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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 24 Hrs
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
MIJ821 low dose weekly
Infusion. MIJ821 low dose weekly - 0.16 mg/kg
干预措施: MIJ821 (Drug)
MIJ821 low dose bi-weekly
Infusion. MIJ821 low dose bi-weekly - 0.16 mg/kg
干预措施: MIJ821 (Drug)
MIJ821 high dose weekly
Infusion. MIJ821 high dose weekly - 0.32 mg/kg
干预措施: MIJ821 (Drug)
MIJ821 high dose bi-weekly
Infusion. MIJ821 high dose bi-weekly - 0.32 mg/kg
干预措施: MIJ821 (Drug)
Placebo weekly
Infusion. Placebo weekly
干预措施: Placebo (Drug)
Ketamine 0.5 mg/kg weekly
Infusion. Ketamine 0.5 mg/kg weekly
干预措施: Ketamine (Drug)
结局指标
主要结局
Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 24 Hrs
时间窗: Baseline, and at 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. 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.
次要结局
- Bech-Rafaelsen Melancholia Scale(Baseline, 24 hours, 48 hours and 6 weeks (Day 43))
- Change From Baseline in the CORE Melancholia Total Scale(Baseline, 24 hours, 48 hrs, and 6 weeks (day 43))
- Change From Baseline in the Dissociative Experiences Total Score(Baseline, 24 hours, 48 hrs, and 6 weeks (day 43))
- Percentage of Participants With Treatment Remissions (MADRS<7)(24 hours, 48 hours, and 6 weeks (Day 43))
- Change From Baseline in the Young Mania Rating Scale(Baseline, 24 hours, and 6 weeks (day 43))
- Sheehan Suicidality Tracking Scale - (SSTS)(Change from baseline at 24 hours, 48 hours, and 6 weeks (Day 43))
- Change From Baseline in the Total Hamilton Anxiety Scale(Baseline, and at 6 weeks (day 43))
- Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale(Baseline, 24 hours, 48 hrs, and 6 weeks (day 43))
- PK Properties of MIJ821 in Plasma - AUClast (h*ng/mL)(Day 1)
- Summary of Adverse Events(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.)
- Clinician-Administered Dissociative States Scale(Change from baseline at 24 hours, 48 hours, and 6 weeks (Day 43))
- 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)
- PK Properties of MIJ821 in Plasma - Cmax (ng/mL)(Day 1)
- PK Properties of MIJ821 in Plasma - Tmax (ng/mL)(Day 1)
- PK Properties of MIJ821 in Plasma - AUC0-24h (h*ng/mL)(Day 1)
- Summary Statistics of Total Hamilton Anxiety Scale - Change From Baseline(Change from baseline at week 6 (Day 43))
- Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor.(24 hours, 48 hours, and 6 weeks (Day 43))