A Long-Term Extension Study for Participants With Treatment-resistant Major Depressive Disorder Who Are Continuing Esketamine Nasal Spray Treatment

NCT ID: NCT04829318

Last Updated: 2025-09-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 183 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-26
• Study Completion Date: 2024-07-22

Brief Summary

The primary purpose of this study is to assess the long-term safety and tolerability of esketamine nasal spray in combination with a selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) in participants who have completed 32 weeks of esketamine nasal spray treatment in Study 54135419TRD3013 (NCT04338321).

Conditions

Depressive Disorder, Major

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Esketamine

Participants who were randomly assigned to the esketamine arm in Study 54135419TRD3013 (NCT04338321), had esketamine nasal spray administered through Week 30 (every 2 weeks dosing) or Week 31 (once weekly dosing), completed the maintenance phase at Week 32 will continue to receive esketamine nasal spray once weekly or every 2 weeks along with serotonin-norepinephrine reuptake inhibitor/selective serotonin reuptake inhibitor (SSRI/SNRI) in this long-term extension (LTE) study. The duration of the study participation is 2 years or when esketamine is commercially available.

Group Type: EXPERIMENTAL

Esketamine

Intervention Type: DRUG

Esketamine will be self-administered as nasal spray.

SSRI/SNRI

Intervention Type: DRUG

Participants will continue to take SSRI/SNRI that is approved for use in depression in their country of participation; off-label use of any SSRI/SNRI is not permitted. The continuing SSRI/SNRI dosage may be optimized throughout the study, at the investigator's discretion and based on the summary of product characteristics (SmPC) (or local equivalent, if applicable). During this LTE study, investigators will be allowed to switch individual participant's SSRI/SNRI for tolerability issues.

Interventions

Esketamine

Esketamine will be self-administered as nasal spray.

Intervention Type: DRUG

SSRI/SNRI

Participants will continue to take SSRI/SNRI that is approved for use in depression in their country of participation; off-label use of any SSRI/SNRI is not permitted. The continuing SSRI/SNRI dosage may be optimized throughout the study, at the investigator's discretion and based on the summary of product characteristics (SmPC) (or local equivalent, if applicable). During this LTE study, investigators will be allowed to switch individual participant's SSRI/SNRI for tolerability issues.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Completed the maintenance phase (Week 32) of Study 54135419TRD3013 (NCT04338321) and had esketamine nasal spray in combination with continuing selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) administered through Week 30 (every 2 week dosing) or Week 31 (once weekly dosing) of Study 54135419TRD3013, and continues to be willing to be treated with esketamine nasal spray
• Must, in the opinion of the investigator, be benefiting from continuation of esketamine nasal spray in combination with their current SSRI/SNRI based on efficacy and tolerability assessed on Day 1 of this study
• Must be medically stable based on the investigator's judgment
• A woman of childbearing potential must have a negative urine pregnancy test on Day 1
• Male participants who are sexually active with a woman of childbearing potential must agree to the following during the intervention period and for at least 1 spermatogenesis cycle (defined as approximately 90 days) after receiving the last dose of study intervention (that is, esketamine nasal spray), must fulfill the following criteria: must be practicing a highly effective method of contraception with his female partner, must use a condom if his partner is pregnant, and must agree not to donate sperm

Exclusion Criteria

• Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (example, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
• Completed Study 54135419TRD3013 while presenting adverse events deemed clinically relevant by the investigator, and which may interfere with safety and well-being of the participant
• Has developed during participation in Study 54135419TRD3013 any of the following cardiovascular-related conditions where an increase in blood pressure or intracranial pressure poses a serious risk: cerebrovascular disease following stroke or transient ischemic attack, aneurysmal vascular disease (including intracranial, thoracic, or abdominal aorta, or peripheral arterial vessels), intracerebral hemorrhage, coronary artery disease following myocardial infarction, unstable angina, or revascularization procedure (example, coronary angioplasty or bypass graft surgery), uncontrolled brady- or tachyarrhythmias that lead to hemodynamic instability, hemodynamically significant valvular heart disease such as mitral regurgitation, aortic stenosis, or aortic regurgitation or heart failure (New York Heart Association [NYHA] Class III-IV) of any etiology
• Significant pulmonary insufficiency, including chronic obstructive pulmonary disease
• Has homicidal ideation or intent, per the investigator's clinical judgment; or has suicidal ideation with some intent to act within 1 month prior to Day 1, per the investigator's clinical judgment; or based on the Columbia-suicide severity rating scale (C-SSRS) performed at Week 32 visit of Study 54135419TRD3013, corresponding to a response of "Yes" on Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) for suicidal ideation
• Pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 90 days after the last dose of study intervention

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen-Cilag Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen-Cilag Ltd. Clinical Trial

Role: STUDY_DIRECTOR

Janssen-Cilag Ltd.

Locations

FunDaMos

Buenos Aires, , Argentina

CEN Consultorios Especializados en Neurociencias

Córdoba, , Argentina

Fundacion Lennox

Córdoba, , Argentina

Instituto Medico DAMIC

Córdoba, , Argentina

Sanatorio Prof Leon S Morra S A

Córdoba, , Argentina

Instituto de Neurociencias San Agustin

La Plata, , Argentina

C I A P Centro de investigacion y Asistencia en Psiquiatria

Rosario, , Argentina

Anima

Alken, , Belgium

Mental Health Center - Rousse

Rousse, , Bulgaria

Multiprofile Hospital for Active Treatment in Neurology and Psychiatry Sveti Naum

Sofia, , Bulgaria

Centre for Mental Health Prof.N.Shipkovenski EOOD

Sofia, , Bulgaria

Psychiatricka ambulance Saint Anne s.r.o.

Brno, , Czechia

Psychiatricka ambulance, MUDr. Marta Holanova

Brno, , Czechia

NeuropsychiatrieHK, s.r.o.

Hradec Králové, , Czechia

A Shine S R O

Pilsen, , Czechia

AD71 s.r.o.

Prague, , Czechia

Medical Services Prague S R O

Prague, , Czechia

Institut Neuropsychiatricke pece

Prague, , Czechia

Mederon LTD at ARTES

Helsinki, , Finland

Medizinisches Versorgungszentrum LiO GmbH

Berlin, , Germany

Praxis Dr. med. Kirsten Hahn

Berlin, , Germany

Klinikum Dortmund gGmbH

Dortmund, , Germany

Universitätsklinikum Freiburg - Abteilung für Psychiatrie u. Psychotherapie mit Poliklinik

Freiburg im Breisgau, , Germany

Klinische Forschung Hamburg

Hamburg, , Germany

Oberhavel Kliniken GmbH

Hennigsdorf, , Germany

Pharmakologisches Studienzentrum Chemnitz GmbH

Mittweida, , Germany

Danuvius Klinik Pfaffenhofen Fachklinik für Psychiatrie, Psychotherapie und Psychosomatik

Pfaffenhofen, , Germany

Somni Bene GmbH

Schwerin, , Germany

Klinische Forschung Schwerin GmbH

Schwerin, , Germany

Psychiatric Clinic 'Agios Charalampos'

Heraklion, , Greece

University General Hospital of Rio Patras

Pátrai, , Greece

G Papanikolaou Hospital of Thessaloniki

Thessaloniki, , Greece

Processus Kft

Budapest, , Hungary

Bugat Pal Korhaz

Gyöngyös, , Hungary

Petz Aladar Megyei Oktato Korhaz

Győr, , Hungary

Hospital Raja Permaisuri Bainun

Ipoh, , Malaysia

University Malaya Medical Centre

Kuala Lumpur, , Malaysia

Hospital Pengajar Universiti Putra Malaysia

Serdang, , Malaysia

Hospital Tuanku Jaafar

Seremban, , Malaysia

Mlynowamed Specjalistyczny Psychiatryczny Gabinet Lekarski Joanna Lazarczyk

Bialystok, , Poland

Osrodek Badan Klinicznych CLINSANTE S C

Bydgoszcz, , Poland

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Centrum Badan Klinicznych PI House sp z o o

Gdansk, , Poland

Centrum Medyczne Care Clinic Katowice

Katowice, , Poland

Niepubliczny Zaklad Opieki Psychiatrycznej MENTIS

Leszno, , Poland

Specjalistyczny Psychiatryczny Zespol Opieki Zdrowotnej w Lodzi Szpital im. J. Babinskiego

Lodz, , Poland

SPZOZ CSK UM w Lodzi Klinika Zaburzen Afektywnych i Psychotycznych

Lodz, , Poland

Osrodek Badan Klinicznych CLINSANTE S C

Torun, , Poland

Cape Town Clinical Research Centre

Cape Town, , South Africa

Gert Bosch Pretoria South Africa

Pretoria, , South Africa

Severance Hospital Yonsei University Health System

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Changhua Christian Hospital

Changhua, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Chang Gung Memorial Hospital

Taoyuan District, , Taiwan

Hacettepe University Medical Faculty

Ankara, , Turkey (Türkiye)

Erenkoy Mental Health Hospital

Istanbul, , Turkey (Türkiye)

Liv Hospital

Samsun, , Turkey (Türkiye)

Countries

Argentina; Belgium; Bulgaria; Czechia; Finland; Germany; Greece; Hungary; Malaysia; Poland; South Africa; South Korea; Taiwan; Turkey (Türkiye)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-004291-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

54135419TRD4010

Identifier Type: OTHER

Identifier Source: secondary_id

CR108992

Identifier Type: -

Identifier Source: org_study_id