Bellerophon, FDA Agree on Design of Phase 3 INOpulse Trial

The U.S. Food and Drug Administration (FDA) and Bellerophon Therapeutics agreed on the design of Bellerophon’s Phase 3 trial to test INOpulse — inhaled nitric oxide — in people with pulmonary fibrosis (PF) who are at risk for pulmonary hypertension (PH), the company said.

INOpulse is a device that delivers nitric oxide (NO) in a form that can be inhaled. NO is a potent vasodilator, a compound that causes blood vessels to widen, lowering blood pressure and allowing more blood to flow. This is the rationale behind its therapeutic use in PH, which is defined by abnormally high blood pressure in the vessels of the lung.

With the conclusion of end-of-Phase 2 meetings, Bellerophon and the FDA agreed that the trial will test INOpulse delivered at a dose of 45 mcg/kg ideal body weight/per hour, and the study’s main goal will be the ability of NO to improve moderate to vigorous physical activity (MVPA) of PF patients at risk for PH.

These parameters are the same as those being used in the ongoing Phase 2/3 iNO-PF (NCT03267108) study for a group of 44 participants randomly assigned to receive INOpulse at 45 mcg/kg or a placebo for four months.

Topline results from the iNO-PF trial showed that patients treated with active NO had statistically significant improvements in MVPA, a parameter that includes walking, climbing stairs, and yard work. The increase of 14 minutes per day in MVPA observed corresponds to a 20% improvement compared with the placebo group.

Moreover, researchers saw significant improvements on the St. George’s Respiratory Questionnaire (SGRQ), which measures the impact of respiratory disease on daily life. On average, the total SGRQ score of patients treated with INOpulse dropped by three points. (Higher scores indicate a lower quality of life). A five-point improvement in the shortness of breath measure on the University of California, San Diego Shortness of Breath Questionnaire was also observed.

“We are very pleased with the alignment reached with the FDA on the design of our pivotal Phase 3 trial, which allows us to move confidently towards the initiation of this important study,” Fabian Tenenbaum, CEO of Bellerophon, said in a press release.

“INOpulse, with its targeted pulmonary vasodilation, would potentially become the first therapy to treat a broad PH-PF population that includes patients at low, intermediate, and high risk of pulmonary hypertension. We look forward to initiating our pivotal Phase 3 study in PH-PF shortly,” Tenenbaum said.