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.

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

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 40
• 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: Gregory

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 have a body mass index (BMI) of 18.0 to 35.0 kg/m2, inclusive.
4. Patient is ≥50 kg.
5. 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. 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 diagnosis confirmed with a MADRS-SIGMA total score >22 and total score CGI-S score > 3 at Screening and Day -1.

7. Concomitant depression therapy:

   1. 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. 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. Patient has undergone involuntary psychiatric hospitalisation in the current episode. Patients with previous involuntary hospitalisation should be carefully considered and only included at the discretion of the Investigator.
4. Current or prior (six weeks before Screening) use of any SSRI/SNRI medication.
5. 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).
6. Patient has a history of non-response to Electroconvulsive Therapy, Vagus Nerve Stimulation, repetitive Transcranial Magnetic Stimulation, or ketamine/esketamine, and psychedelic 5-HT2A receptor agonists used in a clinical trial setting.
7. History of alcohol and/or drug use disorder according to DSM-5 within the last 12 months, or intake of >21 units of alcohol weekly, and the inability to refrain from alcohol use from 24 hours before Screening and each scheduled visit until discharge from the CRU. One unit is equivalent to a 285 mL glass (half-pint) of 3% beer or 1 (25 mL) measure of 40% spirits or 1 small glass (125 mL) of 9% wine.

8. Current or a 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 1 year prior to Screening or on Day -1, 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.
9. Clinically relevant history of abnormal physical or mental health interfering with the study as determined by medical history and physical examinations obtained during Screening as judged by the Investigator (including [but not limited to], cardiac, cardiovascular, pulmonary, gastrointestinal, endocrine, haematologic, rheumatologic, or metabolic, any inflammatory illness, hepatic, or renal disorder).
10. Patient has personal or familial history of epilepsy or other convulsive conditions, moderate to severe brain injury or other factors predisposing to seizures.
11. Any other concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study as outlined in this Protocol, or that would, in the opinion of the Investigator, pose an unacceptable risk to the patients with a MDD diagnosis in this study.
12. History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the ADME of IV GM-2505.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	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.	29 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MADRS-SIGMA total score	Change in MADRS-SIGMA total score between Baseline and Day 29	29 Days

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): July 29, 2024
• Study Completion (Estimated): July 29, 2024

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): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: MDD
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: GM-2505-201; 2023-000846-40 (EudraCT Number)

Drug and device information, study documents

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