Trevena Inc., the leader in G-protein coupled receptor (GPCR) biased ligand drug discovery, today announced the initiation of a Phase 2a clinical trial with its lead program, TRV120027, a beta-arrestin biased angiotensin II type 1 receptor (AT1R) ligand, the first biased ligand designed to treat patients with acute heart failure (AHF).
In this randomized, placebo-controlled, double-blind, dose-ranging study, the hemodynamic effects of TRV120027 will be assessed in patients with stable heart failure. The goal of the phase 2 trial is to demonstrate that TRV120027 rapidly and predictably improves hemodynamics while improving cardiac output and protecting renal function, as seen in preclinical species. In patients suffering from AHF, these titratable pharmacologic effects are expected to result in rapid symptom improvement.
The primary endpoints of the study, expected to enroll approximately 32 patients, are evaluation of the safety and tolerability of TRV120027 and measurement of its effects on pulmonary capillary wedge pressure, an important indicator of dyspnea in patients with heart failure. Secondary trial endpoints include effects on other hemodynamic parameters, neurohormonal activation and renal markers.
"This trial represents a significant milestone for Trevena," said Maxine Gowen, Ph.D., chief executive officer of Trevena. "It will allow us to demonstrate the pharmacology of TRV120027 in heart failure patients, which results from its functional selectivity at this critical receptor."
Results from the trial will build upon the data from extensive preclinical work and a phase 1 study completed in 2010, in which TRV120027 was shown to be safe, well-tolerated and have PK consistent with a high degree of titratability. The effects observed will inform dose selection for supportive and pivotal trials in which the efficacy of TRV120027 will be assessed in patients with AHF. David Soergel, M.D., Head of Clinical Development at Trevena, added, "TRV120027 is a first-in-class agent that, because of its spectrum of biological effects, could provide a major advance in the treatment of AHF. TRV120027 targets the angiotensin receptor in a unique way, producing blockade of the G-protein mediated adverse effects of angiotensin II while simultaneously unmasking beneficial pharmacology mediated by beta-arrestin."
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