A Study of Seltorexant as Adjunctive Therapy to Antidepressants in Adolescents With Major Depressive Disorder Who Have an Inadequate Response to Selective Serotonin Reuptake Inhibitor (SSRI) and Psychotherapy

NCT04951609 | Terminated Phase 1 FDA Drug

• 3 other identifiers: CR1090412021-000567-7742847922MDD1016
• Study Type: interventional
• Target: 31
• Locations: 4 countries
• Sites: 23

Brief Summary

The purpose of this study is to assess the safety and tolerability of Seltorexant as adjunctive therapy to an antidepressant in adolescents with major depressive disorder (MDD) in the short-term compared with placebo.

Conditions

Depressive Disorder, Major

Outcome Measures

Primary Outcomes (10)

• Number of Participants with Treatment Emergent Adverse Events (TEAEs)

  An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs are adverse events with onset during the double-blind treatment phase or that are a consequence of a preexisting condition that has worsened since baseline.

  Up to 12 weeks

• Number of Participants with Adverse Event of Special Interest (AESIs)

  Number of participants with AESIs will be reported. AEs are considered to be of special interest in this study: a) Cataplexy (sudden, transient episode of muscle weakness accompanied by conscious awareness); b) Sleep paralysis (the experience of not being able to move, react, or speak when falling asleep/awakening); c) Complex, sleep-related behaviors/parasomnias such as confusional arousals, somnambulism (sleep walking), sleep terrors, bruxism (teeth grinding), sleep sex, sleep-related eating disorder, and catathrenia (REM-associated end-inspiratory apnea/breath holding); d) Any new suicidal behavior or suicidal ideation.

  Up to 12 weeks

• Pediatric Adverse Event Rating Scale (PAERS)

  The PAERS is a patient-rated scale designed to assess adverse events occurring in pediatric participants treated with psychotropic medication in clinical studies. Individual PAERS (patient-reported version) will rate symptoms and severity of symptoms. This scale has a total of 48 items. There is no overall score and individual item will be rated on a scale of 0 to 4 in which 0 indicates 'not present' and 4 indicates 'very bothersome/an extreme problem'.

  Up to 12 weeks

• Number of Participants with Abnormalities in Clinical Laboratory Values

  Number of participants with abnormalities in clinical laboratory values (hematology, serum chemistry and urinalysis) will be reported.

  Up to 6 weeks

• Number of Participants with Abnormalities in Electrocardiogram (ECG)

  Number of participants with abnormalities in ECG will be reported.

  up to 6 weeks

• Number of Participants with Abnormalities in Vital Signs

  Number of participants with abnormalities in vital sign(blood pressure and pulse/heart rate) will be reported.

  Up to 12 weeks

• Number of Participants with Abnormalities in Physical Examination

  Number of participants with abnormalities in physical examination including weight will be reported.

  Up to 6 weeks

• Suicidality Assessment Using the Columbia Suicide Severity Rating Scale (C-SSRS) Score

  Suicidality assessment using the C-SSRS will be reported. C-SSRS is a clinician rated assessment of suicidal behavior and/ or intent. Scale consists of 28 items in 4 sections: suicide behavior, actual attempts, suicidal ideation, and intensity of ideation. Suicidal ideation consists of 5 yes/no items: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intention to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent. Worsening of suicidal ideation will be an increase in severity of suicidal ideation from baseline.

  Up to 12 weeks

• Withdrawal Symptoms Assessment Using the Physician Withdrawal Checklist (PWC-20)

  Withdrawal symptoms assessment using the PWC-20 will be reported. The PWC-20 is a simple and accurate method used to assess potential withdrawal symptoms following cessation of treatment. The PWC-20 is a reliable and sensitive instrument for the assessment of discontinuation symptoms. Each individual item score ranges from 0 (not present) to 3 (severe), where higher scores = more affected condition.

  2 weeks

• Number of Participants with Menstrual Cycle Tracking

  Number of participants with menstrual cycle tracking will be reported. Menstrual cycles will be tracked during the study in female adolescents or participants who have at least one menses using a participant diary and participant's verbal report.

  Up to 6 weeks

Secondary Outcomes (8)

• Change from Baseline to Week 6/End of Treatment (EOT) in the Children's Depression Rating Scale (CDRS) Total Score

  Baseline up to 6 weeks

• Change from Baseline to Week 6 in Montgomery Asberg Depression Rating Scale (MADRS) Score

  Baseline up to 6 weeks

• Change from Baseline in Clinical Global Impression- severity (CGI-S) Score Over Time

  Baseline up to 6 weeks

• Change from Baseline to Week 6/EOT on Subjective Sleep Assessment (Patient Reported Outcome Measurement Information System-Pediatric-Sleep Disturbance [PROMIS-Pediatric-SD] [Short Form 8a])

  Baseline up to 6 weeks

• Change from Baseline to Week 6/EOT on Objective Sleep Assessment Actigraphy

  Baseline up to 6 weeks

Study Arms (2)

Seltorexant

EXPERIMENTAL

Participants will receive weight based dose of Seltorexant orally once daily from Day 1 to Day 42 (until the end of Week 6). Participants will continue baseline selective serotonin reuptake inhibitor (SSRI) antidepressant (Fluoxetine or escitalopram) orally once daily.

Drug: Seltorexant

Placebo

PLACEBO COMPARATOR

Participants will receive matching placebo tablets to seltorexant orally once daily from Day 1 to Day 42 (until the end of Week 6).

Drug: Placebo

Interventions

Seltorexant DRUG

Participants will receive a single oral dose of seltorexant.

Also known as: JNJ-42827922

Seltorexant

Placebo DRUG

Participants will receive matching placebo orally.

Placebo

Eligibility Criteria

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

You may qualify if:

• Has inadequate response to trial of at least 1, but no more than 2 antidepressant treatments during the current major depressive episode including their current antidepressant fluoxetine or escitalopram (SSRI). Inadequate response is determined as less than (\<) 50 percentage (%) symptom reduction after adequate antidepressant treatment for at least 6 weeks at or above the minimum therapeutic dose prior to screening
• Has had access to adequate psychotherapy in the current depressive episode (based on investigator judgement/local guidance) prior to randomization
• Must have Children's Depression Rating Scale-Revised (CDRS-R) total score greater than or equal to (\>=) 48 at screening and \>=40 at the baseline visit
• Participants weighing between fifth and ninety-fifth percentile for age and sex. Obese participants greater than ninety-fifth percentile and underweight participants below fifth percentile may participate following medical clearance, as long as their baseline weight is \>=30 kilograms (kg)
• A female participant of childbearing potential must have a negative urine pregnancy test at screening and baseline

You may not qualify if:

• Has a history of liver or renal insufficiency, significant cardiac (example, congenital heart disease, cardiomyopathy, or tachyarrhythmias), vascular, pulmonary, gastrointestinal, endocrine (including uncontrolled hyperthyroidism), neurologic (including seizure disorder), hematologic, rheumatologic, psychiatric, or metabolic disturbances. Stable medical conditions are allowed
• Has current the diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) diagnosis of conduct disorder, intellectual disability, autism spectrum disorder, borderline personality disorder, somatoform disorders, or fibromyalgia. A prior history of one or more of these disorders is allowed as long as the disorder(s) are currently stable and major depressive disorder (MDD) is not secondary to the original diagnosis. Has a current or prior DSM-5 diagnosis of a psychotic disorder, or bipolar disorder
• Has a significant primary sleep disorder (example, obstructive sleep apnea, parasomnias) at screening but participants with insomnia or hypersomnia disorders are allowed
• At significant risk of committing suicide based on history or according to the investigator's experience, or based on active suicidal ideation, intent or plan, item 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) within the past 3 months or a history of suicidal behavior within the last 6 months
• Has known allergies, hypersensitivity, or intolerance to seltorexant or its excipients

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (23)

Southwest Autism Research and Resource Center

Phoenix, Arizona, 85006, United States

Location

Advanced Research Center Inc

Anaheim, California, 92805, United States

Location

University of California at San Diego

San Diego, California, 92103-8620, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Sarkis Clinical Trials

Gainesville, Florida, 32607, United States

Location

APG Research LLC

Orlando, Florida, 32803, United States

Location

Baber Research Group

Naperville, Illinois, 60563, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

CincyScience

West Chester, Ohio, 45069, United States

Location

Vanderbilt University

Nashville, Tennessee, 37212, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75247, United States

Location

Family Psychiatry of The Woodlands

The Woodlands, Texas, 77381, United States

Location

G.Gaslini Institute

Genova, 16147, Italy

Location

Ospedale Pediatrico Bambin Gesù

Roma, 00165, Italy

Location

Universita Cattolica del Sacro Cuore - Fondazione Policlinico Universitario 'A. Gemelli'

Roma, 00168, Italy

Location

Hosp. Sant Joan de Deu

Esplugues de Llobregat, 08950, Spain

Location

Hosp. Gral. Univ. Gregorio Maranon

Madrid, 28007, Spain

Location

Clinica Univ. de Navarra Madrid

Madrid, 28027, Spain

Location

Hosp. Univ. Ramon Y Cajal

Madrid, 28034, Spain

Location

Hosp. Univ. Pta. de Hierro Majadahonda

Majadahonda, 28222, Spain

Location

Corporacio Sanitari Parc Tauli

Sabadell, 08208, Spain

Location

South London and Maudsley NHS Foundation Trust of The Maudsley Hospital

London, SE5 8AZ, United Kingdom

Location

Warneford Hospital, NIHR Clinical Research Facility

Oxford, OX7 3JX, United Kingdom

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

seltorexant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2021
• First Posted: July 7, 2021
• Study Start: September 2, 2021
• Primary Completion: April 8, 2024
• Study Completion: April 8, 2024
• Last Updated: April 27, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

IT (3); GB (2); US (12); ES (6)