: RhDNAse Inhalation Solution

Study type

Interventional

Funder types

Other

Identifiers

NCT03994380

3030005151

Details and patient eligibility

About

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

Full 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.

Enrollment

10 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.