A Study of Seltorexant as Monotherapy in Adults and Elderly Participants With Major Depressive Disorder

A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate Efficacy and Safety of Seltorexant as Monotherapy in Adult and Elderly Participants With Major Depressive Disorder (MDD) and an Open-label Long-term Extension Treatment With Seltorexant

The main purpose of this study is to assess how well the study drug (JNJ-42847922) works (efficacy) compared with placebo in improving depressive symptoms in participants with major depressive disorder ([MDD], a common mood disorder that causes a lasting feeling of sadness and a loss of interest in everyday activities) in double-blind treatment phase. Further, to evaluate long-term safety and tolerability of JNJ-42847922 in participants with MDD in the open label treatment phase.

Study Overview

• Status: Recruiting
• Conditions: Depressive Disorder, Major
• Intervention / Treatment: Drug: Placebo; Drug: Seltorexant

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study1@its.jnj.com

Study Locations

• United States
  • Florida
    • Doral, Florida, United States, 33178
      • Recruiting
      • UHC Research
    • Miami, Florida, United States, 33186
      • Recruiting
      • Nuovida Research Center
  • Georgia
    • Snellville, Georgia, United States, 30078
      • Recruiting
      • Accelerated Clinical Research Group LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45215
      • Recruiting
      • Patient Priority Clinical Sites LLC
  • Washington
    • Bellevue, Washington, United States, 98007
      • Recruiting
      • Northwest Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Meet diagnostic and statistical manual of mental disorders-5th edition (DSM-5) diagnostic criteria for major depressive disorder (MDD), without psychotic features based upon clinical assessment
• Experienced at least one MDD episode prior to their current episode
• Current episode of MDD must be a minimum of 2 weeks in duration

• Must meet one of the following criteria regarding current medication status.

  1. Can be presenting for a new episode of MDD on no antidepressant treatment; however, must have been treated with an antidepressant medication in a prior episode for a minimum of 6 weeks at a stable dose at or above the minimum therapeutic level (medical record/source document).

     OR

  2. Have taken up to two antidepressant treatments started in the current episode that were stopped (withdrawn), or will be withdrawn (washed out) due to inadequate response or intolerance.
• Body Mass Index (BMI) between 18 and 40 kilograms per square meter (kg/m^2)
• Must be medically stable on the basis of the following performed at screening and double-blind (DB) baseline: physical examination (including a brief neurological examination), vital signs (including blood pressure), and 12-lead electrocardiogram (ECG)

Exclusion criteria:

• Use of ketamine/esketamine in the current depressive episode (up to 2 doses are allowed prior to screening)
• Has treatment-resistant depression (TRD)
• Has a primary DSM-5 diagnosis of panic disorder, generalized anxiety disorder, social anxiety disorder, or specific phobia which has been the primary focus of psychiatric treatment within the past 2 years
• Current active DSM-5 diagnosis of obsessive-compulsive disorder, posttraumatic stress disorder, anorexia nervosa, bulimia nervosa, or fibromyalgia
• Has a history or current diagnosis of a psychotic disorder, bipolar disorder, autism spectrum disorder, borderline personality disorder, or somatoform disorders
• Has dementia, any dementing disease, intellectual disability, or neurocognitive disorder
• Has a current or recent history of homicidal ideation or serious suicidal ideation within the past 3 months or a history of suicidal behavior within the past 6 months
• Has a history of moderate-to-severe substance use disorder including alcohol use disorder according to DSM-5 criteria within 6 months
• Has any significant sleep disorder, including but not limited to untreated/uncontrolled conditions
• Has known allergies, hypersensitivity, intolerance, or any contraindication to seltorexant or its excipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Seltorexant; Participants will receive seltorexant tablet orally once daily, from Day 1 to Day 42 in double blind (DB) treatment phase. Eligible participants who will enter the open label (OL) treatment phase will receive seltorexant tablet daily from OL baseline until the end of phase/ early withdrawal (EW) visit (up to 6 months).	Drug: Seltorexant; Seltorexant tablet will be administered orally.; Other Names: JNJ-42847922
Placebo Comparator: Placebo; Participants will receive matching placebo tablet orally once daily from Day 1 to Day 42 in double-blind treatment phase. Eligible participants who will enter the OL treatment phase will receive seltorexant tablet daily from OL baseline until the end of phase/ EW visit (up to 6 months).	Drug: Placebo; Placebo tablet will be administered orally.; Drug: Seltorexant; Seltorexant tablet will be administered orally.; Other Names: JNJ-42847922

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Double Blind (DB) Treatment Phase: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score in Participants with Major Depressive Disorder with Moderate-to-Severe Insomnia Symptoms (MDDIS)	The MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale 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 possible score of 60. Higher scores represent a more severe condition.	Baseline up to Day 43
Open-Label (OL) Treatment Phase: Number of Participants with Adverse Events Including Adverse Event of Special Interests (AESIs)	An AE is any untoward medical occurrence in a clinical study participant administered with a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. The following AESIs are considered in this study: Suicidal thoughts, suicidal ideation, and suicidal behavior; Cataplexy; Sleep paralysis; Complex, sleep-related behaviors/parasomnias; Fall and Motor vehicle accident.	OL Baseline (Day 43) Up to 6 months
OL Treatment Phase: Number of Participants with Vital Signs Abnormalities	Number of participants with vital signs (blood pressure and pulse/heart rate measurements) abnormalities will be reported.	OL Baseline (Day 43) Up to 6 months
OL Treatment Phase: Number of Participants with Suicidality Assessment using Columbia-Suicide Severity Rating Scale (C-SSRS)	The C-SSRS is a low-burden measure of the spectrum of suicidal ideation and behavior that was developed to assess severity and track suicidal events through any treatment. The C-SSRS 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.	OL Baseline (Day 43) Up to 6 months
OL Treatment Phase: Number of Participants with Withdrawal Symptoms Assessment Using Physician Withdrawal Checklist (PWC-20)	Potential withdrawal effects will be assessed by the PWC-20. 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.	End of Treatment/Early withdrawal to end of the Follow-up visit (up to 14 days)
OL Treatment Phase: Number of Participants with Abnormalities in Electrocardiogram (ECG)	Number of participants with abnormalities in ECG will be reported.	OL Baseline (Day 43) up to 6 months
OL Treatment Phase: Number of Participants Reporting Sexual Functioning using Arizona Sexual Experiences Scale (ASEX)	The ASEX is a patient-reported 5-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Possible total scores range from 5 to 30, with the higher scores indicating more sexual dysfunction. The scale has shown satisfactory reliability and validity.	Up to 6 months
OL Treatment Phase: Change from Baseline in the Body Weight	Change from baseline in body weight will be reported.	OL Baseline (Day 43) up to 6 months
OL Treatment Phase: Change from Baseline in the Body Mass Index (BMI)	Change from baseline in BMI will be reported.	OL Baseline (Day 43) up to 6 months
OL Treatment Phase: Change from Baseline in the Waist Circumference	Change from baseline in waist circumference will be reported.	OL Baseline (Day 43) up to 6 months
OL Treatment Phase: Number of Participants with Abnormalities in Clinical Laboratory Parameters	Number of participants with laboratory abnormalities related to hematology, serum chemistry will be reported.	OL Baseline (Day 43) up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DB Treatment Phase: Change from Baseline in MADRS-Without Sleep Item (WOSI) Total Score	MADRS-WOSI considered 9 of the 10 MADRS items, excluding "reduced sleep" item. The total score ranged from 0 to 54, with higher scores corresponding to greater symptom severity.	Baseline up to Day 43
DB Treatment Phase: Change from Baseline in Sleep Disturbance using Patient Reported Outcome Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form 10a(8a + 2a ) T-score	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 10-item short form will be used, in which responses are scored 1 to 5 for each item. T-score for the PROMIS-SD scales represent the value obtained after using a conversion table to convert 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. For example, for the adult 10-item form, the lowest possible raw score is 10; the highest possible raw score is 50. Higher overall score indicates more sleep disturbance.	Baseline up to Day 43
DB Treatment phase: Change from Baseline in MADRS-6 Total Score	The MADRS-6 scale is a clinician-administered questionnaire used to measure the severity of major depressive disorder (MDD) symptoms. The MADRS-6 scale is a subset of the MADRS -10 scale, comprised of the following individual questionnaire items: apparent sadness, reported sadness, inner tension, lassitude, inability to feel, and pessimistic thoughts. Scores range from 0 (no apparent symptoms) to 36 (most severe symptoms).	Baseline up to Day 43
DB Treatment Phase: Proportion of Participants with Response on Depressive Symptoms Scale	Responders are defined as proportion of participants with greater than or equal to (>=) 50 percent (%) improvement in the MADRS total score from baseline to Day 43.	Baseline up to Day 43
DB Treatment Phase: Change from Baseline in Sleep Disturbance using PROMIS-SD Short Form 8a T-Score	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. T-score for the PROMIS-SD scales represent the value obtained after using a conversion table to convert 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. For example, for the adult 8-item form, the lowest possible raw score is 8; the highest possible raw score is 40. Higher overall score indicates more sleep disturbance.	Baseline up to Day 43
DB Treatment Phase: Change from Baseline in Patient Health Questionnaire 9-Item (PHQ-9) Total Score	The PHQ-9 is a 9-item, participant reported outcome measure to assess depressive symptoms. The scale scores each of the 9 symptom domains of the DSM-5 MDD criteria. Each item is rated on a 4 point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms.	Baseline up to Day 43
DB Period: Change from Baseline in Work Productivity and Activity Impairment Questionnaire, Depression (WPAI-D) Scores	The WPAI-D questionnaire is a patient-reported instrument to measure impairments in both paid work and unpaid work. It measures absenteeism, presenteeism as well as the impairments in unpaid activity because of health problems during the past 7 days. The WPAI yields four types of scores: (a) Absenteeism (work time missed); (b) Presenteeism (impairment at work / reduced on-the-job effectiveness); (c) Work productivity loss (overall work impairment / absenteeism plus presenteeism); (d) Activity Impairment. The first three scores are derived only for respondents who were working (should be missing for non-working), but the last score is applicable for all respondents. Each score ranges from 0 to 100 with higher scores indicating greater impairment and less productivity. Negative changes in score indicates less impairment and greater productivity.	Baseline up to Day 43
OL Treatment Phase: Change from Baseline Over Time in MADRS Total Score	The MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale 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 possible score of 60. Higher scores represent a more severe condition.	OL Baseline (Day 43) up to 6 months
OL Treatment Phase: Change from Baseline Over Time in Clinical Global Impression-Severity (CGI-S) Score	The CGI-S provides an overall clinician-determined summary measure of the severity of the participant's illness that takes into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. 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 the following criteria: 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 patients.	OL Baseline (Day 43) up to 6 months
OL Treatment Phase: Change from Baseline Over Time in MADRS-WOSI Total Score	MADRS-WOSI considered 9 of the 10 MADRS items, excluding "reduced sleep" item. The total score ranged from 0 to 54, with higher scores corresponding to greater symptom severity.	OL Baseline (Day 43) up to 6 months
OL Treatment Phase: Change from Baseline Over Time in Sleep Disturbance using PROMIS-SD Short Form 10a(8a+2a) T-score	The PROMIS-SD 10a(8a+2a) 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 10-item short form will be used, in which responses are scored 1 to 5 for each item. T-score for the PROMIS-SD 10a(8a+2a) scales represent the value obtained after using a conversion table to convert 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. For example, for the adult 10-item form, the lowest possible raw score is 10; the highest possible raw score is 50. Higher overall score indicates more sleep disturbance.	OL Baseline (Day 43) up to 6 months
OL Treatment Phase: Change from Baseline in Work Productivity and Activity Impairment-Questionnaire Depression (WPAI-D) Score	The WPAI-D questionnaire is a validated short instrument that assesses impairment in work and other regular activities over the past 7 days. The WPAI yields four types of scores: (a) Absenteeism (work time missed); (b) Presenteeism (impairment at work / reduced on-the-job effectiveness); (c) Work productivity loss (overall work impairment / absenteeism plus presenteeism); (d) Activity Impairment. The first three scores are derived only for respondents who were working (should be missing for non-working), but the last score is applicable for all respondents. Each score ranges from 0 to 100 with higher scores indicating greater impairment and less productivity. Negative changes in score indicates less impairment and greater productivity.	OL Baseline (Day 43) up to 6 months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2026
• Primary Completion (Estimated): August 24, 2028
• Study Completion (Estimated): May 3, 2029

Study Registration Dates

• First Submitted: May 1, 2026
• First Submitted That Met QC Criteria: May 1, 2026
• First Posted (Actual): May 7, 2026

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; seltorexant
• Other Study ID Numbers: 42847922MDD3011 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of Johnson & Johnson Innovative Medicine is available at innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes