The U.S. Food and Drug Administration (FDA) has agreed to change the ongoing Phase 2b study evaluating INOpulse in patients with pulmonary hypertension (PH) associated with interstitial lung disease (PH-ILD) into a Phase 2/3 clinical trial, the therapy’s manufacturer, Bellerophon Therapeutics, announced.
With this decision the agency also agreed to change the endpoint of the trial (NCT03267108), which will now be to detect changes in moderate to vigorous physical activity as measured by a wearable activity monitor (actigraphy), promoted by treatment with INOpulse compared to placebo, in PH-ILD patients, including those with pulmonary fibrosis (PF, a type of ILD).
The company expects to complete the ongoing treatment of the second group of patients and initiate the pivotal Phase 3 part of the study in the second half of 2019.
Patient enrollment in this study is ongoing. More information on contacts and locations across the U.S. can be found here.
“Reaching this critical agreement with the FDA for INOpulse in PH-ILD represents a significant milestone for Bellerophon as it confirms the validity of [moderate to vigorous physical activity] as a clinically meaningful endpoint,” Fabian Tenenbaum, CEO at Bellerophon, said in a press release.
“We appreciate the FDA’s support and their agreement on both the primary endpoint and the seamless pivotal Phase 2/3 design, creating the opportunity for INOpulse to become the first approved therapy in PH-ILD,” he added. “[It] enables us to build upon the robust data generated to date from iNO-PF and substantially shortens the regulatory pathway for our therapy in a disease with a serious unmet need.”
iNOpulse was developed to reduce blood pressure in the lungs by using pulsed, inhaled nitric oxide (iNO), a potent vasodilator that relaxes blood vessels. Nitric oxide is delivered via a tube into the nose, and a portable device about the size of a paperback book automatically fine-tunes nitric oxide pulses to the patient’s breathing pattern.
Results from the first group of 41 patients with PH-ILD enrolled in the Phase 2b trial showed that treatment with iNO at a dosage of 30 mcg/kg ideal body weight per hour improved by 8% patients’ moderate activity measured by actigraphy, in contrast to a 26% decrease in participants on placebo.
Actigraphy is a wearable medical device applied to a person’s wrist that monitors gross motor activity linked to functional abilities and clinical outcomes. It is a well-established method used in several clinical applications, such as chronic obstructive pulmonary disease (COPD).
Treatment with iNOpulse was also found to promote other clinically meaningful improvements, including positive changes in oxygen saturation in the blood and in levels of NT-pro brain natriuretic peptide — a biomarker of right ventricular failure.
“iNOpulse is a selective vasodilator that can improve both cardiopulmonary circulation and oxygenation, increasing the ability to perform physical activities,” said Steven D. Nathan, MD, medical director of the Advanced Lung Disease and Lung Transplant Program at Virginia’s Inova Fairfax Hospital and chair of Bellerophon’s steering committee.
“Compared to surrogate endpoints, such as six-minute walk distance [6MWD] or patient-reported outcomes, change in [moderate to vigorous physical activity] provides a direct and continuous measure of physical activity in PH-ILD patients, who have limited ability to perform even the most basic daily tasks,” he said.