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

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ClinicalTrials.gov Identifier: NCT03756129
Recruitment Status : Recruiting
First Posted : November 28, 2018
Last Update Posted : October 1, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This study will evaluate 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 will be conducted in the US and in Europe (Spain). The MIJ821 will be administered via infusion on a weekly or bi-weekly basis. The efficacy will be measured after 24 hours using a specific golden standard scale, the Montgomery-Asberg Depression Rating Scale. The study duration is 6 weeks of treatment plus 1 month of follow up period.

Condition or disease Intervention/treatment Phase
Depressive Disorder, Treatment-Resistant Drug: MIJ821 Drug: Placebo Drug: Ketamine Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 66 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, subject-and Investigator Blinded, Placebo-controlled, Active Comparator, Parallel-group Proof of Concept Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of MIJ821 in Patients With Treatment-resistant Depression
Actual Study Start Date : February 8, 2019
Estimated Primary Completion Date : March 13, 2020
Estimated Study Completion Date : March 13, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Ketamine

Arm Intervention/treatment
Experimental: MIJ821 low dose weekly
Infusion
Drug: MIJ821
Different dosages and different regimen for MIJ821

Experimental: MIJ821 low dose bi-weekly
Infusion
Drug: MIJ821
Different dosages and different regimen for MIJ821

Experimental: MIJ821 high dose weekly
Infusion
Drug: MIJ821
Different dosages and different regimen for MIJ821

Experimental: MIJ821 high dose bi-weekly
Infusion
Drug: MIJ821
Different dosages and different regimen for MIJ821

Placebo Comparator: Placebo weekly
Infusion
Drug: Placebo
Infusion

Active Comparator: Ketamine 0.5 mg/kg weekly
Infusion
Drug: Ketamine
Infusion
Other Name: Ketamine dose to be capped at 40 mg/day for patients over 80 kg




Primary Outcome Measures :
  1. Total score of the Montgomery Asberg Depression Rating Scale (MADRS) [ Time Frame: 24 hours ]
    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.


Secondary Outcome Measures :
  1. Young Mania rating Scale [ Time Frame: 24 hours, 48 hours [if applicable] and 6 weeks ]
    To assess risk of mania induction

  2. Bech-Rafaelsen melancholia scale [ Time Frame: 24 hours, 48 hours [if applicable] and 6 weeks ]
    To assess efficacy in the melancholic subtype of depression

  3. Clinician-Administered Dissociative States Scale [ Time Frame: Change from baseline to 24 hours, 48 hours [if applicable] and 6 weeks ]
    To assess safety and tolerability, especially dissociative side effects

  4. Dissociative Experiences Scale [ Time Frame: Change from baseline to 24 hours, 48 hours [if applicable] and 6 weeks ]
    To assess safety and tolerability, especially dissociative side effects

  5. Montgomery Åsberg Depression Rating Scale (MADRS) [ Time Frame: Score at 6 weeks ]
    To assess most effective dose and dosing regimen

  6. PK properties of MIJ821 in plasma [ Time Frame: 0 hour, 40 minutes, 4 hours, 48 hours [if applicable], 29 days (pre-dose and post-dose) ]
    To assess MIJ821 pharmacokinetics in plasma described by AUClast, Cmax, Tmax

  7. Sheehan Suicidality Tracking Scale [ Time Frame: Changes from baseline at 24 hours, 48 hours [if applicable], and 6 weeks ]
    To assess impact of MIJ821 on suicidality

  8. Percentage of treatment response. [ Time Frame: 24 hours, 48 hours [if applicable], and 6 weeks. ]
    To assess efficacy of MIJ821 on measures of response (defined as >50% improvement in MADRS)

  9. Percentage of treatment remission [ Time Frame: 24 hours, 48 hours [if applicable], and 6 weeks. ]
    To assess efficacy of MIJ821 on measures of remission (MADRS<7), CGI-S and CGI-I scores

  10. Koukopoulos Mixed Depression Rating Scale [ Time Frame: Change from baseline to 24 hours, 48 hours [if applicable], and 6 weeks ]
    To assess efficacy of MIJ821 for mixed mood symptoms

  11. Hamilton Anxiety Scale [ Time Frame: Change from baseline to 24 hours, 48 hours [if applicable], and 6 weeks ]
    To assess efficacy of MIJ821 for anxiety symptoms

  12. Regression model effect size (odds ratio) for Hamilton Anxiety Scale as a predictor and MADRS treatment response as the outcome [ Time Frame: 24 hours, 48 hours [if applicable], and 6 weeks ]
    To assess the impact of anxiety as predictor of treatment response to MIJ821

  13. Regression model effect size (odds ratio) for Bech Rafaelsen Melancholia Scale as a predictor and MADRS treatment response as the outcome [ Time Frame: 24 hours, 48 hours [if applicable], and 6 weeks ]
    To assess the impact of Melancholia as predictor of treatment response to MIJ821

  14. Regression model effect size (odds ratio) for Koukopoulos Mixed Depression Rating Scale as a predictor and MADRS treatment response as the outcome [ Time Frame: 24 hours, 48 hours [if applicable], and 6 weeks ]
    To assess the impact of Mixed Mood symptoms as predictor of treatment response to MIJ821

  15. CORE Melancholia Scale [ Time Frame: 24 hours, 48 hours [if applicable] and 6 weeks ]
    To assess efficacy in melancholic subtype of depression



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • 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

Key Exclusion Criteria:

  • Any current diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorder at screening.
  • Current alcohol or substance use disorder (including marijuana and prescribed amphetamine)) meeting DSM-5 criteria, within the past month at baseline. Nicotine and caffeine use disorders will not be considered as exclusionary.
  • 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.
  • Acute serious and/or imminent suicidal ideation and/or intent within the prior 2 weeks, or any suicide attempt within the prior 4 weeks at screening. Mild to moderate suicidal ideation, using the Sheehan Suicidal Ideation Scale and not meeting the above definition, is not an exclusion criterion.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03756129


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Alabama
Novartis Investigative Site Recruiting
Birmingham, Alabama, United States, 35294
United States, California
Novartis Investigative Site Active, not recruiting
Garden Grove, California, United States, 92845
Novartis Investigative Site Recruiting
Oakland, California, United States, 94607
United States, Florida
Novartis Investigative Site Recruiting
Bradenton, Florida, United States, 34201
United States, Georgia
Novartis Investigative Site Recruiting
Atlanta, Georgia, United States, 30331
United States, Illinois
Novartis Investigative Site Recruiting
Skokie, Illinois, United States, 60076
United States, Maryland
Novartis Investigative Site Recruiting
Rockville, Maryland, United States, 20850
United States, New Jersey
Novartis Investigative Site Recruiting
Berlin, New Jersey, United States, 08009
Spain
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site Recruiting
Palma De Mallorca, Islas Baleares, Spain, 07120
Sponsors and Collaborators
Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03756129     History of Changes
Other Study ID Numbers: CMIJ821X2201
First Posted: November 28, 2018    Key Record Dates
Last Update Posted: October 1, 2019
Last Verified: September 2019
Individual Participant Data (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 www.clinicalstudydatarequest.com


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Refractory Depression; Therapy-Resistant Depression; Treatment Resistant Depression; MDE; MDD
Additional relevant MeSH terms:
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Depression
Depressive Disorder
Depressive Disorder, Treatment-Resistant
Behavioral Symptoms
Mood Disorders
Mental Disorders
Ketamine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action