Evaluating the Safety and Efficacy of TLD in Patients With COPD (AIRFLOW-4)

Nuvaira

Status and phase: Begins enrollment this month; Phase 3

Conditions: Chronic Obstructive Pulmonary Disease; COPD

Treatments: Drug: Standard medical care; Device: Targeted Lung Denervation (TLD)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07051707

D0836

Details and patient eligibility

About

The dNerva Lung Denervation System is one-time treatment intended to improve breathing in Chronic Obstructive Pulmonary Disease (COPD) patients on standard medical care. The purpose of this study is to confirm the safety and efficacy of the Nuvaira Lung Denervation System in the treatment of COPD.

Full description

The primary objective of this study is to demonstrate the superiority of treatment with the dNerva Lung Denervation System on top of standard medical care (Treatment arm) compared to standard medical care alone (Control arm) to improve lung function in COPD participants with high RV and low emphysema.

The secondary objective is to compare other efficacy assessments between the Treatment arm and the Control arm, and to confirm the safety profile of lung denervation.

Enrollment: 400 estimated patients

Sex: All

Ages: 40 to 80 years old

Volunteers: No Healthy Volunteers

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 at the time of screening?
• mMRC ≥ 2; CAT score ≥ 10 at the time of screening?
• Diagnosis of moderate to severe COPD as defined by FEV1/FVC < 70% (post-bronchodilator), FEV1 25-<60% 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 a long-acting bronchodilator, (LABA, LAMA, LABA/ICS or LAMA/LABA) for at least 2 months prior to consent?
• If participant has participated in a formal pulmonary rehabilitation program recently, program completion must have occurred ≥3 months prior to consent; if in a maintenance program, participant 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 started taking a monoclonal antibody (mAb), or a PDE3/PDE4 inhibitor less than 6 months prior to screening. (Participants on these medications for less than 6 months must wait until 6 months has passed prior to screening.)?
• Participant is currently enrolled in another drug or interventional clinical trial that has not completed follow-up?

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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400 participants in 2 patient groups

Targeted Lung Denervation (TLD) treatment with standard medical care prior to randomization

Experimental group

Description:

Targeted Lung Denervation (TLD)Therapy is a bronchoscopically guided, minimally invasive procedure using the Nuvaira™ Lung Denervation System while taking regular maintenance medication that minimally includes a long acting bronchodilator with or without a corticosteroid.

Treatment:

Drug: Standard medical care

Device: Targeted Lung Denervation (TLD)

Continuing the standard medical care prior to randomization

Other group

Description:

Continuing standard of care COPD maintenance medication that minimally includes LABA/ICS, LAMA/LABA or LABA/LAMA/ICS.

Treatment:

Drug: Standard medical care