Clinical trial NCT04722666: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Major Depressive Disorder With Suicidal Ideation With Intent
Keywords: 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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-01-25
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change from baseline in the total score of the Montgomery Åsberg Depression Rating Scale (MADRS)
timeFrame: Baseline (first infusion) at 24 hours and up to 52 weeks
Secondary outcomes:
measure: Number and severity of treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESI)
timeFrame: Baseline up to 6 weeks
measure: Pharmacokinetics (PK) of MIJ821 in plasma
timeFrame: Baseline up to 52 weeks
measure: Percentage of participants meeting response criteria of ≥50% reduction
timeFrame: Baseline up to 6 weeks
measure: Percentage of participants meeting criteria for sustained response of ≥50% reduction
timeFrame: Baseline up to 6 weeks
measure: Percentage of participants meeting remission criteria of MADRS total score of ≤12
timeFrame: Baseline up to 6 weeks
measure: Percentage of participants meeting sustained remission criteria of MADRS total score of ≤12
timeFrame: Baseline up to 6 weeks
measure: Percentage of participants meeting criteria for relapse in the Extension Period
timeFrame: From 6 weeks up to 52 weeks
measure: Percentage of relapsing participants meeting response criteria or remission criteria after the first infusion
timeFrame: From 6 weeks up to 52 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Farmington
country: United States
facility: Novartis Investigative Site
state: Connecticut
city: Oakland Park
country: United States
facility: Novartis Investigative Site
state: Florida
city: Atlanta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Rockville
country: United States
facility: Novartis Investigative Site
state: Maryland
city: DeSoto
country: United States
facility: Novartis Investigative Site
state: Texas
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Fortaleza
country: Brazil
facility: Novartis Investigative Site
state: Ceara
city: Sao Bernardo do Campo
country: Brazil
facility: Novartis Investigative Site
state: Sao Paulo
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Toyoake-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Bunkyo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Kodaira
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Seremban
country: Malaysia
facility: Novartis Investigative Site
state: Negeri Sembilan
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
city: Monterrey
country: Mexico
facility: Novartis Investigative Site
state: Nuevo Leon
city: Mazatlan
country: Mexico
facility: Novartis Investigative Site
state: Sinaloa
city: San Luis Potosi
country: Mexico
facility: Novartis Investigative Site
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Lodz
country: Poland
facility: Novartis Investigative Site
state: Lodzkie
city: Pruszkow
country: Poland
facility: Novartis Investigative Site
state: Mazowieckie
city: Bialystok
country: Poland
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Swiecie n/W
country: Poland
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Palma De Mallorca
country: Spain
facility: Novartis Investigative Site
state: Islas Baleares
city: Vitoria-Gasteiz
country: Spain
facility: Novartis Investigative Site
state: Pais Vasco
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Bursa
country: Turkey
facility: Novartis Investigative Site
state: Gorukle
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
state: TUR
city: Izmir
country: Turkey
facility: Novartis Investigative Site
Study officials:
References: