First Patient Enrolled in Phase 3 REBUILD Trial of INOpulse

The first patient has enrolled in REBUILD, a Phase 3 clinical trial that will assess the safety and efficacy of Bellerophon Therapeutics’ INOpulse, an experimental treatment for patients with pulmonary fibrosis (PF) who are at risk of developing pulmonary hypertension (PH)

“We are pleased to have enrolled the first patient in our Phase 3 REBUILD study, as it marks an important milestone in our efforts to develop the first potential therapy to treat a broad [PF] population that includes patients at risk of pulmonary hypertension,” Fabian Tenenbaum, CEO of Bellerophon, said in a press release.

In patients with PH-PF,  the pulmonary arteries that normally carry blood from the heart to the lungs are narrowed, causing blood pressure to increase and eventually lowering the amount of blood pumped by the heart.

INOpulse is designed to deliver an inhaled form of nitric oxide (NO), a potent vasodilator that reduces blood pressure by opening blood vessels, to the patients’ lungs.

Top-line data from a previous Phase 2/3 trial, called iNO-PF (NCT03267108), showed that when given over four months at a dose of 45 mcg/kg ideal body weight/per hour (mcg/kg IBW/hr), INOpulse was able to improve patients’ moderate-to-vigorous physical activity (MVPA) by 20% compared to a placebo.

Treatment also improved participants’ self-reported quality of life, lowered their shortness of breath, and was generally safe and well-tolerated.

Top-line results from another open-label Phase 2b trial, called PHPF-002 (NCT03727451), showed INOpulse was able to lower blood pressure in the pulmonary arteries by an average of 12%, and blood flow resistance by 21%.

These benefits were particularly striking in PH-PF patients receiving the therapy at a dose of 45 mcg/kg IBW/hour, which was later defined as the optimal dose to be given in future studies.

“The REBUILD study builds on the positive results from our Phase 2 trial that demonstrated the safety and efficacy of INOpulse in improving MVPA [moderate to vigorous physical activity], multiple quality of life measures and key hemodynamic [blood flow] parameters. We look forward to sharing top-line results from this important study in 2022,” Tenenbaum said.

REBUILD (NCT03267108) will evaluate the safety and efficacy of iNOpulse in up to 300 PH-PF patients, ages 18–80, who have been on long-term oxygen therapy (minimum of four weeks). The trial is active at 21 U.S. sites and still recruiting participants at sites in Phoenix, Arizona, Atlanta, Gerogia, and Richmond, Virginia. More information about trial contacts and recruiting sites is available here.

During the study, patients will be assigned randomly to receive either inhaled NO (at the 45 mcg/kg optimal dose) or a placebo through the INOpulse device for 16 weeks.

After the initial 16-week treatment period, patients will have the option to enroll in an open-label extension study to continue treatment with INOpulse.

The primary goal of REBUILD is to assess if INOpulse may be superior to the placebo at improving patients’ MVPA over the first 16 weeks of the study. This primary goal, along with other details of the study’s design, were defined earlier this year, after the company consulted with the U.S. Food and Drug Administration (FDA). 

“Fibrotic ILD [interstitial lung disease] is a severe disease where patients face debilitating functional impairment, poor quality of life and limited life expectancy. The benefits we observed in [previous studies] underscore INOpulse’s potential to address this significant unmet medical need,” Jeremy Feldman, MD, director of Arizona Pulmonary Specialists’ PH program, and one of REBUILD’s lead investigators, said. 

“I am excited to advance the Phase 3 study with the enrollment of the first patient, and look forward to the continued development of the promising INOpulse therapy for fILD,” Feldman said.