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

• Sponsor: Janssen-Cilag Ltd. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04829318
• Collaborator: (none)
• Enrollment: 190
• Locations: 110
• Arm: 1
• Anticipated Duration (Months): 40.1
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Depressive Disorder, Major	Drug: Esketamine; Drug: SSRI/SNRI	Phase 4

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 190 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Apr 26, 2021
• Anticipated Primary Completion Date: Aug 5, 2024
• Anticipated Study Completion Date: Aug 30, 2024

Arms and Interventions

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. Participants will receive esketamine nasal spray until it is commercially available in participant's country.

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.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants with Intervention-emergent Adverse Events (AEs) [Up to Week 104]

   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.

2. Percentage of Participants with Intervention-emergent AEs of special interest (AESI) [Up to Week 104]

   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.

3. Suicidal Ideation and Behavior as Assessed by Columbia-suicide Severity Rating Scale (C-SSRS) Score [Up to Week 104]

   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.

Secondary Outcome Measures

1. Percentage of Participants with no Relapse Until the end of the Prospective Observation Period at Week 104 [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 14 to 28 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.

2. Change from Baseline in Study 54135419TRD3013 with Clinician-rated MADRS Scale Score [Baseline, up to Week 104]

   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.

3. Change from Baseline in Study 54135419TRD3013 with Clinical Global Impression -severity (CGI-S) Scale Score [Baseline, up to Week 104]

   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).

4. Change from Baseline in Study 54135419TRD3013 with Patient Health Questionnaire (PHQ) 9-item Total Score [Baseline, up to Week 104]

   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.

5. Change from Baseline in Study 54135419TRD3013 with European Quality of Life (EuroQol) Group, 5 Dimension, 5-Level (EQ-5D-5L) Questionnaire Score [Baseline, up to Week 104]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 74 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	FunDaMos	Ciudad Autonoma de Buenos Aires		Argentina	C1405BOA
2	CEN-Consultorios Especializados en Neurociencias	Cordoba		Argentina	5000FJF
3	Fundacion Lennox	Cordoba		Argentina	5000
4	Instituto Médico DAMIC	Cordoba		Argentina	X5003DCE
5	Sanatorio Prof. Leon S. Morra S.A	Cordoba		Argentina	X5009BIN
6	Instituto de Neurociencias San Agustín	La Plata		Argentina	1900
7	C.I.A.P. (Centro de investigación y Asistencia en Psiquiatría)	Rosario		Argentina	2000
8	Anima	Alken		Belgium	3570
9	State Psychiatric Hospital Kardzhali	Kardzhali		Bulgaria	6600
10	UMHAT 'Dr. Georgi Stranski', EAD	Pleven		Bulgaria	5800
11	Mental Health Center - Plovdiv	Plovdiv		Bulgaria	4002
12	Mental Health Center - Rousse	Rousse		Bulgaria	7003
13	Multiprofile Hospital for Active Treatment in Neurology and Psychiatry Sveti Naum	Sofia		Bulgaria	1113
14	MHC - Sofia, EOOD	Sofia		Bulgaria	1202
15	Centre for Mental Health Prof.N.Shipkovenski EOOD	Sofia		Bulgaria	1377
16	University Multiprofile Hospital for Active Treatment - UMHAT Alexandrovska EAD	Sofia		Bulgaria	1431
17	Psychiatricka ambulance Saint Anne s.r.o.	Brno		Czechia	60200
18	Psychiatricka ambulance, MUDr. Marta Holanova	Brno		Czechia	61500
19	NeuropsychiatrieHK, s.r.o.	Hradec Kralove-Vekose		Czechia	50341
20	A-Shine s.r.o.	Plzen		Czechia	31200
21	Institut Neuropsychiatricke pece	Prague		Czechia	18600
22	Clintrial s.r.o.	Praha 10		Czechia	10000
23	AD71 s.r.o.	Praha 10		Czechia	109 00
24	Medical Services Prague s.r.o.	Praha 6		Czechia	16000
25	Mederon LTD at ARTES	Helsinki		Finland	00270
26	Psykiatrinen Palvelukeskus Solvum Oy	Helsinki		Finland	120
27	Savon Psykiatripalvelu	Kuopio		Finland	70110
28	Universitaetsklinikum der RWTH Aachen	Aachen		Germany	52074
29	Rheinhessen Fachklinik Alzey	Alzey		Germany	55232
30	Emovis GmbH	Berlin		Germany	10629
31	Charite Campus Benjamin Franklin	Berlin		Germany	12203
32	Medizinisches Versorgungszentrum LiO GmbH	Berlin		Germany	12209
33	Alexander Schulze - Germany	Berlin		Germany	13156
34	Praxis Dr. med. Kirsten Hahn	Berlin		Germany	13187
35	Vivantes Klinikum Spandau	Berlin		Germany	13585
36	Klinikum Dortmund gGmbH	Dortmund		Germany	44287
37	Universitatsklinikum Carl Gustav Carcus Dresden	Dresden		Germany	01307
38	Universitätsklinikum Freiburg - Abteilung für Psychiatrie u. Psychotherapie mit Poliklinik	Freiburg		Germany	79104
39	Klinische Forschung Hamburg	Hamburg		Germany	20253
40	Klinische Forschung Hannover-Mitte GmbH	Hannover		Germany	30159
41	Medizinische Hochschule Hannover	Hannover		Germany	30625
42	Oberhavel Kliniken GmbH	Hennigsdorf		Germany	16761
43	Universitätsklinikum des Saarlandes	Homburg		Germany	66424
44	Universitätsklinikum Jena	Jena		Germany	7743
45	Panakeia - Arzneimittelforschung GmbH	Leipzig		Germany	04275
46	Universitaetsklinikum Magdeburg A.oe.R	Magdeburg		Germany	39120
47	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz		Germany	55131
48	Pharmakologisches Studienzentrum Chemnitz GmbH	Mittweida		Germany	09111
49	Universitätsklinikum Münster	Munster		Germany	48147
50	Praxis Prof. Steinwachs	Nurnberg		Germany	90402
51	Danuvius Klinik Pfaffenhofen Fachklinik für Psychiatrie, Psychotherapie und Psychosomatik	Pfaffenhofen		Germany	85276
52	Somni Bene GmbH	Schwerin		Germany	19053
53	Klinische Forschung Schwerin GmbH	Schwerin		Germany	19055
54	Aiginition Hospital of Athens	Athens		Greece	11528
55	'Dafni' Psychiatric Hospital of Attica	Athens		Greece	124 62
56	Venizeleio General Hospital	Crete		Greece	71409
57	Psychiatric Clinic 'Agios Charalampos'	Heraklion		Greece	71305
58	University General Hospital of Ioannina	Ioannina		Greece	45110
59	University General Hospital of Rio Patras	Patra		Greece	26504
60	424 Military Hospital of Thessaloniki	Thessaloniki		Greece	54636
61	Psychiatric Hospital of Thessaloniki	Thessaloniki		Greece	56430
62	'G. Papanikolaou' Hospital of Thessaloniki	Thessaloniki		Greece	57010
63	Semmelweis Egyetem	Budapest		Hungary	1083
64	Észak-Közép-budai Centrum, Új Szent János Kórház és Szakrendelő Budai Családközpontú	Budapest		Hungary	1125
65	Nyírő Gyula Kórház	Budapest		Hungary	1135
66	Processus Kft.	Budapest		Hungary	1137
67	Debreceni Egyetem, Kenézy Gyula Egyetemi Oktatókórház	Debrecen		Hungary	4031
68	Bugat Pal Korhaz	Gyongyos		Hungary	3200
69	Petz Aladar Megyei Oktato Korhaz	Gyor		Hungary	H-9024
70	Bács-Kiskun Megyei Kórház a Szegedi Tudományegyetem Általános Orvostudományi Kar Oktató Kórháza	Kalocsa		Hungary	6300
71	Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz	Nyiregyhaza		Hungary	4400
72	Pecsi Tudomanyegyetem Klinikai Kozpont	Pecs		Hungary	7623
73	KyungHee University Hospital	Seoul		Korea, Republic of	02447
74	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
75	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
76	Samsung Medical Center	Seoul		Korea, Republic of	06351
77	Hospital Raja Permaisuri Bainun	Ipoh		Malaysia	30990
78	University Malaya Medical Centre	Kuala Lumpur		Malaysia	59100
79	Hospital Pengajar Universiti Putra Malaysia	Serdang		Malaysia	43400
80	Hospital Tuanku Jaafar	Seremban		Malaysia	70300
81	Mlynowamed Specjalistyczny Psychiatryczny Gabinet Lekarski Joanna Lazarczyk	Bialystok		Poland	15-404
82	Osrodek Badan Klinicznych CLINSANTE S.C.	Bydgoszcz		Poland	85-794
83	Uniwersyteckie Centrum Kliniczne	Gdansk		Poland	80-214
84	Centrum Badań Klinicznych PI-House sp. z o.o.	Gdansk		Poland	80-546
85	Centrum Medyczne Care Clinic Katowice	Katowice		Poland	40-568
86	Niepubliczny Zaklad Opieki Psychiatrycznej MENTIS	Leszno		Poland	64-100
87	Specjalistyczny Psychiatryczny Zespol Opieki Zdrowotnej w Lodzi Szpital im. J. Babinskiego	Lodz		Poland	91-229
88	SPZOZ CSK UM w Lodzi Klinika Zaburzen Afektywnych i Psychotycznych	Lodz		Poland	92-216
89	Centrum Medyczne Luxmed Sp z o o	Lublin		Poland	20-109
90	Osrodek Badan Klinicznych CLINSANTE S.C.	Torun		Poland	87-100
91	Cape Town Clinical Research Centre	Cape Town		South Africa	7530
92	Flexivest 14 Research	Cape Town		South Africa	7550
93	Gert Bosch - Pretoria South Africa	Pretoria		South Africa	0 042
94	Changhua Christian Hospital	ChangHua		Taiwan	500
95	Chang Gung Memorial Hospital	Kaohsiung		Taiwan	83342
96	Taipei Medical University	Taipei City		Taiwan	110
97	National Taiwan University Hospital	Taipei		Taiwan	10002
98	Taipei Veterans General Hospital	Taipei		Taiwan	11217
99	Chang Gung Memorial Hospital	Taoyuan		Taiwan	333
100	Hacettepe University Medical Faculty	Ankara		Turkey	6100
101	Ankara Sehir Hastanesi	Ankara		Turkey	6800
102	Uludag University Medical Faculty	Bursa		Turkey	16059
103	Bursa Yuksek Ihtisas Training and Research Hospital	Bursa		Turkey	16285
104	Bakirkoy Mental Health Training and Research Hospital	Istanbul		Turkey	34147
105	Erenkoy Mental Health Hospital	Istanbul		Turkey	34736
106	Uskudar University Neuropsychiatry Hospital	Istanbul		Turkey	34768
107	Ege Universitesi Tip Fakultesi	Izmir		Turkey
108	Selcuk University Medical Faculty	Konya		Turkey	42130
109	Liv Hospital	Samsun		Turkey	55020
110	Namik Kemal University	Tekirdag		Turkey	59030

Sponsors and Collaborators

• Janssen-Cilag Ltd.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen-Cilag Ltd.
• ClinicalTrials.gov Identifier: NCT04829318
• Other Study ID Numbers: CR108992; 2020-004291-18; 54135419TRD4010
• First Posted: Apr 2, 2021
• Last Update Posted: Aug 18, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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
• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Esketamine

Study Results

No Results Posted as of Aug 18, 2022