ESKETAMINE for Major depressive disorder

Inclusion criteria

• {"criterion_text":"- In- or out patients, at least 18 years of age up until 65."}
• {"criterion_text":"- Being willing and able to provide written informed consent. Having a legal guardian to cosign is allowed. Informed consent will be signed at visit 1, before any study procedure."}
• {"criterion_text":"- Female participants of child bearing potential must use effective contraception during the trial as per the requirements of the applicable SmPCs and should have a negative pregnancy test at visit 1 or 2 (before randomisation)"}
• {"criterion_text":"- Meeting diagnostic criteria for a primary diagnosis of major depressive disorder (without psychotic features), according to DSM-5. The primary diagnosis will be confirmed by the Mini International Neuropsychiatric Interview (MINI v7.0.2)."}
• {"criterion_text":"- Participant experiences a current treatment failure due to lack of efficacy in the current episode, as confirmed by a CGI-I ≥3y; preferably this treatment is a first-line pharmacotherapeutic agent for the primary DSM-5 diagnosis, and was prescribed for at least 4 weeks within an effective dose range as specified in the Summary of Product Characteristics (SmPCs). However, other treatments are accepted."}
• {"criterion_text":"- Participant and clinician intend to change pharmacotherapeutic treatment."}
• {"criterion_text":"- A minimum symptom severity threshold needs to be present (moderate level; see below) and participant needs to experience functional impairment. - The minimum symptom severity threshold is at least 2 PANSS positive or negative items with a score of 4, or at least one PANSS positive or negative item with a score of 5 - Functional impairment is defined as a score of 5 or higher on any of the three scales of the Sheehan Disability Scale (SDS)."}

Exclusion criteria

• {"criterion_text":"- Being pregnant or breastfeeding."}
• {"criterion_text":"- Participants with active suicidal ideation with some intent to act, without specific plan (“Yes” to question 4 of the Columbia-Suicide Severity Rating Scale (C-SSRS)) or active suicidal ideation with specific plan and intent (“Yes” to question 5 of the C-SSRS), followed by an assessment by the treating clinician who determines it is not safe for the subject to participate in the study"}
• {"criterion_text":"- Participant meets criteria for current substance use disorder, as confirmed by the Mini International Neuropsychiatric Interview (MINI v7.0.2). Nicotine dependency is allowed, as well as mild and moderate alcohol and/or cannabis use disorder (as defined by MINI v7.0.2). Severe alcohol and/or cannabis use disorder are not allowed."}
• {"criterion_text":"- Participants dependent on the sponsor, investigator or trial site must be excluded from participation in advance."}
• {"criterion_text":"- Participants have not been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities."}
• {"criterion_text":"- Participant has used (es)ketamine previously for the treatment of depressive symptoms."}
• {"criterion_text":"- Participant has a known intolerance to (es)ketamine or to all TAU medication options."}
• {"criterion_text":"- Meeting any of the contraindications for (es)ketamine or to all TAU medication options, as specified within the applicable SmPC, supported by clinically significant abnormal values on local laboratory tests, electrocardiogram (ECG) or physical examinations."}
• {"criterion_text":"- Participant has participated in another clinical trial in which the subject received an experimental or investigational drug or agent within 30 days before visit 1."}
• {"criterion_text":"- Participant experiences any other significant disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial."}

Primary endpoints

• {"endpoint_text":"- Mean change from baseline (visit 2) in symptom severity as measured by the MADRS total score at six weeks (visit 4) will be compared between the two treatment arms (EIPT vs. TAU) for the lines of treatment separately (subgroup analysis wherein the focus will be on participants who had a first time treatment failure on their first-line treatment) and for the group as a whole (irrespective of line of treatment).","definition_or_measurement_approach":"Change from baseline (visit 2) to week 6 (visit 4) in MADRS total score; baseline = visit 2, assessment at visit 4 (six weeks); comparison EIPT vs TAU, subgroup and overall analyses."}

Secondary endpoints

• {"endpoint_text":"- 1.a. Change from baseline (visit 2) in the severity sub-score of the Clinical Global Impression Scale (CGI) at visit 4; EIPT vs TAU. 1.b. Improvement sub-score of the Clinical Global Impression Scale (CGI) at visit 4; EIPT vs TAU.","definition_or_measurement_approach":"CGI severity sub-score and CGI improvement sub-score measured at visit 4 compared to baseline (visit 2); EIPT vs TAU."}
• {"endpoint_text":"- Changes from baseline (visit 2) in total Hospital Anxiety and Depression Scale (HADS) total score and anxiety and depression subscales at visit 4; EIPT vs TAU.","definition_or_measurement_approach":"HADS total score and subscales measured at visit 4 vs baseline (visit 2); EIPT vs TAU."}
• {"endpoint_text":"- Change from baseline (visit 2) in quality of life and functioning measures (Q-LES-Q-SF, LAPS, QLS-100 and SDS ) at visit 4; EIPT vs TAU.","definition_or_measurement_approach":"Multiple QoL and functioning instruments (Q-LES-Q-SF, LAPS, QLS-100, SDS) change from baseline to visit 4."}
• {"endpoint_text":"- Changes from baseline (visit 2) on Trail Making Test, Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test as well as the Perceived Deficits Questionnaire at visit 4; EIPT vs TAU.","definition_or_measurement_approach":"Cognitive test battery (Trail Making, Digit Symbol Substitution, Rey AVLT, Perceived Deficits Questionnaire) change from baseline to visit 4."}
• {"endpoint_text":"- Presence of symptomatic remission at visit 4; EIPT vs TAU. Remission is defined as a MADRS score ≤ 12.","definition_or_measurement_approach":"Symptomatic remission at visit 4 defined as MADRS ≤ 12; proportion compared between arms."}
• {"endpoint_text":"- Presence of reported side effects as measured through General Assessment of Side Effects Scale (GASE) and reported spontaneously throughout the studyat visit 4; EIPT vs TAU.","definition_or_measurement_approach":"Adverse events captured via GASE and spontaneous reporting throughout study, assessed at visit 4."}
• {"endpoint_text":"- Concomitant medication use throughout the studyat visit 4; EIPT vs TAU.","definition_or_measurement_approach":"Record and compare concomitant medication use during study, assessed at visit 4."}
• {"endpoint_text":"- Premature treatment discontinuation before visit 4 and time to treatment discontinuation and reported reason of discontinuation; EIPT vs TAU.","definition_or_measurement_approach":"Time-to-discontinuation and reasons for discontinuation before visit 4 compared between arms."}
• {"endpoint_text":"- Changes on the Columbia-Suicide Severity Rating Scale (C-SSRS) throughout the study; EIPT vs TAU","definition_or_measurement_approach":"C-SSRS changes assessed throughout the study; compared between arms."}

Austria

Earliest CTIS Part Ii Submission Date

05-12-2023

Latest Decision Or Authorization Date

09-02-2026

Processing Time Days

797

Number Of Sites

1

Number Of Participants

20

Germany

Earliest CTIS Part Ii Submission Date

04-12-2023

Latest Decision Or Authorization Date

03-02-2026

Processing Time Days

792

Number Of Sites

4

Number Of Participants

180

Italy

Earliest CTIS Part Ii Submission Date

19-10-2023

Latest Decision Or Authorization Date

05-02-2026

Processing Time Days

840

Number Of Sites

4

Number Of Participants

110

Spain

Earliest CTIS Part Ii Submission Date

01-12-2023

Latest Decision Or Authorization Date

06-02-2026

Processing Time Days

798

Number Of Sites

1

Number Of Participants

15

Greece

Earliest CTIS Part Ii Submission Date

27-11-2024

Latest Decision Or Authorization Date

09-02-2026

Processing Time Days

439

Number Of Sites

1

Number Of Participants

35

Primary sponsor

Full Name

Universitair Medisch Centrum Utrecht

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Contract research organisations

Name

Castor EDC

Responsibilities

Randomisation module

Name

Kairos

Third parties

• {"country":"Germany","full_name":"Fraunhofer-Institut für Algorithmen und Wissenschaftliches","duties_or_roles":"","organisation_type":"Industry"}
• {"country":"Netherlands","full_name":"Castor EDC","duties_or_roles":"Randomisation module","organisation_type":"Industry"}
• {"country":"Germany","full_name":"Ludwig Maximilian University Of Munich","duties_or_roles":"Laboratory Management","organisation_type":"Educational Institution"}
• {"country":"Germany","full_name":"Kairos","duties_or_roles":"","organisation_type":"Industry"}