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

Depressive Disorder, Major Clinical Trial

— ESCAPE-LTE  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04829318
• Other study ID #: CR108992
• Secondary ID: 2020-004291-1854
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: April 26, 2021
• Est. completion date: July 19, 2024

Study information

• Verified date: June 2024
• Source: Janssen-Cilag Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 183
• Est. completion date: July 19, 2024
• Est. primary completion date: July 19, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major

Intervention

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

Locations

Country	Name	City	State
Argentina	FunDaMos	Ciudad Autonoma de Buenos Aires
Argentina	CEN Consultorios Especializados en Neurociencias	Cordoba
Argentina	Fundacion Lennox	Cordoba
Argentina	Instituto Medico DAMIC	Cordoba
Argentina	Sanatorio Prof Leon S Morra S A	Cordoba
Argentina	Instituto de Neurociencias San Agustin	La Plata
Argentina	C I A P Centro de investigacion y Asistencia en Psiquiatria	Rosario
Belgium	Anima	Alken
Bulgaria	Mental Health Center - Rousse	Rousse
Bulgaria	Centre for Mental Health Prof.N.Shipkovenski EOOD	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment in Neurology and Psychiatry Sveti Naum	Sofia
Czechia	Psychiatricka ambulance Saint Anne s.r.o.	Brno
Czechia	Psychiatricka ambulance, MUDr. Marta Holanova	Brno
Czechia	NeuropsychiatrieHK, s.r.o.	Hradec Kralove
Czechia	A-Shine s.r.o.	Plzen
Czechia	Institut Neuropsychiatricke pece	Prague
Czechia	AD71 s.r.o.	Praha 10
Czechia	Medical Services Prague s.r.o.	Praha 6
Finland	Mederon LTD at ARTES	Helsinki
Germany	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
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	Klinische Forschung Schwerin GmbH	Schwerin
Germany	Somni Bene GmbH	Schwerin
Greece	Psychiatric Clinic 'Agios Charalampos'	Heraklion
Greece	University General Hospital of Rio Patras	Patras
Greece	G Papanikolaou Hospital of Thessaloniki	Thessaloniki
Hungary	Processus Kft	Budapest
Hungary	Bugat Pal Korhaz	Gyongyos
Hungary	Petz Aladar Megyei Oktato Korhaz	Gyor
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Malaysia	Hospital Raja Permaisuri Bainun	Ipoh
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Hospital Pengajar Universiti Putra Malaysia	Serdang
Malaysia	Hospital Tuanku Jaafar	Seremban
Poland	Mlynowamed Specjalistyczny Psychiatryczny Gabinet Lekarski Joanna Lazarczyk	Bialystok
Poland	Osrodek Badan Klinicznych CLINSANTE S.C.	Bydgoszcz
Poland	Centrum Badan Klinicznych PI-House sp. z o.o.	Gdansk
Poland	Uniwersyteckie Centrum Kliniczne	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
South Africa	Cape Town Clinical Research Centre	Cape Town
South Africa	Gert Bosch Pretoria South Africa	Pretoria
Taiwan	Changhua Christian Hospital	ChangHua
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital	Taoyuan
Turkey	Hacettepe University Medical Faculty	Ankara
Turkey	Erenkoy Mental Health Hospital	Istanbul
Turkey	Liv Hospital	Samsun

Sponsors (1)

Lead Sponsor	Collaborator
Janssen-Cilag Ltd.

Countries where clinical trial is conducted

Argentina,  Belgium,  Bulgaria,  Czechia,  Finland,  Germany,  Greece,  Hungary,  Korea, Republic of,  Malaysia,  Poland,  South Africa,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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