A Study of Aticaprant Plus an Antidepressant to Prevent Return of Depression Symptoms in Participants With Major Depressive Disorder Who Experience a Loss of Interest and Pleasure (VENTURA-5)

A Randomized, Double-blind, Multicenter, Placebo-controlled Study of Adjunctive Aticaprant Plus an Antidepressant for Relapse Prevention in Major Depressive Disorder (MDD) With Moderate-to-severe Anhedonia

The purpose of this study is to assess how well aticaprant works compared to placebo when given in addition to antidepressant therapy (selective serotonin reuptake inhibitor [SSRI] or serotonin-norepinephrine reuptake inhibitor [SNRI]) in preventing return of depression symptoms in participants with major depressive disorder who experience a loss of interest and pleasure and who achieve a stable response after treatment with adjunctive aticaprant.

Study Overview

• Status: Terminated
• Conditions: Anhedonia; Depressive Disorder, Major
• Intervention / Treatment: Other: Placebo; Drug: Aticaprant

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1199ABB
    • Hospital Italiano de Buenos Aires
  • Córdoba, Argentina, X5004FJF
    • Centro Medico Instituto Modelo de Neurologia y Neurorehabilitacion
• Belgium
  • Alken, Belgium, 3570
    • Anima
  • Assebroek, Belgium, 8310
    • AZ Sint-Lucas
  • Brussels, Belgium, 1090
    • UZ Brussel
  • Oudenaarde, Belgium, 9700
    • AZ Oudenaarde
  • Sint-Niklaas, Belgium, 9100
    • Vitaz
• Brazil
  • Campinas, Brazil, 13087 567
    • CAEP Centro Avancado De Estudos E Pesquisas
  • São Bernardo do Campo, Brazil, 09726 150
    • Centro Integrado Facili
• Bulgaria
  • Rousse, Bulgaria, 7003
    • Mental Health Center - Rousse
  • Sofia, Bulgaria, 1408
    • DCC 'Sv. Vrach and Sv. Sv. Kuzma and Damyan', OOD
  • Sofia, Bulgaria, 1000
    • Medical Centre Akademika EOOD
  • Varna, Bulgaria, 9020
    • Diagnostic Consulting Center Mladost - M Varna
  • Vratsa, Bulgaria, 3000
    • Mental Health Center - Vratsa EOOD
• France
  • Besançon, France, 25000
    • CHRU Besancon Hopital Jean Minjoz
  • Montpellier, France, 34090
    • Hôpital La Colombière
  • Nantes, France, 44093
    • CHU de Nantes hotel Dieu
  • Sotteville-lès-Rouen, France, 76300
    • CHS du Rouvray
  • Toulon, France, 83200
    • Hôpital Sainte Musse
• Germany
  • Berlin, Germany, 10117
    • Klinische Forschung Berlin-Mitte GmbH
  • Berlin, Germany, 13187
    • Praxis Dr. med. Kirsten Hahn
  • Chemnitz, Germany, 09111
    • Pharmakologisches Studienzentrum Chemnitz GmbH
  • Frankfurt am Main, Germany, 60528
    • Universitätsklinikum Frankfurt
  • Hamburg, Germany, 20253
    • Klinische Forschung Hamburg
  • Hennigsdorf, Germany, 16761
    • Oberhavel Kliniken GmbH
  • Münster, Germany, 48149
    • Universitaetsklinikum Muenster
  • Rosenheim, Germany, 83022
    • Boehm Peters Praxis fur Psychiatrie Psychotherapie Neurologie PartGmbB
  • Schwerin, Germany, 19055
    • Klinische Forschung Schwerin GmbH
• Greece
  • Athens, Greece, 115 28
    • Eginitio Hospital
  • Athens, Greece, 124 62
    • Attikon University General Hospital of Attica
  • Heraklion, Greece, 715 00
    • University Hospital of Heraklion
  • Ioannina, Greece, 45110
    • University General Hospital of Ioannina
  • Thessaloniki, Greece, 570 10
    • G Papanikolaou Hospital of Thessaloniki
• Mexico
  • León, Mexico, 37000
    • Hospital Aranda de la Parra S A de C V
  • Mexico City, Mexico, 04100
    • Ketamine Mexico S de RL de C V
  • Monterrey, Mexico, 64610
    • cit NEUROPSIQUE
  • México, Mexico, 14050
    • Human Science Research Trials S de RL de CV
• Poland
  • Bydgoszcz, Poland, 85 794
    • Osrodek Badan Klinicznych CLINSANTE S C Ewa Galczak Nowak Malgorzata Trzaska
  • Grudziądz, Poland, 86 300
    • NZOZ Euromedica Grudziadz
  • Leszno, Poland, 64-100
    • Niepubliczny Zaklad Opieki Psychiatrycznej MENTIS
  • Lublin, Poland, 20 109
    • Centrum Medyczne Luxmed Sp z o o
  • Poznan, Poland, 60 192
    • Praktyka Lekarska dr n med Malgorzata Wojtanowska Bogacka
  • Suchy Las, Poland, 62-002
    • Indywidualna Specjalistyczna Praktyka Lekarska Agnieszka Remlinger Molenda
  • Warsaw, Poland, 02-172
    • MTZ Clinical Research Powered by Pratia
  • Warsaw, Poland, 00 719
    • Care Access Warszawa
  • Warsaw, Poland, 00-774
    • Szpital Nowowiejski Osrodek Badan Klinicznych
  • Wroclaw, Poland, 50 302
    • Centrum Zdrowia Mosty
• Romania
  • Bucharest, Romania, 041914
    • Spitalul Clinic de Psihiatrie Prof Dr Alexandru Obregia
  • Bucharest, Romania, 60222
    • Centrul de Evaluarea si Tratament al Toxicodependentelor pentru Tineri Sf. Stelian
  • Craiova, Romania, 200157
    • Centrul Medical Melchisedec
  • Craiova, Romania, 200473
    • Spitalul Clinic de Neuropsihiatrie
  • Focşani, Romania, 620117
    • CMI Dr. Sarpe Marcel-Claudiu
  • Galați, Romania, 800179
    • Spitalul De Psihiatrie Elisabeta Doamna Galaţi
  • Sibiu, Romania, 550082
    • Spitalul Clinic De Psihiatrie Doctor Gheorghe Preda
• Spain
  • Bilbao, Spain, 48013
    • Hosp. Univ. de Basurto
  • Córdoba, Spain, 14004
    • Hosp Reina Sofia
  • Granada, Spain, 18014
    • Hosp. Univ. Virgen de Las Nieves
  • Madrid, Spain, 28046
    • Hosp. Univ. La Paz
  • Málaga, Spain, 29010
    • Hosp Virgen de La Victoria
  • Palma, Spain, 07120
    • Hosp. Univ. Son Espases
  • Pamplona, Spain, 31008
    • Clinica Univ. de Navarra
  • Ponferrada, Spain, 24404
    • Hosp. El Bierzo
  • Zaragoza, Spain, 50015
    • Hosp. Royo Villanova
• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye), 34736
    • Erenkoy Mental Health Hospital
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Preferred Research Partners
  • California
    • Encino, California, United States, 91316
      • Wake Research PRI Encino
    • Newport Beach, California, United States, 92660
      • Wr Pri Llc
    • Orange, California, United States, 92866
      • ATP Clinical Research
    • Redlands, California, United States, 92373
      • Myndful Research
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
  • Florida
    • Doral, Florida, United States, 33178
      • UHC Research
    • Miami, Florida, United States, 33183
      • International Research Associates, LLC
    • Miami, Florida, United States, 33126
      • Pharmax Research Clinic Inc
    • Miami, Florida, United States, 33173
      • GTL Medical and Research Group
    • North Miami Beach, Florida, United States, 33162
      • Harmony Clinical Research Inc
    • Orlando, Florida, United States, 32803
      • APG Research LLC
    • Tampa, Florida, United States, 33629
      • Interventional Psychiatry of Tampa Bay
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Synexus Clinical Research US Inc
  • Illinois
    • Chicago, Illinois, United States, 60634
      • Chicago Research Center
    • Skokie, Illinois, United States, 60076
      • Psychiatric Medicine Associates LLC
  • Maryland
    • Towson, Maryland, United States, 21204
      • Continental Clinical Solutions
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri Health Care
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • IMA Clinical Research PC
  • New York
    • Brooklyn, New York, United States, 11229
      • Integrative Clinical Trials LLC
    • Mount Kisco, New York, United States, 10549
      • Bioscience Research LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45215
      • Patient Priority Clinical Sites LLC
    • Independence, Ohio, United States, 44131
      • Insight Clinical Trials
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Laureate Institute for Brain Research
  • Pennsylvania
    • Plymouth Meeting, Pennsylvania, United States, 19462
      • Keystone Clinical Studies LLC
  • South Carolina
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center
  • Texas
    • DeSoto, Texas, United States, 75115
      • InSite Clinical Research LLC
    • Friendswood, Texas, United States, 77546
      • Earle Research
  • Utah
    • Clinton, Utah, United States, 84015
      • Alpine Research Organization
    • St. George, Utah, United States, 84770
      • Elligo Integrated Research Sites Integrated Clinical Research LLC Integrated Psych

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Be medically stable based on physical examination (including a brief neurologic examination), medical history, vital signs (including blood pressure), and 12-lead electrocardiogram (ECG) performed at screening and OL baseline
• Be medically stable based on clinical laboratory tests performed at screening
• Meet DSM-5 diagnostic criteria for recurrent or single episode MDD, without psychotic features upon clinical assessment and confirmed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-5) Axis I Disorders-Clinical Trials version (SCID-CT)
• Have symptoms of anhedonia based on clinical assessment and confirmed by presence of anhedonia (positive response to major depressive episode (MDE) module symptom Item 2) on the SCID-CT at screening

Exclusion Criteria:

• Has had no response to 2 or more consecutive antidepressant treatments administered at adequate dose and duration in the current episode of depression including the current selective SSRI/SNRI 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 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
• Has cognitive impairment per investigator judgment that would render the informed consent invalid or limit the ability of the participant to comply with the study requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo will be administered orally.
Experimental: Aticaprant	Drug: Aticaprant; Aticaprant will be administered orally.; Other Names: JNJ-67953964

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Randomization Into Double Blind (DB) Treatment Maintenance Phase to the First Documentation of Relapse	Relapse is defined as any of the following: MADRS total score >=22 for 2 consecutive assessments separated by 7 (+/-3) days and/or hospitalization or observation for worsening depression, or any clinically relevant event per clinical judgment suggestive of relapse of depressive illness, such as active suicidal ideation with intent or evidence of suicidal behavior based on the Columbia-Suicide Severity Rating Scale (C-SSRS), suicide attempt, completed suicide, or hospitalization for suicide prevention. Relapse date is defined by the second MADRS assessment. MADRS is a clinician-rated 10-item scale scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms), with higher scores indicating more severe symptoms. C-SSRS is clinician-rated and reports severity and frequency of suicide-related ideation and behavior, categorized as no ideation/behavior (0), suicidal ideation (1 -5), or suicidal behavior (6 -10), with higher scores reflecting greater severity.	From date of DB randomization (Day 113) up to first documentation of relapse (up to early termination of study [Day 140])

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Sexual Function (SF) Measured by Changes in Sexual Functioning Questionnaire - Short-Form (CSFQ-14) Total Score From DB Baseline to End of Week 4 of the DB Treatment Maintenance Phase	Change in SF measured by CSFQ-14 total score from DB baseline to end of week 4 of DB treatment maintenance phase will be reported.	From Week 16 (DB baseline) to end of week 4 of DB treatment maintenance phase (i.e., up to Week 20 of the study)
Change from DB baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score to End of DB Treatment Maintenance Phase	Change from DB baseline in the MADRS total score to end of DB treatment maintenance phase will be reported.	From Week 16 (DB baseline) up to 2 years 2 months in the DB phase
Percentage of Participants With Remission of Depressive Symptoms MADRS Total Score Less Than or Equal to (<=) 10	Percentage of participants with remission of depressive symptoms defined as MADRS total score <= 10 will be reported.	From Week 16 (DB baseline) up to 2 years 2 months in the DB phase
Percentage of Participants With Remission of Depressive Symptoms (PHQ-9 Total Score <=4)	Percentage of participants with remission of depressive symptoms defined by Patient Health Questionnaire, 9-item (PHQ-9) total score <=4 will be reported.	From Week 16 (DB baseline) up to 2 years 2 months in the DB phase
Percentage of Participants With Response of Depressive Symptoms Based on MADRS Total Score Over Time	Percentage of participants with response defined as greater than or equal to (>=) 50% improvement in the MADRS total score over time will be reported.	For open-label (OL) treatment phase: Baseline (Day 1) up to Week 16; For DB Phase: From Week 16 (DB Baseline) up to 2 years 2 months in DB phase
Percentage of Participants With Response of Depressive Symptoms Based on PHQ-9 Total Score Over Time	Percentage of participants with response of depressive symptoms based on PHQ-9 total score over time will be reported.	For OL treatment phase: Baseline (Day 1) up to Week 16; For DB Phase: From Week 16 (DB Baseline) up to 2 years 2 months in the DB phase
Change from DB Baseline in the Clinical Global Impression - Severity (CGI-S) Depression Scale Score	Change from DB baseline in the CGI-S depression scale score will be reported.	From Week 16 (DB baseline) up to 2 years 2 months in the DB phase
Change from DB Baseline in PHQ-9 Total Score	Change from DB baseline in PHQ-9 total score will be reported.	From Week 16 (DB baseline) up to 2 years 2 months in the DB phase
Change From DB Baseline in Anhedonia as Assessed by the Dimensional Anhedonia Rating Scale (DARS) Total Score	Change from DB baseline in Anhedonia as assessed by the DARS total score will be reported.	From Week 16 (DB baseline) up to 2 years 2 months in the DB phase
Change from DB Baseline in Snaith-Hamilton Pleasure Scale (SHAPS) Score to End of DB Treatment Phase	Change from DB baseline in SHAPS score to end of DB treatment phase will be reported.	From Week 16 (DB baseline) up to 2 years 2 months in the DB phase
Percentage of Participants who Relapse and Have Evidence of Anhedonia Over Time	Percentage of participants who relapse and have evidence of anhedonia over time will be reported.	From Week 16 (DB baseline) up to 2 years 2 months in the DB phase
Change from DB Baseline in the Generalized Anxiety Disorder 7-Item Scale (GAD-7) Total Score Over Time	Change from DB baseline in the GAD-7 total score over time will be reported.	From Week 16 (DB baseline) up to 2 years 2 months in the DB phase
Change from DB Baseline in SF Measured by CSFQ-14 Total Score and SF Domain Scores Over Time	Change from DB baseline in SF measured by CSFQ-14 total score and SF domain scores over time will be reported.	From Week 16 (DB baseline) up to 2 years 2 months in the DB phase

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2024
• Primary Completion (Actual): April 9, 2025
• Study Completion (Actual): April 25, 2025

Study Registration Dates

• First Submitted: October 9, 2024
• First Submitted That Met QC Criteria: October 9, 2024
• First Posted (Actual): October 10, 2024

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Neurobehavioral Manifestations; Mood Disorders; Depressive Disorder; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Depressive Disorder, Major; Anhedonia; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Aticaprant
• Other Study ID Numbers: 67953964MDD3005 (Other Identifier: Janssen Research & Development, LLC); 2024-511057-22-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No