The registry has caught up to a verdict the market reached months ago. Johnson & Johnson’s VENTURA-5 study — designed to test whether aticaprant, an investigational kappa-opioid receptor (KOR) antagonist, could keep depression from coming back — is now listed on ClinicalTrials.gov as TERMINATED, with the reason given verbatim as “early study termination due to insufficient efficacy.” There were no new safety signals, and there was very little of a trial left to read.
VENTURA-5 (NCT06635135) was a Phase 3, randomized, double-blind, multicenter, placebo-controlled relapse-prevention study of adjunctive aticaprant plus an antidepressant in major depressive disorder with moderate-to-severe anhedonia, sponsored by Janssen Research & Development. The design was conventional: enrich for responders during open-label adjunctive aticaprant, stabilize them, then randomize the stable responders to continue the drug or switch to placebo. The primary endpoint was time from randomization into the double-blind maintenance phase to first documented relapse — defined as a MADRS total score of 22 or higher on two consecutive assessments, or a clinically relevant relapse event.
That funnel never filled. Of 47 participants enrolled into the open-label initial phase, which began on September 19, 2024, 18 entered the stabilization phase. By the time the double-blind maintenance phase opened, just 2 participants had been randomized — both to aticaprant, none to placebo — before the study was stopped. Primary completion came on April 9, 2025, and the study completed on April 25, 2025. With so few patients randomized, the primary endpoint was uninterpretable by construction: the posted results show that no participants experienced a relapse, so median time-to-relapse could not be calculated.
A registry formality, not a new failure
The termination is bookkeeping. Aticaprant’s adjunctive MDD program had already missed across the VENTURA Phase 3 studies, and J&J discontinued the asset for insufficient efficacy, with no new safety signals. VENTURA-5 was the relapse-prevention arm of a program that no longer had a drug to prevent relapse for.
No participant in any phase had a death or a serious adverse event. In the open-label phase, the most common adverse event was pruritus, affecting 5 of 47 aticaprant-treated participants.
The safety read is unremarkable and consistent with the KOR-antagonist class: itch, headache, diarrhea, and dyspepsia in the open-label phase, nothing serious. That matters less than the efficacy ledger. With aticaprant’s discontinuation, another mechanistically novel, non-monoaminergic approach to depression — and specifically to anhedonia — exits Phase 3 without a positive registrational signal, leaving the field’s hunt for a differentiated antidepressant where it was.