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

NCT ID: NCT04599855

Last Updated: 2025-04-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 477 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-04
• Study Completion Date: 2024-01-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Esketamine 56 Milligram (mg)

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).

Group Type: EXPERIMENTAL

Esketamine 56 mg

Intervention Type: DRUG

Esketamine 56 mg will be self administered as nasal spray.

Esketamine 84 mg

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).

Group Type: EXPERIMENTAL

Esketamine 84 mg

Intervention Type: DRUG

Esketamine 84 mg will be self administered as nasal spray.

Placebo

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).

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Matching placebo will be self administered as nasal spray.

Interventions

Esketamine 56 mg

Esketamine 56 mg will be self administered as nasal spray.

Intervention Type: DRUG

Esketamine 84 mg

Esketamine 84 mg will be self administered as nasal spray.

Intervention Type: DRUG

Placebo

Matching placebo will be self administered as nasal spray.

Intervention Type: DRUG

Other Intervention Names

JNJ-54135419; JNJ-54135419

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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 a current or history of seizures (uncomplicated childhood febrile seizures with no sequelae are not exclusionary)
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

UAB Department of Psychiatry and Behavioral Neurobiology

Birmingham, Alabama, United States

UAB Huntsville Regional Medical Campus

Huntsville, Alabama, United States

Preferred Research Partners

Little Rock, Arkansas, United States

Behavioral Research Specialists LLC

Glendale, California, United States

CalNeuro Research

Los Angeles, California, United States

Pacific Research Partners

Oakland, California, United States

Anderson Clinical Research

Redlands, California, United States

University of California at San Diego

San Diego, California, United States

Artemis Institute for Clinical Research

San Diego, California, United States

UCSF Nancy Friend Pritzker Psychiatry Building

San Francisco, California, United States

Velocity Clinical Research

Santa Ana, California, United States

CMB Clinical Trials

Santee, California, United States

University of Connecticut Health Center

Farmington, Connecticut, United States

Velocity Clinical Research, Hallandale Beach

Hallandale, Florida, United States

Accel Research Sites

Lakeland, Florida, United States

APG Research LLC

Orlando, Florida, United States

USF, Department of Psychiatry and Behavioral Neurosciences

Tampa, Florida, United States

Neuroscience Research Institute

West Palm Beach, Florida, United States

Atlanta Behavioral Research, LLC

Atlanta, Georgia, United States

Psych Atlanta, P.C.

Marietta, Georgia, United States

Rush University Medical Center

Chicago, Illinois, United States

Chicago Research Center

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

Joliet Center for Clinical Research

Joliet, Illinois, United States

Pillar Clinical Research, LLC

Lincolnwood, Illinois, United States

Psychiatric Medicine Associates LLC

Skokie, Illinois, United States

Ascension via Christi Research

Wichita, Kansas, United States

University of Kansas School of Medicine

Wichita, Kansas, United States

Sheppard Pratt Health System

Baltimore, Maryland, United States

CBH Health

Gaithersburg, Maryland, United States

Copley Clinical

Boston, Massachusetts, United States

Adams Clinical

Watertown, Massachusetts, United States

University of Massachusetts Medical School

Worcester, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Rochester Center for Behavioral Medicine (RCBM)

Rochester Hills, Michigan, United States

Midwest Research Group - St. Charles Psychiatric Associates

Saint Charles, Missouri, United States

Clinilabs

New York, New York, United States

The Medical Research Network, LLC

New York, New York, United States

Stony Brook University Medical Center

Stony Brook, New York, United States

Ohio State University

Columbus, Ohio, United States

Midwest Clinical Research Center

Dayton, Ohio, United States

Paradigm Research Professionals, LLC

Oklahoma City, Oklahoma, United States

Lehigh Center for Clinical Research

Allentown, Pennsylvania, United States

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, United States

The Warren Alpert Medical School of Brown University - Butler Hospital

Providence, Rhode Island, United States

BioBehavioral Research of Austin PC

Austin, Texas, United States

Relaro Medical Trials

Dallas, Texas, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Brain Health Consultants and TMS Center

Houston, Texas, United States

The University of Texas Health Science Center at Houston

Houston, Texas, United States

Pillar Clinical Research, LLC

Richardson, Texas, United States

Family Psychiatry of The Woodlands

The Woodlands, Texas, United States

Grayline Research Center

Wichita Falls, Texas, United States

University of Virginia Center for Psychiatric Clinical Research

Charlottesville, Virginia, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 40601310 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

54135419TRD4005

Identifier Type: OTHER

Identifier Source: secondary_id

CR108741

Identifier Type: -

Identifier Source: org_study_id