Study of efficacy, safety, tolerability and pharmacokinetics of MIJ821 in participants with treatment- resistant depression (TRD)
- Conditions
- Treatment Resistant DepressionMedDRA version: 21.1Level: PTClassification code 10057840Term: Major depressionSystem Organ Class: 10037175 - Psychiatric disordersTherapeutic area: Psychiatry and Psychology [F] - Psychological processes [F02]
- Registration Number
- EUCTR2021-005992-38-PL
- Lead Sponsor
- ovartis Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 56
- 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.
- Participant has a diagnosis of recurrent MDD and a current major depressive episode of at least 8 weeks in duration as defined by DSM-5 criteria and confirmed by both the SCID-5 and an adequate clinical psychiatric evaluation at screening.
- MADRS = 24 at screening and before randomization on Day 1.
- Failure to respond to 2 or more antidepressant treatments but no more than 5, where the two failed treatments are two different antidepressants and at least one of which was used in the current depressive episode, with adequate dose and duration (= 6 weeks duration, doses defined per agent), as identified by the MGHAntidepressant Treatment Response Questionnaire, based on the patient's report and prior psychiatric history, assessed by the investigator, and further documented by medical records. Patients with historical treatment failure to esketamine, ketamine or arketamine are
excluded.
- Participant 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 protocol recommendations) during the trial duration.
- If the participant is taking any other type of psychotropic drugs, the dose of these drugs needs to be stable, where a stable dose of psychotropic drugs is defined as no changes in dose or type of e.g. antipsychotics or mood stabilizers for at least 6 weeks prior to baseline (if applicable).
- The antidepressant should be at a stable dose for at least 4 weeks before baseline. No new antidepressant initiated 6 weeks or less before baseline. No psychotherapy initiated 4 weeks or less before baseline.
- Able to communicate well, and to understand and comply with study requirements.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 55
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1
- Current acute depressive episode lasting longer than two years continuously, or participants receiving electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS) or deep brain stimulation (DBS) in the current episode or within last year prior to screening (whichever is longer).
- Any prior or current diagnosis of MDD with psychotic features, bipolar disorder, schizophrenia, or schizoaffective disorder as obtained from SCID-5 at screening.
- Participants with acute alcohol or substance use disorder or withdrawal symptoms requiring detoxification, or participants who went through detoxification treatment (inpatient or outpatient) within 1 month before Screening, as obtained from SCID-5 at screening.
- Participants with current borderline personality disorder or antisocial personality disorder assessed at Screening, based on DSM-5 criteria and investigator judgment.
- Current clinical diagnosis of autism, dementia, or intellectual disability.
- Participants with a history of suicidal attempt or suicidal behaviour within last year prior to screening and participants presenting suicidal ideation with intent documented by C-SSRS by Yes response to Q4 or Q5 at screening or baseline.
- Participants with evidence of significant renal insufficiency, indicated by an estimated glomerular filtration rate (eGFR) of < 40 mL/min/1.73 m2 at screening.
- Use of other investigational drugs at the time of screening, or within 30 days or 5 half lives of screening, whichever is longer.
- History of hypersensitivity to any of the study treatments or excipients or to drugs of similar mechanism of action (i.e. drugs that affect the NMDA receptor).
- Active hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or active COVID-19 infection as per medical history and/or available medical records.
- History of seizures. Note: childhood febrile seizures are not exclusionary.
- Cardiac or cardiac repolarization abnormality
- Resting QTcF =450 msec (male) or =460 msec (female) at screening or baseline
- Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia
- Participant has mean systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg at Screening or pre first dose on Day 1; or past history of hypertensive crisis.
- History of hemorrhagic stroke or known cerebrovascular disorders (e.g. aneurysm or arteriovenous malformation) or known aneurysmal vascular disease in other location (e.g. aorta).
- Pregnancy (including a positive human chorionic gonadotropin [hCG] test) or lactation at screening or baseline.
- 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.
- Sexually active males unwilling to use a condom during intercourse while taking investigational drug and for 1 week after stopping study treatment. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of the investigational drug via seminal fluid to their partner. In addition, male participants should not donate sperm for the time period specified above.
- Any other condition (e.g. known liver disease/liver dysfunction, active m
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess efficacy of MIJ821 (versus placebo) in treatment resistant depression after single s.c. injection;Secondary Objective: - To assess safety and tolerability of MIJ821 after single s.c. injection<br>- To assess MIJ821 PK in plasma after single s.c. injection<br>- To assess the duration of antidepressant effect of MIJ821<br>- To characterize the dose-response and exposure-response relationship of MIJ821;Primary end point(s): MADRS total score at 24 hours after s.c. injection compared to baseline assessment;Timepoint(s) of evaluation of this end point: 24 hours post dose from baseline
- Secondary Outcome Measures
Name Time Method