Clinical trial NCT05550532: A Study of Aticaprant 10 Milligrams (mg) as Adjunctive Therapy in Adult Participants With 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: 2022-09-22
Enrollment: 444
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 MDD with ANH+. The total duration of the study will be up to 87 days. Safety evaluation 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 (that is, an improvement of more than 20 percent \[%\] on their HDRS-17 total score) 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 structural 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
* 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 (at or above the minimum therapeutic dose per Massachusetts General Hospital Antidepressant Treatment Response Questionnaire \[MGH-ATRQ\] 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 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 diagnostic and statistical manual of mental disorders-5th edition (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 (that is, at least 7 treatments), 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 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent), 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 diagnostic and statistical manual of mental disorders-5th edition (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 major depressive disorder (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-Asberg 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 as Assessed by MADRS Total Score
timeFrame: Baseline to Day 43
measure: Percentage of Participants With Remission of Depressive Symptoms at Day 43 as Assessed by MADRS Total Score
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 Over Time in the Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form - Ability to Participate in Social Roles and Activities 8a (PROMIS-APS 8a)
timeFrame: Baseline up to Day 57
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Lafayette
country: United States
facility: Sunwise Clinical Research
state: California
city: Orange
country: United States
facility: Pacific Neuropsychiatric Specialists
state: California
city: Rancho Cucamonga
country: United States
facility: Prospective Research Innovations Inc
state: California
city: San Diego
country: United States
facility: University of California San Diego Medical Center
state: California
city: Santee
country: United States
facility: CMB Clinical Trials
state: California
city: Sherman Oaks
country: United States
facility: California Neuroscience Research
state: California
city: Upland
country: United States
facility: Pacific Clinical Research Medical Group
state: California
city: West Covina
country: United States
facility: Next Level Clinical Trials, LLC
state: California
city: Colorado Springs
country: United States
facility: MCB Clinical Research Centers LLC
state: Colorado
city: Coral Springs
country: United States
facility: CNS Clinical Research Group
state: Florida
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: Hialeah
country: United States
facility: New Life Medical Research Center, Inc.
state: Florida
city: Maitland
country: United States
facility: K2 Medical Research
state: Florida
city: Miami
country: United States
facility: Vital Care Research
state: Florida
city: Miami
country: United States
facility: Global Medical Institutes
state: Florida
city: Miami
country: United States
facility: LCC Medical Research Institute Inc
state: Florida
city: Miami
country: United States
facility: Florida Research Center Inc.
state: Florida
city: Miami
country: United States
facility: Ezy Medical Research
state: Florida
city: Miami
country: United States
facility: Felicidad Medical Research
state: Florida
city: North Bay Village
country: United States
facility: Bravo Health Care Center
state: Florida
city: Orlando
country: United States
facility: APG Research LLC
state: Florida
city: Orlando
country: United States
facility: Combined Research Orlando
state: Florida
city: Pompano Beach
country: United States
facility: Quantum Laboratories
state: Florida
city: Port Saint Lucie
country: United States
facility: CDC Research Institute LLC
state: Florida
city: Skokie
country: United States
facility: Psychiatric Medicine Associates
state: Illinois
city: Marrero
country: United States
facility: Tandem Clinical Research
state: Louisiana
city: Gaithersburg
country: United States
facility: CBH Health
state: Maryland
city: Ann Arbor
country: United States
facility: Michigan Clinical Research Institute
state: Michigan
city: Farmington Hills
country: United States
facility: Revive Research Institute
state: Michigan
city: Saint Charles
country: United States
facility: Midwest Research Group
state: Missouri
city: Lincoln
country: United States
facility: Premier Psychiatric Research Institute, LLC
state: Nebraska
city: Buffalo
country: United States
facility: Erie County Medical Center
state: New York
city: New York
country: United States
facility: Manhattan Behavioral Medicine
state: New York
city: Charlotte
country: United States
facility: New Hope Clinical Research
state: North Carolina
city: Monroe
country: United States
facility: Monroe Biomedical Research
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Wexner Medical Center at the Ohio State University
state: Ohio
city: Edmond
country: United States
facility: Conrad Clinical Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: Sooner Clinical Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: Paradigm Research Professionals, LLC
state: Oklahoma
city: Allentown
country: United States
facility: Lehigh Center for Clinical Research LLC
state: Pennsylvania
city: Moosic
country: United States
facility: Global Medical Institutes
state: Pennsylvania
city: Charleston
country: United States
facility: Clinical Trials of South Carolina
state: South Carolina
city: Austin
country: United States
facility: Donald J Garcia Jr MD PA
state: Texas
city: Dallas
country: United States
facility: Relaro Medical Trials
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Stafford
country: United States
facility: R and H Clinical Research
state: Texas
city: Murray
country: United States
facility: Cedar Psychiatry
state: Utah
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Everett
country: United States
facility: Core Clinical Research
state: Washington
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Fundacion para el Estudio y Tratamiento de las Enfermedades Mentales
city: Cordoba
country: Argentina
facility: CEN Consultorios Especializados en Neurociencias
city: Cordoba
country: Argentina
facility: Instituto Medico DAMIC
city: Cordoba
country: Argentina
facility: Centro Medico Luquez
city: La Plata
country: Argentina
facility: INSA Instituto de Neurociencias San Agustín
city: La Plata
country: Argentina
facility: Clinica Privada de Salud Mental Santa Teresa de Ávila
city: Rosario
country: Argentina
facility: C I A P Centro de investigacion y Asistencia en Psiquiatria
city: San Miguel de Tucuman
country: Argentina
facility: Clinica Mayo de UMCB
city: Santiago del Estero
country: Argentina
facility: Clinica El Jardin
city: Curitiba
country: Brazil
facility: Trial Tech Tecnologia em Pesquisas com Medicamentos
city: Porto Alegre
country: Brazil
facility: Associacao Hospitalar Moinhos de Vento
city: São Bernardo do Campo
country: Brazil
facility: CEMEC - Centro Multidisciplinar de Estudos Clínicos
city: Sofia
country: Bulgaria
facility: MHC - Sofia, EOOD
city: Sofia
country: Bulgaria
facility: DCC 'Sv. Vrach and Sv. Sv. Kuzma and Damyan', OOD
city: Sofia
country: Bulgaria
facility: Medical Center Hera EOOD
city: Sofia
country: Bulgaria
facility: Medical Center Intermedica, OOD
city: Varna
country: Bulgaria
facility: Diagnostic Consulting Center Mladost - M Varna
city: Sherbrooke
country: Canada
facility: DIEX Recherche Sherbrooke Inc
state: Quebec
city: Quebec
country: Canada
facility: Alpha Recherche Clinique
city: Baoding
country: China
facility: Hebei Mental Health Center
city: Beijing
country: China
facility: Beijing Anding Hospital of Capital Medical University
city: Beijing
country: China
facility: Beijing Huilongguan Hospital
city: Beijing
country: China
facility: Peking University Sixth Hospital
city: Changsha
country: China
facility: The second Xiangya Hospital of Central South University
city: Chengdu
country: China
facility: West China Hospital Sichuan University
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
city: Hu Zhou
country: China
facility: Huzhou third people's Hospital
city: Shanghai
country: China
facility: Shanghai Mental Health Center
city: Shanghai
country: China
facility: Tongji Hospital of Tongji University
city: Shijiazhuang
country: China
facility: The First Hospital of Hebei Medical University
city: Suzhou
country: China
facility: Suzhou Guangji Hospital
city: Tianjin
country: China
facility: Tianjin Anding Hospital
city: Wuhan
country: China
facility: Wuhan Mental Health Center
city: Wuhu
country: China
facility: Wuhu Hospital of Beijing Anding hospital
city: XI An
country: China
facility: XiAn Mental Healthcare Center
city: Zheng Zhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
city: Brno
country: Czechia
facility: Psychiatricka ambulance, MUDr. Marta Holanova
city: Kutna Hora
country: Czechia
facility: Neuroterapie KH S R O
city: Praha 6
country: Czechia
facility: Medical Services Prague S R O
city: Praha 8
country: Czechia
facility: Institut Neuropsychiatricke pece
city: Bohars
country: France
facility: CHU de Brest - Hopital de la Cavale Blanche
city: Clermont Ferrand
country: France
facility: CHU Clermont-Ferrand - Hopital Gabriel Montpied
city: Douai
country: France
facility: Cabinet Medical des Drs Prizac-Desbonnet Scottez
city: Nantes
country: France
facility: CHU de Nantes hotel Dieu
city: Paris
country: France
facility: Hopital Sainte Anne
city: Tours cedex 9
country: France
facility: CHRU de Tours Clinique Psychiatrique Universitaire
city: Bucheon-si
country: Korea, Republic of
facility: Bucheon St. Mary's Hospital
city: Busan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Goyang
country: Korea, Republic of
facility: CHA University ilsan Medical Center
city: Gyeonggi-do
country: Korea, Republic of
facility: Korea University Ansan Hospital
city: Seoul
country: Korea, Republic of
facility: KyungHee University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Yeouido St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Bydgoszcz
country: Poland
facility: Clinsante Osrodek Badan Klinicznych
city: Katowice
country: Poland
facility: Centrum Medyczne Care Clinic Katowice
city: Poznan
country: Poland
facility: Filip Rybakowski Specjalistyczna Praktyka Lekarska
city: Suchy Las
country: Poland
facility: Indywidualna Specjalistyczna Praktyka Lekarska Agnieszka Remlinger Molenda
city: Banska Bystrica
country: Slovakia
facility: Psychomed-Svatosavsky, s.r.o.
city: Bojnice
country: Slovakia
facility: Nemocnica s poliklinikou Prievidza so sidlom v Bojniciach
city: Bratislava
country: Slovakia
facility: Psychiatricka Ambulancia Mentum S.R.O.
city: Koshice
country: Slovakia
facility: Epamed sro
city: Kosice
country: Slovakia
facility: Univerzitna nemocnica L. Pasteura Kosice
city: Liptovsky Mikulas
country: Slovakia
facility: Liptovska Nemocnica S Poliklinikou Mudr. Ivana Stodolu
city: Rimavska Sobota
country: Slovakia
facility: Psychiatricka Ambulancia Psycholine S.R.O.
city: Vranov nad Toplou
country: Slovakia
facility: Crystal Comfort s.r.o.
city: Cape Town
country: South Africa
facility: Cape Town Clinical Research Centre
city: Pretoria
country: South Africa
facility: Gert Bosch Pretoria South Africa
city: Strand
country: South Africa
facility: Somerset West Clinical Research Unit
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei City
country: Taiwan
facility: Taipei Medical University
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Cheng Hsin General Hospital
city: Brighton
country: United Kingdom
facility: University of Sussex
city: Edinburgh
country: United Kingdom
facility: Royal Edinburgh Hospital
city: London
country: United Kingdom
facility: Institute of Psychiatry
city: Paisley
country: United Kingdom
facility: Renfrewshire CMHT
city: Southampton
country: United Kingdom
facility: Moorgreen Hospital
city: Wigan And Leigh
country: United Kingdom
facility: Crisis Resolution and Home Treatment Team
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: