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

NCT07573176 | Not Yet Recruiting Phase 3 FDA Drug

• 1 other identifier: 42847922MDD3011
• Study Type: interventional
• Target: 600
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Depressive Disorder, Major

Outcome Measures

Primary Outcomes (11)

• 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 Outcomes (12)

• DB Treatment Phase: Change from Baseline in MADRS-Without Sleep Item (WOSI) Total Score

  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

  Baseline up to Day 43

• DB Treatment phase: Change from Baseline in MADRS-6 Total Score

  Baseline up to Day 43

• DB Treatment Phase: Proportion of Participants with Response on Depressive Symptoms Scale

  Baseline up to Day 43

• DB Treatment Phase: Change from Baseline in Sleep Disturbance using PROMIS-SD Short Form 8a T-Score

  Baseline up to Day 43

Study Arms (2)

Seltorexant

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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: Seltorexant; Drug: Placebo

Interventions

Seltorexant DRUG

Seltorexant tablet will be administered orally.

Also known as: JNJ-42847922

Placebo; Seltorexant

Placebo DRUG

Placebo tablet will be administered orally.

Placebo

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

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

Central Study Contacts

Study Contact

CONTACT

844-434-4210; Participate-In-This-Study1@its.jnj.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2026
• First Posted: May 7, 2026
• Study Start: May 4, 2026
• Primary Completion (Estimated): August 24, 2028
• Study Completion (Estimated): May 3, 2029
• Last Updated: May 7, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share