Clinical TrialDepressive DisordersMajor Depressive Disorder (MDD)KetaminePlaceboRecruiting

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

This Phase III, double-blind, randomised, placebo-controlled trial (n=258) will evaluate the efficacy and safety of intranasal esketamine 84 mg in addition to comprehensive standard of care for rapidly reducing symptoms of major depressive disorder (MDD) in adolescent participants aged 12 to 17 with acute suicidal ideation or behaviour. The primary outcome is the change in depressive symptoms measured by the Children's Depression Rating Scale - Revised (CDRS-R) total score at 24 hours post-first dose. Participants will be randomly assigned to receive either intranasal esketamine (84 mg, with potential dose adjustments to 56 mg) plus oral placebo or intranasal placebo plus oral midazolam (0.0625 mg/kg) twice weekly for four weeks. The treatment will occur on specific days, with assessments conducted to monitor the efficacy and safety of the interventions. The trial is sponsored by Janssen Research & Development, LLC, with an estimated start date of January 8, 2026, and a completion date of September 15, 2031.

Target Enrollment
258 participants
Study Type
Phase III interventional
Design
Randomized, double Blind

Detailed Description

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.

Study Arms & Interventions

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.

Interventions

  • Ketamine84 mg
    via Inhalation• twice weekly for four weeks• 8 doses total

    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.

Intranasal Placebo + Oral Midazolam

inactive

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.

Interventions

  • Placebo

    Unmatched intervention: Midazolam

Participants

Ages
12 – 17
Sexes
Male & Female

Inclusion Criteria

  • 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

Exclusion Criteria

  • 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

Study Details

Locations

Peachford Hospital-Atlanta Behavioral Research — Atlanta, Georgia, United States
University of Cincinnati — Cincinnati, Ohio, United States

Your Library