E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment Resistant Depression |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Psychological processes [F02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057840 |
E.1.2 | Term | Major depression |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess efficacy of MIJ821 (versus placebo) in treatment resistant depression after single s.c. injection |
|
E.2.2 | Secondary objectives of the trial |
- To assess safety and tolerability of MIJ821 after single s.c. injection - To assess MIJ821 PK in plasma after single s.c. injection - To assess the duration of antidepressant effect of MIJ821 - To characterize the dose-response and exposure-response relationship of MIJ821 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Signed informed consent must be obtained prior to participation in the study. - Male and female participants, 18 to 65 years of age (inclusive) at screening. - Participant has a diagnosis of recurrent MDD and a current major depressive episode of at least 8 weeks in duration as defined by DSM-5 criteria and confirmed by both the SCID-5 and an adequate clinical psychiatric evaluation at screening. - MADRS ≥ 24 at screening and before randomization on Day 1. - Failure to respond to 2 or more antidepressant treatments but no more than 5, where the two failed treatments are two different antidepressants and at least one of which was used in the current depressive episode, with adequate dose and duration (≥ 6 weeks duration, doses defined per agent), as identified by the MGHAntidepressant Treatment Response Questionnaire, based on the patient's report and prior psychiatric history, assessed by the investigator, and further documented by medical records. Patients with historical treatment failure to esketamine, ketamine or arketamine are excluded. - Participant must agree to receive pharmacological standard of care treatment to treat their MDD (as determined by the treating physician(s) based on clinical judgement and protocol recommendations) during the trial duration. - If the participant is taking any other type of psychotropic drugs, the dose of these drugs needs to be stable, where a stable dose of psychotropic drugs is defined as no changes in dose or type of e.g. antipsychotics or mood stabilizers for at least 6 weeks prior to baseline (if applicable). - The antidepressant should be at a stable dose for at least 4 weeks before baseline. No new antidepressant initiated 6 weeks or less before baseline. No psychotherapy initiated 4 weeks or less before baseline. - Able to communicate well, and to understand and comply with study requirements.
|
|
E.4 | Principal exclusion criteria |
- Current acute depressive episode lasting longer than two years continuously, or participants receiving electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS) or deep brain stimulation (DBS) in the current episode or within last year prior to screening (whichever is longer). - Any prior or current diagnosis of MDD with psychotic features, bipolar disorder, schizophrenia, or schizoaffective disorder as obtained from SCID-5 at screening. - Participants with acute alcohol or substance use disorder or withdrawal symptoms requiring detoxification, or participants who went through detoxification treatment (inpatient or outpatient) within 1 month before Screening, as obtained from SCID-5 at screening. - Participants with current borderline personality disorder or antisocial personality disorder assessed at Screening, based on DSM-5 criteria and investigator judgment. - Current clinical diagnosis of autism, dementia, or intellectual disability. - Participants with a history of suicidal attempt or suicidal behaviour within last year prior to screening and participants presenting suicidal ideation with intent documented by C-SSRS by Yes response to Q4 or Q5 at screening or baseline. - Participants with evidence of significant renal insufficiency, indicated by an estimated glomerular filtration rate (eGFR) of < 40 mL/min/1.73 m2 at screening. - Use of other investigational drugs at the time of screening, or within 30 days or 5 half lives of screening, whichever is longer. - History of hypersensitivity to any of the study treatments or excipients or to drugs of similar mechanism of action (i.e. drugs that affect the NMDA receptor). - Active hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or active COVID-19 infection as per medical history and/or available medical records. - History of seizures. Note: childhood febrile seizures are not exclusionary. - Cardiac or cardiac repolarization abnormality - Resting QTcF ≥450 msec (male) or ≥460 msec (female) at screening or baseline - Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia - Participant has mean systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg at Screening or pre first dose on Day 1; or past history of hypertensive crisis. - History of hemorrhagic stroke or known cerebrovascular disorders (e.g. aneurysm or arteriovenous malformation) or known aneurysmal vascular disease in other location (e.g. aorta). - Pregnancy (including a positive human chorionic gonadotropin [hCG] test) or lactation at screening or baseline. - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 1 week after stopping of investigational drug. - Sexually active males unwilling to use a condom during intercourse while taking investigational drug and for 1 week after stopping study treatment. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of the investigational drug via seminal fluid to their partner. In addition, male participants should not donate sperm for the time period specified above. - Any other condition (e.g. known liver disease/liver dysfunction, active malignancy etc.) which in the opinion of the investigator would put the safety of the participant at risk, affect compliance or make the patient an unsuitable candidate for the study.
See protocol for full exclusion criteria. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
MADRS total score at 24 hours after s.c. injection compared to baseline assessment |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
24 hours post dose from baseline |
|
E.5.2 | Secondary end point(s) |
- Incidence and severity of treatment-emergent adverse events (TEAEs), including AEs of special interest; standard safety assessments such as vital signs, ECG, hematology, blood chemistry, urinalysis; Clinician-Administered Dissociative States Scale (CADSS) score, Modified Observer's Assessment of Alertness/Sedation (MOAA/S), C-SSRS, memory assessment using orientation questions, results of local tolerability assessments - PK properties of MIJ821 in plasma described by Area under the curve from time zero to time of last measurable concentration (AUClast), maximum plasma drug concentration (Cmax), time to reach maximum plasma concentration (Tmax) (parameters not limited). - MADRS total score at Day 8, 15, 22 and 29 visits compared to baseline - Dose-response relationship of MIJ821 with respect to change from baseline in MADRS total score at 24 hours after single s.c. injection - Exposure-response relationship of MIJ821 with respect to change from baseline in MADRS total score at 24 hours (Day 2)
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
24 hours post dose from baseline, Day 8, Day 15, Day 22 and Day 29 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Japan |
United States |
Czechia |
Poland |
Spain |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 19 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |