A Study of Esketamine Nasal Spray, Administered as Monotherapy, in Adult Participants With Treatment-resistant Depression

NCT04599855 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: CR10874154135419TRD4005
• Study Type: interventional
• Target: 477
• Locations: 1 country
• Sites: 54

Brief Summary

The purpose of this study is to evaluate the efficacy of each individual dose of esketamine nasal spray, 56 milligram (mg) and 84 mg, compared with placebo nasal spray in improving depressive symptoms in participants with treatment resistant depression (TRD), as assessed by the change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score from Day 1 (prerandomization) to the end of the 4 week double-blind treatment phase (Day 28).

Conditions

Depressive Disorder, Treatment-Resistant

Outcome Measures

Primary Outcomes (1)

• Double-blind Treatment Phase: Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Day 1 (Pre-randomization) to Day 28

  The MADRS was a clinician-rated scale designed to measure depression severity and detect changes due to antidepressant treatment. The scale consisted of 10 items, each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score was the sum of scores from individual question items, which ranged from 0 to 60, higher scores represented a more severe condition. The MADRS evaluated apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, inability to feel (interest level), pessimistic thoughts, and suicidal thoughts. Negative change in MADRS total score indicated improvement.

  Day 1 (pre-randomization) to Day 28 (end of DB treatment phase)

Secondary Outcomes (1)

• Double-blind Treatment Phase: Change in MADRS Total Score From Day 1 (Pre-randomization) to Day 2 (24 Hours Post First Dose on Day 1)

  Day 1 (pre-randomization) to Day 2 of DB treatment phase (24 hours post first dose on Day 1)

Study Arms (3)

Esketamine 56 Milligram (mg)

EXPERIMENTAL

Participants will receive nasal spray treatment with esketamine 56 mg twice a week for 4 weeks. Participants may participate in an open-label treatment/observation phase, following completion of the double-blind treatment phase assessments (which includes the Day 28 Montgomery-Asberg Depression Rating Scale \[MADRS\] assessment).

Drug: Esketamine 56 mg

Esketamine 84 mg

EXPERIMENTAL

Participants will receive nasal spray treatment with esketamine 84 mg twice a week for 4 weeks. Participants may participate in an open-label treatment/observation phase, following completion of the double-blind treatment phase assessments (which includes the Day 28 MADRS assessment).

Drug: Esketamine 84 mg

Placebo

EXPERIMENTAL

Participants will receive nasal spray treatment with placebo twice a week for 4 weeks. Participants may participate in an open-label treatment/observation phase, following completion of the double-blind treatment phase assessments (which includes the Day 28 MADRS assessment).

Drug: Placebo

Interventions

Esketamine 56 mg DRUG

Esketamine 56 mg will be self administered as nasal spray.

Also known as: JNJ-54135419

Esketamine 56 Milligram (mg)

Esketamine 84 mg DRUG

Esketamine 84 mg will be self administered as nasal spray.

Also known as: JNJ-54135419

Esketamine 84 mg

Placebo DRUG

Matching placebo will be self administered as nasal spray.

Placebo

Eligibility Criteria

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

You may qualify if:

• Participant must meet the Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5) diagnostic criteria for single-episode MDD or recurrent MDD, without psychotic features, based upon clinical assessment and confirmed by the MINI. Participants 65 years of age or older must have had the first onset of depression prior to 55 years of age
• Participant must have had nonresponse (\<=25% improvement) to \>=2 oral antidepressant treatments in the current episode of depression, assessed using the MGH-ATRQ, and confirmed by documented records (example, medical/pharmacy/prescription records or a letter from a treating physician)
• Participant must have an Inventory of Depressive Symptomatology-Clinician rated, 30-item (IDS-C30) total score of \>=34
• The participant's current major depressive episode, depression symptom severity, and antidepressant treatment response in the current depressive episode, must be confirmed by the State vs. Trait, Assessibility, Face Validity, Ecological Validity, Rule of Three P's (SAFER) Interview

You may not qualify if:

• Participant must be medically stable on the basis of clinical laboratory tests performed in the screening phase. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator: (a) Participants with a pre-existing history of thyroid disease/disorder who are treated with thyroid hormones must be on a stable dosage for 3 months prior to the start of the screening phase; (b) For any participant (regardless of thyroid history), if the thyroid-stimulating hormone (TSH) value is out of range, a free thyroxine (FT4) will be conducted. If the FT4 value is abnormal and considered to be clinically significant (after discussion with the medical monitor), the participant is not eligible
• Participant must be comfortable with self-administration of nasal spray medication and be able to follow the nasal spray administration instructions provided
• The participant has used ketamine/esketamine (lifetime)
• The participant's depressive symptoms have previously demonstrated nonresponse to an adequate course of treatment with electroconvulsive therapy (ECT) in the current major depressive episode, defined as at least 7 treatments with unilateral/bilateral ECT
• Participant has received vagal nerve stimulation (VNS) or has received deep brain stimulation (DBS) in the current episode of depression
• Participant has any anatomical or medical condition that, per the investigator's clinical judgment based on assessment, may impede delivery or absorption of nasal spray study drug

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (54)

UAB Department of Psychiatry and Behavioral Neurobiology

Birmingham, Alabama, 35294, United States

Location

UAB Huntsville Regional Medical Campus

Huntsville, Alabama, 35801, United States

Location

Preferred Research Partners

Little Rock, Arkansas, 72211, United States

Location

Behavioral Research Specialists LLC

Glendale, California, 91206, United States

Location

CalNeuro Research

Los Angeles, California, 90025, United States

Location

Pacific Research Partners

Oakland, California, 94607, United States

Location

Anderson Clinical Research

Redlands, California, 92374, United States

Location

University of California at San Diego

San Diego, California, 92103-8620, United States

Location

Artemis Institute for Clinical Research

San Diego, California, 92103, United States

Location

UCSF Nancy Friend Pritzker Psychiatry Building

San Francisco, California, 94143, United States

Location

Velocity Clinical Research

Santa Ana, California, 91704, United States

Location

CMB Clinical Trials

Santee, California, 92071, United States

Location

University of Connecticut Health Center

Farmington, Connecticut, 06032, United States

Location

Velocity Clinical Research, Hallandale Beach

Hallandale, Florida, 33009, United States

Location

Accel Research Sites

Lakeland, Florida, 33803, United States

Location

APG Research LLC

Orlando, Florida, 32803, United States

Location

USF, Department of Psychiatry and Behavioral Neurosciences

Tampa, Florida, 33613, United States

Location

Neuroscience Research Institute

West Palm Beach, Florida, 33407, United States

Location

Atlanta Behavioral Research, LLC

Atlanta, Georgia, 30338, United States

Location

Psych Atlanta, P.C.

Marietta, Georgia, 30060, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Chicago Research Center

Chicago, Illinois, 60634, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Joliet Center for Clinical Research

Joliet, Illinois, 60435, United States

Location

Pillar Clinical Research, LLC

Lincolnwood, Illinois, 60712, United States

Location

Psychiatric Medicine Associates LLC

Skokie, Illinois, 60076, United States

Location

Ascension via Christi Research

Wichita, Kansas, 67214, United States

Location

University of Kansas School of Medicine

Wichita, Kansas, 67214, United States

Location

Sheppard Pratt Health System

Baltimore, Maryland, 21204, United States

Location

CBH Health

Gaithersburg, Maryland, 20877, United States

Location

Copley Clinical

Boston, Massachusetts, 02116, United States

Location

Adams Clinical

Watertown, Massachusetts, 02472, United States

Location

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Rochester Center for Behavioral Medicine (RCBM)

Rochester Hills, Michigan, 48307, United States

Location

Midwest Research Group - St. Charles Psychiatric Associates

Saint Charles, Missouri, 63304, United States

Location

Clinilabs

New York, New York, 10016, United States

Location

The Medical Research Network, LLC

New York, New York, 10128, United States

Location

Stony Brook University Medical Center

Stony Brook, New York, 11794, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Midwest Clinical Research Center

Dayton, Ohio, 45417, United States

Location

Paradigm Research Professionals, LLC

Oklahoma City, Oklahoma, 73118, United States

Location

Lehigh Center for Clinical Research

Allentown, Pennsylvania, 18104, United States

Location

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

The Warren Alpert Medical School of Brown University - Butler Hospital

Providence, Rhode Island, 02906, United States

Location

BioBehavioral Research of Austin PC

Austin, Texas, 78759, United States

Location

Relaro Medical Trials

Dallas, Texas, 75243, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75247, United States

Location

Brain Health Consultants and TMS Center

Houston, Texas, 77046, United States

Location

The University of Texas Health Science Center at Houston

Houston, Texas, 77054, United States

Location

Pillar Clinical Research, LLC

Richardson, Texas, 75080, United States

Location

Family Psychiatry of The Woodlands

The Woodlands, Texas, 77381, United States

Location

Grayline Research Center

Wichita Falls, Texas, 76309, United States

Location

University of Virginia Center for Psychiatric Clinical Research

Charlottesville, Virginia, 22903, United States

Location

Related Publications (1)

• Janik A, Qiu X, Lane R, Popova V, Drevets WC, Canuso CM, Macaluso M, Mattingly GW, Shelton RC, Zajecka JM, Fu DJ. Esketamine Monotherapy in Adults With Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2025 Sep 1;82(9):877-887. doi: 10.1001/jamapsychiatry.2025.1317.

  PMID: 40601310 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Esketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Results Point of Contact

• Title: Global Medical Head
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2020
• First Posted: October 23, 2020
• Study Start: November 4, 2020
• Primary Completion: January 31, 2024
• Study Completion: January 31, 2024
• Last Updated: April 25, 2025
• Results First Posted: March 4, 2025

Record last verified: 2025-04

Locations

US (54)