Phase 3 INOpulse Trial Enrolls First Patient at Risk of PF-associated PH

A Phase 3 clinical trial evaluating Bellerophon Therapeutics’ investigational therapy INOpulse — inhaled nitric oxide — in patients with pulmonary fibrosis (PF) at risk of developing pulmonary hypertension (PH) has enrolled its first patient.

Top-line data from the trial, called REBUILD (NCT03267108), are expected by 2022.

“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.

“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,” Tenenbaum added.

INOpulse is a device that delivers nitric oxide (NO), a potent vasodilator, in a form that can be inhaled through a nasal cannula. Vasodilators are compounds that widen and relax blood vessels, lowering blood pressure and allowing more blood to flow.

As such, INOpulse has the potential to lower or normalize the abnormally high blood pressure in lung blood vessels that characterizes PH.

Top-line results from the previous Phase 2 iNO-PF trial (NCT03267108) showed that four months of treatment with INOpulse — at a dose of 45 mcg/kg ideal body weight/per hour — significantly improved MVPA by 20% in PF patients at risk of PH, compared with a placebo. MVPA may include activities such as walking, climbing stairs, and yard work, among similar tasks.

INOpulse also reduced the impact of lung disease on patients’ daily life and lessened their shortness of breath, as assessed with validated patient-reported questionnaires.

In agreement, the same dose also was shown to significantly lower blood pressure (by 12%) and blood flow resistance (by 21%) in the arteries supplying blood to the lungs in another Phase 2 trial, called PHPF-002 (NCT03727451).

INOpulse was generally safe and well-tolerated in both trials.

These positive data supported the use of 45 mcg/kg of inhaled NO as the optimal dose to be tested in the larger, confirmatory Phase 3 REBUILD trial.

“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 added.

REBUILD will evaluate the safety and effectiveness of INOpulse in up to 300 PF patients, ages 18 to 80, at risk of PH and who have been on oxygen therapy by nasal cannula for at least four weeks.

Participants, who are being recruited at several sites across the U.S., will be assigned randomly to receive either inhaled NO (at the 45 mcg/kg dose) or a placebo through the INOpulse device for four months.

REBUILD’s main goal is to assess whether INOpulse is superior to a placebo at improving patients’ MVPA, as previously agreed upon with the U.S. Food and Drug Administration (FDA).

Secondary goals include assessing changes in patients’ overall activity, shortness of breath, exercise capability or resistance, and in the disease impact on daily life, as well as time to clinical worsening and improvement.

After completing the four-month treatment period, participants may choose to enter the trial’s open-label extension, in which all will receive INOpulse-NO.