Clinical Trial Results:
A phase 1/2 study of GH001 in patients with treatment-resistant depression
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Summary
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EudraCT number |
2018-004208-20 |
Trial protocol |
NL |
Global end of trial date |
06 Nov 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Apr 2025
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First version publication date |
12 Apr 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
GH001-TRD-102
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04698603 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
GH Research Ireland Limited
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Sponsor organisation address |
28 Baggot Street Lower, Dublin 2, Dublin, Ireland, D02 NX43
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Public contact |
Padraig O'Grady, GH Research Ireland Limited, clinicaltrials@ghres.com
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Scientific contact |
Padraig O'Grady, GH Research Ireland Limited, clinicaltrials@ghres.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
11 Jul 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
06 Nov 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Nov 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Primary objective of Part A (Phase 1): To assess the safety and tolerability of single-day, single dosing of GH001 in a controlled environment in patients with treatment-resistant depression (TRD).
Primary objective of Part B (Phase 2): To assess the effects of single-day, multiple dose of GH001 on the severity of depression.
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Protection of trial subjects |
This trial was conducted according to the code of ethics on human experimentation established by the Declaration of Helsinki (1964) and amended in Fortaleza (2013), the International Council for Harmonization guidelines on good clinical practice, and current regulatory regulations (Medical Research Involving Human Subjects Act [Wet Medisch-wetenschappelijk Onderzoek met Mensen or WMO in Dutch]). Before a patient participated in the trial, written informed consent was obtained. The patient was asked to read a patient information section of the consent form that was approved by the Medical Ethics Committee and to sign it to indicate consent to participate in the trial. Informed consent was obtained before the initiation of any trial procedures for each patient. A Study Safety Group (SSG) was established to monitor the safety of the trial population and to advise the sponsor on modifications to the protocol and/or the continuation of the trial. The SSG members evaluated the safety and efficacy data from all patients at each review timepoint. The doses in Part 1 and Part 2 of the trial were chosen based on SSG evaluation of data from a previously conducted trial with GH001 (GH001-HV-101). Additionally, the results from Part 1 of this trial were reviewed by the SSG and provided further information to inform the doses to be used in Part 2.
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Background therapy |
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Evidence for comparator |
- | ||
Actual start date of recruitment |
13 Jan 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Netherlands: 16
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Worldwide total number of subjects |
16
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EEA total number of subjects |
16
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
16
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were enrolled from a single site in the Netherlands. Potential patients for the trial were identified from the ongoing clinical practice of the trial psychiatrist or registered psychologist. There was also a Dutch-language website and Dutch-language internet advertisements and social media materials were used to assist with recruitment. | |||||||||
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Pre-assignment
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Screening details |
A total of 250 potential participants were prescreened, 67 of whom subsequently underwent medical and psychiatric screening. Of these, 49 were excluded as they did not meet eligibility criteria, or as the trial had concluded. A total of 16 patients were enrolled, all of whom were dosed and completed the trial. There were no withdrawals. | |||||||||
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Period 1
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Period 1 title |
Part A - Phase 1
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | |||||||||
Blinding implementation details |
The trial part was an open-label design, so no blinding or randomization was performed. However, to avoid expectancy effects, patients were not informed of the name of the active molecule or their specific dose administered.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Part A - 12 mg | |||||||||
Arm description |
Patients received a single dose of GH001 12 mg. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Mebufotenin
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Investigational medicinal product code |
GH001
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Other name |
5-MeO-DMT
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Pharmaceutical forms |
Inhalation vapour, solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
Single dose of GH001 12 mg administered via inhalation through a mouthpiece.
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Arm title
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Part A - 18 mg | |||||||||
Arm description |
Patients received a single dose of GH001 18 mg. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Mebufotenin
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Investigational medicinal product code |
GH001
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Other name |
5-MeO-DMT
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Pharmaceutical forms |
Inhalation vapour, solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
Single dose of GH001 18 mg administered via inhalation through a mouthpiece.
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: The Sponsor has reviewed this and does not see any discrepencies. |
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Period 2
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Period 2 title |
Part B - Phase 2
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Is this the baseline period? |
No | |||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | |||||||||
Blinding implementation details |
The trial was an open-label design, so no blinding or randomization was performed. However, to avoid expectancy effects, patients were not informed of the name of the active molecule or their specific dose administered.
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Arms
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Arm title
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Part B - Individualized Dosing Regimen | |||||||||
Arm description |
In Part B, a dose-escalation regimen (IDR) was applied. The patients received at least one and up to three doses of GH001 in a single day. If no peak experience (PE) was achieved with 6 mg doses, and the 6 mg dose level was well tolerated, a higher dose (12 mg) was administered; if no PE was achieved with 12 mg doses, and the 12 mg dose level was well tolerated, a third dose (18 mg) was administered. Any subsequent dose was administered approximately 3 hours after the prior dose. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Mebufotenin
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Investigational medicinal product code |
GH001
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Other name |
5-MeO-DMT
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Pharmaceutical forms |
Inhalation vapour, solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
Up to three doses of GH001 administered via inhalation through a mouthpiece.
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Baseline characteristics reporting groups
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Reporting group title |
Part A - 12 mg
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Reporting group description |
Patients received a single dose of GH001 12 mg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part A - 18 mg
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Reporting group description |
Patients received a single dose of GH001 18 mg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Part B - Phase 2
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Part B - Phase 2
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End points reporting groups
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Reporting group title |
Part A - 12 mg
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Reporting group description |
Patients received a single dose of GH001 12 mg. | ||
Reporting group title |
Part A - 18 mg
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Reporting group description |
Patients received a single dose of GH001 18 mg. | ||
Reporting group title |
Part B - Individualized Dosing Regimen
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Reporting group description |
In Part B, a dose-escalation regimen (IDR) was applied. The patients received at least one and up to three doses of GH001 in a single day. If no peak experience (PE) was achieved with 6 mg doses, and the 6 mg dose level was well tolerated, a higher dose (12 mg) was administered; if no PE was achieved with 12 mg doses, and the 12 mg dose level was well tolerated, a third dose (18 mg) was administered. Any subsequent dose was administered approximately 3 hours after the prior dose. | ||
Subject analysis set title |
Part B - Phase 2
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Part B - Phase 2
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End point title |
The safety and tolerability of GH001 administered via inhalation after vaporization as evaluated by a panel of measures: AE reporting, safety laboratory analyses, vital signs, ECG, BPRS, CADSS, C-SSRS, PVT and DSST*† [1] | |||||||||||||||||||||
End point description |
AE=Adverse event, ECG=Electrocardiogram, BPRS=Brief Psychiatric Rating Scale, CADSS=Clinician Administered Dissociative States Scale, C SSRS=Columbia-Suicide Severity Rating Scale; PVT=Psychomotor Vigilance Test and DSST=Digit Symbol Substitution Test.
* Primary endpoint for Part A of the trial
†No clinically significant trends or abnormalities were observed for vital signs, ECG, BPRS, CADSS, C SSRS, PVT and DSST.
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End point type |
Primary
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End point timeframe |
From Day 1 through to the end of the trial (Day 7).
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No comparison group. |
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
The effect of GH001 on the severity of depression, as evaluated by the proportion of patients in remission (MADRS ≤10) at 7 days after dosing* [2] | ||||||||
End point description |
MADRS=Montgomery-Åsberg Depression Rating Scale
*Primary endpoint for Part B of the trial
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End point type |
Primary
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End point timeframe |
From Day 1 through to the end of the trial (Day 7).
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This trial was not compared with another group and there is no option to state this. The primary endpoint (proportion of patients in remission [MADRS>/=] on Day 7) was compared to baseline. |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From Day 1 through to the end of the trial (Day 7).
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Adverse event reporting additional description |
Data presented here is for treatment-emergent adverse events (TEAEs), defined as any AE that began or worsened on or following the start of dosing.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.1
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Reporting groups
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Reporting group title |
Part A - 12 mg
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Reporting group description |
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Reporting group title |
Part A - 18 mg
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Reporting group description |
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Reporting group title |
Part B - IDR
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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19 Sep 2019 |
a. Summary of GH001-HV-101 trial results included.
b. Dose range in Part A specified.
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26 Nov 2019 |
a. Appendix 2.1 (standalone document) amended to update list of excluded concomitant medications. |
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24 Dec 2019 |
a. Revised exclusion criterion to clarify assessment of suicidality risk. |
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24 Sep 2020 |
a. Changes to trial endpoints. |
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27 Apr 2021 |
a. Dose regimen in Part B specified. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/34912222 |
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