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

Novartis

Status and phase: Terminated; Phase 2

Conditions: Major Depressive Disorder With Suicidal Ideation With Intent

Treatments: Drug: MIJ821 Intravenous Injection; Drug: Placebo Intravenous Injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT04722666

CMIJ821A12201

Details and patient eligibility

About

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

Full 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.

Enrollment: 200 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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200 participants in 7 patient groups, including a placebo group

MIJ821 (mg/kg) - very low dose

Experimental group

Description:

MIJ821 (mg/kg) very low dose for 40 minutes IV infusion on Day 1, Day 15 and Day 29

Treatment:

Drug: MIJ821 Intravenous Injection

MIJ821 (mg/kg) - low dose

Experimental group

Description:

MIJ821 (mg/kg) low dose for 40 minutes IV infusion on Day 1, Day 15 and Day 29

Treatment:

Drug: MIJ821 Intravenous Injection

MIJ821(mg/kg) - high dose

Experimental group

Description:

MIJ821 (mg/kg) high dose for 40 minutes IV infusion on Day 1, Day 15 and Day 29

Treatment:

Drug: MIJ821 Intravenous Injection

MIJ821 (mg/kg) - very high dose

Experimental group

Description:

MIJ821 (mg/kg) very high dose for 40 minutes IV infusion on Day 1, Day 15 and Day 29

Treatment:

Drug: MIJ821 Intravenous Injection

Placebo

Placebo Comparator group

Description:

40 minutes IV infusion of 0.9% sodium chloride on Day 1, Day 15 and Day 29

Treatment:

Drug: Placebo Intravenous Injection

MIJ821 (mg/kg) - high dose/Placebo

Experimental group

Description:

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

Treatment:

Drug: MIJ821 Intravenous Injection

Drug: Placebo Intravenous Injection

MIJ821 (mg/kg) - very high dose/Placebo

Experimental group

Description:

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

Treatment:

Drug: MIJ821 Intravenous Injection

Drug: Placebo Intravenous Injection