This is a phase 2b clinical trial in patients with TRD consisting of a 7-day randomized, placebo-controlled, DB Part 1 and a 6-month, single-arm, OLE Part 2. All patients who complete the DB Part 1 will directly transition into the OLE Part 2 on Day 7 of the DB Part 1.~In both parts, GH001 is administered as an individualized dosing regimen (IDR) consisting of up to 3 increasing doses of GH001 (6 mg, 12 mg, and 18 mg) on a single day, where the second and third doses are only administered if the patient did not achieve intense psychoactive effects (a peak experience [PE]) at the previously administered dose.~In the DB Part 1, patients receive a single GH001 IDR or placebo IDR;~In the OLE Part 2, patients can receive up to 5 GH001 IDRs as needed across 6 months, based on the patient's clinical response.~In both parts, an IDR clinic visit on Day (D)0 is followed by a telephone call on D1 and a clinic visit on D7 (±1 day).~The primary objective of this study is to determine the efficacy of a single day IDR of GH001 compared with placebo in improving depressive symptoms as assessed by the MADRS at the end of the 7-day DB Part 1.~Other efficacy objectives of this study are to assess the effects of the GH001 IDR on various measures of depression, anxiety and quality of life during the DB part and during the OLE. The safety of GH001 will also be assessed.~GH001 is an inhalation formulation of synthetic mebufotenin (5-MeO-DMT). The study drug is administered as an aerosol via pulmonary inhalation.
The aim of this randomized, double-blind, placebo-controlled, phase 2b clinical trial is to investigate the safety and efficacy of GH001 (containing mebufotenin [5-methoxy-N,N-dimethyltryptamine; 5-MeO-DMT]) in patients with treatment-resistant depression (TRD). The study is comprised of a 7-day double-blind (DB) part (Part 1) and a 6-month open-label extension (OLE) part (Part 2). Patients will be randomized to receive GH001 or placebo in a 1:1 ratio. The primary endpoint is the mean change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to Day 7.