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

Open-label Long-Term Extension Study for Participants With Treatment-Resistant Major Depressive Disorder Who Are Continuing Esketamine Nasal Spray Treatment From Study 54135419TRD3013

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Depressive Disorder, Major
• Intervention / Treatment: Drug: Esketamine; Drug: SSRI/SNRI

• Study Type: Interventional
• Enrollment (Actual): 183
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma de Buenos Aires, Argentina, C1405BOA
    • FunDaMos
  • Cordoba, Argentina, 5000
    • Fundacion Lennox
  • Cordoba, Argentina, X5003DCE
    • Instituto Medico DAMIC
  • Cordoba, Argentina, 5000FJF
    • CEN Consultorios Especializados en Neurociencias
  • Cordoba, Argentina, X5009BIN
    • Sanatorio Prof Leon S Morra S A
  • La Plata, Argentina, 1900
    • Instituto de Neurociencias San Agustin
  • Rosario, Argentina, 2000
    • C I A P Centro de investigacion y Asistencia en Psiquiatria
• Belgium
  • Alken, Belgium, 3570
    • Anima
• Bulgaria
  • Rousse, Bulgaria, 7003
    • Mental Health Center - Rousse
  • Sofia, Bulgaria, 1113
    • Multiprofile Hospital for Active Treatment in Neurology and Psychiatry Sveti Naum
  • Sofia, Bulgaria, 1377
    • Centre for Mental Health Prof.N.Shipkovenski EOOD
• Czechia
  • Brno, Czechia, 60200
    • Psychiatricka ambulance Saint Anne s.r.o.
  • Brno, Czechia, 61500
    • Psychiatricka ambulance, MUDr. Marta Holanova
  • Hradec Kralove, Czechia, 50002
    • NeuropsychiatrieHK, s.r.o.
  • Plzen, Czechia, 31200
    • A-Shine s.r.o.
  • Prague, Czechia, 18600
    • Institut Neuropsychiatricke pece
  • Praha 10, Czechia, 109 00
    • AD71 s.r.o.
  • Praha 6, Czechia, 16000
    • Medical Services Prague s.r.o.
• Finland
  • Helsinki, Finland, 00270
    • Mederon LTD at ARTES
• Germany
  • Berlin, Germany, 12209
    • Medizinisches Versorgungszentrum LiO GmbH
  • Berlin, Germany, 13187
    • Praxis Dr. med. Kirsten Hahn
  • Dortmund, Germany, 44287
    • Klinikum Dortmund gGmbH
  • Freiburg, Germany, 79104
    • Universitätsklinikum Freiburg - Abteilung für Psychiatrie u. Psychotherapie mit Poliklinik
  • Hamburg, Germany, 20253
    • Klinische Forschung Hamburg
  • Hennigsdorf, Germany, 16761
    • Oberhavel Kliniken GmbH
  • Mittweida, Germany, 09111
    • Pharmakologisches Studienzentrum Chemnitz GmbH
  • Pfaffenhofen, Germany, 85276
    • Danuvius Klinik Pfaffenhofen Fachklinik für Psychiatrie, Psychotherapie und Psychosomatik
  • Schwerin, Germany, 19055
    • Klinische Forschung Schwerin GmbH
  • Schwerin, Germany, 19053
    • Somni Bene GmbH
• Greece
  • Heraklion, Greece, 71305
    • Psychiatric Clinic 'Agios Charalampos'
  • Patras, Greece, 26504
    • University General Hospital of Rio Patras
  • Thessaloniki, Greece, 57010
    • G Papanikolaou Hospital of Thessaloniki
• Hungary
  • Budapest, Hungary, 1137
    • Processus Kft
  • Gyongyos, Hungary, 3200
    • Bugat Pal Korhaz
  • Gyor, Hungary, H-9024
    • Petz Aladar Megyei Oktato Korhaz
• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital Yonsei University Health System
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• Malaysia
  • Ipoh, Malaysia, 30990
    • Hospital Raja Permaisuri Bainun
  • Kuala Lumpur, Malaysia, 59100
    • University Malaya Medical Centre
  • Serdang, Malaysia, 43400
    • Hospital Pengajar Universiti Putra Malaysia
  • Seremban, Malaysia, 70300
    • Hospital Tuanku Jaafar
• Poland
  • Bialystok, Poland, 15-404
    • Mlynowamed Specjalistyczny Psychiatryczny Gabinet Lekarski Joanna Lazarczyk
  • Bydgoszcz, Poland, 85-794
    • Osrodek Badan Klinicznych CLINSANTE S.C.
  • Gdansk, Poland, 80-546
    • Centrum Badan Klinicznych PI-House sp. z o.o.
  • Gdansk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne
  • Katowice, Poland, 40-568
    • Centrum Medyczne Care Clinic Katowice
  • Leszno, Poland, 64-100
    • Niepubliczny Zaklad Opieki Psychiatrycznej MENTIS
  • Lodz, Poland, 91-229
    • Specjalistyczny Psychiatryczny Zespol Opieki Zdrowotnej w Lodzi Szpital im. J. Babinskiego
  • Lodz, Poland, 92-216
    • SPZOZ CSK UM w Lodzi Klinika Zaburzen Afektywnych i Psychotycznych
  • Torun, Poland, 87-100
    • Osrodek Badan Klinicznych CLINSANTE S.C.
• South Africa
  • Cape Town, South Africa, 7530
    • Cape Town Clinical Research Centre
  • Pretoria, South Africa, 0 042
    • Gert Bosch Pretoria South Africa
• Taiwan
  • ChangHua, Taiwan, 500
    • Changhua Christian Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital
• Turkey
  • Ankara, Turkey, 6100
    • Hacettepe University Medical Faculty
  • Istanbul, Turkey, 34736
    • Erenkoy Mental Health Hospital
  • Samsun, Turkey, 55020
    • Liv Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: Esketamine; Esketamine will be self-administered as nasal spray.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Intervention-emergent Adverse Events (AEs)	Intervention-emergent AEs are AEs occurring or worsening in severity after the start of study intervention. An AE is any untoward medical occurrence attributed to study drug in a participant who received study drug.	Up to Week 104
Percentage of Participants with Intervention-emergent AEs of special interest (AESI)	Percentage of Participants with Intervention-emergent (AESI) will be summarized separately grouped by category (sedation, dissociation, events suggestive of abuse potential, cystitis, hepatic impairment, and suicidality [including suicidal ideation and behavior] will be reported.	Up to Week 104
Suicidal Ideation and Behavior as Assessed by Columbia-suicide Severity Rating Scale (C-SSRS) Score	Suicidal ideation or behavior will be measured using C-SSRS score. C-SSRS is a clinician rated assessment of suicidal behavior and/ or intent. 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. Worsening of suicidal ideation will be an increase in severity of suicidal ideation from baseline.	Up to Week 104

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with no Relapse Until the end of the Prospective Observation Period at Week 104	Percentage of participants with no relapse until the end of the prospective observation period at Week 104 will be reported. A relapse is defined by any of following: (a) Worsening of depressive symptoms as indicated by montgomery-asberg depression rating scale (MADRS) total score greater than or equal to (>=) 22 confirmed by 1 additional assessment of MADRS total score >=22 within the next 5 to 31 days. The date of the second MADRS assessment will be used for the date of relapse; (b) Any psychiatric hospitalization for: worsening of depression, suicide prevention or due to a suicide attempt for any of these events, the start date of hospitalization will be used for the date of relapse; (c) Suicide attempt, completed suicide, or any other clinically relevant event determined per the investigator's clinical judgment to be indicative of a relapse of depressive illness, but for which the participant was not hospitalized. The onset of the event will be used for the date of relapse.	Week 104
Change from Baseline in Study 54135419TRD3013 with Clinician-rated MADRS Scale Score	The MADRS is a clinician-rated scale designed to measure depression severity and detect changes due to anti-depressants (AD) 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. The MADRS evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, inability to feel (interest level), pessimistic thoughts, and suicidal thoughts.	Baseline, up to Week 104
Change from Baseline in Study 54135419TRD3013 with Clinical Global Impression -severity (CGI-S) Scale Score	The CGI-S measures illness severity and is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (among the most severely ill participants).	Baseline, up to Week 104
Change from Baseline in Study 54135419TRD3013 with Patient Health Questionnaire (PHQ) 9-item Total Score	The PHQ-9 is a validated 9-item, patient-reported outcome (PRO) measure to assess depressive symptoms. The scale scores each of the 9-symptom domains of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition major depressive disorder (DSM-5 MDD) criteria. Each item is rated on a 4 point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms.	Baseline, up to Week 104
Change from Baseline in Study 54135419TRD3013 with European Quality of Life (EuroQol) Group, 5 Dimension, 5-Level (EQ-5D-5L) Questionnaire Score	The EQ-5D-5L is standardized instrument for use as measure of health outcome, primarily designed for self-completion by respondents. It consists of EQ-5D-5L descriptive system and EQ-VAS. EQ-5D-5L descriptive system comprises the following 5 dimensions: Mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of 5 dimensions is divided into 5 levels of perceived problems (1 indicating no problem, 2 indicating slight problems, 3 indicating moderate problems, 4 indicating severe problems, 5 indicating extreme problems). Participant selects an answer for each of 5 dimensions considering the response that best matches his or her health "today". The responses to the 5 dimensions are used to compute a single score ranging from 0 (worst health state) to 100 (better health state) representing the general health status of the individual.	Baseline, up to Week 104

Collaborators and Investigators

• Sponsor: Janssen-Cilag Ltd.
• Investigators: Study Director: Janssen-Cilag Ltd. Clinical Trial, Janssen-Cilag Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2021
• Primary Completion (Estimated): July 19, 2024
• Study Completion (Estimated): July 19, 2024

Study Registration Dates

• First Submitted: April 1, 2021
• First Submitted That Met QC Criteria: April 1, 2021
• First Posted (Actual): April 2, 2021

Study Record Updates

• Last Update Posted (Estimated): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Treatment resistant depression
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Psychotropic Drugs; Antidepressive Agents; Esketamine
• Other Study ID Numbers: CR108992; 2020-004291-18 (EudraCT Number); 54135419TRD4010 (Other Identifier: Janssen-Cilag Ltd.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes