Proof of Concept Study Evaluating the Efficacy and Safety of MIJ821 in Patients With Treatment-resistant Depression
Condition: Depressive Disorder, Treatment-Resistant
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
Intervention: MIJ821; Placebo; Ketamine
Intervention description: Different dosages and different regimen for MIJ821; Infusion; Infusion
Intervention MeSH terms: Ketamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
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)
Enrollment: 70.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
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

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.
    

Eligibility 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.