Proof of Concept Study Evaluating the Efficacy and Safety of MIJ821 in Patients With Treatment-resistant Depression

NCT03756129 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CMIJ821X2201
• Study Type: interventional
• Target: 70
• Locations: 2 countries
• Sites: 12

Brief Summary

This study evaluated the efficacy and safety of the compound MIJ821 compared to placebo in patients aged from 18 to 65 years diagnosed with treatment-resistant depression. The study was conducted in the US and in Europe (Spain). The MIJ821 was administered via infusion on a weekly or bi-weekly basis. The efficacy was measured after 24 hours using a specific golden standard scale, the Montgomery-Asberg Depression Rating Scale. The study duration was 6 weeks of treatment plus 1 month of follow up period.

Conditions

Depressive Disorder, Treatment-Resistant

Keywords

Refractory Depression; Therapy-Resistant Depression; Treatment Resistant Depression; MDE; MDD; Major depressive disorder (MDD); clinical depression; major depression; unipolar depression; unipolar mood disorder; depression; the blues; mood disorder

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 24 Hrs

  Efficacy. To assess change from baseline in the total MADRS score. The efficacy of MIJ821 in treatment-resistant depression will be compared to the placebo after single dose administration. MADRS 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.

  Baseline, and at 24 hours

Secondary Outcomes (18)

• Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 48 Hrs

  Baseline, and at 48 hours

• Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at Week 6

  Baseline, and at Week 6

• Change From Baseline in the Young Mania Rating Scale

  Baseline, 24 hours, and 6 weeks (day 43)

• Bech-Rafaelsen Melancholia Scale

  Baseline, 24 hours, 48 hours and 6 weeks (Day 43)

• PK Properties of MIJ821 in Plasma - Cmax (ng/mL)

  Day 1

Study Arms (6)

MIJ821 low dose weekly

EXPERIMENTAL

Infusion. MIJ821 low dose weekly - 0.16 mg/kg

Drug: MIJ821

MIJ821 low dose bi-weekly

EXPERIMENTAL

Infusion. MIJ821 low dose bi-weekly - 0.16 mg/kg

Drug: MIJ821

MIJ821 high dose weekly

EXPERIMENTAL

Infusion. MIJ821 high dose weekly - 0.32 mg/kg

Drug: MIJ821

MIJ821 high dose bi-weekly

EXPERIMENTAL

Infusion. MIJ821 high dose bi-weekly - 0.32 mg/kg

Drug: MIJ821

Placebo weekly

PLACEBO COMPARATOR

Infusion. Placebo weekly

Drug: Placebo

Ketamine 0.5 mg/kg weekly

ACTIVE COMPARATOR

Infusion. Ketamine 0.5 mg/kg weekly

Drug: Ketamine

Interventions

MIJ821 DRUG

Different dosages and different regimen for MIJ821

MIJ821 high dose bi-weekly; MIJ821 high dose weekly; MIJ821 low dose bi-weekly; MIJ821 low dose weekly

Placebo DRUG

Infusion

Placebo weekly

Ketamine DRUG

Infusion

Also known as: Ketamine dose to be capped at 40 mg/day for patients over 80 kg

Ketamine 0.5 mg/kg weekly

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent.
• Male and female subjects, 18 to 65 years of age (inclusive) at screening.
• SCID-based DSM-5 defined major depressive episode at the time of screening
• Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥ 24 at screening and baseline
• Failure to respond to two or more antidepressant treatments, where two failed treatments are of two different antidepressants and at least one of which is in the current depressive episode, with adequate dose and duration (≥ 8 weeks duration, doses defined per agent), as identified by the Maudsley Treatment Inventory, and prior psychiatric history, assessed by the investigator, and further documented by medical records and/or third party report (family, friends, clinician-treaters) where available
• If patients are taking any type of psychotropic drugs, a stable dose of psychotropic drugs at screening is defined as no changes in dose or type of antidepressants, antipsychotics, or mood stabilizers for at least 2 weeks prior to screening, if applicable.
• No new antidepressant initiated 4 weeks or less before baseline, and 6 weeks or less before baseline if subject is initiated on fluoxetine
• At least one prior clinical depressive episode (recurrent major depressive disorder), as identified by prior psychiatric history assessed by the investigator, and further documented by medical records and third party report (family, friends, clinician-treaters) where available.
• Able to communicate well, and to understand and comply with study requirements

You may not qualify if:

• Any current diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorder at screening.
• Prior suicidality caused by or associated with ketamine, as identified by prior psychiatric history assessed by the investigator, and augmented by medical records and third party report (family, friends, clinician-treaters) where available.
• Use of other investigational drugs within 30 days or 5 half-lives of randomization, whichever was longer; or longer if required by local regulations at baseline
• Current pregnancy or lactation.
• Positive HIV, Hepatitis B or C test.
• Resting QTcF ≥450 msec (male) or ≥460 msec (female) at pre-treatment baseline
• History of multiple and recurring allergies or allergy to the investigational compound/compound class being used in this study.
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 3 years, regardless of whether there is evidence of local recurrence or metastases.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 1 week after stopping of investigational drug.
• History of hypersensitivity to any of the study treatments or excipients or to drugs similar to chemical classes that affect NMDA receptor.
• Current diagnosis of borderline personality disorder or antisocial personality disorder, based on DSM-5 criteria.
• Current acute depressive episode lasting longer than two years continuously, defined as no two week or longer period where depressive symptoms are subsyndromal in severity for a full DSM-5 acute major depressive episode.
• Considered by the investigator, for any other reason, to be an unsuitable candidate for the study.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (12)

Novartis Investigative Site

Birmingham, Alabama, 35294, United States

Location

Novartis Investigative Site

Garden Grove, California, 92845, United States

Location

Novartis Investigative Site

Oakland, California, 94607, United States

Location

Novartis Investigative Site

Bradenton, Florida, 34201, United States

Location

Novartis Investigative Site

Atlanta, Georgia, 30331, United States

Location

Novartis Investigative Site

Skokie, Illinois, 60076, United States

Location

Novartis Investigative Site

Rockville, Maryland, 20850, United States

Location

Novartis Investigative Site

Berlin, New Jersey, 08009, United States

Location

Novartis Investigative Site

Palma de Mallorca, Balearic Islands, 07120, Spain

Location

Novartis Investigative Site

Vitoria-Gasteiz, Basque Country, 01004, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

Novartis Investigative Site

Barcelona, 08006, Spain

Location

Related Publications (1)

• Shelton RC, Litman RE, Hassman H, Walling DP, Ros Montalban S, Salva-Coll J, Zajecka J, Sverdlov O, Gomez-Mancilla B, Healy MP, Shanker YG, Berkheimer M, Faller T, von Raison F, Serban C, Cha JH, Ghaemi SN. Rapid Onset and Sustained Efficacy of Onfasprodil (MIJ821), a Novel NR2B Negative Allosteric Modulator, in Patients With Treatment-Resistant Depression: A Phase 2, Randomized, Placebo-Controlled, Proof-of-Concept Study. J Clin Psychiatry. 2025 Aug 6;86(3):23m15246. doi: 10.4088/JCP.23m15246.

  PMID: 40767837 DERIVED

Related Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major; Depressive Disorder; Depression; Mood Disorders

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a non-confirmatory, multi-center, 6-treatment arm in the EU countries and 5-treatment arm in the USA (no ketamine arm), randomized, subject and investigator blinded, parallel group, placebo controlled study in treatment-resistant depression patients. The study allows for the inclusion of subjects seeking treatment for their disease from both an 'inpatient' or 'outpatient' clinic setting.

Study Record Dates

• First Submitted: November 13, 2018
• First Posted: November 28, 2018
• Study Start: February 8, 2019
• Primary Completion: March 23, 2020
• Study Completion: March 23, 2020
• Last Updated: October 8, 2021
• Results First Posted: May 19, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share

Locations

US (8); ES (4)