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

• ClinicalTrials.gov Identifier: NCT04722666
• Recruitment Status: Terminated
• First Posted: January 25, 2021
• Last Update Posted: April 22, 2024
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder With Suicidal Ideation With Intent	Drug: MIJ821 Intravenous Injection; Drug: Placebo Intravenous Injection	Phase 2

Detailed Description:

The main purpose of this study is 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 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 will explore 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 consists 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 will explore durability of the effect of the study treatment and the effect of MIJ821 on relapse rate, as well as safety of repeated MIJ821 administration.

All patients in the extension period will receive active treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: July 20, 2021
• Actual Primary Completion Date: September 26, 2023
• Actual Study Completion Date: September 26, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change from baseline in the total score of the Montgomery Åsberg Depression Rating Scale (MADRS) [ Time Frame: Baseline (first infusion) at 24 hours and up to 52 weeks ]
   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 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

Secondary Outcome Measures :

1. Number and severity of treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESI) [ Time Frame: Baseline up to 6 weeks ]
   Treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESIs) will be collected at all study visits
2. Pharmacokinetics (PK) of MIJ821 in plasma [ Time Frame: Baseline up to 52 weeks ]
   PK parameters of MIJ821 in plasma after 1st infusion described by AUClast, Cmax, Tmax and after each other infusion described by Cmax and Tmax. In order to better define the PK profile, the timing of the PK sample collection may be altered based on emergent data.
3. Percentage of participants meeting response criteria of ≥50% reduction [ Time Frame: Baseline up to 6 weeks ]
   Response criteria of ≥50% reduction from baseline in MADRS total score over time in the Core Period.
4. Percentage of participants meeting criteria for sustained response of ≥50% reduction [ Time Frame: Baseline up to 6 weeks ]
   Sustained response from baseline in MADRS total score for a period of at least four weeks in the Core Period
5. Percentage of participants meeting remission criteria of MADRS total score of ≤12 [ Time Frame: Baseline up to 6 weeks ]
   Remission criteria of MADRS total score of ≤12 over time in the Core Period
6. Percentage of participants meeting sustained remission criteria of MADRS total score of ≤12 [ Time Frame: Baseline up to 6 weeks ]
   Remission criteria of MADRS total score of ≤12 sustained for a period of at least four weeks in the Core Period
7. Percentage of participants meeting criteria for relapse in the Extension Period [ Time Frame: From 6 weeks up to 52 weeks ]
   Relapse for all patients meeting criteria for relapse over fixed period in the Extension Period
8. Percentage of relapsing participants meeting response criteria or remission criteria after the first infusion [ Time Frame: From 6 weeks up to 52 weeks ]
   Relapsing participants meeting response criteria or remission criteria after the first infusion of MIJ821 retreatment in the Extension Period

Eligibility Criteria

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

Criteria

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 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. Monoamine oxidase inhibitors (MAOIs) 14 days before Screening
   3. Non-stable psychotherapy regimen and/or started less than 6 weeks 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.

Contacts and Locations

Locations

United States, Alabama

Novartis Investigative Site

Birmingham, Alabama, United States, 35294-3300

United States, Connecticut

Novartis Investigative Site

Farmington, Connecticut, United States, 06030-3100

United States, Florida

Novartis Investigative Site

Oakland Park, Florida, United States, 33334

United States, Georgia

Novartis Investigative Site

Atlanta, Georgia, United States, 30331

United States, Maryland

Novartis Investigative Site

Rockville, Maryland, United States, 20850

United States, Texas

Novartis Investigative Site

DeSoto, Texas, United States, 75115

Argentina

Novartis Investigative Site

Buenos Aires, Argentina, C1429DUC

Brazil

Novartis Investigative Site

Fortaleza, Ceara, Brazil, 60430-270

Novartis Investigative Site

Sao Bernardo do Campo, Sao Paulo, Brazil, 09726-150

Canada, Ontario

Novartis Investigative Site

Toronto, Ontario, Canada, M5B 1W8

Germany

Novartis Investigative Site

Frankfurt, Germany, 60590

Novartis Investigative Site

Muenchen, Germany, 81377

Japan

Novartis Investigative Site

Toyoake-city, Aichi, Japan, 470-1168

Novartis Investigative Site

Bunkyo-ku, Tokyo, Japan, 113-8519

Novartis Investigative Site

Kodaira, Tokyo, Japan, 187-8551

Malaysia

Novartis Investigative Site

Seremban, Negeri Sembilan, Malaysia, 70300

Novartis Investigative Site

Kuala Lumpur, Malaysia, 59100

Mexico

Novartis Investigative Site

Monterrey, Nuevo Leon, Mexico, 64460

Novartis Investigative Site

Mazatlan, Sinaloa, Mexico, 82140

Novartis Investigative Site

San Luis Potosi, Mexico, 78213

Netherlands

Novartis Investigative Site

Groningen, Netherlands, 9713 GZ

Poland

Novartis Investigative Site

Lodz, Lodzkie, Poland, 91-229

Novartis Investigative Site

Pruszkow, Mazowieckie, Poland, 05-802

Novartis Investigative Site

Bialystok, Poland, 15 276

Novartis Investigative Site

Gdansk, Poland, 80 952

Novartis Investigative Site

Swiecie n/W, Poland, 86-100

Russian Federation

Novartis Investigative Site

Moscow, Russian Federation, 107258

Novartis Investigative Site

Moscow, Russian Federation, 115419

Spain

Novartis Investigative Site

Barcelona, Catalunya, Spain, 08003

Novartis Investigative Site

Barcelona, Catalunya, Spain, 08035

Novartis Investigative Site

Palma De Mallorca, Islas Baleares, Spain, 07120

Novartis Investigative Site

Vitoria-Gasteiz, Pais Vasco, Spain, 01004

Novartis Investigative Site

Barcelona, Spain, 08025

Novartis Investigative Site

Barcelona, Spain, 08041

Taiwan

Novartis Investigative Site

Taipei, Taiwan, 10048

Novartis Investigative Site

Taipei, Taiwan, 11217

Turkey

Novartis Investigative Site

Bursa, Gorukle, Turkey, 16059

Novartis Investigative Site

Istanbul, TUR, Turkey, 34098

Novartis Investigative Site

Izmir, Turkey, 35100

Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04722666
• Other Study ID Numbers: CMIJ821A12201
• First Posted: January 25, 2021
• Last Update Posted: April 22, 2024
• Last Verified: October 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Major Depressive Disorder; Mental disorder; Mood disorder; Depression; Suicide; Suicidal Ideation; Suicidal intent; Suicidal risk; Self-Injurious Behavior; MIJ821; Antidepressive Agent; Psychotropic Drug; Hospitalization; Intravenous; Placebo; Adult

Additional relevant MeSH terms:

Depressive Disorder; Depression; Depressive Disorder, Major; Suicidal Ideation; Mood Disorders; Mental Disorders; Behavioral Symptoms; Suicide; Self-Injurious Behavior