Study of Efficacy, Safety, Tolerability and Pharmacokinetics of MIJ821 in Participants With Treatment- Resistant Depression (TRD)

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate safety and efficacy of a single injection of MIJ821 in addition to standard of care (SoC) pharmacological anti-depressant treatment in participants with treatment-resistant depression (TRD)

Detailed Description
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Approximately 56 participants will be randomized in a total of 20-25 centers worldwide. The trial consists of screening period of up to 28 days. On Day 1, eligible participants will be randomized to one of the treatment arms (low, medium or high dose of MIJ821) or placebo and receive study treatment administered as a single subcutaneous injection. Participant will remain at the clinic for at least 4 hours after administration of study treatment for safety observation including assessment of local tolerability by visual inspection of the injection area. Post-dose clinic visits will occur 24 hours post dose (Day 2), Days 8, 15, 22 and 29 to evaluate efficacy and safety. Efficacy assessments will include the Montgomery-Asberg Depression Scale (MADRS) and other clinical outcome assessments (COAs). Safety assessments include laboratory tests, ECGs, vital signs and physical examinations. In addition phone calls will be conducted 3 days after each on-site clinic visit with the exception of End-of-study (EOS) visit. EOS visit will be completed on site on Day 29. The total duration of the study is approximately 8 weeks (56 days), including screening.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel-group Trial to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Single Subcutaneous MIJ821 Injection in Addition to Standard of Care in Participants With Treatment-resistant Depression

Conditions
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Treatment-Resistant Depression

Intervention / Treatment
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* Drug: MIJ821 Subcutaneous Injection - low dose
* Drug: MIJ821 Subcutaneous Injection - medium dose
* Drug: MIJ821 Subcutaneous Injection - high dose
* Drug: Placebo Subcutaneous Injection


Participation Criteria
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Eligibility Criteria
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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. DSM-5 defined major depressive disorder (MDD) and a current major depressive episode (MDE) MADRS score ≥ 24 Failure to respond to 2 or more antidepressant treatments where the two failed treatments are two different antidepressants Exclusion Criteria: Any prior or current diagnosis of MDD with psychotic features, bipolar disorder, schizophrenia, or schizoaffective disorder Participants with acute alcohol or substance use disorder or withdrawal symptoms requiring detoxification, or participants who went through detoxification treatment within 1 month before Screening. Participants with current borderline personality disorder or antisocial personality disorder Current clinical diagnosis of autism, dementia, or intellectual disability.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MIJ821 - low dose<br>Single subcutaneous administration of low dose of MIJ821 on Day 1 | Drug: MIJ821 Subcutaneous Injection - low dose<br>* MIJ821 supplied in vials as a powder for solution for injection, to be reconstituted, and administered as a single subcutaneous injection on Day 1<br>|
| Experimental: MIJ821 - medium dose<br>Single subcutaneous administration of medium dose of MIJ821 on Day 1 | Drug: MIJ821 Subcutaneous Injection - medium dose<br>* MIJ821 supplied in vials as a powder for solution for injection, to be reconstituted, and administered as a single subcutaneous injection on Day 1<br>|
| Experimental: MIJ821 - high dose<br>Single subcutaneous administration of high dose of MIJ821 on Day 1 | Drug: MIJ821 Subcutaneous Injection - high dose<br>* MIJ821 supplied in vials as a powder for solution for injection, to be reconstituted, and administered as a single subcutaneous injection on Day 1<br>|
| Placebo Comparator: Placebo<br>Single subcutaneous administration of 0.9% sodium chloride on Day 1 | Drug: Placebo Subcutaneous Injection<br>* 0.9% sodium chloride solution to be administered as a single subcutaneous injection on Day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in MADRS total score 24 hours after injection | The Montgomery Asberg Depression Rating Scale (MADRS, SIGMA version) is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment: the test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. The MADRS evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts and suicidal thoughts. The MADRS will be collected electronically by qualified personnel. | Baseline and 24 hours after s.c. injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment-emergent adverse events (TEAEs), including AEs of special interest (AESIs) | Number of treatment-emergent adverse events (TEAEs), including AEs of special interest (AESIs) will be collected at all study visits. AESIs include dissociation, sedation, cardiovascular and respiratory effect, suicidality, memory gaps/amnesia, cystitis or lower urinary tract adverse events | Baseline up to 29 days | 
| Pharmacokinetics (PK) of MIJ821 in plasma for AUClast | AUClast is the AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) | Baseline, 0.17 hour, 0.33 hour, 0.5 hour, 0.75 hour, 1, 1.5, 2, 4 and 24 hours post injection | 
| Pharmacokinetics (PK) of MIJ821 in plasma for Cmax | Cmax is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1) | Baseline, 0.17 hour, 0.33 hour, 0.5 hour, 0.75 hour, 1, 1.5, 2, 4 and 24 hours post injection | 
| Pharmacokinetics (PK) of MIJ821 in plasma for Tmax | Tmax is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time) | Baseline, 0.17 hour, 0.33 hour, 0.5 hour, 0.75 hour, 1, 1.5, 2, 4 and 24 hours post injection | 
| MADRS total scores | The Montgomery Asberg Depression Rating Scale (MADRS, SIGMA version) is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment: the test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. The MADRS evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts and suicidal thoughts. The MADRS will be collected electronically by qualified personnel. | Baseline, Day 8, Day 15, Day 22 and 29 | 
| Dose-response relationship of MIJ821 | Correlation between MIJ821 dose and change from baseline in the Montgomery Asberg Depression Rating Scale (MADRS) total score at 24 hours. The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment: the test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. | Baseline up to 24 hours | 
| Exposure-response relationship of MIJ821 | Correlation between MIJ821 exposure and the Montgomery Asberg Depression Rating Scale (MADRS) total score at 24 hours. MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment: the test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. | Baseline up to 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MIJ821, Treatment-Resistant Depression, Major Depressive Episode, Major Depressive Disorder, Anti-depressive Agent, Subcutaneous, Placebo, Adult