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
Phase IIa, multi-centre, randomized, double-blind, placebo- and active-comparator-controlled study (n=66) evaluating single IV infusions of MIJ821 (multiple dose cohorts) versus ketamine and placebo in adults with treatment-resistant depression; primary outcome MADRS at 24 hours.
Detailed Description
Randomized, double-blind, parallel-group Phase II study in 66 adults with treatment-resistant depression comparing multiple MIJ821 intravenous dose cohorts against placebo and an active ketamine comparator; single IV infusion with primary efficacy assessment at 24 hours post-infusion.
Key secondary assessments include dissociative effects, mania risk, melancholic and mixed‑mood symptom effects, anxiety, suicidality, and pharmacokinetics; scheduled assessments at 24 hours, 48 hours and 6 weeks.
IMPs: MIJ821 (lyophilisate for solution for infusion; product code MIJ821; concentration 20 mg) administered IV; active comparator KETOLAR (ketamine) IV solution 50 mg/ml; matching placebo IV solution used.
Study Protocol
Preparation
Dosing
Integration
Study Arms & Interventions
MIJ821 cohort 1
experimentalMIJ821 intravenous infusion cohort (dose per protocol).
Interventions
- Ketaminevia IV• single dose
MIJ821 (lyophilisate for solution for infusion; product code MIJ821; concentration 20 mg) given as single IV infusion per protocol; specific dose cohort as per protocol.
MIJ821 cohort 2
experimentalMIJ821 intravenous infusion cohort (dose per protocol).
Interventions
- Ketaminevia IV• single dose
MIJ821 (lyophilisate for solution for infusion; concentration 20 mg) given as single IV infusion per protocol; specific dose cohort as per protocol.
MIJ821 cohort 3
experimentalMIJ821 intravenous infusion cohort (dose per protocol).
Interventions
- Ketaminevia IV• single dose
MIJ821 (lyophilisate for solution for infusion; concentration 20 mg) given as single IV infusion per protocol; specific dose cohort as per protocol.
MIJ821 cohort 4
experimentalMIJ821 intravenous infusion cohort (dose per protocol).
Interventions
- Ketaminevia IV• single dose
MIJ821 (lyophilisate for solution for infusion; concentration 20 mg) given as single IV infusion per protocol; specific dose cohort as per protocol.
Ketamine (KETOLAR)
active comparatorActive comparator ketamine intravenous infusion.
Interventions
- Ketaminevia IV• single dose
Ketamine (KETOLAR) solution for injection, 50 mg/ml; administered IV as active comparator per protocol.
Placebo
inactiveMatching placebo intravenous infusion.
Interventions
- Placebovia IV• single dose
Matching IV solution for infusion (placebo).
Participants
Inclusion Criteria
- Signed informed consent.
- Male and female subjects, 18 to 65 years of age (inclusive) at screening.
- DSM-5 defined major depressive episode at the time of screening.
- Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥24 at baseline.
- Failure to respond to two or more antidepressant treatments, at least one in the current depressive episode, with adequate dose and duration.
- Stable dose of psychotropic drugs for at least 2 weeks prior to randomization if applicable.
- No new antidepressant initiated ≤4 weeks before baseline (≤6 weeks if fluoxetine).
- At least one prior clinical depressive episode (recurrent major depressive disorder).
- Able to communicate well and comply with study requirements.
Exclusion Criteria
- Any prior or current diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorder.
- Current alcohol or substance use (other than nicotine or caffeine) meeting DSM-5 criteria for addiction within the past month.
- Prior suicidality caused by or associated with ketamine, as identified by prior psychiatric history and corroborated by records or third-party report 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.
- Use of other investigational drugs at randomization or within 30 days or 5 half-lives, whichever is longer.
- 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/class.
- History of malignancy within the past 3 years (except localized basal cell carcinoma or in-situ cervical cancer).
- Women of child-bearing potential must use highly effective contraception during dosing and for 1 week after stopping investigational drug.
- History of hypersensitivity to study treatments or excipients.
- Current diagnosis of borderline personality disorder or antisocial personality disorder.
- Current acute depressive episode lasting >2 years continuously.
- Considered by investigator to be an unsuitable candidate for the study.