A Clinical Study to Evaluate of Single and Multiple Oral Doses of GM-1020 in Patients With MDD

A Two-Part Controlled Clinical Study to Evaluate Safety, Tolerability, Response, Pharmacokinetics and Pharmacodynamics of Single and Multiple Oral Doses of GM-1020 in Patients With Major Depressive Disorder

The aim of this Phase 2a study in patients with MDD is to assess safety and tolerability and preliminary antidepressant efficacy.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: GM-1020

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom
    • MAC Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Patient is male or female, of any ethnic origin.
2. Patient is aged between 18 to 65 years, inclusive.
3. Patient has a body mass index (BMI) of 18.0 to 35.0 kg/m2, inclusive.
4. Patient is ≥50 kg.
5. Patient meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for recurrent MDD without psychotic features based on the Mini-International Neuropsychiatric Interview (MINI) at Screening. Comorbid anxiety disorders (e.g., social anxiety disorder, panic disorder, generalised anxiety disorder, specific phobia, agoraphobia) and cluster C personality disorders (avoidant, dependent and obsessive-compulsive) are allowed, provided that MDD is considered the primary diagnosis.
6. Current moderate to severe MDD as confirmed with a MADRS-SIGMA total score >22 and CGI-S score >3 at Screening and Day -1.

7. Patient is either not currently taking antidepressants (and hasn't for at least 6 weeks prior to Screening) or is being treated with an SSRI or SNRI antidepressant drug according to national guidelines during the current MDD episode.

   a. If the patient is currently being treated with SSRI or SNRI antidepressants, these have been prescribed at a stable dose and the dose has remained unchanged for at least 6 weeks prior to Screening. However, the following medications are not permitted during the study at any time: NMDA receptor antagonists (including ketamine, esketamine) and 5-HT2A receptor agonists (including psilocybin, DMT, 5-MeO-DMT). No augmentation strategies will be permitted.

8. Changes in current drug treatment or psychological treatment for depression are not foreseen for the duration of the study.

Key Exclusion Criteria:

1. Current or recent history of clinically significant suicidal ideation or behaviours as defined by:

   1. Suicidal ideation as endorsed on items 4 or 5 on the C-SSRS within 6 months prior to Screening, or
   2. Suicidal behaviours within 1 year prior to Screening, or
   3. Clinical assessment of significant suicidal risk. Patients with a prior suicide attempt of any sort, or prior serious suicidal ideation/plan >6 months ago, should be carefully screened for current suicidal ideation and only included at the discretion of the Investigator.
2. Involuntary psychiatric hospitalisation in the current episode. Previous involuntary psychiatric hospitalisation should be carefully considered and only included at the discretion of the Investigator.
3. Lifetime diagnosis of any DSM-5 psychotic disorders, bipolar or related disorders, post-traumatic stress disorder (PTSD), complex-PTSD and borderline personality disorder. Other psychiatric disorders besides MDD should not be the primary disorder.
4. Patient has failed previous treatment with rapidly acting antidepressant drugs, such as NMDA receptor antagonists (e.g., ketamine, esketamine) or 5-HT2A receptor agonists (e.g., psilocybin, DMT, 5-MeO-DMT) or neuromodulating treatments, such as electroconvulsive therapy, transcranial magnetic stimulation, vagus nerve stimulation, or deep brain stimulation.
5. Patient is currently or has recently (within 6 weeks prior to Day 1) been treated with antipsychotic medication.
6. Use of psychoactive substances (including ketamine, esketamine or psychedelics, excluding cannabis) during the 6 weeks prior to Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active; GM-1020 (oral)	Drug: GM-1020; N-methyl-D-aspartate (NMDA) receptor antagonist
Placebo Comparator: Placebo; Placebo (oral)	Drug: GM-1020; N-methyl-D-aspartate (NMDA) receptor antagonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment Emergent Adverse Events	Clinical monitoring of safety data from AE reporting, 12-lead ECG, vital signs, clinical laboratory evaluations, emergence of suicidal thoughts and ideations (Columbia-Suicidal Severity Rating Scale) and sedation (Modified Observer's Assessment of Alertness and Sedation).	Baseline, Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MADRS Total Score Change From Baseline to 24 Hours	The Structured Interview Guide for the Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item clinician-rated scale used to assess the severity of depressive symptoms in patients. It consists of 10 items, each scored from 0 to 6, yielding a total score ranging from 0 to 60, with higher scores indicating greater depression severity. Part A change from baseline MADRS was analyzed for Period 1 due to carryover effects as per SAP-defined analysis.	Baseline, 24 hours
MADRS Total Score Change From Baseline to Day 8	The Structured Interview Guide for the Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item clinician-rated scale used to assess the severity of depressive symptoms in patients. It consists of 10 items, each scored from 0 to 6, yielding a total score ranging from 0 to 60, with higher scores indicating greater depression severity. Part A change from baseline MADRS was analyzed for Period 1 due to carryover effects as per SAP-defined analysis.	Day 8

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part B Remission Rate, Day 42	Observed percentage of participants with a MADRS total Score <= 10.	Day 42
Part B Remission Rate at Day 67	Observed percentage of participants with a MADRS total Score <= 10.	Day 67

Collaborators and Investigators

• Sponsor: Gilgamesh Pharmaceuticals
• Investigators: Study Chair: Gerard Marek, MD, Gilgamesh Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Actual): March 4, 2025
• Study Completion (Actual): March 27, 2025

Study Registration Dates

• First Submitted: January 29, 2024
• First Submitted That Met QC Criteria: March 6, 2024
• First Posted (Actual): March 13, 2024

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: MDD
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: GLG-100X

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No