On Jul. 26, 2021, Trevena announced that the first COVID-19 patient had been enrolled in the NIH-funded ACTIV-4 Host Tissue (Accelerating COVID-19 Therapeutic Interventions and Vaccines) trial.

The trial, known as ACTIV-4 Host Tissue, is testing four investigational agents that combat dysregulation of the renin-angiotensin-aldosterone system (RAAS) and the immune system caused by a COVID-19 infection. TRV027 is a novel AT₁ receptor selective agonist that specifically binds to and rebalances AT₁ receptor activation within the RAAS, blocking the damaging pathway that leads to acute lung damage and abnormal blood clotting, while activating the cellular pathway that selectively targets reparative actions that improve lung function and promote anti-inflammatory effects.

The trial is enrolling approximately 1,600 patients at over 50 sites in the U.S. TRV027 is part of the initial trial launch, and additional study arms will be added to the trial over time. The study is evaluating the impact of each intervention on recovery, supplemental oxygen use, need for mechanical ventilation, organ failure, and mortality.

This is a multi-site, randomized, placebo-controlled, clinical trial with multiple treatment arms, each enrolling approximately 300-400 COVID-19 patients ≥ 18 years old. Four trial arms are testing investigational agents, including TRV027, that target the RAAS or the immune system through distinct mechanisms of action. The objective of the trial is to determine whether modulation of these systems is an effective strategy for preventing progression to critical illness, multiorgan failure, or mortality in hospitalized COVID-19 patients.

The trial is funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the NIH.