Bellerophon Therapeutics announced that is moving forward with a planned Phase 2b trial that will investigate INOpulse as a therapy for pulmonary hypertension associated with chronic obstructive pulmonary disease (PH-COPD), following an agreement with the U.S. Food and Drug Administration regarding the study’s design.
INOpulse therapy is based on the active agent nitric oxide, a molecule that is naturally produced by the cells lining blood vessels, called endothelial cells. Nitric oxide has a key role in promoting vessel’s vasodilation, i.e., opening.
In INOpulse, nitric oxide is inhaled and administrated through a tube in the nose with a portable device about the size of a paperback book. The device automatically adjusts nitric oxide pulses to a patient’s breathing pattern. This delivery system reduces the risk of side effects while widening blood vessels.
The Phase 2b study will be a double-blind, placebo-controlled trial in which PH-COPD patients will receive nitric oxide, administrated by inhalation with the INOpulse system. The trial, to be performed in the U.S., is expected to enroll about 90 PH-COPD patients.
Its primary objective or endpoint is changes in the six-minute walking distance (6MWD), a test of the distance a person can cover talking at maximal intensity in six minutes — a measure of a patient’s functional exercise level.
Secondary endpoints to be assessed include right ventricular function — how well the heart’s right side pumps blood up through the pulmonary valve and through the pulmonary artery to the lungs. This side of the heart is often impaired in patients with PH.
The new trial follows a positive Phase 2a study (NCT02267655) showing that INOpulse therapy resulted in meaningful increases in 6MWD after two and four weeks of treatment, relative to the trial’s start, in patients with PH-COPD.
Treatment with INOpulse also led to a significant increase in blood vessel volume (by 4.2%) and improvements in ventilation-vasodilation, supporting the therapy’s positive effect in patients’ lung airways. As a result, their systolic pulmonary arterial pressure significantly decreased (by 20%).
The therapy was well-tolerated with no related safety concerns.
“Reaching agreement with the FDA on the Phase 2b study design in PH-COPD represents an important achievement for our INOpulse development program,” Fabian Tenenbaum, chief executive officer of Bellerophon, said in a press release.
“Based on the data generated to date and INOpulse’s dual mechanism of action, to provide targeted vasodilation as well as improve ventilation-perfusion matching, we believe INOpulse has the potential to be the first treatment approved for PH-COPD and we look forward to advancing our INOpulse therapy in this serious and unmet medical condition,” Tenenbaum concluded.