Study of Efficacy and Safety of MIJ821 in Addition to Comprehensive Standard of Care on the Rapid Reduction of Symptoms of Major Depressive Disorder in Subjects Who Have Suicidal Ideation With Intent

A Double-blind, Placebo-controlled, Randomized Dose-ranging Trial to Investigate Efficacy and Safety of Intravenous MIJ821 Infusion in Addition to Comprehensive Standard of Care on the Rapid Reduction of Symptoms of Major Depressive Disorder in Subjects Who Have Suicidal Ideation With Intent

Study of efficacy and safety of MIJ821 in addition to comprehensive standard of care on the rapid reduction of symptoms of Major Depressive Disorder (MDD) in subjects who have suicidal ideation with intent

Study Overview

• Status: Terminated
• Conditions: Major Depressive Disorder With Suicidal Ideation With Intent
• Intervention / Treatment: Drug: MIJ821 Intravenous Injection; Drug: Placebo Intravenous Injection

Detailed Description

The main purpose of this study was to support the dose selection for future Phase III clinical trials by evaluating efficacy and safety of four MIJ821 doses (very low, low, high and very high) administered every other week for 6 weeks (3 infusions) by intravenous infusion on top of pharmacological antidepressant treatment, compared with placebo, for the rapid reduction of the symptoms of MDD in participants who have suicidal ideation with intent. In addition, the study explored the effect of single dose administration of very high and high doses to treat MDD in participants who have suicidal ideation with intent.

The study consisted of three periods: a Screening Period (up to 48 hrs), a double-blind Core Period (6 weeks) and Extension Period (up to 52 weeks). The Extension Period explored durability of the effect of the study treatment and the effect of MIJ821 on relapse rate, as well as safety of MIJ821 administration.

Those patients that responded to treatment at the end of the Core period were followed for up to a 52-week Extension period and were allowed to be retreated due to a relapse once with the same active treatment regimen as in the Core period (participants treated with placebo in the Core period were randomly switched to an MIJ821 regimen).

• Study Type: Interventional
• Enrollment (Actual): 199
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1429DUC
    • Novartis Investigative Site
• Brazil
  • São Paulo, Brazil, 09726-150
    • Novartis Investigative Site
  • Ceará
    • Fortaleza, Ceará, Brazil, 60430-270
      • Novartis Investigative Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • Novartis Investigative Site
• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 81377
      • Novartis Investigative Site
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60590
      • Novartis Investigative Site
• Japan
  • Aichi-ken
    • Toyoake, Aichi-ken, Japan, 470-1168
      • Novartis Investigative Site
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 1138519
      • Novartis Investigative Site
    • Kodaira, Tokyo, Japan, 187-8551
      • Novartis Investigative Site
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Novartis Investigative Site
  • Negeri Sembilan
    • Seremban, Negeri Sembilan, Malaysia, 70300
      • Novartis Investigative Site
• Mexico
  • San Luis Potosí City, Mexico, 78213
    • Novartis Investigative Site
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Novartis Investigative Site
  • Sinaloa
    • Mazatlán, Sinaloa, Mexico, 82103
      • Novartis Investigative Site
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Novartis Investigative Site
• Poland
  • Bialystok, Poland, 15 276
    • Novartis Investigative Site
  • Gdansk, Poland, 80-214
    • Novartis Investigative Site
  • Gmina Świecie, Poland, 86-100
    • Novartis Investigative Site
  • Masovian Voivodeship
    • Pruszków, Masovian Voivodeship, Poland, 05-802
      • Novartis Investigative Site
  • Łódź Voivodeship
    • Lodz, Łódź Voivodeship, Poland, 91-229
      • Novartis Investigative Site
• Russia
  • Moscow, Russia, 107258
    • Novartis Investigative Site
  • Moscow, Russia, 115419
    • Novartis Investigative Site
• Spain
  • Araba, Spain, 01004
    • Novartis Investigative Site
  • Barcelona, Spain, 08035
    • Novartis Investigative Site
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Barcelona, Spain, 08025
    • Novartis Investigative Site
  • Balearic Islands
    • Palma, Balearic Islands, Spain, 07120
      • Novartis Investigative Site
  • Catalonia
    • Barcelona, Catalonia, Spain, 08003
      • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Taipei, Taiwan, 11217
    • Novartis Investigative Site
• Turkey (Türkiye)
  • Izmir, Turkey (Türkiye), 35100
    • Novartis Investigative Site
  • Fatih
    • Istanbul, Fatih, Turkey (Türkiye), 34098
      • Novartis Investigative Site
  • Nilufer
    • Bursa, Nilufer, Turkey (Türkiye), 16059
      • Novartis Investigative Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • Univ of Alabama at Birmingham
  • Connecticut
    • Farmington, Connecticut, United States, 06030-3100
      • University of Connecticut Health Center
  • Florida
    • Oakland Park, Florida, United States, 33334
      • Research Centers of America LLC
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center for Medical Research
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Centers for Behavioral Research
  • Texas
    • DeSoto, Texas, United States, 75115
      • InSite Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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) 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" 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

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. Participants taking medications prohibited by the protocol

8. Intake of the following medications/ psychotherapy:

   1. Esketamine or Ketamine 2 months before Screening
   2. Current Monoamine oxidase inhibitors (MAOIs) 14 days before Screening
   3. known worsening or new appearance of suicidal ideation or behavior during a prior treatment, or within 2 months after last administration
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MIJ821 (mg/kg) - very low dose; MIJ821 (mg/kg) very low dose for 40 minutes IV infusion on Day 1, Day 15 and Day 29	Drug: MIJ821 Intravenous Injection; MIJ821 supplied in vials to be prepared on a mg/kg basis and to be administered for 40 minutes IV infusion on Day 1, Day 15 and Day 29
Experimental: MIJ821 (mg/kg) - low dose; MIJ821 (mg/kg) low dose for 40 minutes IV infusion on Day 1, Day 15 and Day 29	Drug: MIJ821 Intravenous Injection; MIJ821 supplied in vials to be prepared on a mg/kg basis and to be administered for 40 minutes IV infusion on Day 1, Day 15 and Day 29
Experimental: MIJ821(mg/kg) - high dose; MIJ821 (mg/kg) high dose for 40 minutes IV infusion on Day 1, Day 15 and Day 29	Drug: MIJ821 Intravenous Injection; MIJ821 supplied in vials to be prepared on a mg/kg basis and to be administered for 40 minutes IV infusion on Day 1, Day 15 and Day 29
Experimental: MIJ821 (mg/kg) - very high dose; MIJ821 (mg/kg) very high dose for 40 minutes IV infusion on Day 1, Day 15 and Day 29	Drug: MIJ821 Intravenous Injection; MIJ821 supplied in vials to be prepared on a mg/kg basis and to be administered for 40 minutes IV infusion on Day 1, Day 15 and Day 29
Placebo Comparator: Placebo; 40 minutes IV infusion of 0.9% sodium chloride on Day 1, Day 15 and Day 29	Drug: Placebo Intravenous Injection; 40 minutes IV infusion of 0.9% sodium chloride solution on Day1, Day 15 and Day 29
Experimental: MIJ821 (mg/kg) - high dose/Placebo; MIJ821 (mg/kg) high dose for 40 minutes IV infusion on Day 1, 0.9% sodium chloride for 40 minutes IV infusion on Day 15 and Day 29	Drug: MIJ821 Intravenous Injection; MIJ821 supplied in vials to be prepared on a mg/kg basis and to be administered for 40 minutes IV infusion on Day 1, Day 15 and Day 29; Drug: Placebo Intravenous Injection; 40 minutes IV infusion of 0.9% sodium chloride solution on Day1, Day 15 and Day 29
Experimental: MIJ821 (mg/kg) - very high dose/Placebo; MIJ821 (mg/kg) very high dose for 40 minutes IV infusion on Day 1, 0.9% sodium chloride for 40 minutes IV infusion on Day 15 and Day 29	Drug: MIJ821 Intravenous Injection; MIJ821 supplied in vials to be prepared on a mg/kg basis and to be administered for 40 minutes IV infusion on Day 1, Day 15 and Day 29; Drug: Placebo Intravenous Injection; 40 minutes IV infusion of 0.9% sodium chloride solution on Day1, Day 15 and Day 29

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Total Score of the Montgomery Åsberg Depression Rating Scale (MADRS)	The Montgomery Åsberg 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 0 - 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 was collected electronically by qualified personnel. Since the MADRS total score at 24 hours was evaluated post the single first infusion (prior to the second infusion), the bi-weekly and single dosing regimens of the same dose level are pooled as one arm for 0.048 mg/kg and 0.16 mg/kg.	Baseline, 24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Adverse Events of Special Interest (AESI) During the Core Period	Treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESIs) in Core period	6 weeks
AUClast - Pharmacokinetics (PK) of MIJ821 in Plasma	AUClast of MIJ821 in plasma after 1st infusion. AUClast is the Area Under the Curve (AUC) from time zero to the last measurable concentration sampling time (tlast). Since PK was evaluated post the single first infusion, the bi-weekly and single dosing regimens of the same dose level are pooled as one arm for 0.048 mg/kg and 0.16 mg/kg.	Pre-dose, 20min, 40min, 4hours and 24hours post 1st infusion
Cmax - Pharmacokinetics (PK) of MIJ821 in Plasma	Cmax of MIJ821 in plasma after 1st infusion. AUClast is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration. Since PK was evaluated post the single first infusion, the bi-weekly and single dosing regimens of the same dose level are pooled as one arm for 0.048 mg/kg and 0.16 mg/kg.	Pre-dose, 20min, 40min, 4hours and 24hours post 1st infusion
Number of Participants Meeting Response Criteria of ≥50% Reduction in MADRS Total Score.	Response criteria of ≥50% reduction from baseline in MADRS total score over time in the Core Period. The Montgomery Åsberg 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 has a total possible score of 0 - 60. Higher scores represent a more severe condition.	6 weeks
Number of Participants Meeting Criteria for Sustained Response of ≥50% Reduction in MADRS Total Score	Sustained response (≥50% reduction from baseline) from baseline in MADRS total score for a period of at least four weeks in the Core Period. The Montgomery Åsberg 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 has a total possible score of 0 - 60. Higher scores represent a more severe condition.	6 weeks
Number of Participants Meeting Remission Criteria of MADRS Total Score of ≤12	Remission criteria of MADRS total score of ≤12 over time in the Core Period. The Montgomery Åsberg 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 has a total possible score of 0 - 60. Higher scores represent a more severe condition.	6 weeks
Number of Participants Meeting Sustained Remission Criteria of MADRS Total Score of ≤12	Remission criteria of MADRS total score of ≤12 sustained for a period of at least four weeks in the Core Period. The Montgomery Åsberg 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 has a total possible score of 0 - 60. Higher scores represent a more severe condition.	6 weeks
Number of Participants Meeting Criteria for Relapse in the Extension Period	For participants classified as responders in the core period who entered the extension period. Response is defined as a ≥ 50% reduction from the baseline MADRS score at any visit during the study. All participants meeting criteria for relapse over fixed period in the Extension Period. A relapse manifests as the appearance of new depressive symptoms or worsening of previously stable or improving MDD symptoms. During the Extension Period, participants experiencing deterioration must be assessed by the treating physician and the relapse must be confirmed by assessment with MADRS during scheduled or unscheduled visit.	From 6 weeks up to 58 weeks
Number of Relapsing Participants Meeting Response Criteria After the First Retreatment Infusion in the Extension Period	Relapsing participants meeting response criteria or remission criteria after the first infusion of MIJ821 retreatment in the Extension Period. Response criteria (>=50% reduction from baseline in MADRS total score). Reinfusions are given at Day 1, 15 and 29 after relapse.	Up to 52 weeks after first retreatment infusion. Timepoints are relative to first retreatment (R) infusion for each patient, including Follow Up (F/U).
Number of Relapsing Participants Meeting Remission Criteria After the First Retreatment Infusion in the Extension Period	Relapsing participants meeting response criteria or remission criteria after the first infusion of MIJ821 retreatment in the Extension Period. Remission criteria (MADRS total score <=12). Reinfusions are given at Day 1, 15 and 29 after relapse.	Up to 52 weeks after first retreatment infusion. Timepoints are relative to first retreatment (R) infusion for each patient, including Follow Up (F/U).

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2021
• Primary Completion (Actual): September 26, 2023
• Study Completion (Actual): September 26, 2023

Study Registration Dates

• First Submitted: January 21, 2021
• First Submitted That Met QC Criteria: January 21, 2021
• First Posted (Actual): January 25, 2021

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Depression; Adult; Suicide; Major Depressive Disorder; Intravenous; Placebo; Suicidal Ideation; Hospitalization; Self-Injurious Behavior; Mental disorder; Mood disorder; Antidepressive Agent; MIJ821; Suicidal intent; Suicidal risk; Psychotropic Drug
• Additional Relevant MeSH Terms: Behavioral Symptoms; Depressive Disorder; Behavior; Suicide; Suicidal Ideation; Depression; Mood Disorders; Mental Disorders; Depressive Disorder, Major; Self-Injurious Behavior
• Other Study ID Numbers: CMIJ821A12201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No