Compass Pathways plc (Nasdaq: CMPS) announced it is working with the U.S. Department of Veterans Affairs (VA) on a clinical trial evaluating its investigational psilocybin compound in veterans with treatment-resistant depression (TRD).

The multi-site, double-blind, randomized controlled trial, named PIVOT — Psilocybin Intervention for Veterans Overcoming Treatment-Resistant Depression — will enroll veterans diagnosed with TRD, with or without concurrent post-traumatic stress disorder (PTSD). The trial will compare outcomes between two doses of COMP360, Compass's synthetic psilocybin formulation, with an option for a second open-label administration four weeks after the initial dose.

The primary efficacy measure will be depression severity, assessed using the Montgomery-Åsberg Depression Rating Scale. Secondary outcomes will include PTSD symptom severity, tolerability, and patient-reported depression. The lead site is the Birmingham VA Health Care System in Alabama, with four additional VA sites in Tuscaloosa, Portland, Seattle, and Philadelphia.

Compass will donate COMP360 for the study and provide training materials, guidance, and consultation on administration protocols to investigators.

"TRD is a critical and complex mental health challenge among veterans, often occurring alongside PTSD," said Kabir Nath, Chief Executive Officer of Compass Pathways.

Dr. Lori Davis, Principal Investigator at Birmingham VA Healthcare System, said the study will explore psilocybin's potential to treat both TRD and comorbid PTSD, which she described as "an area that remains largely unexplored."

According to the press release, an estimated one in seven veterans with depression may have TRD, defined as an inadequate response to at least two courses of approved antidepressant medications. COMP360 holds Breakthrough Therapy designation from the U.S. Food and Drug Administration for TRD.