Clinical Study of GH001 in Depression

A Phase 1/2 Study of GH001 in Patients With Treatment-Resistant Depression

The aim of the study is to investigate the safety of GH001 (containing 5-methoxy-dimethyltryptamine; 5-MeO-DMT), and to investigate its effects on severity of depressive symptoms, and its dose-related psychoactive effects in patients with Treatment-Resistant Depression (TRD).

The study is comprised of two open-label, single-arm study parts where Part A evaluates single doses of GH001 at two dose levels and Part B evaluates a specific individualized dosing regimen of GH001.

Study Overview

• Status: Completed
• Conditions: Depression; Major Depressive Disorder; Treatment Resistant Depression
• Intervention / Treatment: Drug: 5 Methoxy N,N Dimethyltryptamine

Detailed Description

Phase 1 (Part A):

The primary objective of this study is to assess the safety and tolerability of single doses of GH001 (containing 5-methoxy-dimethyltryptamine; 5-MeO-DMT) in patients with TRD.

The secondary objectives of the study are to assess the effects of single doses of GH001 on various measures of depression, and on dose-related psychoactive effects.

Phase 2 (Part B):

The primary objective of this study is to assess the effects of an individualized dosing regimen of GH001 on the severity of depression.

The secondary objectives of the study are to assess the safety and tolerability of an individualized dosing regimen of GH001 in patients with TRD and its effects on the severity of depression, other measures of depression, and on dose-related psychoactive effects.

Study design: Phase 1/2 study in two parts.

Intervention: In the Phase 1 (Part A), a single dose of GH001 will be administered per patient. Two different dose levels will be investigated with four patients at each dose level. In the Phase 2 (Part B), an individualized dosing regimen will be administered.

In both parts, GH001 will be administered via inhalation.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands
    • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 62 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has a body mass index (BMI) in the range of 18.5 and 35.0 kg/m2 (inclusive);
• Meets the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria for single-episode major depressive disorder (MDD) or recurrent MDD, without psychotic features confirmed by the Mini-International Neuropsychiatric Interview (MINI);
• Treatment-Resistant Depression as evaluated by the Antidepressant Treatment History Form - Short Form (ATHF-SF);
• Has outpatient status at screening and enrolment visits;

Exclusion Criteria:

• Has a current or prior diagnosis of a psychiatric comorbidity that renders the patient unsuitable for the study according to a study psychiatrist or registered psychologist;
• Has received any investigational medication within the last 1 month;
• Has a current medically significant condition (e.g., severe infection) or has a history of a medically significant condition (e.g., medical history of seizure, uncontrolled hypertension, uncontrolled diabetes, severe cardiovascular disease, hepatic or renal failure, etc.) that renders the patient unsuitable for the study according to the medical supervisor's judgment;
• Takes any medication or other substance that renders the patient unsuitable for the study according to the medical supervisor's judgment;
• Has a clinically significant abnormality in physical examination, vital signs, ECG, or clinical laboratory parameters, which renders the patient unsuitable for the study according to the medical supervisor's judgment;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 (Part A): GH001 dose A	Drug: 5 Methoxy N,N Dimethyltryptamine; GH001 administered via inhalation; Other Names: GH001; 5-MeO-DMT
Experimental: Phase 1 (Part A): GH001 dose B	Drug: 5 Methoxy N,N Dimethyltryptamine; GH001 administered via inhalation; Other Names: GH001; 5-MeO-DMT
Experimental: Phase 2 (Part B): GH001 Individualized Dosing Regimen	Drug: 5 Methoxy N,N Dimethyltryptamine; GH001 administered via inhalation; Other Names: GH001; 5-MeO-DMT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: The safety and tolerability of GH001 as a combined measure of outcomes 5 to 13.	Phase 1: The primary endpoint is a binary variable (yes/no) reflecting a combined medical/clinical evaluation of the occurrence of Outcomes 5 to 13. The endpoint will be considered met for any dose level or regimen if the Study Safety Group (SSG) - through a qualitative medical/clinical evaluation - considers that dose level or regimen sufficiently safe and tolerable for potential further clinical development in a subsequent study.	up to 7 days
Phase 2: The effects of GH001 on the severity of depression evaluated by the Montgomery-Asberg Depression Rating Scale (MADRS)	Phase 2: The assessment is done with the Montgomery-Asberg Depression Rating Scale (MADRS), a diagnostic questionnaire with ten items for measuring the severity of depressive episodes in patients with mood disorders. A higher MADRS score indicates more severe depression, and each item is scored from 0 to 6. The overall score ranges from 0 to 60.	up to 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: The effects of GH001 on the severity of depression evaluated by the Montgomery-Asberg Depression Rating Scale (MADRS)	Phase 1: The assessment is done with the Montgomery-Asberg Depression Rating Scale (MADRS), a diagnostic questionnaire with ten items for measuring the severity of depressive episodes in patients with mood disorders. A higher MADRS score indicates more severe depression, and each item is scored from 0 to 6. The overall score ranges from 0 to 60.	up to 7 days
Phase 2: The safety and tolerability of GH001 as a combined measure of outcomes 5 to 13	Phase 2: The secondary endpoint is a binary variable (yes/no) reflecting a combined medical/clinical evaluation of the occurrence of Outcomes 5 to 13. The endpoint will be considered met for any dose level or regimen if the Study Safety Group (SSG) - through a qualitative medical/clinical evaluation - considers that dose level or regimen sufficiently safe and tolerable for potential further clinical development in a subsequent study.	up to 7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type and Frequency of Adverse Events	Adverse events reported in the study and coded by MedDRA.	up to 7 days
Frequency of clinically significant changes from baseline in the safety laboratory analyses (biochemistry, hematology, urinalysis)	Safety laboratory analyses are analyses of blood samples (biochemistry, hematology) and urine samples (urinalysis). Changes are defined as any clinically significant change from baseline as determined by the medical supervisor at the site.	up to 7 days
Frequency of clinically significant changes from baseline in Vital Signs	Vital signs include heart rate (beats per minute), blood pressure (mmHg), respiratory rate (breaths per minute), oxygen saturation (%), and temperature (degrees celsius). Changes are defined as any clinically significant change from baseline as determined by the medical supervisor at the site.	up to 7 days
Frequency of clinically significant changes from baseline in Electrocardiogram (ECG) parameters	Clinically significant changes in ECG include any significant change in rate or rhythm as determined by the medical supervisor at the site.	up to 3 hours after administration of GH001
Change from baseline in the Brief Psychiatric Rating Scale (BPRS)	Change from baseline in the Brief Psychiatric Rating Scale (BPRS). A scale to measure psychiatric symptoms. Each symptom is rated 1-7 and a total of 18 symptoms are scored. Combined score ranges from 18 to 126.	up to 7 days
Change from baseline in the Clinician Administered Dissociative States Scale (CADSS)	Change from baseline in the Clinician Administered Dissociative States Scale (CADSS). The CADSS comprises 19 subjective items, ranging from 0 'not at all' to 4 'extremely. Summed together, these subscales form a total dissociative score. Combined score ranges from 0 to 76.	up to 7 days
Change from baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS)	Change from baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS). A detailed questionnaire assessing both suicidal behaviour and suicidal ideation. No combined score is created.	up to 7 days
Change from baseline in the Psychomotor Vigilance Test (PVT)	Change from baseline in the Psychomotor Vigilance Test (PVT). A computerized test assessing the reaction time in response to a visual stimulus. Outcome measures are Response Time and the number of attentional lapses (Response Time ≥ 500 msec).	up to 7 days
Change from baseline in Digit Symbol Substitution Test (DSST)	Change from baseline in the Digit Symbol Substitution Test (DSST). A computerized test with the task is to match digits with symbols from encoding list. The number of digits correctly encoded within 3 minutes is the performance measure.	up to 7 days

Collaborators and Investigators

• Sponsor: GH Research Ireland Limited
• Investigators: Study Director: GH Research Clinical Team, GH Research Ireland Limited

Publications and helpful links

General Publications

• Reckweg JT, van Leeuwen CJ, Henquet C, van Amelsvoort T, Theunissen EL, Mason NL, Paci R, Terwey TH, Ramaekers JG. A phase 1/2 trial to assess safety and efficacy of a vaporized 5-methoxy-N,N-dimethyltryptamine formulation (GH001) in patients with treatment-resistant depression. Front Psychiatry. 2023 Jun 20;14:1133414. doi: 10.3389/fpsyt.2023.1133414. eCollection 2023.

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2019
• Primary Completion (Actual): November 6, 2021
• Study Completion (Actual): November 6, 2021

Study Registration Dates

• First Submitted: November 17, 2020
• First Submitted That Met QC Criteria: January 6, 2021
• First Posted (Actual): January 7, 2021

Study Record Updates

• Last Update Posted (Actual): August 15, 2023
• Last Update Submitted That Met QC Criteria: August 11, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Treatment; 5-MeO-DMT; 5-methoxy-dimethyltryptamine
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Agents; Serotonin Receptor Agonists; Serotonin Antagonists; Hallucinogens; N,N-Dimethyltryptamine
• Other Study ID Numbers: GH001-TRD-102; 2018-004208-20 (EudraCT Number)

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