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

NCT04829318 | Completed Phase 4 Results FDA Drug

• 3 other identifiers: CR1089922020-004291-1854135419TRD4010
• Study Type: interventional
• Target: 183
• Locations: 14 countries
• Sites: 59

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

Keywords

Treatment resistant depression

Outcome Measures

Primary Outcomes (9)

• Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)

  Percentage of participants with TEAEs were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious adverse events.

  From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)

• Incidence Rate of Treatment-emergent Adverse Events (TEAEs)

  Incidence rate of TEAEs were reported. AE Incidence rate was defined as incidence rate per 100 patient-months = (number of participants with AE divided by sum of days at risk for AE) \* 100\*365.25/12. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious adverse events.

  From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)

• Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs)

  Percentage of participants with TESAEs were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent.

  From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)

• Incidence Rate of Treatment-emergent Serious Adverse Events (TESAEs)

  Incidence rate of with TESAEs were reported. AE Incidence rate was defined as incidence rate per 100 patient-months = (number of participants with AE divided by sum of days at risk for AE) \* 100\*365.25/12. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent.

  From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)

• Percentage of of Participants With TEAEs Leading to Death

  Percentage of participants with TEAEs leading to death were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious adverse events.

  From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)

• Incidence Rate of TEAEs Leading to Death

  Incidence rate of TEAEs leading to death were reported. AE Incidence rate was defined as incidence rate per 100 patient-months = (number of participants with AE divided by sum of days at risk for AE) \* 100\*365.25/12. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious adverse events.

  From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)

• Percentage of Participants With Treatment-emergent AEs of Special Interest (AESIs)

  Percentage of participants with TEAEs of special interest were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious AEs. AEs of special interest were separately grouped by categories sedation, dissociation, suicidality, suggestive of abuse potential, cystitis and hepatic impairment.

  From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)

• Incidence Rate of Treatment-emergent AEs of Special Interest (AESIs)

  AE Incidence rate: incidence rate per 100 patient-months=(number of participants with AE divided by sum of days at risk for AE)\* 100\*365.25/12. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with intervention. SAE: AE resulting in any following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial intervention administration up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious AEs. AEs of special interest were grouped as categories sedation, dissociation, suicidality, suggestive of abuse potential, cystitis and hepatic impairment.

  From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)

• Number of Participants With Suicidal Ideation and Behavior in Study 54135419TRD4010 as Assessed by Columbia-suicide Severity Rating Scale (C-SSRS) Score

  Number of participants with suicidal ideation and behavior in study 54135419TRD4010 as assessed by C-SSRS score were reported. C-SSRS score: an assessment tool that evaluated suicidal ideation and behavior. Suicidal ideation (5 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, and active suicidal ideation with specific plan and intent. Suicidal behavior (5 items): preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt (non-fatal), and suicide. Total score from 10 categories was summarized into 3 categories: No suicidal ideation or behavior (0), Suicidal ideation (1 to 5), Suicidal behavior (6 to 10). Total score ranged from 0 to 10. Higher scores indicated more severe suicidal ideation and behavior.

  Baseline (Day 1 of Study 54135419TRD3013) up to Week 104 of study 54135419TRD4010 (up to Week 136)

Secondary Outcomes (7)

• Percentage of Participants With No Relapse and Without Discontinuation Until the End of the Prospective Observation Period at Week 104

  Baseline (Day 1 of Study 54135419TRD3013) up to Week 104 of study 54135419TRD4010 (up to Week 136)

• Change From Baseline of Study 54135419TRD3013 in Clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) Total Score

  Baseline (Day 1 of study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010

• Change From Baseline of Study 54135419TRD3013 in Clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) Score Individual Items

  Baseline (Day 1 of study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010

• Change From Baseline of Study 54135419TRD3013 in Clinical Global Impression -Severity (CGI-S) Scale Score

  Baseline (Day 1 of study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010

• Change From Baseline of Study 54135419TRD3013 in Patient Health Questionnaire (PHQ) 9-item Total Score

  Baseline (Day 1 of study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010

Study Arms (1)

Esketamine

EXPERIMENTAL

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.

Drug: Esketamine; Drug: SSRI/SNRI

Interventions

Esketamine DRUG

Esketamine will be self-administered as nasal spray.

Esketamine

SSRI/SNRI 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.

Esketamine

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen-Cilag Ltd.: lead

Study Sites (59)

FunDaMos

Buenos Aires, C1405BOA, Argentina

Location

CEN Consultorios Especializados en Neurociencias

Córdoba, 5000FJF, Argentina

Location

Fundacion Lennox

Córdoba, 5000, Argentina

Location

Instituto Medico DAMIC

Córdoba, X5003DCE, Argentina

Location

Sanatorio Prof Leon S Morra S A

Córdoba, X5009BIN, Argentina

Location

Instituto de Neurociencias San Agustin

La Plata, 1900, Argentina

Location

C I A P Centro de investigacion y Asistencia en Psiquiatria

Rosario, 2000, Argentina

Location

Anima

Alken, 3570, Belgium

Location

Mental Health Center - Rousse

Rousse, 7003, Bulgaria

Location

Multiprofile Hospital for Active Treatment in Neurology and Psychiatry Sveti Naum

Sofia, 1113, Bulgaria

Location

Centre for Mental Health Prof.N.Shipkovenski EOOD

Sofia, 1377, Bulgaria

Location

Psychiatricka ambulance Saint Anne s.r.o.

Brno, 60200, Czechia

Location

Psychiatricka ambulance, MUDr. Marta Holanova

Brno, 61500, Czechia

Location

NeuropsychiatrieHK, s.r.o.

Hradec Králové, 50002, Czechia

Location

A Shine S R O

Pilsen, 31200, Czechia

Location

AD71 s.r.o.

Prague, 109 00, Czechia

Location

Medical Services Prague S R O

Prague, 16000, Czechia

Location

Institut Neuropsychiatricke pece

Prague, 18600, Czechia

Location

Mederon LTD at ARTES

Helsinki, 00270, Finland

Location

Medizinisches Versorgungszentrum LiO GmbH

Berlin, 12209, Germany

Location

Praxis Dr. med. Kirsten Hahn

Berlin, 13187, Germany

Location

Klinikum Dortmund gGmbH

Dortmund, 44287, Germany

Location

Universitätsklinikum Freiburg - Abteilung für Psychiatrie u. Psychotherapie mit Poliklinik

Freiburg im Breisgau, 79104, Germany

Location

Klinische Forschung Hamburg

Hamburg, 20253, Germany

Location

Oberhavel Kliniken GmbH

Hennigsdorf, 16761, Germany

Location

Pharmakologisches Studienzentrum Chemnitz GmbH

Mittweida, 09111, Germany

Location

Danuvius Klinik Pfaffenhofen Fachklinik für Psychiatrie, Psychotherapie und Psychosomatik

Pfaffenhofen, 85276, Germany

Location

Somni Bene GmbH

Schwerin, 19053, Germany

Location

Klinische Forschung Schwerin GmbH

Schwerin, 19055, Germany

Location

Psychiatric Clinic 'Agios Charalampos'

Heraklion, 71305, Greece

Location

University General Hospital of Rio Patras

Pátrai, 26504, Greece

Location

G Papanikolaou Hospital of Thessaloniki

Thessaloniki, 57010, Greece

Location

Processus Kft

Budapest, 1137, Hungary

Location

Bugat Pal Korhaz

Gyöngyös, 3200, Hungary

Location

Petz Aladar Megyei Oktato Korhaz

Győr, H-9024, Hungary

Location

Hospital Raja Permaisuri Bainun

Ipoh, 30990, Malaysia

Location

University Malaya Medical Centre

Kuala Lumpur, 59100, Malaysia

Location

Hospital Pengajar Universiti Putra Malaysia

Serdang, 43400, Malaysia

Location

Hospital Tuanku Jaafar

Seremban, 70300, Malaysia

Location

Mlynowamed Specjalistyczny Psychiatryczny Gabinet Lekarski Joanna Lazarczyk

Bialystok, 15-404, Poland

Location

Osrodek Badan Klinicznych CLINSANTE S C

Bydgoszcz, 85 794, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80 214, Poland

Location

Centrum Badan Klinicznych PI House sp z o o

Gdansk, 80 546, Poland

Location

Centrum Medyczne Care Clinic Katowice

Katowice, 40-568, Poland

Location

Niepubliczny Zaklad Opieki Psychiatrycznej MENTIS

Leszno, 64-100, Poland

Location

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

Lodz, 91-229, Poland

Location

SPZOZ CSK UM w Lodzi Klinika Zaburzen Afektywnych i Psychotycznych

Lodz, 92-216, Poland

Location

Osrodek Badan Klinicznych CLINSANTE S C

Torun, 87 100, Poland

Location

Cape Town Clinical Research Centre

Cape Town, 7530, South Africa

Location

Gert Bosch Pretoria South Africa

Pretoria, 0 042, South Africa

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Changhua Christian Hospital

Changhua, 500, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Chang Gung Memorial Hospital

Taoyuan District, 333, Taiwan

Location

Hacettepe University Medical Faculty

Ankara, 6100, Turkey (Türkiye)

Location

Erenkoy Mental Health Hospital

Istanbul, 34736, Turkey (Türkiye)

Location

Liv Hospital

Samsun, 55020, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant

Interventions

Esketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Results Point of Contact

• Title: Director Global Medical Affairs Lead
• Organization: Janssen-Cilag Limited

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen-Cilag Ltd. Clinical Trial

  Janssen-Cilag Ltd.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2021
• First Posted: April 2, 2021
• Study Start: April 26, 2021
• Primary Completion: July 22, 2024
• Study Completion: July 22, 2024
• Last Updated: September 18, 2025
• Results First Posted: September 18, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

TU (3); CZ (7); AR (7); BU (3); BE (1); FI (1); HU (3); MY (4); DE (10); PL (9); ZA (2); KR (2); TW (4); GR (3)