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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04722666

Collaborator

(none)

195

Enrollment

Locations

Arms

30.4

Anticipated Duration (Months)

4.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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

Anticipated Enrollment :

195 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 :

Jul 20, 2021

Anticipated Primary Completion Date :

Jan 30, 2024

Anticipated Study Completion Date :

Jan 30, 2024

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

Change from baseline in the total score of the Montgomery Åsberg Depression Rating Scale (MADRS) [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

Number and severity of treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESI) [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 [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 [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 [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 [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 [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 [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 [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

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed informed consent must be obtained prior to participation in the study
Male and female participants, 18 to 65 years of age (inclusive) at screening
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
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
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
Montgomery-Åsberg Depression Rating Scale (MADRS) score > 28 at Screening and before randomization on Day 1
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
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:

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
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.
Participant has a current clinical diagnosis of autism, dementia, or intellectual disability
History of seizures. Note: childhood febrile seizures are not exclusionary
Participants with borderline personality disorder as obtained from M.I.N.I. at Screening.
Participants with suicidal ideation or behavior caused primarily by another non-MDD condition as obtained from M.I.N.I. at Screening
Participants taking medications prohibited by the protocol
Intake of the following medications/ psychotherapy:
Esketamine or Ketamine 2 months before Screening
Monoamine oxidase inhibitors (MAOIs) 14 days before Screening
Non-stable psychotherapy regimen and/or started less than 6 weeks before Screening
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

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Birmingham	Alabama	United States	35294-3300
2	Novartis Investigative Site	Garden Grove	California	United States	92845
3	Novartis Investigative Site	Farmington	Connecticut	United States	06030-3100
4	Novartis Investigative Site	Oakland Park	Florida	United States	33334
5	Novartis Investigative Site	Atlanta	Georgia	United States	30331
6	Novartis Investigative Site	Rockville	Maryland	United States	20850
7	Novartis Investigative Site	Columbus	Ohio	United States	43210
8	Novartis Investigative Site	Auckland		Australia	1309
9	Novartis Investigative Site	Fortaleza	Ceara	Brazil	60430-270
10	Novartis Investigative Site	Sao Bernardo do Campo	Sao Paulo	Brazil	09726-150
11	Novartis Investigative Site	Toronto	Ontario	Canada	M5B 1W8
12	Novartis Investigative Site	Frankfurt		Germany	60590
13	Novartis Investigative Site	Jena		Germany	07740
14	Novartis Investigative Site	Toyoake-city	Aichi	Japan	470-1168
15	Novartis Investigative Site	Bunkyo-ku	Tokyo	Japan	113-8519
16	Novartis Investigative Site	Kodaira	Tokyo	Japan	187-8551
17	Novartis Investigative Site	Setagaya-ku	Tokyo	Japan	157-8577
18	Novartis Investigative Site	Seremban	Negeri Sembilan	Malaysia	70300
19	Novartis Investigative Site	Kuala Lumpur		Malaysia	59100
20	Novartis Investigative Site	Monterrey	Nuevo Leon	Mexico	64460
21	Novartis Investigative Site	San Luis Potosi		Mexico	78213
22	Novartis Investigative Site	Groningen		Netherlands	9713 GZ
23	Novartis Investigative Site	Lodz	Lodzkie	Poland	91-229
24	Novartis Investigative Site	Pruszkow	Mazowieckie	Poland	05-802
25	Novartis Investigative Site	Choroszcz		Poland	16-070
26	Novartis Investigative Site	Gdansk		Poland	80 952
27	Novartis Investigative Site	Moscow		Russian Federation	107258
28	Novartis Investigative Site	Moscow		Russian Federation	115419
29	Novartis Investigative Site	Hospitalet de Llobregat	Barcelona	Spain	08907
30	Novartis Investigative Site	Barcelona	Catalunya	Spain	08003
31	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
32	Novartis Investigative Site	Palma De Mallorca	Islas Baleares	Spain	07120
33	Novartis Investigative Site	Vitoria-Gasteiz	Pais Vasco	Spain	01004
34	Novartis Investigative Site	Barcelona		Spain	08025
35	Novartis Investigative Site	Taipei		Taiwan	11217
36	Novartis Investigative Site	Bursa	Gorukle	Turkey	16059
37	Novartis Investigative Site	Istanbul	TUR	Turkey	34098
38	Novartis Investigative Site	Adana		Turkey
39	Novartis Investigative Site	Izmir		Turkey	35100
40	Novartis Investigative Site	Preston		United Kingdom	PR2 9HT