Esketamine nasal spray vs placebo for adults with treatment-resistant depression

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a phase 3 randomized, controlled trial comparing esketamine nasal spray at 56 mg and 84 mg to placebo in adults with treatment-resistant depression. Participants have major depressive disorder with insufficient response to at least two antidepressants and are assessed using structured diagnostic tools. The study uses active and placebo nasal sprays administered in addition to standard care, with outcomes focused on changes in depressive symptoms during the current episode. Enrollment is limited to sites in California and Connecticut, led by Janssen as sponsor. The trial aims to determine whether esketamine can provide a meaningful benefit for this difficult-to-treat population.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Participant must meet the diagnostic and statistical manual of mental disorders (5th edition) (DSM-5) diagnostic criteria for single-episode major depressive disorder (MDD) (if single episode MDD, the duration of the episode must be greater than or equal to \[\>=\] 12 months) or recurrent MDD, without psychotic features, based upon clinical assessment and confirmed by the mini international neuropsychiatric interview (MINI) as the primary diagnosis. Participant must have had the first onset of depression prior to 55 years of age
* Participant must have had nonresponse (less than or equal to \[\<=\] 25 percent \[%\] improvement) to \>=2 oral antidepressant treatments in the current episode of depression, assessed using the massachusetts general hospital-antidepressant treatment response questionnaire (MGH-ATRQ), and confirmed by documented records (for example, medical/pharmacy/prescription records or a letter from a treating physician)
* The participant's current major depressive episode, depression symptom severity, and antidepressant treatment response in the current depressive episode, must be confirmed by the state versus trait, assessability, face validity, ecological validity, rule of three P's (SAFER) Interview
* Participant must be comfortable with self-administration of nasal spray medication and be able to follow the nasal spray administration instructions provided
* A female participant of childbearing potential must have a negative highly sensitive serum (β-human chorionic gonadotropin \[β-hCG\]) at the start of screening and a negative urine pregnancy test must be obtained before the first dose of study drug on Day 1, prior to randomization

Exclusion Criteria:

* The participant has used ketamine/esketamine (lifetime)
* The participant's depressive symptoms have demonstrated nonresponse in the current major depressive episode to an adequate course of treatment with electroconvulsive therapy (ECT), defined as at least 7 treatments with unilateral/bilateral ECT, or to adequate course of treatment with transcranial magnetic stimulation (TMS), defined as at least 4 weeks of treatment with 5 sessions per week
* Participant has received vagal nerve stimulation (VNS) or deep brain stimulation (DBS) in the current episode of depression
* Participant has homicidal ideation/intent, per the investigator's clinical judgment, or has suicidal ideation with some intent to act within 6 months prior to the start of the screening phase, per the investigator's clinical judgment or based on the columbia suicide severity rating scale (C-SSRS), corresponding to a response of "Yes" on Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) for suicidal ideation on the C-SSRS, or a history of suicidal behavior within the past year prior to the start of the screening phase. Participants reporting suicidal ideation with intent to act or suicidal behavior prior to the start of the double-blind treatment phase should be excluded
* Participant has a history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria, except nicotine or caffeine, within 6 months before the start of the screening phase. a. A history (lifetime) of ketamine, phencyclidine (PCP), lysergic acid diethylamide (LSD), or 3, 4-methylenedioxy-methamphetamine (MDMA) hallucinogen-related use disorder is exclusionary
* Participant has a current or history of seizures (uncomplicated childhood febrile seizures with no sequelae are not exclusionary)

Where it's running

• Anderson Clinical Research
  Redlands, California, United States Recruiting
• Artemis Institute for Clinical Research
  San Diego, California, United States Recruiting
• University of Connecticut Health Center
  Farmington, Connecticut, United States Recruiting
• American Family Research Group
  Cape Coral, Florida, United States Recruiting
• Pharmax Research Clinic Inc
  Miami, Florida, United States Recruiting
• Charter Research Orlando
  Orlando, Florida, United States Recruiting

Study contacts

• Study coordinator: Study Contact
• Email: Participate-In-This-Study1@its.jnj.com
• Phone: 844-434-4210

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.