Clinical trial NCT05455684: A Study of Aticaprant as Adjunctive Therapy in Adult Participants With Major Depressive Disorder (MDD) With Moderate-to-severe Anhedonia and Inadequate Response to Current Antidepressant Therapy
Official title: A Randomized, Double-blind, Multicenter, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Aticaprant 10 mg as Adjunctive Therapy in Adult Participants With Major Depressive Disorder (MDD) With Moderate-to-severe Anhedonia and Inadequate Response to Current Antidepressant Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Depressive Disorder, Major
Anhedonia
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2022-07-13
Enrollment: 513
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 aticaprant compared with placebo as adjunctive therapy to an antidepressant in improving depressive symptoms in adult participants with major depressive disorder (MDD) with moderate-to-severe anhedonia (ANH+) who have had an inadequate response to current antidepressant therapy with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI).

Detailed description: Depression is a common and serious psychiatric disorder which is a leading cause of disability worldwide and is associated with elevated mortality and suicide risk. Aticaprant (JNJ-67953964) is a once daily, highly selective kappa opioid receptor (KOR) antagonist, with demonstrated selectivity over mu opioid receptor (MOR) and delta opioid receptor (DOR) being developed for adjunctive treatment of major depressive disorder (MDD) with moderate-to-severe anhedonia (ANH+). The study consists of a screening phase (up to 30 days prior to randomization), double-blind treatment phase (43 days), and follow-up phase (up to 14 days). The total duration of the study will be up to 87 days. Safety evaluations including adverse events, physical examinations, urine drug test, alcohol breath tests, and clinical laboratory tests will be assessed at specific time points during this study.

Eligibility criteria: Inclusion Criteria:

* Be medically stable on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening and baseline
* Have a Hamilton Depression Rating Scale 17 item (HDRS-17) total score of 20 or higher at the first and second screening interviews and must not demonstrate a clinically significant improvement between the first and the second independent HDRS-17 assessments
* Meet Diagnostic and Statistical Manual of Mental Disorders-5th edition (DSM-5) diagnostic criteria for recurrent or single episode major depressive disorder (MDD), without psychotic features, based upon clinical assessment and confirmed by the structured clinical interview for DSM-5 Axis I disorders-clinical trials version (SCID-CT). Participants 65 years of age or older must have had the first onset of depression prior to 55 years of age
* Have had an inadequate response to at least 1 oral antidepressant treatment, administered at an adequate dose (at or above the minimum therapeutic dose per Massachusetts General Hospital Antidepressant Treatment Response Questionnaire \[MGH ATRQ\]) and duration (at least 6 weeks) in the current episode of depression. An inadequate response is defined as less than(\<) 50% reduction in depressive symptom severity but with some improvement (\>0%) (ie, there may be minimal to moderate symptomatic improvement since the initiation of treatment, but some of the initial symptoms are still present, troubling to the participant and affecting behavior and function), as assessed by the MGH ATRQ
* Is currently receiving and tolerating well any one of the following selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) for depressive symptoms at screening, in any approved formulation and available in the participating country/territory: citalopram, duloxetine, escitalopram, fluvoxamine, fluoxetine, milnacipran, levomilnacipran, paroxetine, sertraline, venlafaxine, desvenlafaxine at a stable dose for at least 6 weeks. The current antidepressant cannot be the first antidepressant treatment for the first lifetime episode of depression
* Participant's current major depressive episode, and antidepressant treatment response in the current depressive episode, must all be confirmed by the site independent qualification assessment

Exclusion Criteria:

* Have had in the current depressive episode, no response (treatment failure) to 5 or more antidepressant treatments including the current SSRI/SNRI (that is, the one presumed to be continued in the treatment phase) assessed using the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH ATRQ)
* Has a history or evidence of clinically meaningful noncompliance with current antidepressant therapy
* Has a history of moderate-to-severe substance use disorder including alcohol use disorder according to DSM-5 criteria within 6 months before screening
* Has had in the current episode an inadequate response to adequate course of intravenous or intranasal ketamine or esketamine, electroconvulsive therapy, vagal nerve stimulation, or deep brain stimulation device
* Has current, or a history (past 6 months), of seizures
* Has a current homicidal ideation/intent, per the investigator's clinical judgment, or has suicidal ideation with some intent to act within 3 months prior to the start of the Screening Phase, 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 or Item 5, or a history of suicidal behavior within the past 6 months prior to the start of the Screening Phase. Participants reporting suicidal ideation with intent to act or suicidal behavior at baseline should be excluded
* Has one or more of the following diagnoses: a) A DSM-5 diagnosis (which has been the primary focus of psychiatric treatment within the past 2 years) of any of the following: panic disorder, generalized anxiety disorder, social anxiety disorder, specific phobia; b) A current (in the past year) DSM-5 diagnosis of: obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), anorexia nervosa, bulimia nervosa; c) A current or prior (lifetime) DSM-5 diagnosis of: a psychotic disorder or MDD with psychotic features, bipolar or related disorders, intellectual disability, autism spectrum disorder, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, narcissistic personality disorders, somatoform disorders

Primary outcomes:
measure: Change from Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score to Day 43
timeFrame: Baseline to Day 43
Secondary outcomes:
measure: Change from Baseline in Dimensional Anhedonia Rating Scale (DARS) Total Score to Day 43
timeFrame: Baseline to Day 43
measure: Change from Baseline in MADRS Total Score over Time
timeFrame: Baseline up to Day 57
measure: Percentage of Responders on Depressive Symptoms Scale from Baseline to Day 43
timeFrame: Baseline to Day 43
measure: Percentage of Participants with Remission of Depressive Symptoms Defined as a MADRS Total Score <=10 at Day 43
timeFrame: Day 43
measure: Change from Baseline in Patient Health Questionnaire, 9-Item (PHQ-9) Total Score to Day 43
timeFrame: Baseline to Day 43
measure: Change from Baseline in DARS Total Score Over Time
timeFrame: Baseline up to Day 57
measure: Change from Baseline in the PHQ-9 Anhedonia-specific Item (PHQ-9, item 1) Over Time
timeFrame: Baseline up to Day 57
measure: Percentage of Participants with a Score Less than (<) 2 in the PHQ-9 Anhedonia-specific Item (PHQ-9, Item 1) at Day 43
timeFrame: Day 43
measure: Change from Baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) Short Form-Ability to Participate in Social Roles and Activities - 8a (PROMIS-APS 8a) Over Time
timeFrame: Baseline up to Day 57
measure: Change from Baseline over Time in the Work Productivity and Activity Impairment (WPAI:D)
timeFrame: Baseline up to Day 43
Other outcomes:
Locations:
city: Tucson
country: United States
facility: SW Biomedical Research LLC
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Anaheim
country: United States
facility: Advanced Research Center Inc
state: California
city: Culver City
country: United States
facility: Proscience Research Group
state: California
city: Glendale
country: United States
facility: Behavioral Research Specialists LLC
state: California
city: Long Beach
country: United States
facility: Asclepes Research
state: California
city: Oceanside
country: United States
facility: Excell Research Inc
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research
state: California
city: Temecula
country: United States
facility: Viking Clinical Research Ltd
state: California
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: Clearwater
country: United States
facility: Innovative Research of West Florida, Incorporated
state: Florida
city: Clermont
country: United States
facility: Vertex Research Group, Inc
state: Florida
city: Fort Myers
country: United States
facility: Gulfcoast Medical Research Center
state: Florida
city: Hialeah
country: United States
facility: New Life Medical Research Center, Inc.
state: Florida
city: Hialeah
country: United States
facility: Amedica Research Institute Inc
state: Florida
city: Hialeah
country: United States
facility: Convenient Medical Center
state: Florida
city: Hialeah
country: United States
facility: Galiz Research
state: Florida
city: Miami Gardens
country: United States
facility: Meridian International Research
state: Florida
city: Miami Lakes
country: United States
facility: University of Miami
state: Florida
city: Miami
country: United States
facility: Pharmax Research Clinic Inc
state: Florida
city: Miami
country: United States
facility: A Plus Research
state: Florida
city: Orange City
country: United States
facility: Medical Research Group of Central Florida
state: Florida
city: Tampa
country: United States
facility: USF, Department of Psychiatry and Behavioral Neurosciences
state: Florida
city: Berwyn
country: United States
facility: Research Network America
state: Illinois
city: Chicago
country: United States
facility: Chicago Research Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Institute
state: Kansas
city: Monroe
country: United States
facility: Clinical Trials of America
state: Louisiana
city: Methuen
country: United States
facility: ActivMed Practices and Research
state: Massachusetts
city: O'Fallon
country: United States
facility: Psychiatric Care and Research Center (PCRC)
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center PRIME
state: New York
city: Mount Kisco
country: United States
facility: Bioscience Research LLC
state: New York
city: New York
country: United States
facility: Fieve Clinical Research Inc
state: New York
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Cincinnati
country: United States
facility: Patient Priority Clinical Sites LLC
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Dayton
country: United States
facility: Midwest Clinical Research Center
state: Ohio
city: Garfield Heights
country: United States
facility: Charak Center for Health and Wellness
state: Ohio
city: Media
country: United States
facility: Suburban Research Associates
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania - Perelman School of Medicine
state: Pennsylvania
city: Bellaire
country: United States
facility: West Houston Clinical Research Service
state: Texas
city: Fort Worth
country: United States
facility: North Texas Clinical Trials
state: Texas
city: Friendswood
country: United States
facility: Bay Area Clinical Services
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network - Houston
state: Texas
city: Clinton
country: United States
facility: Alpine Research Organization
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: CENydET - Centro Neurobiologico y de Stress Traumatico
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Hospital Italiano
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: STAT Research S A
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: CIPREC
city: Ciudad de Mendoza
country: Argentina
facility: Resolution
city: Cordoba
country: Argentina
facility: Fundacion Lennox
city: La Plata
country: Argentina
facility: CENPIA
city: Rosario
country: Argentina
facility: Instituto Medico de La Fundacion Estudios Clinicos
city: Frankston
country: Australia
facility: Peninsula Therapeutic & Research Group
city: Melbourne
country: Australia
facility: Albert Road Clinic
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Alken
country: Belgium
facility: Anima
city: Bruxelles
country: Belgium
facility: C.H.U. Brugmann
city: Duffel
country: Belgium
facility: Pz Duffel
city: Sint Niklaas
country: Belgium
facility: Vitaz
city: Fortaleza
country: Brazil
facility: Universidade Federal do Ceara Hospital Universitario Walter Cantidio
city: Goiania
country: Brazil
facility: Instituto Goiano de Neuropsiquiatria
city: Porto Alegre
country: Brazil
facility: NPCRS Nucleo de Pesquisa Clinica do Rio Grande do Sul
city: Rio de Janeiro
country: Brazil
facility: Ruschel Medicina e Pesquisa Clínica Ltda
city: Sao Jose do Rio Preto
country: Brazil
facility: Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto Hospital de Base
city: Sao Paulo
country: Brazil
facility: BR Trials
city: São Bernardo do Campo
country: Brazil
facility: CEMEC - Centro Multidisciplinar de Estudos Clínicos
city: São Paulo
country: Brazil
facility: CPQuali Pesquisa Clinica LTDA ME
city: Cherven Bryag
country: Bulgaria
facility: Ambulatory for Individual Practice for Specialized Medical Care in Psychiatry Dr. Ivo Natsov ET
city: Plovdiv
country: Bulgaria
facility: Ambulatory Group practice for specialized help in psychiary Philipopolis ODD
city: Plovdiv
country: Bulgaria
facility: Medical Center Mentalcare OOD
city: Ruse
country: Bulgaria
facility: Mental Health Center - Rousse
city: Sofia
country: Bulgaria
facility: Medical Center St. Naum
city: Veliko Tarnovo
country: Bulgaria
facility: Mental Health Center - Veliko Tarnovo EOOD
city: Klecany
country: Czechia
facility: Narodni ustav dusevniho zdravi
city: Plzen
country: Czechia
facility: A Shine S R O
city: Prague 5
country: Czechia
facility: Praglandia s r o
city: Praha 10
country: Czechia
facility: Clintrial s r o
city: Praha 10
country: Czechia
facility: AD71 s.r.o.
city: Praha 6
country: Czechia
facility: NeuropsychiatrieHK, s.r.o.
city: Usti nad Labem
country: Czechia
facility: Psychiatricka ordinace
city: Budapest
country: Hungary
facility: Obudai Egeszsegugyi Centrum Kft
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Nyiro Gyula Korhaz
city: Gyongyos
country: Hungary
facility: Bugat Pal Korhaz
city: Kalocsa
country: Hungary
facility: Dr Mathe es Tarsa Bt
city: Pecs
country: Hungary
facility: PsychoTech Kft
city: Szekszárd
country: Hungary
facility: Tolna Megyei Balassa Janos Korhaz
city: Bergamo
country: Italy
facility: Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)
city: Catanzaro
country: Italy
facility: Azienda Ospedaliero Universitaria Mater Domini
city: Lecce
country: Italy
facility: AUSL LE di Lecce
city: Milano
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: ASST Fatebenefratelli Sacco
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria alle Scotte
city: Belchatow
country: Poland
facility: Gabinet Lekarski Psychiatryczny Ireneusz Kaczorowski
city: Bialystok
country: Poland
facility: Mlynowamed Specjalistyczny Psychiatryczny Gabinet Lekarski Joanna Lazarczyk
city: Gdansk
country: Poland
facility: Centrum Badan Klinicznych PI House sp z o o
city: Lodz
country: Poland
facility: Specjalistyczna Indywidualna Praktyka Lekarska
city: Lodz
country: Poland
facility: SPZOZ Uniwersytecki Szpi.Klin. nr 4 UM w Lodzi
city: Poznan
country: Poland
facility: Osrodek Badan Klinicznych CROMED
city: Torun
country: Poland
facility: Specjalistyczny Gabinet Psychiatryczny Kowalkowski Gerard
city: Braga
country: Portugal
facility: Hospital de Braga
city: Lisboa
country: Portugal
facility: Hospital CUF Inf. Santo
city: Lisboa
country: Portugal
facility: Fund. Champalimaud
city: Barcelona
country: Spain
facility: Institucion Hosp Hestia Palau
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Madrid
country: Spain
facility: Hosp. Univ. La Paz
city: Malaga
country: Spain
facility: Hosp Regional Univ de Malaga
city: Palma de Mallorca
country: Spain
facility: Hosp. Univ. Son Espases
city: Ponferrada
country: Spain
facility: Hosp. El Bierzo
city: Sabadell
country: Spain
facility: Corporacio Sanitari Parc Tauli
city: Vigo
country: Spain
facility: Hosp. Alvaro Cunqueiro
city: Vitoria
country: Spain
facility: Hosp. Psiquiatrico Alava
city: Goteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
city: Lund
country: Sweden
facility: ProbarE i Lund AB
city: Stockholm
country: Sweden
facility: ProbarE i Stockholm AB
city: Stockholm
country: Sweden
facility: Studieenheten Akademiskt Specialistcentrum Stockholm
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: