One-time targeted lung denervation (dNerva) for people with COPD and lung hyperinflation

A Multicenter, Randomized, Study to Evaluate Safety and Efficacy After Treatment With the dNerva Lung Denervation System in Subjects With Chronic Obstructive Pulmonary Disease (COPD) (AIRFLOW-4)

This will see if a single dNerva targeted lung denervation procedure, added to usual COPD medications, improves breathing and lung function in people with COPD who have high residual lung volume and low emphysema.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 40 Years to 80 Years
• Sex: All
• Sponsor: Nuvaira, Inc. (industry)
• Drugs / interventions: chemotherapy, radiation, prednisone
• Locations: 10 sites (Birmingham, Alabama and 9 other locations)
• Trial ID: NCT07051707 on ClinicalTrials.gov

What this trial studies

Adults with moderate-to-severe COPD who meet strict lung-function criteria (high residual volume, low emphysema, and FEV1 25–70% predicted) and who are on standard inhaled therapy are enrolled and assigned to either a one-time dNerva targeted lung denervation plus standard care or to continued standard care alone. The trial measures lung function (including RV/TLC and FEV1), symptom scores, and safety outcomes over follow-up to determine whether the added procedure leads to superior improvement. Secondary endpoints include other efficacy measures and a thorough safety assessment of the lung denervation device and procedure. Treatment is delivered at participating US tertiary centers experienced in interventional pulmonology.

Who should consider this trial

Good fit: Ideal candidates are people aged 40–80 with moderate-to-severe COPD on optimized inhaled therapy, with documented high residual volume (RV ≥175% predicted and RV/TLC >55%) and relatively low emphysema.

Not a fit: Patients with predominant emphysema, low lung hyperinflation, active smoking, very severe gas exchange abnormalities, or those not on optimized medical therapy are unlikely to benefit.

Why it matters

Potential benefit: If successful, this could provide a single-procedure option to reduce lung hyperinflation and improve breathing and quality of life for a subset of COPD patients.

How similar studies have performed: Prior clinical work on targeted lung denervation has shown promising but mixed results on symptom and exacerbation outcomes, and safety continues to be characterized in ongoing studies.

Eligibility criteria

Inclusion Criteria:

* ≥ 40 and ≤ 80 years of age at the time of consent.
* Women of childbearing potential must not be pregnant, evidenced by a negative pregnancy test (blood or urine) pre-treatment, or lactating and agree not to become pregnant for the duration of the study.
* Smoking history of at least 10 pack years.
* Not smoking or using any other inhaled substance (e.g. cigarettes, vaping, cannabis, pipes) for a minimum of 2 months prior to consent and agrees to not start for the duration of the study.
* Resting SpO2 ≥ 89% on room air.
* MMRC ≥ 2; CAT score ≥ 10.
* Diagnosis of moderate to severe COPD as defined by FEV1/FVC \< 70% (post-bronchodilator), 25% ≤ FEV1 ≤ 70% predicted, and PaCO2 \< 50 (if FEV1 \< 30%).
* RV ≥ 175% of predicted and RV/TLC \> 55% (post-bronchodilator).
* Participant is on standard medical care, defined as a minimum of therapy with LABA/ICS, LAMA/LABA, or LAMA/LABA/ICS for at least 2 months prior to consent.
* If subject has participated in a formal pulmonary rehabilitation program recently, program completion must have occurred ≥3 months prior to consent; if in a maintenance program, subject agrees to continue their current program through their 12-month follow-up visit; NOTE: Prior participation in a pulmonary rehabilitation program is not required for inclusion in the study.
* Participant is a candidate for bronchoscopy in the opinion of the investigator or per hospital guidelines and is able to discontinue blood thinning medication peri-procedurally.
* Participant is able and agrees to complete all protocol required baseline and follow up tests and assessments including taking certain medications (e.g., azithromycin, prednisolone/prednisone).

Exclusion Criteria:

* Body Mass Index (BMI) \<18 or \>32.
* Participant has an implantable electronic device and has not received appropriate medical clearance.
* Uncontrolled diabetes in the opinion of the investigator.
* 4 or more respiratory related hospitalizations within 1 year of consent.
* Malignancy treated with radiation or chemotherapy within 1 year of consent.
* Participant diagnosed with a dominant non-COPD lung disease, or condition affecting the lungs, which is the main driver of the participant's clinical symptoms (e.g., cystic fibrosis, paradoxical vocal cord motion, eosinophilic granulomatosis with polyangiitis (EGPA), allergic bronchopulmonary aspergillosis, interstitial lung disease or active tuberculosis or Asthma) or has a documented medical history of pneumothorax within 1 year of consent.
* Clinically relevant bronchiectasis, defined as \> 1/3 cup mucous expectoration daily.
* Pre-existing diagnosis of pulmonary hypertension, clinical evidence of pulmonary hypertension (e.g., cardiovascular function impairment including peripheral edema) and mPAP ≥25 mmHg at rest by right heart catheterization (or estimated right ventricular systolic pressure \>50 mmHg by echocardiogram if no previous right heart catheterization).
* Myocardial infarction within last 6 months, evidence of life-threatening arrhythmias or acute ischemia, pre-existing documented evidence of a LVEF \< 40%, stage C or D (ACC/AHA) or Class III or IV (NYHA) congestive heart failure.
* Surgical procedure(s) on the stomach, esophagus or pancreas performed ≤2 years of consent, or ongoing related symptoms within the past year.
* Symptomatic gastric motility disorder(s) (e.g., gastroparesis) as evidenced by GCSI score ≥18.0, severe uncontrolled GERD (e.g., refractory heartburn, endoscopic esophagitis) or severe dysphagia (e.g., esophageal stricture, achalasia, esophageal spasm). NOTE: Participants with a hiatal hernia are allowed if Participant meets all other enrollment criteria.
* Any disease or condition that might interfere with completion of a procedure or this study (e.g., structural esophageal disorder, life expectancy \<3 years).
* Prior lung or chest procedure (e.g., BLVR explant procedure, median sternotomy, bullectomy, lobectomy, segmentectomy or other interventional lung or chest procedure) performed ≤1 year of consent? Participants with lung transplant, BLVR valves, LVRS, metal stents within 5cm of the anticipated treatment location; presence of lung volume reduction valves, coils or other lung implants.
* Daily use of \>20 mg of prednisone or its equivalent at the time of consent.
* Known contraindication or allergy to medications required for bronchoscopy or general anesthesia (e.g., lidocaine, atropine, propofol, sevoflurane) that cannot be medically controlled.
* Baseline chest CT scan reveals bronchial anatomy cannot be treated with available catheter sizes; presence of whole lung emphysema \>20% (-950 HU), single lung emphysema \>26% (-950 HU), severe bullous disease (\>1/3 hemithorax) or discovery of a mass that requires treatment.
* Participant is currently enrolled in another drug or interventional clinical trial that has not completed follow-up.

Where this trial is running

Birmingham, Alabama and 9 other locations

• University of Alabama-Birmingham Hospital - UAB Lung Health Center — Birmingham, Alabama, United States (RECRUITING)
• Mayo Clinic Jacksonville — Jacksonville, Florida, United States (RECRUITING)
• Henry Ford Hospital - Lung and Pulmonary Care — Detroit, Michigan, United States (RECRUITING)
• Wake Forest School of Medicine — Salem, North Carolina, United States (NOT_YET_RECRUITING)
• Ohio State University Medical Center - Ohio State Lung Center — Columbus, Ohio, United States (RECRUITING)
• Penn Highlands - Lung Innovations/Clinical Research Associates — DuBois, Pennsylvania, United States (RECRUITING)
• Temple University - Temple Lung Center — Philadelphia, Pennsylvania, United States (RECRUITING)
• University of Pittsburgh Medical Center - UMPC Comprehensive Lung Center — Pittsburgh, Pennsylvania, United States (NOT_YET_RECRUITING)
• Virginia Commonwealth University Health System — Richmond, Virginia, United States (NOT_YET_RECRUITING)
• Medical College of Wisconsin — Milwaukee, Wisconsin, United States (NOT_YET_RECRUITING)

Study contacts

• Principal investigator: Prof. Gerard Criner, MD — Temple Health
• Study coordinator: John Carline

Conditions: COPD, Chronic Obstructive Pulmonary Disease, Optimal Medical Care, Device: dNerva Lung Denervation System, Device: Targeted Lung Denervation