A Double-blind, Placebo-controlled, Randomized Dose-ranging Trial to Investigate Efficacy and Safety of Intravenous MIJ821 Infusion in Addition to Comprehensive Standard of Care on the Rapid Reduction of Symptoms of Major Depressive Disorder in Subjects Who Have Suicidal Ideation With Intent
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 199
- 试验地点
- 40
- 主要终点
- Change from baseline in the total score of the Montgomery Åsberg Depression Rating Scale (MADRS)
研究概览
简要总结
Study of efficacy and safety of MIJ821 in addition to comprehensive standard of care on the rapid reduction of symptoms of Major Depressive Disorder (MDD) in subjects who have suicidal ideation with intent
详细描述
The main purpose of this study was to support the dose selection for future Phase III clinical trials by evaluating efficacy and safety of four MIJ821 doses (very low, low, high and very high) administered every other week for 6 weeks (3 infusions) by intravenous infusion on top of pharmacological antidepressant treatment, compared with placebo, for the rapid reduction of the symptoms of MDD in participants who have suicidal ideation with intent. In addition, the study explored the effect of single dose administration of very high and high doses to treat MDD in participants who have suicidal ideation with intent.
The study consisted of three periods: a Screening Period (up to 48 hrs), a double-blind Core Period (6 weeks) and Extension Period (up to 52 weeks). The Extension Period explored durability of the effect of the study treatment and the effect of MIJ821 on relapse rate, as well as safety of MIJ821 administration.
Those patients that responded to treatment at the end of the Core period were followed for up to a 52-week Extension period and were allowed to be retreated due to a relapse once with the same active treatment regimen as in the Core period (participants treated with placebo in the Core period were randomly switched to an MIJ821 regimen).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 must be obtained prior to participation in the study
- •Male and female participants, 18 to 65 years of age (inclusive) at screening
- •DSM-5 defined major depressive disorder (MDD) with a current major depressive episode (MDE) without psychotic features at the time of screening based upon clinical assessment and confirmed by the Mini International Neuropsychiatric Interview (M.I.N.I.) assessed at Screening
- •Participants must have current suicidal ideation with intent, confirmed by a "Yes" response to Question B3 AND either Question B10 or Question B11 obtained from the M.I.N.I., assessed at Screening
- •Current suicidal ideation with intent, confirmed by "Yes" response to Question 3 AND either Question 9 or Question 10 obtained from the SSTS at Baseline
- •Montgomery-Åsberg Depression Rating Scale (MADRS) score > 28 at Screening and before randomization on Day 1
- •Participants must agree to receive pharmacological standard of care treatment to treat their MDD (as determined by the treating physician(s) based on clinical judgement and local treatment guidelines) during the trial duration
- •In the physician's opinion, acute psychiatric hospitalization is clinically warranted to treat the patient's condition, and the patient is either already in the hospital or agrees to be hospitalized voluntarily for the required per protocol period
排除标准
- •Any prior or current diagnosis of bipolar disorder, MDD with psychotic features, schizophrenia, or schizoaffective disorder as obtained from M.I.N.I. at Screening
- •Patients with acute alcohol or substance use disorder or withdrawal symptoms requiring detoxification, or patients who went through detoxification treatment (inpatient or outpatient) within 1 month before Screening.
- •Participant has a current clinical diagnosis of autism, dementia, or intellectual disability
- •History of seizures. Note: childhood febrile seizures are not exclusionary
- •Participants with current borderline personality disorder as obtained from M.I.N.I. at Screening.
- •Participants with suicidal ideation or behavior caused primarily by another non-MDD condition as obtained from M.I.N.I. at Screening
- •Participants taking medications prohibited by the protocol
- •Intake of the following medications/ psychotherapy:
- •Esketamine or Ketamine 2 months before Screening
- •Current Monoamine oxidase inhibitors (MAOIs) 14 days before Screening
- •known worsening or new appearance of suicidal ideation or behavior during a prior treatment, or within 2 months after last administration
- •Any other condition (e.g. known liver disease/liver dysfunction, active malignancy, etc.) which in the opinion of the investigator would put the safety of the participant at risk, impede compliance or hinder completion of the study.
研究组 & 干预措施
MIJ821 (mg/kg) - very low dose
MIJ821 (mg/kg) very low dose for 40 minutes IV infusion on Day 1, Day 15 and Day 29
干预措施: MIJ821 Intravenous Injection (Drug)
MIJ821 (mg/kg) - low dose
MIJ821 (mg/kg) low dose for 40 minutes IV infusion on Day 1, Day 15 and Day 29
干预措施: MIJ821 Intravenous Injection (Drug)
MIJ821(mg/kg) - high dose
MIJ821 (mg/kg) high dose for 40 minutes IV infusion on Day 1, Day 15 and Day 29
干预措施: MIJ821 Intravenous Injection (Drug)
MIJ821 (mg/kg) - very high dose
MIJ821 (mg/kg) very high dose for 40 minutes IV infusion on Day 1, Day 15 and Day 29
干预措施: MIJ821 Intravenous Injection (Drug)
Placebo
40 minutes IV infusion of 0.9% sodium chloride on Day 1, Day 15 and Day 29
干预措施: Placebo Intravenous Injection (Drug)
MIJ821 (mg/kg) - high dose/Placebo
MIJ821 (mg/kg) high dose for 40 minutes IV infusion on Day 1, 0.9% sodium chloride for 40 minutes IV infusion on Day 15 and Day 29
干预措施: MIJ821 Intravenous Injection (Drug)
MIJ821 (mg/kg) - high dose/Placebo
MIJ821 (mg/kg) high dose for 40 minutes IV infusion on Day 1, 0.9% sodium chloride for 40 minutes IV infusion on Day 15 and Day 29
干预措施: Placebo Intravenous Injection (Drug)
MIJ821 (mg/kg) - very high dose/Placebo
MIJ821 (mg/kg) very high dose for 40 minutes IV infusion on Day 1, 0.9% sodium chloride for 40 minutes IV infusion on Day 15 and Day 29
干预措施: MIJ821 Intravenous Injection (Drug)
MIJ821 (mg/kg) - very high dose/Placebo
MIJ821 (mg/kg) very high dose for 40 minutes IV infusion on Day 1, 0.9% sodium chloride for 40 minutes IV infusion on Day 15 and Day 29
干预措施: Placebo Intravenous Injection (Drug)
结局指标
主要结局
Change from baseline in the total score of the Montgomery Åsberg Depression Rating Scale (MADRS)
时间窗: Baseline (first infusion) at 24 hours and up to 52 weeks
The Montgomery Åsberg Depression Rating Scale (MADRS, SIGMA version), 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. The MADRS evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts and suicidal thoughts. The MADRS will be collected electronically by qualified personnel
次要结局
- Number and severity of treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESI)(Baseline up to 6 weeks)
- Pharmacokinetics (PK) of MIJ821 in plasma(Baseline up to 52 weeks)
- Percentage of participants meeting response criteria of ≥50% reduction(Baseline up to 6 weeks)
- Percentage of participants meeting criteria for sustained response of ≥50% reduction(Baseline up to 6 weeks)
- Percentage of participants meeting remission criteria of MADRS total score of ≤12(Baseline up to 6 weeks)
- Percentage of participants meeting sustained remission criteria of MADRS total score of ≤12(Baseline up to 6 weeks)
- Percentage of participants meeting criteria for relapse in the Extension Period(From 6 weeks up to 52 weeks)
- Percentage of relapsing participants meeting response criteria or remission criteria after the first infusion(From 6 weeks up to 52 weeks)