Clinical trial NCT02872298: Evaluating the Safety and Feasibility of TLD for the Treatment of Severe Asthma
Official title: A pRospective, Multicenter, Single-arm Study EvaLuating the Safety and feasIbility of Targeted Lung Denervation (TLD) for the trEatment oF Severe Asthma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Asthma
Keywords: Severe
Refractory
Lead sponsor: Nuvaira, Inc.
Sponsor class: INDUSTRY
First posted: 2016-08-19
Enrollment: 2
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Prospective, multicenter, single-arm (non-randomized) study of Targeted Lung Denervation (TLD) Therapy in subjects with severe asthma.

Detailed description: Prospective, multicenter, single-arm (non-randomized) study. All patients will undergo a run in period on optimal medical therapy as part of eligibility testing. Final determination to initiate treatment will be made after initial airway inspection. A total of 20 patients will be treated. Inflammatory biomarkers (washes and brushes) will be collected in all patients and bronchial biopsies will be collected from the last 10 patients at the time of treatment and at 90-days post-treatment. All patients will be prescribed peri-procedural antibiotics and steroids to minimize procedural risks. All patients will be provided a mobile handheld spirometer to measure and record daily peak expiratory flow both before and after treatment to monitor lung function. Patient follow-up will be conducted out to 3 years.

Eligibility criteria: Inclusion Criteria:

* Patient has provided written informed consent;
* Diagnosis of severe asthma as defined by the 2018 GINA Report, and are taking regular maintenance medication as specified in the study protocol;
* Pre-bronchodilator FEV1 ≥50% predicted after a 4 week medication run-in;
* Subject has at least two days of asthma symptoms during the 4-weeks of the Baseline Diary Period;
* Women of child bearing potential must have a negative pregnancy test and agree not to become pregnant for the duration during the study;
* Non-smoker for at least 6 months and agree to continue not smoking for duration of the study;
* Patient is a candidate for bronchoscopy in the opinion of the physician or per hospital guidelines;
* Patient is a candidate to undergo methacholine challenge testing;
* Patient is willing, able and agrees to complete all protocol required baseline and follow up testing and comply with medication requirements.

Exclusion Criteria:

* In the 24 months prior to enrollment, the subject has: been intubated for asthma, had intensive care unit (ICU) admission(s) for asthma, or been treated with immunosuppressant therapy for any reason (steroids excluded);
* In the 12 months prior to enrollment, the subject has had: ≥4 lower respiratory tract infections requiring antibiotics or ≥4 hospitalizations for asthma exacerbations;
* In the 3 months prior to enrollment, the subject has taken/used an opioid(s);
* In the 6 weeks prior to enrollment the subject has had a lower respiratory tract infection or asthma exacerbation that required: antibiotics, unscheduled physician visits for asthma care, changes in use of asthma maintenance medication, taking of rescue medication over normal dose in a 24-hour period for asthma symptoms and a steroid burst (pulse);
* Current use of greater than 10 mg of oral steroids per day at the time of enrollment;
* History of poor medication compliance;
* Prior lung or chest procedure;
* Other chronic pulmonary disorders associated with asthma-like symptoms, including (but not limited to) cystic fibrosis, chronic obstructive pulmonary disease, chronic bronchitis, vocal chord dysfunction, eosinophilic granulomatosis with polyangiitis (EGPA) or interstitial lung disease that is the sole cause of asthma symptoms, severe scoliosis or chest wall deformities that affect lung function, or congenital disorders of the lungs or airways;
* Pre-existing diagnosis of pulmonary hypertension as defined in the study protocol;
* Uncontrolled diabetes as evidenced by an HbA1c \> 7%;
* Patient has an implantable electronic device;
* Known contraindication or allergy to anticholinergic drugs or components;
* Known contraindication of allergy to medications required for bronchoscopy, general anesthesia or peri-procedural therapy that cannot be medically controlled;
* Patient is unable to stop blood thinning medication for 7 days prior and 7 days after procedure;
* Documented history of untreated severe obstructive sleep apnea;
* Patient has any disease or condition that might interfere with completion of a procedure or this study or patient safety;
* Screening chest CT scan reveals bronchi anatomy cannot be fully treated with the available catheter sizes or discovery of a pulmonary nodule requiring follow-up or intervention unless proven benign;
* Patients who had abdominal surgical procedures on stomach, esophagus or pancreas;
* Patients with a Gastroparesis Cardinal Symptom Index (GCSI) score ≥ 18 prior to treatment;
* Patient is currently enrolled in another clinical trial that has not completed follow-up.

Primary outcomes:
measure: Freedom from device related therapeutic interventions
timeFrame: 7 days, 1 month, 3 months, 6 months, and 12 months post-procedure
Secondary outcomes:
measure: Device Success
timeFrame: 1 day
measure: Technical Success
timeFrame: 1 day
measure: Change in Quality of Life (QOL)
timeFrame: Through study completion, an average of 3 years
measure: Change in Asthma Control
timeFrame: Through study completion, an average of 3 years
Other outcomes:
measure: Rate of respiratory and non-respiratory adverse events
timeFrame: Through study completion, an average of 3 years
measure: Change in morning and evening peak expiratory flow (PEF)
timeFrame: Through 1 year follow-up
measure: Change in pre- and post-bronchodilator FEV1
timeFrame: Through study completion, an average of 3 years
measure: Change in methacholine PC20
timeFrame: Through 1 year follow-up
measure: Change in rescue medication usage
timeFrame: Through study completion, an average of 3 years
measure: Number and level of asthma exacerbations
timeFrame: Through study completion, an average of 3 years
measure: Number of respiratory-related unscheduled physician office visits
timeFrame: Through study completion, an average of 3 years
measure: Number of emergency department visits
timeFrame: Through study completion, an average of 3 years
measure: Number of hospitalizations
timeFrame: Through study completion, an average of 3 years
measure: Change in inflammatory markers and bronchoscopic specimens
timeFrame: 90 days
measure: Change in visual and quantitative lung attenuation via CT scan
timeFrame: 1 Year
measure: Change in Cough
timeFrame: Through study completion, an average of 3 years
Locations:
city: Grenoble
country: France
facility: CHU de Grenoble
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Groningen
country: Netherlands
facility: Universtity Medical Center Groningen
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
state: Scotland
city: London
country: United Kingdom
facility: Chelsea & Westminster Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Royal Brompton & Harefield NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: NUH Nottingham City Hospital
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
Study officials:
affiliation: University Medical Center Groningen (UMCG)
name: Nick ten Hacken, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Brompton & Harefield NHS Foundation Trust
name: Pallav Shah, MD
role: PRINCIPAL_INVESTIGATOR
References: