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

Depressive Disorder, Major Clinical Trial

Official title:

A Short-term Exploratory Study to Evaluate Safety, Tolerability and Pharmacokinetics of Seltorexant as Adjunctive Therapy to Antidepressants in Adolescents With Major Depressive Disorder Who Have an Inadequate Response to SSRI Monotherapy and Psychotherapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04951609
• Other study ID #: CR109041
• Secondary ID: 2021-000567-7742
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 2, 2021
• Est. completion date: March 3, 2025

Study information

• Verified date: April 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The prevalence of major depression is approximately 4 percentage (%) to 8% in adolescents, with the highest incidence of MDD in child onset depression occurring during mid- to late adolescence (that is, 14 to 18 years of age). Seltorexant (JNJ-42847922) is a potent and selective antagonist of the human orexin-2 receptor (OX2R) that is being developed for the treatment of adjunctive treatment of MDD with insomnia symptoms (MDDIS).The study will be conducted in 3 phases: a screening phase (up to 30 days prior to first dose administration), a double-blind (DB) treatment phase (6 weeks), and a follow-up phase (up to 2 weeks including a telephone consult and on-site follow-up visit. The total study duration for each participant will be up to 12 weeks. Efficacy, safety, pharmacokinetics, and biomarkers will be assessed at specified time points during this study. The hypothesis for this study is that the safety, tolerability, and pharmacokinetics in the adolescent MDD population. There is no formal statistical hypothesis testing due to the exploratory and descriptive nature of this study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 31
• Est. completion date: March 3, 2025
• Est. primary completion date: April 8, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 17 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major

Intervention

Drug:
• Seltorexant
Participants will receive a single oral dose of seltorexant.
• Placebo
Participants will receive matching placebo orally.

Locations

Country	Name	City	State
Italy	G.Gaslini Institute	Genova
Italy	Ospedale Pediatrico Bambin Gesù	Roma
Italy	Universita Cattolica del Sacro Cuore - Fondazione Policlinico Universitario 'A. Gemelli'	Roma
Spain	Hosp. Sant Joan de Deu	Esplugues de Llobregat
Spain	Clinica Univ. de Navarra Madrid	Madrid
Spain	Hosp. Gral. Univ. Gregorio Maranon	Madrid
Spain	Hosp. Univ. Ramon Y Cajal	Madrid
Spain	Hosp. Univ. Pta. de Hierro Majadahonda	Majadahonda
Spain	Corporacio Sanitari Parc Tauli	Sabadell
United Kingdom	South London and Maudsley NHS Foundation Trust of The Maudsley Hospital	London
United Kingdom	Warneford Hospital, NIHR Clinical Research Facility	Oxford
United States	Advanced Research Center Inc	Anaheim	California
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Sarkis Clinical Trials	Gainesville	Florida
United States	Baber Research Group	Naperville	Illinois
United States	Vanderbilt University	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	APG Research LLC	Orlando	Florida
United States	Southwest Autism Research and Resource Center	Phoenix	Arizona
United States	University of California at San Diego	San Diego	California
United States	Family Psychiatry of The Woodlands	The Woodlands	Texas
United States	CincyScience	West Chester	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Number of Participants with Abnormalities in Electrocardiogram (ECG)	Number of participants with abnormalities in ECG will be reported.	up to 6 weeks
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Change from Baseline to Week 6/End of Treatment (EOT) in the Children's Depression Rating Scale (CDRS) Total Score	Change from baseline to week 6/EOT in the CDRS total score will be reported. The CDRS-R is a validated 17-item, clinician-rated instrument that measures the severity of a participant's depressive symptoms. The CDRS-R total score is the sum of the responses to 17 questions. Each question is graded on a 5- or 7-point scale. The highest possible score is 113 (the most severe measure of depression), and the lowest is 17 (not suffering from depression).	Baseline up to 6 weeks
Secondary	Change from Baseline to Week 6 in Montgomery Asberg Depression Rating Scale (MADRS) Score	Change from baseline in MADRS score will be reported. The 10-item MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher score represents a more severe condition.	Baseline up to 6 weeks
Secondary	Change from Baseline in Clinical Global Impression- severity (CGI-S) Score Over Time	Change from baseline over time in the CGI-S score will be reported. The CGI-S provides an overall clinician-determined summary measure of the severity of the participant's illness. The CGI-S evaluates the severity of psychopathology on a scale of 1 to 7. Considering total clinical experience with the depression population, a participant is assessed on severity of illness at the time of rating according to: 1=normal (not at all ill); 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill participants.	Baseline up to 6 weeks
Secondary	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])	Change from baseline to week 6/EOT on subjective sleep assessment (PROMIS-Pediatric-SD [short form 8a]) will be reported. The PROMIS-SD is used to assess self-reported perceptions of sleep quality, sleep depth and restoration associated with sleep. The full PROMIS-SD includes 27 items with each item based on a 7-day recall period and assessed on a 5 level Likert-type scale. The 8-item short form will be used in this study, in which responses are scored 1 to 5 for each item. A higher score on 5 of the 8 items reflects a worse outcome, whereas a higher score on 3 items reflects an improved outcome; therefore, the directionality of the 8 item scores is first synchronized prior to calculation of the total raw score. To find the total raw score for a short form with all questions answered, sum the values of the response to each question. Higher overall score indicates more sleep disturbance.	Baseline up to 6 weeks
Secondary	Change from Baseline to Week 6/EOT on Objective Sleep Assessment Actigraphy	Change from baseline to week 6/EOT on objective sleep assessment actigraphy will be reported. The primary purpose of actigraphy in this study is to have an objective measure of sleep parameters prior to treatment to complement the Consensus Sleep Diary (CSD) as well as other sleep-related PROs.	Baseline up to 6 weeks
Secondary	Cognitive Performance on a Neurocognitive Battery at Baseline and Week 6/EOT	The cogstate computerized cognitive battery is a validated set of assessments which will be performed to assess verbal learning and memory and evaluate cognitive function. The battery will provide assessment of multiple cognitive domains, including attention, visual learning and memory, and executive function. All measures in the cognitive battery have been validated against traditional neuropsychological tests and are sensitive to the effects of various drugs on cognitive performance, including alcohol and benzodiazepines. The participants completed Cogstate computerized cognitive battery has been used for cognitive assessment in several child and adolescent research trials including attention deficit hyperactivity disorder, and demonstrates good reliability and validity in child and adolescent populations. The ISLT has also been used in adolescent trials, demonstrating sensitivity, reliability and validity.	Baseline, Week 6
Secondary	Change in Subjective Sleep Related Impairment (PROMIS-Pediatric- Sleep-Related Impairment [SRI])	Change in subjective sleep related impairment (PROMIS-Pediatric-SRI) will be reported. The PROMIS_SRI is used to assess self reported daytime sleepiness and impact on functioning. . The full PROMIS-SD includes 27 items with each item based on a 7-day recall period and assessed on a 5 level Likert-type scale. The 8-item short form will be used in this study, in which responses are scored 1 to 5 for each item. A higher score on 5 of the 8 items reflects a worse outcome, whereas a higher score on 3 items reflects an improved outcome; therefore, the directionality of the 8 item scores is first synchronized prior to calculation of the total raw score. To find the total raw score for a short form with all questions answered, sum the values of the response to each question. Higher overall score indicates more sleep disturbance.	Up to 6 weeks
Secondary	Plasma Concentration of Seltorexant	Plasma concentration of seltorexant will be reported using a validated, specific, and sensitive liquid chromatography/mass spectrometry/mass spectrometry (LC-MS/MS) method.	Up to 6 weeks