Clinical trial NCT03852160: A Study of Esketamine Nasal Spray Plus a New Standard-of-care Oral Antidepressant or Placebo Nasal Spray Plus a New Standard-of-care Oral Antidepressant in Adult and Elderly Participants With Treatment-resistant Depression
Official title: A Randomized, Double-Blind, Active-Controlled, International, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Flexibly-dosed Esketamine Nasal Spray Plus a New Standard-of-care Oral Antidepressant or Placebo Nasal Spray Plus a New Standard-of-care Oral Antidepressant in Adult and Elderly Participants With Treatment-resistant Depression
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Depressive Disorder, Treatment-Resistant
Lead sponsor: Janssen-Cilag International NV
Sponsor class: INDUSTRY
First posted: 2019-02-25
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy of treating participants with treatment-resistant depression (TRD) who have failed at least 2 (and no more than 6) prior antidepressant (AD) treatments in the current moderate to severe depressive episode with flexibly-dosed esketamine nasal spray plus a newly initiated oral standard-of-care AD compared with placebo nasal spray plus a newly-initiated standard-of-care oral AD, in achieving remission and staying relapse-free after remission.

Detailed description: Depression is a major cause of morbidity and mortality, with global estimates of 300 million treated and untreated individuals worldwide. In its severe forms, depression is the most common diagnosis associated with suicide. Esketamine (S-ketamine) is the S-enantiomer of ketamine. Ketamine profoundly affects fast excitatory glutamate transmission, increases brain-derived neurotrophic factor release, and stimulates synaptogenesis, in contrast to conventional antidepressants (ADs) which are modulatory transmitters. The goal of any new antidepressant (AD) treatment would be the rapid and long-lasting relief of depressive symptoms. The study includes screening phase (2 weeks, with possible extension up to 4 weeks), Induction phase (Week 1 to Week 4), Maintenance once-weekly phase (Week 5 to Week 8), Maintenance flexible-frequency phase (Week 9 to Week 32) and Follow-up phase (2 Weeks Duration). Total duration of study will be approximately up to 36 weeks. The safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* At screening, each participant must meet Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) diagnostic criteria for single episode major depressive disorder (MDD) or recurrent MDD, without psychotic features, based on clinical assessment and confirmed by the Mini International Neuropsychiatric Interview (MINI)
* At baseline, each participant must have an Inventory of Depressive Symptomology Clinician-Rated 30 Items Scale (IDS-C30) total score of greater than or equal to (\>= ) 34
* At screening, participants must have had a documented nonresponse to at least 2 but not more than 6 oral antidepressants (AD) treatments taken at adequate dosage and for adequate duration within the current episode of depression evaluated retrospectively. Nonresponse documentation at screening must include the sequence of retrospectively failed antidepressants and combination and or augmentation for retrospectively failed antidepressants
* Must be medically stable based on physical examination, medical history, vital signs (including blood pressure). If there are any abnormalities that are not specified in the inclusion and exclusion criteria, their clinical significance must be determined by the investigator and recorded in the participant's source documents
* Must be comfortable with self-administration of nasal medication and be able to follow the nasal administration instructions provided
* A woman of childbearing potential must have a negative highly sensitive serum (Beta human chorionic gonadotropin \[Beta hCG\]) at screening and a negative urine pregnancy test prior to the first dose of study intervention on Day 1 of the induction phase prior to randomization

Exclusion Criteria:

* Depressive symptoms that have previously not responded to any of the following:

a Esketamine or ketamine in a major depressive episode per clinical judgment, or b All of the classes of oral ADs in the study or an adequate AD augmentation/combination therapy in the current major depressive episode, or c An adequate course of treatment with electroconvulsive therapy in the current major depressive episode, defined as at least 7 treatments with unilateral/bilateral electroconvulsive therapy

* Received vagal nerve stimulation (VNS) or has received deep brain stimulation (DBS) in the current episode of depression
* Has a current or prior DSM-5 diagnosis of a psychotic disorder or MDD with psychotic features, bipolar or related disorders (confirmed by the MINI), intellectual disability, autism spectrum disorder, borderline personality disorder, antisocial personality disorder
* 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 screening, per the investigator's clinical judgment; or based on the Columbia Suicide Severity Rating Scale (C-SSRS), 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 on the C SSRS, or a history of suicidal behavior within the past year prior to screening. Participants reporting suicidal ideation with intent to act or suicidal behavior prior to the start of the induction phase should also be excluded
* History of moderate or severe substance use disorder or severe alcohol use disorder according to DSM-5 criteria, except nicotine or caffeine, within 6 months before the start of the screening or current clinical signs
* Has other inflammatory diseases that might confound the evaluations of benefit of guselkumab therapy, including but not limited to Rheumatoid arthritis (RA), axial spondyloarthritis (this does not include a primary diagnosis of psoriatic spondylitis \[PsA\] with spondylitis), systemic lupus erythematosus, or Lyme disease

Primary outcomes:
measure: Percentage of Participants with Remission as Assessed by the Montgomery-Asberg Depression Rating Scale (MADRS) (Total Score of less than or Equal to [<=] 10) at the end of Week 8
timeFrame: Week 8
Secondary outcomes:
measure: Percentage of Participants with Remission at Week 8 Without Relapse Until Week 32
timeFrame: Week 32
measure: Change from Baseline in Clinician-reported MADRS Scale Score
timeFrame: Baseline, up to 32 Week
measure: Change in MADRS Total Score from Baseline at Week 4
timeFrame: Baseline, Week 4
measure: Change from Baseline in Patient Health Questionnaire (PHQ) 9-item Total Score
timeFrame: Baseline, up to 32 Weeks
measure: Change from Baseline in Clinical Global Impression - Severity (CGI-S) Scale Score
timeFrame: Baseline, up to 32 Weeks
measure: Clinical Global Impression - Change (CGI-C) Scale Score
timeFrame: Up to 32 Weeks
measure: Change from Baseline in Sheehan Disability Scale (SDS) Total Score
timeFrame: Baseline, up to 32 Weeks
measure: Change from Baseline in Health-Related Quality of life Status as Assessed by 36-item Short-Form Health Survey (SF-36) Domain Scores
timeFrame: Baseline, up to 32 Weeks
measure: Change from Baseline in Quality of Life in Depression Scale (QLDS) Total Score
timeFrame: Baseline, up to 32 Weeks
measure: Change from Baseline in European Quality of Life (EuroQol) Group, 5 Dimension, 5-Level (EQ-5D-5L): EQ-VAS
timeFrame: Baseline, up to 32 weeks
measure: Change from Baseline in European Quality of Life (EuroQol) Group, 5 Dimension, 5-Level (EQ-5D-5L): Health Status Index
timeFrame: Baseline, up to 32 Weeks
measure: Change from Baseline in Work Productivity and Activity Impairment- Specific Health Problem (WPAI-SHP) Questionnaire Scores
timeFrame: Baseline, up to 32 Weeks
measure: Medical Resource Utilization
timeFrame: Up to 32 weeks
measure: Number of Participants with Treatment-Emergent Adverse Events
timeFrame: Up to 32 Weeks
measure: Suicidal ideation and behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: Baseline, up to 32 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Janssen-Cilag International NV
name: Janssen-Cilag International NV Clinical Trial
role: STUDY_DIRECTOR
References: