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

NCT ID: NCT05455684

Last Updated: 2025-11-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 513 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-22
• Study Completion Date: 2024-09-18

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.

Conditions

Depressive Disorder, Major; Anhedonia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Aticaprant

Participants will receive aticaprant tablets orally once daily for 42 days during double-blind treatment phase in addition to the current antidepressant selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) therapy. Participants who will complete the double-blind treatment phase (Day 43) may be eligible to participate in a separate 52-week open-label long-term safety study (67953964MDD3003).

Group Type: EXPERIMENTAL

Aticaprant

Intervention Type: DRUG

Aticaprant will be administered orally as tablets.

Placebo

Participants will receive matching placebo orally once daily for 42 days during double-blind treatment phase in addition to their current antidepressant (SSRI/SNRI) therapy. Participants who will complete the double-blind treatment phase (Day 43) may be eligible to participate in a separate 52-week open-label long-term safety study (67953964MDD3003).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo will be administered orally as tablets.

Interventions

Aticaprant

Aticaprant will be administered orally as tablets.

Intervention Type: DRUG

Placebo

Placebo will be administered orally as tablets.

Intervention Type: OTHER

Other Intervention Names

JNJ-67953964

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

SW Biomedical Research LLC

Tucson, Arizona, United States

University of Arizona

Tucson, Arizona, United States

Advanced Research Center Inc

Anaheim, California, United States

Proscience Research Group

Culver City, California, United States

Behavioral Research Specialists LLC

Glendale, California, United States

Asclepes Research

Long Beach, California, United States

Excell Research Inc

Oceanside, California, United States

Syrentis Clinical Research

Santa Ana, California, United States

Viking Clinical Research Ltd

Temecula, California, United States

University of Connecticut Health Center

Farmington, Connecticut, United States

Innovative Research of West Florida, Incorporated

Clearwater, Florida, United States

Vertex Research Group, Inc

Clermont, Florida, United States

Gulfcoast Medical Research Center

Fort Myers, Florida, United States

New Life Medical Research Center, Inc.

Hialeah, Florida, United States

Amedica Research Institute Inc

Hialeah, Florida, United States

Convenient Medical Center

Hialeah, Florida, United States

Galiz Research

Hialeah, Florida, United States

Pharmax Research Clinic Inc

Miami, Florida, United States

A Plus Research

Miami, Florida, United States

Meridian International Research

Miami Gardens, Florida, United States

University of Miami

Miami Lakes, Florida, United States

Medical Research Group of Central Florida

Orange City, Florida, United States

USF, Department of Psychiatry and Behavioral Neurosciences

Tampa, Florida, United States

Research Network America

Berwyn, Illinois, United States

Chicago Research Center

Chicago, Illinois, United States

University of Kansas Medical Center Research Institute

Kansas City, Kansas, United States

Clinical Trials of America

Monroe, Louisiana, United States

ActivMed Practices and Research

Methuen, Massachusetts, United States

Psychiatric Care and Research Center (PCRC)

O'Fallon, Missouri, United States

Bioscience Research LLC

Mount Kisco, New York, United States

Fieve Clinical Research Inc

New York, New York, United States

Finger Lakes Clinical Research

Rochester, New York, United States

Montefiore Medical Center PRIME

The Bronx, New York, United States

Patient Priority Clinical Sites LLC

Cincinnati, Ohio, United States

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Midwest Clinical Research Center

Dayton, Ohio, United States

Charak Center for Health and Wellness

Garfield Heights, Ohio, United States

Suburban Research Associates

Media, Pennsylvania, United States

University of Pennsylvania - Perelman School of Medicine

Philadelphia, Pennsylvania, United States

West Houston Clinical Research Service

Bellaire, Texas, United States

North Texas Clinical Trials

Fort Worth, Texas, United States

Bay Area Clinical Services

Friendswood, Texas, United States

Clinical Trial Network - Houston

Houston, Texas, United States

Alpine Research Organization

Clinton, Utah, United States

University of Virginia

Charlottesville, Virginia, United States

Northwest Clinical Research Center

Bellevue, Washington, United States

Hospital Italiano

Buenos Aires, , Argentina

STAT Research S A

Buenos Aires, , Argentina

CIPREC

Buenos Aires, , Argentina

CENydET - Centro Neurobiologico y de Stress Traumatico

Ciudad Autonoma Buenos Aires, , Argentina

Fundacion Lennox

Córdoba, , Argentina

CENPIA

La Plata, , Argentina

Resolution

Mendoza, , Argentina

Instituto Medico de La Fundacion Estudios Clinicos

Rosario, , Argentina

Peninsula Therapeutic & Research Group

Frankston, , Australia

Albert Road Clinic

Melbourne, , Australia

The Alfred Hospital

Melbourne, , Australia

Anima

Alken, , Belgium

C.H.U. Brugmann

Brussels, , Belgium

Pz Duffel

Duffel, , Belgium

Vitaz

Sint-Niklaas, , Belgium

Universidade Federal do Ceara Hospital Universitario Walter Cantidio

Fortaleza, , Brazil

Instituto Goiano de Neuropsiquiatria

Goiânia, , Brazil

NPCRS Nucleo de Pesquisa Clinica do Rio Grande do Sul

Porto Alegre, , Brazil

Ruschel Medicina e Pesquisa Clínica Ltda

Rio de Janeiro, , Brazil

CEMEC - Centro Multidisciplinar de Estudos Clínicos

São Bernardo do Campo, , Brazil

Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto Hospital de Base

São José do Rio Preto, , Brazil

CPQuali Pesquisa Clinica LTDA ME

São Paulo, , Brazil

BR Trials

São Paulo, , Brazil

Ambulatory for Individual Practice for Specialized Medical Care in Psychiatry Dr. Ivo Natsov ET

Cherven Bryag, , Bulgaria

Ambulatory Group practice for specialized help in psychiary Philipopolis ODD

Plovdiv, , Bulgaria

Medical Center Mentalcare OOD

Plovdiv, , Bulgaria

Mental Health Center - Rousse

Rousse, , Bulgaria

Medical Center St. Naum

Sofia, , Bulgaria

Mental Health Center - Veliko Tarnovo EOOD

Veliko Tarnovo, , Bulgaria

Narodni ustav dusevniho zdravi

Klecany, , Czechia

A Shine S R O

Pilsen, , Czechia

Clintrial s r o

Prague, , Czechia

AD71 s.r.o.

Prague, , Czechia

Praglandia s r o

Prague, , Czechia

NeuropsychiatrieHK, s.r.o.

Prague, , Czechia

Psychiatricka ordinace

Ústí nad Labem, , Czechia

Obudai Egeszsegugyi Centrum Kft

Budapest, , Hungary

Semmelweis Egyetem

Budapest, , Hungary

Nyiro Gyula Korhaz

Budapest, , Hungary

Bugat Pal Korhaz

Gyöngyös, , Hungary

Dr Mathe es Tarsa Bt

Kalocsa, , Hungary

PsychoTech Kft

Pécs, , Hungary

Tolna Megyei Balassa Janos Korhaz

Szekszárd, , Hungary

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)

Bergamo, , Italy

Azienda Ospedaliero Universitaria Mater Domini

Catanzaro, , Italy

AUSL LE di Lecce

Lecce, , Italy

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, , Italy

ASST Fatebenefratelli Sacco

Milan, , Italy

Ospedale San Raffaele

Milan, , Italy

Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria alle Scotte

Siena, , Italy

Gabinet Lekarski Psychiatryczny Ireneusz Kaczorowski

Bełchatów, , Poland

Mlynowamed Specjalistyczny Psychiatryczny Gabinet Lekarski Joanna Lazarczyk

Bialystok, , Poland

Centrum Badan Klinicznych PI House sp z o o

Gdansk, , Poland

Specjalistyczna Indywidualna Praktyka Lekarska

Lodz, , Poland

SPZOZ Uniwersytecki Szpi.Klin. nr 4 UM w Lodzi

Lodz, , Poland

Osrodek Badan Klinicznych CROMED

Poznan, , Poland

Specjalistyczny Gabinet Psychiatryczny Kowalkowski Gerard

Torun, , Poland

Hospital de Braga

Braga, , Portugal

Hospital CUF Inf. Santo

Lisbon, , Portugal

Fund. Champalimaud

Lisbon, , Portugal

Institucion Hosp Hestia Palau

Barcelona, , Spain

Hosp Univ Vall D Hebron

Barcelona, , Spain

Hosp Clinic de Barcelona

Barcelona, , Spain

Hosp. Univ. La Paz

Madrid, , Spain

Hosp Regional Univ de Malaga

Málaga, , Spain

Hosp. Univ. Son Espases

Palma de Mallorca, , Spain

Hosp. El Bierzo

Ponferrada, , Spain

Corporacio Sanitari Parc Tauli

Sabadell, , Spain

Hosp. Alvaro Cunqueiro

Vigo, , Spain

Hosp. Psiquiatrico Alava

Vitoria-Gasteiz, , Spain

Sahlgrenska Universitetssjukhuset

Gothenburg, , Sweden

ProbarE i Lund AB

Lund, , Sweden

ProbarE i Stockholm AB

Stockholm, , Sweden

Studieenheten Akademiskt Specialistcentrum Stockholm

Stockholm, , Sweden

Countries

South Korea; United States; Argentina; Australia; Belgium; Brazil; Bulgaria; Czechia; Hungary; Italy; Poland; Portugal; Spain; Sweden

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

67953964MDD3001

Identifier Type: OTHER

Identifier Source: secondary_id

2022-000439-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR109217

Identifier Type: -

Identifier Source: org_study_id