A randomized, double-blind, placebo-controlled, Phase 2b trial with an open-label extension to determine the safety and efficacy of GH001 in patients with treatment-resistant depression.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

GH Research Ireland Limited

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

30 Mar 2023 → 11 Mar 2025

Decision date (initial)

2024-10-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

GH Research Ireland Ltd.

External identifiers

EU CT number

2023-510047-37-00

EudraCT number

2022-000574-26

ClinicalTrials.gov

NCT05800860

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Therapy, Efficacy, Safety

To determine the efficacy of a single day individualized dosing regimen (IDR) of GH001 compared with placebo in improving depressive symptoms as assessed by MADRS in patients with treatment-resistant depression (TRD) at the end of the 7-day double-blind (DB) Part 1.

Secondary objectives 2

1. To determine the effect of a single day IDR of GH001 compared with placebo on depressive symptoms as assessed by MADRS, global disease severity as assessed by CGI-S, anxiety as assessed by HAM-A, and quality of life as assessed by Q-LES-Q-SF in patients with TRD at the end of the 7-day DB Part 1.
2. To determine the effect of GH001 IDR as needed on depressive symptoms as assessed by MADRS, global disease severity as assessed by CGI-S, anxiety as assessed by the HAM-A, and quality of life as assessed by Q-LES-Q-SF in patients with TRD during the 6-month open-label extension (OLE) Part 2.

Conditions and MedDRA coding

Treatment-resistant depression (TRD)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Is in the age range between 18 and 64 years (inclusive) at the time of informed consent.
2. Meets the trial criteria for TRD as assessed by a study psychiatrist: a.Meets the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) criteria for single-episode MDD or recurrent MDD, without psychotic features confirmed by the Mini-International Neuropsychiatric Interview (MINI) 7.0.2 with current episode duration of ≤2 years. b.The current MDE must be deemed "valid" based upon the Massachusetts General Hospital State versus trait Assessability Face and Ecological validity Rule of 3Ps (MGH SAFER) criteria interview. c.Had nonresponse (≤25% improvement) to ≥2 and ≤5 oral antidepressant treatments started during the current episode of depression.

Exclusion criteria 8

1. Has, based on history, psychiatric assessment, and evaluation of the MINI during the screening period, a first MDD episode after age 60, a current or prior diagnosis of a psychotic disorder, MDD, or other mood disorder with psychotic features, bipolar disorder, obsessive compulsive disorder, posttraumatic stress disorder, autism spectrum disorder, borderline personality disorder, schizophrenia, delusional disorder, paranoid personality disorder, schizoaffective disorder, clinically significant intellectual disability, antisocial personality disorder, schizotypal personality disorder, or any other psychiatric comorbidity that renders the patient unsuitable for the trial according to a study psychiatrist.
2. Has significant suicide risk as defined by (a) suicidal ideation as endorsed on items 4 or 5 on the C-SSRS within the past year, during the screening period, or at Baseline; or (b) suicidal behaviors within the past year; or (c) clinical assessment of significant suicidal risk during clinical interview; or (d) non-suicidal self-injury within the past year.
3. Has 1 or more first degree relatives with a current or prior diagnosis of bipolar disorder, psychotic disorder, or other mood disorder (including MDD) with psychotic features.
4. Undergoing systematic psychotherapy (including cognitive behavioral therapy [CBT]) that is planned to be modified or planning to initiate psychotherapy during the trial. CBT must have been ongoing for the last 3 months prior to Baseline.
5. Has any current or past clinically significant condition (e.g., severe infection, severe pulmonary disease, uncontrolled hypertension, uncontrolled diabetes, severe cardiovascular disease, valvulopathy, pulmonary hypertension, myocardial infarction, angina or clinically significant arrythmia within the past year, severe hepatic or severe renal failure, brain disorder including seizure, stroke, dementia, aneurysm, history of intracerebral hemorrhage, degenerative neurologic diseases, meningitis, encephalitis, and head injury with loss of consciousness) that may interfere with the interpretation of the trial results, constitute a health risk for the patient, or that otherwise renders the patient unsuitable for the trial according to the investigator's judgement.
6. Fulfils criteria for DSM 5 alcohol or substance use disorder (excluding tobacco and caffeine use disorders) within the preceding 1 year, as assessed via the MINI.
7. Takes or has taken disallowed recent or concomitant treatments or it is anticipated that the patient will require treatment with at least 1 of the disallowed concomitant treatments during the trial.
8. Has previously experienced a significant adverse reaction to a hallucinogenic or psychedelic drug (e.g., psilocybin, Psilocybe spp. mushrooms, 5 MeO DMT, DMT, ayahuasca, LSD, mescaline) according to the investigator's judgement.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean change in MADRS from Baseline to Day 7

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

GH Research Ireland Limited

Sponsor organisation

GH Research Ireland Limited

Address

Joshua Dawson House, Dawson Street Dawson Street

City

Dublin 2

Postcode

D02 RY95

Country

Ireland

Scientific contact point

Organisation

GH Research Ireland Limited

Contact name

GH Research Project Manager

Public contact point

Organisation

GH Research Ireland Limited

Contact name

GH Research Project Manager

Third parties 6

Locations

5 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 32 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications