A Phase 2a Study to Evaluate the Safety and Tolerability of GM-2505 in Patients With MDD

A Phase 2a Study to Evaluate the Safety and Tolerability of Two Repeated Doses of GM-2505 at a 2-Week Interval in Patients With Major Depressive Disorder.

This is a three-part Phase 2a study. The aim of Part A is to assess the safety and tolerability and preliminary antidepressant efficacy in patients with MDD who are not currently on an antidepressant therapy. The aim of Part B is to assess the antidepressant efficacy, safety and tolerability in patients with MDD who are partial responders while on a current and adequate single SSRI or SNRI treatment. Part C aims to replicate the monotherapy findings of Part A, but with a lower control group dose.

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: GM-2505

• Study Type: Interventional
• Enrollment (Estimated): 124
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jason Winters; Phone Number: 6097385579; Email: jason@gilgameshpharmaceutical.com

Study Locations

• United Kingdom
  • Manchester, United Kingdom
    • Recruiting
    • MAC Clinical Research
    • Contact: Babajida

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Patients are male or female, of any ethnic origin.
2. Patients are aged between 18 to 65 years, inclusive.
3. Patients meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for recurrent MDD without psychotic features, as assessed with the Mini-International Neuropsychiatric Interview (MINI) at Screening.
4. Current moderate to severe MDD diagnosis confirmed with a MADRS-SIGMA

5. Concomitant depression therapy:

   1. (Part A) Patients need to be stable and must not have taken any SSRI or SNRI for at least 6 weeks prior to Screening and must be willing to avoid starting a new pharmacological treatment for MDD until the end of the study procedures and assessments. Discontinuing current treatment is not allowed if done for the purposes of achieving eligibility for this study.
   2. (Part B) Patients need to be on stable treatment with any SSRI or SNRI for at least 6 weeks prior to screening and must be willing to remain on the SSRI or SNRI for the duration of the trial
   3. Patients receiving any form of psychotherapy or counselling must have been receiving therapy at Screening and must be willing to remain in therapy until the end of the study procedures and assessments.

Key Exclusion Criteria:

1. Patient has current or past primary DSM-5 diagnosis of a psychotic disorder or MDD with psychotic features, bipolar, or related disorders. A current diagnosis of PTSD, complex PTSD and borderline personality disorder are exclusionary. Other psychiatric disorders besides MDD should not be the primary disorder.
2. In first degree relatives, a history of schizophrenia, psychosis, bipolar disorder, delusional disorder, paranoid personality disorder or schizoaffective disorder.
3. Current or prior (six weeks before Screening) use of any SSRI/SNRI medication (Part A only).
4. Current or prior (five weeks before Screening) use of any monoamine oxidase inhibitor ([MAO-I]; including phenelzine, tranylcypromine, isocarboxazid, iproniazid, selegiline, rasagiline, the reversible MAO-I moclobemide and the antibiotic linezolid).or any tricyclic antidepressant

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Dose to High Dose of GM-2505	Drug: GM-2505; IV
Experimental: Moderate Dose to High Dose of GM-2505	Drug: GM-2505; IV
Active Comparator: Experimental very low dose to very low dose of GM-2505	Drug: GM-2505; IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability (Part A, B, and C)	The primary objective of this study is to evaluate the safety and tolerability of two doses of GM-2505 administered to MDD patients at a 2-week interval between doses.	99 Days
MADRS Score (Part B and C)	The estimated difference between Arm 1 and Arm 2 in the changes from baseline in MADRS-SIGMA total score	29 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MADRS-SIGMA total score (Part A)	Change in MADRS-SIGMA total score between Baseline and Day 29 and comparison of Day 1 low dose vs moderate dose at Day 14	Days 14 and 29
MADRS-SIGMA total score (Part B and C)	MADRS-SIGMA scores (change from baseline)	All additional timepoints
MADRS-SIGMA total score (Part B and C)	Response and Remission	Days 14, 29, 43, 71, and 99
PK of GM-2505 (Part C)	Assess the pharmacokinetics of GM-2505 at very low, moderate, and high doses	Day 16

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: January 23, 2024
• First Submitted That Met QC Criteria: January 30, 2024
• First Posted (Actual): February 1, 2024

Study Record Updates

• Last Update Posted (Actual): February 9, 2026
• Last Update Submitted That Met QC Criteria: February 5, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: MDD; Adjunctive; antidepressant; 5HT2a agonist
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: GM-2505-201; 2023-000846-40 (EudraCT Number); M26-286 (Other Identifier: Gilgamesh Pharmaceuticals)

Drug and device information, study documents

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