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 )

Tracking Information

• First Submitted Date: January 21, 2021
• First Posted Date: January 25, 2021
• Last Update Posted Date: April 22, 2024
• Actual Study Start Date: July 20, 2021
• Actual Primary Completion Date: September 26, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 21, 2021)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 21, 2021)

• 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
• 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.
• 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.
• 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
• 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
• 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
• 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
• 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• 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

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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Major Depressive Disorder With Suicidal Ideation With Intent

Intervention

• 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

Study Arms

• 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
  Intervention: Drug: MIJ821 Intravenous Injection
• Experimental: MIJ821 (mg/kg) - low dose
  MIJ821 (mg/kg) low dose for 40 minutes IV infusion on Day 1, Day 15 and Day 29
  Intervention: Drug: MIJ821 Intravenous Injection
• Experimental: MIJ821(mg/kg) - high dose
  MIJ821 (mg/kg) high dose for 40 minutes IV infusion on Day 1, Day 15 and Day 29
  Intervention: Drug: MIJ821 Intravenous Injection
• 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
  Intervention: Drug: MIJ821 Intravenous Injection
• Placebo Comparator: Placebo
  40 minutes IV infusion of 0.9% sodium chloride on Day 1, Day 15 and Day 29
  Intervention: Drug: Placebo Intravenous Injection
• 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
  Interventions:

  • Drug: MIJ821 Intravenous Injection
  • Drug: Placebo Intravenous Injection
• 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
  Interventions:

  • Drug: MIJ821 Intravenous Injection
  • Drug: Placebo Intravenous Injection

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: October 31, 2023): 200
• Original Estimated Enrollment (submitted: January 21, 2021): 195
• Actual Study Completion Date: September 26, 2023
• Actual Primary Completion Date: September 26, 2023 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Brazil, Canada, Germany, Japan, Malaysia, Mexico, Netherlands, Poland, Russian Federation, Spain, Taiwan, Turkey, United States
• Removed Location Countries: Australia, United Kingdom

Administrative Information

• NCT Number: NCT04722666
• Other Study ID Numbers: CMIJ821A12201
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

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/

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Novartis
• Verification Date: October 2023