UK: Phase IIa Trial Results of SPL026

Patients who received at least one active dose of SPL026 with supportive therapy showed a durable improvement in depression symptoms, according to top-line results from a Phase IIa trial.

The trial showed that an intravenous N, N-Dimethyltryptamine (DMT), SPL026, with supportive therapy for major depressive disorder (MDD), met the primary endpoint. SPL026 demonstrated a statistically significant and clinically relevant reduction in depressive symptoms at two weeks post-dose than placebo. Further study of key secondary endpoints showed a long-lasting and rapid antidepressant effect to 12 weeks.

The trial investigated the safety and efficacy of intravenous SPL026 with supportive therapy among 34 patients with moderate/severe MDD. Dosing of patients was done with a short IV infusion of 21.5mg SPL026, leading to a 20 to 30-minute psychedelic experience. People who entered the trial on pharmacological antidepressant medication were withdrawn from their treatment before dosing.

The two-staged Phase IIa study included a randomized, blinded, placebo-controlled phase. The primary endpoint was to examine the efficacy of an SPL026's single dose with supportive therapy (N=17) compared to a placebo with therapy (N=17) at two weeks post-dose. All study participants were subsequently enrolled on an open-label phase where they received an SPL026 single dose with supportive treatment and were followed for further 12 weeks in the study.

MADRS (Montgomery-Asberg Depression Rating scale) was used to assess the efficacy of measuring any potential change in depression from baseline. MADRS assessment was done by independent raters who were absent at dosing and were blinded to the overall treatment.

Study Findings

• The study met the primary endpoint revealing a statistically significant and clinically relevant reduction in depressive symptoms two weeks following a dose of SPL026 with supportive therapy versus placebo, demonstrating a -7.4 point difference in MADRS.
• Analysis of key secondary endpoints showed a rapid onset of antidepressant effect one-week post-dose, with a statistically significant difference in MADRS score of -10.8 between the active and placebo groups.
• Patients who received at least one active SPL026 dose with supportive therapy showed a durable improvement in depression symptoms across the 12-week open-label phase.
• The authors did not observe any apparent difference in antidepressant effect between a one and two-dose regimen of SPL026.
• At 12 weeks, the total mean reduction in MADRS was –15.4 from baseline after a single dose of SPL026.

The detailed findings of the trial are expected to be presented at upcoming scientific meetings and featured in a peer-reviewed journal.