Recruiting
Phase 3

Esketamine

Sponsor:

Janssen Research & Development, LLC

Code:

NCT07716098

Conditions

Depressive Disorder, Treatment-Resistant

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Esketamine 56 mg

Esketamine 84 mg

Placebo

Study Details

Brief summary:

The purpose of this study is to evaluate how well each individual dose of esketamine (56 milligrams \[mg\] and 84 mg) works when compared with placebo in improving depressive symptoms in participants with treatment resistant depression (individuals with major depressive disorder \[MDD\] who have not responded to at least 2 different antidepressant treatments given at an adequate dose for an adequate duration in the current episode of depression).

Conditions

Depressive Disorder, Treatment-Resistant

Study ID

NCT07716098

Start date

Jul 23, 2026

Status verified date

Aug, 2026

Completion date

Sep 12, 2029

Anticipated

Primary completion date

Dec 27, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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)

Study Design

Enrollment

348 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Esketamine 56 milligram (mg)

Participants will be randomized to receive double-blind (DB) treatment with esketamine 56 mg, twice a week for 4 weeks. Participants who complete the DB treatment phase on Day 28 may be eligible to participate in an open-label treatment phase and receive either esketamine 56 or 84 mg.

experimental: Esketamine 84 mg

Participants will be randomized to receive DB treatment with esketamine 84 mg, twice a week for 4 weeks. Participants who complete the DB treatment phase on Day 28 may be eligible to participate in an open-label treatment phase and receive either esketamine 56 or 84 mg.

placebo comparator: Placebo

Participants will be randomized to receive DB treatment with placebo twice a week for 4 weeks. Participants who complete the DB treatment phase on Day 28 may be eligible to participate in an open-label treatment phase and receive either esketamine 56 mg or 84 mg.

Interventions

Esketamine 56 mg

Participants will self-administer 56 mg of esketamine as intranasal spray into each nostril.

Esketamine 84 mg

Participants will self-administer 84 mg of esketamine as intranasal spray into each nostril.

Placebo

Participants will self-administer placebo as intranasal spray into each nostril.

Primary outcome measure

  • Double-Blind (DB) Treatment Phase: Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Day 1 to the End of the 4-Week Double-Blind Treatment Phase [ Time Frame: Baseline (Day 1 [prerandomization]) up to end of the 4-Week DB treatment phase (Day 28) ]

Central Contacts and Locations

Central contacts

Study Contact

844-434-4210Participate-In-This-Study1@its.jnj.com

Locations

Anderson Clinical Research

Recruiting

Redlands, California, United States, 92374

Psychiatric Medicine Associates LLC

Recruiting

Skokie, Illinois, United States, 60076

The Medical Research Network, LLC

Recruiting

New York, New York, United States, 10128

More Information

Sponsor

Janssen Research & Development, LLC

Last update posted

Aug 28, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Janssen Research & Development, LLC on 2026-08-28.