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

NCT05455684 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: CR10921767953964MDD30012022-000439-22
• Study Type: interventional
• Target: 513
• Locations: 13 countries
• Sites: 120

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).

Conditions

Depressive Disorder, Major; Anhedonia

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Day 43 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score

  The MADRS is a clinician-rated scale designed to measure depression severity and detect changes due to antidepressant treatment. The scale consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score is the sum of scores from individual question items, which ranges from 0 to 60; higher scores represent a more severe condition. Negative change in MADRS total score indicates improvement.

  Baseline (Day 1) to Day 43

Secondary Outcomes (12)

• Change From Baseline to Day 43 in Dimensional Anhedonia Rating Scale (DARS) Total Score

  Baseline (Day 1) to Day 43

• Change From Baseline Over Time in MADRS Total Score

  Baseline (Day 1), Days 15, 29 and 43

• Percentage of Participants Who Achieved Response on Depressive Symptoms Scale Based on MADRS Total Score at Day 43

  At Day 43

• Percentage of Participants With Remission of Depressive Symptoms Based on MADRS Total Score at Day 43

  At Day 43

• Change From Baseline to Day 43 in Patient Health Questionnaire, 9-Item (PHQ-9) Total Score

  Baseline (Day 1) to Day 43

Study Arms (2)

Aticaprant

EXPERIMENTAL

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).

Drug: Aticaprant

Placebo

PLACEBO COMPARATOR

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).

Other: Placebo

Interventions

Aticaprant DRUG

Aticaprant will be administered orally as tablets.

Also known as: JNJ-67953964

Aticaprant

Placebo OTHER

Placebo will be administered orally as tablets.

Placebo

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (120)

SW Biomedical Research LLC

Tucson, Arizona, 85712, United States

Location

University of Arizona

Tucson, Arizona, 85713, United States

Location

Advanced Research Center Inc

Anaheim, California, 92805, United States

Location

Proscience Research Group

Culver City, California, 90230, United States

Location

Behavioral Research Specialists LLC

Glendale, California, 91206, United States

Location

Asclepes Research

Long Beach, California, 90807, United States

Location

Excell Research Inc

Oceanside, California, 92056, United States

Location

Syrentis Clinical Research

Santa Ana, California, 92705, United States

Location

Viking Clinical Research Ltd

Temecula, California, 92591, United States

Location

University of Connecticut Health Center

Farmington, Connecticut, 06030, United States

Location

Innovative Research of West Florida, Incorporated

Clearwater, Florida, 33756, United States

Location

Vertex Research Group, Inc

Clermont, Florida, 34711, United States

Location

Gulfcoast Medical Research Center

Fort Myers, Florida, 33912, United States

Location

New Life Medical Research Center, Inc.

Hialeah, Florida, 33012, United States

Location

Amedica Research Institute Inc

Hialeah, Florida, 33013, United States

Location

Convenient Medical Center

Hialeah, Florida, 33013, United States

Location

Galiz Research

Hialeah, Florida, 33016, United States

Location

Pharmax Research Clinic Inc

Miami, Florida, 33126, United States

Location

A Plus Research

Miami, Florida, 33144, United States

Location

Meridian International Research

Miami Gardens, Florida, 33014, United States

Location

University of Miami

Miami Lakes, Florida, 33016, United States

Location

Medical Research Group of Central Florida

Orange City, Florida, 32763, United States

Location

USF, Department of Psychiatry and Behavioral Neurosciences

Tampa, Florida, 33613, United States

Location

Research Network America

Berwyn, Illinois, 60402, United States

Location

Chicago Research Center

Chicago, Illinois, 60634, United States

Location

University of Kansas Medical Center Research Institute

Kansas City, Kansas, 66160, United States

Location

Clinical Trials of America

Monroe, Louisiana, 71203, United States

Location

ActivMed Practices and Research

Methuen, Massachusetts, 01844, United States

Location

Psychiatric Care and Research Center (PCRC)

O'Fallon, Missouri, 63368, United States

Location

Bioscience Research LLC

Mount Kisco, New York, 10549, United States

Location

Fieve Clinical Research Inc

New York, New York, 10168, United States

Location

Finger Lakes Clinical Research

Rochester, New York, 14618, United States

Location

Montefiore Medical Center PRIME

The Bronx, New York, 10467, United States

Location

Patient Priority Clinical Sites LLC

Cincinnati, Ohio, 45215, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

Midwest Clinical Research Center

Dayton, Ohio, 45417, United States

Location

Charak Center for Health and Wellness

Garfield Heights, Ohio, 44125, United States

Location

Suburban Research Associates

Media, Pennsylvania, 19063, United States

Location

University of Pennsylvania - Perelman School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

West Houston Clinical Research Service

Bellaire, Texas, 77401, United States

Location

North Texas Clinical Trials

Fort Worth, Texas, 76104, United States

Location

Bay Area Clinical Services

Friendswood, Texas, 77546, United States

Location

Clinical Trial Network - Houston

Houston, Texas, 77074, United States

Location

Alpine Research Organization

Clinton, Utah, 84015, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Northwest Clinical Research Center

Bellevue, Washington, 98007, United States

Location

Hospital Italiano

Buenos Aires, 1199, Argentina

Location

STAT Research S A

Buenos Aires, C1013AAB, Argentina

Location

CIPREC

Buenos Aires, C1061AAS, Argentina

Location

CENydET - Centro Neurobiologico y de Stress Traumatico

Ciudad Autonoma Buenos Aires, 1058 AAJ, Argentina

Location

Fundacion Lennox

Córdoba, 5000, Argentina

Location

CENPIA

La Plata, 1902, Argentina

Location

Resolution

Mendoza, M5502AHV, Argentina

Location

Instituto Medico de La Fundacion Estudios Clinicos

Rosario, S2000DEJ, Argentina

Location

Peninsula Therapeutic & Research Group

Frankston, 3199, Australia

Location

Albert Road Clinic

Melbourne, 3004, Australia

Location

The Alfred Hospital

Melbourne, 3004, Australia

Location

Anima

Alken, 3570, Belgium

Location

C.H.U. Brugmann

Brussels, 1020, Belgium

Location

Pz Duffel

Duffel, 2570, Belgium

Location

Vitaz

Sint-Niklaas, 9100, Belgium

Location

Universidade Federal do Ceara Hospital Universitario Walter Cantidio

Fortaleza, 60430-370, Brazil

Location

Instituto Goiano de Neuropsiquiatria

Goiânia, 74093 040, Brazil

Location

NPCRS Nucleo de Pesquisa Clinica do Rio Grande do Sul

Porto Alegre, 90430001, Brazil

Location

Ruschel Medicina e Pesquisa Clínica Ltda

Rio de Janeiro, 22270 060, Brazil

Location

CEMEC - Centro Multidisciplinar de Estudos Clínicos

São Bernardo do Campo, 09715-090, Brazil

Location

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

São José do Rio Preto, 15090-000, Brazil

Location

CPQuali Pesquisa Clinica LTDA ME

São Paulo, 01228-900, Brazil

Location

BR Trials

São Paulo, 05003 020, Brazil

Location

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

Cherven Bryag, 5980, Bulgaria

Location

Ambulatory Group practice for specialized help in psychiary Philipopolis ODD

Plovdiv, 4002, Bulgaria

Location

Medical Center Mentalcare OOD

Plovdiv, 4004, Bulgaria

Location

Mental Health Center - Rousse

Rousse, 7003, Bulgaria

Location

Medical Center St. Naum

Sofia, 1113, Bulgaria

Location

Mental Health Center - Veliko Tarnovo EOOD

Veliko Tarnovo, 5000, Bulgaria

Location

Narodni ustav dusevniho zdravi

Klecany, 25067, Czechia

Location

A Shine S R O

Pilsen, 301 00, Czechia

Location

Clintrial s r o

Prague, 100 00, Czechia

Location

AD71 s.r.o.

Prague, 109 00, Czechia

Location

Praglandia s r o

Prague, 15000, Czechia

Location

NeuropsychiatrieHK, s.r.o.

Prague, 160 00, Czechia

Location

Psychiatricka ordinace

Ústí nad Labem, 400 01, Czechia

Location

Obudai Egeszsegugyi Centrum Kft

Budapest, 1036, Hungary

Location

Semmelweis Egyetem

Budapest, 1083, Hungary

Location

Nyiro Gyula Korhaz

Budapest, 1135, Hungary

Location

Bugat Pal Korhaz

Gyöngyös, 3200, Hungary

Location

Dr Mathe es Tarsa Bt

Kalocsa, 6300, Hungary

Location

PsychoTech Kft

Pécs, 7633, Hungary

Location

Tolna Megyei Balassa Janos Korhaz

Szekszárd, 7100, Hungary

Location

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

Bergamo, 24127, Italy

Location

Azienda Ospedaliero Universitaria Mater Domini

Catanzaro, 88100, Italy

Location

AUSL LE di Lecce

Lecce, 73100, Italy

Location

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

ASST Fatebenefratelli Sacco

Milan, 20157, Italy

Location

Ospedale San Raffaele

Milan, Italy

Location

Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria alle Scotte

Siena, 53100, Italy

Location

Gabinet Lekarski Psychiatryczny Ireneusz Kaczorowski

Bełchatów, 97-400, Poland

Location

Mlynowamed Specjalistyczny Psychiatryczny Gabinet Lekarski Joanna Lazarczyk

Bialystok, 15-404, Poland

Location

Centrum Badan Klinicznych PI House sp z o o

Gdansk, 80 546, Poland

Location

Specjalistyczna Indywidualna Praktyka Lekarska

Lodz, 90-009, Poland

Location

SPZOZ Uniwersytecki Szpi.Klin. nr 4 UM w Lodzi

Lodz, 92-215, Poland

Location

Osrodek Badan Klinicznych CROMED

Poznan, 61-360, Poland

Location

Specjalistyczny Gabinet Psychiatryczny Kowalkowski Gerard

Torun, 87 100, Poland

Location

Hospital de Braga

Braga, 4710-243, Portugal

Location

Hospital CUF Inf. Santo

Lisbon, 1350 179, Portugal

Location

Fund. Champalimaud

Lisbon, 1400 038, Portugal

Location

Institucion Hosp Hestia Palau

Barcelona, 08025, Spain

Location

Hosp Univ Vall D Hebron

Barcelona, 08035, Spain

Location

Hosp Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hosp. Univ. La Paz

Madrid, 28046, Spain

Location

Hosp Regional Univ de Malaga

Málaga, 29011, Spain

Location

Hosp. Univ. Son Espases

Palma de Mallorca, 07120, Spain

Location

Hosp. El Bierzo

Ponferrada, 24404, Spain

Location

Corporacio Sanitari Parc Tauli

Sabadell, 08208, Spain

Location

Hosp. Alvaro Cunqueiro

Vigo, 36312, Spain

Location

Hosp. Psiquiatrico Alava

Vitoria-Gasteiz, 01006, Spain

Location

Sahlgrenska Universitetssjukhuset

Gothenburg, 416 85, Sweden

Location

ProbarE i Lund AB

Lund, 22222, Sweden

Location

ProbarE i Stockholm AB

Stockholm, 113 29, Sweden

Location

Studieenheten Akademiskt Specialistcentrum Stockholm

Stockholm, 113 61, Sweden

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Anhedonia

Interventions

Aticaprant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Executive Medical Director
• Organization: Janssen Research and Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2022
• First Posted: July 13, 2022
• Study Start: June 22, 2022
• Primary Completion: September 18, 2024
• Study Completion: September 18, 2024
• Last Updated: November 6, 2025
• Results First Posted: November 6, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

IT (7); PL (7); BU (6); CZ (7); AU (3); BR (8); AR (8); PT (3); SE (4); BE (4); HU (7); US (46); ES (10)