E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Major Depressive Disorder with suicidal ideation with intent |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
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 |
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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 investigate the dose response relationship for 4 doses of MIJ821 vs.placebo |
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E.2.2 | Secondary objectives of the trial |
To assess safety and tolerability of MIJ821
To assess the effect of MIJ821 on sustained response and remission
To assess MIJ821 pharmacokinetics in plasma |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent must be obtained prior to participation in the study
2. Male and female participants, 18 to 65 years of age (inclusive), body weight from 50 kg to 120 kg (inclusive) at screening
3. DSM-5 defined major depressive disorder (MDD) with a current major depressive episode (MDE) without psychotic features at the time of screening based upon clinical assessment and confirmed by the Mini International Neuropsychiatric Interview (M.I.N.I.) assessed at Screening
4. Participants must have current suicidal ideation with intent, confirmed by a "Yes" response to Question B3 AND either Question B10 or Question B11 obtained from the M.I.N.I., assessed at Screening
5. Current suicidal ideation with intent, confirmed by "Yes" (>0) response to Question 3 AND either Question 9 or Question 10 obtained
from the SSTS at Baseline
6. Montgomery-Åsberg Depression Rating Scale (MADRS) score > 28 at Screening and before randomization on Day 1
7. Participants 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 local treatment guidelines) during the trial duration
8. In the physician's opinion, acute psychiatric hospitalization is clinically warranted to treat the patient’s condition, and the patient is either already in the hospital or agrees to be hospitalized voluntarily for the required per protocol period |
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E.4 | Principal exclusion criteria |
1. Any prior or current diagnosis of bipolar disorder, MDD with psychotic features, schizophrenia, or schizoaffective disorder as obtained from M.I.N.I. at Screening
2. Patients with acute alcohol or substance use disorder or withdrawal symptoms requiring detoxification, or patients who went through detoxification treatment (inpatient or outpatient) within 1 month before Screening.
3. Participant has a current clinical diagnosis of autism, dementia, or intellectual disability
4. History of seizures. Note: childhood febrile seizures are not exclusionary
5. Participants with current borderline personality disorder as obtained from M.I.N.I. at Screening.
6. Participants with suicidal ideation or behavior caused primarily by another non-MDD condition as obtained from M.I.N.I. at Screening
7. Known worsening or new appearance of suicidal ideation or behavior during a prior treatment with ketamine or esketamine or within 2 months after last ketamine or esketamine administration
8. Intake of the following medications: a. Esketamine or Ketamine within 2 months before Screening b. Monoamine oxidase inhibitors (MAOIs) within 14 days before Screening
9. 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, impede compliance or hinder completion of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in the total score of the Montgomery Åsberg Depression Rating Scale (MADRS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Number and severity of treatment-emergent adverse events (TEAEs), including AEs of special interest in the Core Period
- Pharmacokinetics (PK) of MIJ821 in plasma
- Percentage of participants meeting response criteria; criteria for sustained response; remission criteria and sustained remission criteria
- Percentage of participants meeting criteria for relapse and response criteria or remission criteria |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to 6 weeks for Core phase, Up to 52 Weeks for Extension phase |
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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 | No |
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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | 7 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 |
Argentina |
Malaysia |
Taiwan |
Australia |
Brazil |
Canada |
Germany |
Japan |
Mexico |
Netherlands |
Poland |
Russian Federation |
Slovakia |
Spain |
Turkey |
United Kingdom |
United States |
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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
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Last Patient Last Visit (i.e. when the last participant finishes their Study Completion visit) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 16 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |