A Study to Evaluate the Efficacy and Safety of Esketamine for Reduction of Symptoms of Major Depressive Disorder

NCT07227454 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: 54135419SUI30032024-518615-19-00
• Study Type: interventional
• Target: 258
• Locations: 6 countries
• Sites: 27

Brief Summary

The purpose of this study is to evaluate how well JNJ-54135419 works (efficacy) in addition to comprehensive standard of care (SoC) in rapidly reducing the symptoms of major depressive disorder (MDD, a mental disorder characterized by a persistent feeling of sadness and loss of interest in activities) as compared with psychoactive placebo (does not contain JNJ-54135419) plus SoC in adolescent participants with acute suicidal ideation or behavior.

Conditions

Depressive Disorder, Major

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Depressive Symptoms Measured by Children's Depression Rating Scale - Revised (CDRS-R) Total Score at 24 Hours Post First Dose

  The CDRS-R is a 17-item, clinician-reported outcome measure of children's depressive symptom severity. Out of the 17-item, 3 items were non-verbal behavior (listless speech, hypoactivity, and depressed affect) rated on a 5 point scale from 1 (no depression) to 5 (severe depression) and 14 items were rated on a 7-point scale from 1 (no depression) to 7 (severe depression), where higher score indicated more severe depression. The CDRS-R total score was the sum of the 17-tems score and it ranged from 17 (normal) to 113 (severe depression). Higher score indicated more severe depression and worse outcome.

  Baseline (pre-dose on Day 1) and 24 hours post first dose (i.e., Day 2)

Secondary Outcomes (13)

• Change from Baseline in CDRS-R Total Score at Day 25

  Baseline (predose on Day 1) and Day 25 (4 hours post dose)

• Change from Baseline in Clinical Global Impression - Severity of Suicidality - Revised (CGI-SS-R) Score at 24 Hours Post First Dose

  Baseline (pre-dose on Day 1) and 24 hours post first dose (i.e., Day 2)

• Change From Baseline in Symptoms of MDD During the Double-Blind (DB) Treatment Phase as Measured by CDRS-R Total Score

  From Baseline up to Day 25

• Percentage of Participants with Remission of Depressive Symptoms During the DB Treatment Phase

  Up to Day 25

• Percentage of Responders on Depressive Symptoms During the DB Treatment Phase

  Up to Day 25

Study Arms (2)

Intranasal Esketamine + Oral Placebo

EXPERIMENTAL

Participants will receive intranasal esketamine 84 milligrams (mg) along with oral placebo solution twice weekly for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25). On Day 4 a decrease to intranasal esketamine 56 mg (in a blinded fashion per investigator's judgment) is permitted. Thereafter, dose may be flexed between 56 mg and 84 mg during the treatment period.

Drug: Esketamine; Other: Oral Placebo

Intranasal Placebo + Oral Midazolam

PLACEBO COMPARATOR

Participants will receive oral midazolam (0.0625 milligrams per kilograms \[mg/kg\]) and intranasal placebo twice weekly for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25). On Day 4 a sham decrease to esketamine 56 mg dose (in a blinded fashion per investigator's judgment) is permitted. Thereafter, sham dose may be flexed between 56 mg and 84 mg during the treatment period.

Drug: Midazolam; Other: Intranasal Placebo

Interventions

Esketamine DRUG

Esketamine will be administered as intranasal solution.

Also known as: JNJ-54135419

Intranasal Esketamine + Oral Placebo

Midazolam DRUG

Midazolam will be administered as oral solution.

Intranasal Placebo + Oral Midazolam

Oral Placebo OTHER

Placebo will be administered as oral solution.

Intranasal Esketamine + Oral Placebo

Intranasal Placebo OTHER

Intranasal placebo will be administered as nasal solution.

Intranasal Placebo + Oral Midazolam

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Must meet diagnostic and statistical manual of mental disorders (5th edition) (DSM-5) diagnostic criteria for major depressive disorder (MDD) based upon clinical assessment and confirmed by the mini-international neuropsychiatric interview for children and adolescents (MINI-KID)
• Must have a clinical global impression - severity of suicidality - revised (CGI-SS-R) score of "Markedly" or greater (that is, greater than or equal to \[\>=\] 4) at both screening and baseline (predose) visits
• Must have a children's depression rating scale - revised (CDRS-R) total score \>= 58 at baseline (predose)
• In the physician's opinion, acute psychiatric hospitalization is clinically warranted due to subject's acute suicidality
• Must be medically stable based on physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening

You may not qualify if:

• Participant has a current DSM-5 diagnosis of bipolar (or related disorders), intellectual disability, autism spectrum disorder, conduct disorder, oppositional defiant disorder
• Participant currently meets DSM-5 criteria for borderline personality disorder
• Participant has a current or prior DSM-5 diagnosis of a psychotic disorder, or MDD with psychosis
• Participant has a history of seizure disorder
• Participant has known allergies, hypersensitivity, intolerance or contraindications to midazolam, esketamine or ketamine, or their excipients

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (27)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

Peachford Hospital-Atlanta Behavioral Research

Atlanta, Georgia, 30338, United States

RECRUITING

University of Cincinnati

Cincinnati, Ohio, 45219, United States

RECRUITING

Bradley Hospital

East Providence, Rhode Island, 02915, United States

RECRUITING

Sociedade Literaria e Caritativa Santo Agostinho Hospital Sao Jose

Criciúma, 88811 000, Brazil

RECRUITING

Instituto Apice

Salvador, 40170 108, Brazil

RECRUITING

Centro Integrado Facili

São Bernardo do Campo, 09726 150, Brazil

RECRUITING

Instituto de Pesquisa Pensi Sandra Mutarelli Setubal

São Paulo, 01 227 200, Brazil

RECRUITING

Fundacao Faculdade de Medicina Hospital da Clinicas da Faculdade de Medicina de Sao Paulo

São Paulo, 05403 010, Brazil

RECRUITING

Debreceni Egyetem Klinikai Kozpont

Debrecen, 4031, Hungary

RECRUITING

Petz Aladar Megyei Oktato Korhaz

Győr, 9023, Hungary

RECRUITING

Szegedi Tudomanyegyetem

Szeged, 6720, Hungary

RECRUITING

Presidio Ospedaliero Santa Marta e Santa Venera

Acireale, 95024, Italy

RECRUITING

AOU Meyer

Florence, 50134, Italy

RECRUITING

Azienda Ospedaliera Universitaria Policlinico Riuniti di Foggia

Foggia, 71122, Italy

RECRUITING

Azienda Ospedaliera Universitaria Federico II

Naples, 80131, Italy

RECRUITING

Azienda Ospedaliero Universitaria di Sassari

Sassari, 07100, Italy

RECRUITING

Hosp. Clinic de Barcelona

Barcelona, 08036, Spain

RECRUITING

Fundacio Althaia Xarxa Assistencial Universitaria de Manresa

Manresa, 08243, Spain

RECRUITING

Hosp. Univ. Central de Asturias

Oviedo, 33011, Spain

RECRUITING

Clinica Univ. de Navarra

Pamplona, 31008, Spain

RECRUITING

Hosp.Univ.Parc Tauli

Sabadell, 08208, Spain

RECRUITING

Mackay Memorial Hospital Tamsui Branch

New Taipei City, 251, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, 100, Taiwan

RECRUITING

Taipei Medical University Hospital

Taipei, 110, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, 112, Taiwan

RECRUITING

Tri-Service General Hospital

Taipei, 114, Taiwan

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Esketamine; Midazolam

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Study Contact

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2025
• First Posted: November 12, 2025
• Study Start: January 8, 2026
• Primary Completion (Estimated): April 9, 2031
• Study Completion (Estimated): September 15, 2031
• Last Updated: June 5, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share

Locations

HU (3); US (4); TW (5); BR (5); ES (5); IT (5)