Clinical trial NCT04698603: Clinical Study of GH001 in Depression
Official title: A Phase 1/2 Study of GH001 in Patients With Treatment-Resistant Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Treatment Resistant Depression
Major Depressive Disorder
Depression
Keywords: Treatment
5-MeO-DMT
5-methoxy-dimethyltryptamine
Lead sponsor: GH Research Ireland Limited
Sponsor class: INDUSTRY
First posted: 2021-01-07
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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;

Primary outcomes:
measure: Phase 1: The safety and tolerability of GH001 as a combined measure of outcomes 5 to 13.
timeFrame: up to 7 days
measure: Phase 2: The effects of GH001 on the severity of depression evaluated by the Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: up to 7 days
Secondary outcomes:
measure: Phase 1: The effects of GH001 on the severity of depression evaluated by the Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: up to 7 days
measure: Phase 2: The safety and tolerability of GH001 as a combined measure of outcomes 5 to 13
timeFrame: up to 7 days
Other outcomes:
measure: Type and Frequency of Adverse Events
timeFrame: up to 7 days
measure: Frequency of clinically significant changes from baseline in the safety laboratory analyses (biochemistry, hematology, urinalysis)
timeFrame: up to 7 days
measure: Frequency of clinically significant changes from baseline in Vital Signs
timeFrame: up to 7 days
measure: Frequency of clinically significant changes from baseline in Electrocardiogram (ECG) parameters
timeFrame: up to 3 hours after administration of GH001
measure: Change from baseline in the Brief Psychiatric Rating Scale (BPRS)
timeFrame: up to 7 days
measure: Change from baseline in the Clinician Administered Dissociative States Scale (CADSS)
timeFrame: up to 7 days
measure: Change from baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: up to 7 days
measure: Change from baseline in the Psychomotor Vigilance Test (PVT)
timeFrame: up to 7 days
measure: Change from baseline in Digit Symbol Substitution Test (DSST)
timeFrame: up to 7 days
Locations:
city: Maastricht
country: Netherlands
facility: Clinical Trial Site
Study officials:
affiliation: GH Research Ireland Limited
name: GH Research Clinical Team
role: STUDY_DIRECTOR
References:
citation: 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.