Clinical Study of GH001 in Depression

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Treatment Resistant Depression, Major Depressive Disorder, Depression

Intervention / Treatment
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* Drug: 5 Methoxy N,N Dimethyltryptamine


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Phase 1 (Part A): Two dose levels of GH001 investigated in single doses. Phase 2 (Part B): GH001 investigated in an individualized dosing regimen.
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment, 5-MeO-DMT, 5-methoxy-dimethyltryptamine