Clinical trial NCT03756129: Proof of Concept Study Evaluating the Efficacy and Safety of MIJ821 in Patients With Treatment-resistant Depression
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-11-28
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Detailed description: This was a non-confirmatory, multi-center, 6-treatment arm in European (Spain) and 5-treatment arm in the US (no ketamine arm), randomized, subject and investigator blinded, parallel-group, placebo-controlled study in patients with treatment-resistant depression. The total duration for each subject in the study was maximum 14 weeks: a screening period of maximum 4 weeks, a 36-day treatment period and a 5-week 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.

Primary outcomes:
measure: Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 24 Hrs
timeFrame: Baseline, and at 24 hours
Secondary outcomes:
measure: Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 48 Hrs
timeFrame: Baseline, and at 48 hours
measure: Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at Week 6
timeFrame: Baseline, and at Week 6
measure: Change From Baseline in the Young Mania Rating Scale
timeFrame: Baseline, 24 hours, and 6 weeks (day 43)
measure: Bech-Rafaelsen Melancholia Scale
timeFrame: Baseline, 24 hours, 48 hours and 6 weeks (Day 43)
measure: PK Properties of MIJ821 in Plasma - Cmax (ng/mL)
timeFrame: Day 1
measure: PK Properties of MIJ821 in Plasma - Tmax (ng/mL)
timeFrame: Day 1
measure: PK Properties of MIJ821 in Plasma - AUClast (h*ng/mL)
timeFrame: Day 1
measure: PK Properties of MIJ821 in Plasma - AUC0-24h (h*ng/mL)
timeFrame: Day 1
measure: Change From Baseline in the CORE Melancholia Total Scale
timeFrame: Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)
measure: Summary of Adverse Events
timeFrame: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 post treatment, up to a maximum duration of 66 days.
measure: Clinician-Administered Dissociative States Scale
timeFrame: Change from baseline at 24 hours, 48 hours, and 6 weeks (Day 43)
measure: Change From Baseline in the Dissociative Experiences Total Score
timeFrame: Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)
measure: Sheehan Suicidality Tracking Scale - (SSTS)
timeFrame: Change from baseline at 24 hours, 48 hours, and 6 weeks (Day 43)
measure: Percentage of Participants With Treatment Remissions (MADRS<7)
timeFrame: 24 hours, 48 hours, and 6 weeks (Day 43)
measure: Change From Baseline in the Total Hamilton Anxiety Scale
timeFrame: Baseline, and at 6 weeks (day 43)
measure: Summary Statistics of Total Hamilton Anxiety Scale - Change From Baseline
timeFrame: Change from baseline at week 6 (Day 43)
measure: Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale
timeFrame: Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)
measure: Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor.
timeFrame: 24 hours, 48 hours, and 6 weeks (Day 43)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Garden Grove
country: United States
facility: Novartis Investigative Site
state: California
city: Oakland
country: United States
facility: Novartis Investigative Site
state: California
city: Bradenton
country: United States
facility: Novartis Investigative Site
state: Florida
city: Atlanta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Skokie
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Rockville
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Berlin
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Palma De Mallorca
country: Spain
facility: Novartis Investigative Site
state: Islas Baleares
city: Vitoria-Gasteiz
country: Spain
facility: Novartis Investigative Site
state: Pais Vasco
city: Barcelona
country: Spain
facility: Novartis Investigative Site
Study officials:
References: