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

Janssen (J&J Innovative Medicine)

Status and phase: Enrolling; Phase 3

Conditions: Depressive Disorder, Major

Treatments: Drug: Esketamine; Other: Oral Placebo; Other: Intranasal Placebo; Drug: Midazolam

Study type: Interventional

Funder types: Industry

Identifiers

NCT07227454

54135419SUI3003 (Other Identifier)

2024-518615-19-00 (Registry Identifier)

Details and patient eligibility

About

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.

Enrollment: 258 estimated patients

Sex: All

Ages: 12 to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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258 participants in 2 patient groups, including a placebo group

Intranasal Esketamine + Oral Placebo

Experimental group

Description:

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.

Treatment:

Other: Oral Placebo

Drug: Esketamine

Intranasal Placebo + Oral Midazolam

Placebo Comparator group

Description:

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.

Treatment:

Drug: Midazolam

Other: Intranasal Placebo