Clinical Evidence
Results across our clinical development program demonstrate the safety and impact of Targeted Lung Denervation (TLD) using the dNerva® Lung Denervation System. Detailed information regarding Nuvaira clinical studies can also be found at www.clinicaltrials.gov.
Our AIRFLOW-3 Trial is Enrolling Now!
dNerva® Clinical Development Program

Phase 1A (Proof of Concept/Dose Ranging)
- N = 37
- Single Arm
- Multicenter EU

Phase 2A (Safety/Dose Ranging)
- N = 46
- Single Arm
- Multicenter EU
3-Year Data Published21

Phase 2B (Safety and Feasibility)
- N = 82
- 1:1 Randomized Sham Controlled Double-Blinded (for one year)
- Crossover
- Multicenter EU
2-Year Data Published2

Phase 3 (Pivotal)
- N = Up to 400
- 1:1 Randomized Sham Controlled Double-Blinded (for one year)
- Crossover
- Multicenter USA / EU
Studies
Find out more about each of the studies in Nuvaira’s clinical development program.
Published in the International Journal of Chronic Obstructive Pulmonary Disease, November 20202
The clinical impact of TLD is durable, as it is found to reduce the risk of serious COPD adverse events over 2 years with stabilized lung function. The reduction of severe COPD exacerbations has the potential to improve long-term clinical outcomes and reduce healthcare costs.
AIRFLOW-2 Study Conclusions
Robust study design
Positive Safety Profile
TLD demonstrated a significantly lower risk of hospitalized COPD exacerbations
Lung function and quality of life remained stable over 2 years
AIRFLOW-2 Study Details
Trial Design / Phase
Evaluate the safety and impact of TLD in moderate-to-severe, symptomatic COPD patients on optimal medical therapy
Patient population
Diagnosed, moderate-to-severe, symptomatic COPD patients at risk of COPD exacerbation (GOLD 2/3, Group D)
Principal investigator(s)
Arschang Valipour, MD, Otto-Wagner Spital (Vienna, Austria)
Dirk-Jan Slebos, MD, Ph.D., UMCG (Groningen, Netherlands)
Primary Endpoint
Difference in rates (percentage) of pre-defined respiratory adverse events between 3 and 6.5 months post-treatment, between TLD and Sham control groups
Sites / Patients
N = 82 (1:1 randomization)
Multicenter EU
Follow-up
0 – 12.5 months (to unblinding), follow-up annually to 2 years
Published in Respiratory Research, February 202121
TLD in COPD patients demonstrated a positive safety profile out to 3 years, with no late-onset serious adverse events related to denervation therapy. Clinical stability in lung function, quality of life, and exacerbations were observed in TLD treated patients over 3 years of follow up.
Results: Observed Clinical Stability after Three Years21,22
Stable Quality of Life
Stable COPD Exacerbation Rates
Stable Lung Function
AIRFLOW-1 Study Details
Trial Design / Phase
International multicenter safety and dose-ranging study with a randomized (N=30) and confirmatory (N=16) phase
Patient population
Diagnosed, moderate-to-severe, symptomatic COPD patients
Principal investigator(s)
Arschang Valipour, MD, Otto-Wagner Spital (Vienna, Austria)
Dirk-Jan Slebos, MD, Ph.D., UMCG (Groningen, Netherlands)
Primary Endpoint
Rate of airway effects requiring intervention through 3 months (randomized), and rate and frequency of adverse events at one month compared to 32W dose group (confirmatory)
Sites / Patients
N=46
Multicenter EU
Follow-up
Three years
1:1 Randomized, Double-Blind, Sham-Controlled FDA Pivotal Trial
Primary Endpoint:
Up to 400 participants
Multicenter (USA, Europe)
AIRFLOW-3 Study Details
Trial Design / Phase
International Multicenter, Randomized, Double-blinded, Sham-Controlled, Superiority
Phase III Pivotal trial
Patient population
Diagnosed, moderate-to-severe, symptomatic COPD patients at risk of COPD exacerbation (GOLD 2/3, Group D)
Principal investigator(s)
Frank Sciurba, MD, UPMC (Pittsburgh PA USA)
Dirk-Jan Slebos, MD, Ph.D., UMCG (Groningen Netherlands)
Primary Endpoint
Comparison of rate of moderate or severe COPD exacerbations (time-to-first-event analysis) between TLD+Medical Management vs. Sham+Medical Management, 0-12 months
Sites / Patients
N = Up to 400 (1:1 randomization)
40 total sites: USA (25), OUS (15)
Follow-up
Primary Endpoint: one year
Unblinding and opportunity to cross over for patients in sham arm: one year
Annual follow-up to 5 years
Publications
Targeted Lung Denervation Bibliography
Targeted Lung Denervation Mechanism of Action Bibliography
COPD Exacerbations are the Problem.
Be a Part of the Solution.

The AIRFLOW-3 Clinical Trial is the first interventional COPD trial targeting exacerbation risk reduction in patients on optimal drug therapy.