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 (VENTURA-2)

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

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).

Study Overview

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

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.

• Study Type: Interventional
• Enrollment (Actual): 444
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1133AAH
    • Fundacion para el Estudio y Tratamiento de las Enfermedades Mentales
  • Córdoba, Argentina, X5003DCE
    • Instituto Médico DAMIC
  • Córdoba, Argentina, 5000FJF
    • CEN Consultorios Especializados en Neurociencias
  • Córdoba, Argentina, X5006IKK
    • Centro Medico Luquez
  • La Plata, Argentina, 1900
    • INSA Instituto de Neurociencias San Agustín
  • La Plata, Argentina, Thanks
    • Clinica Privada de Salud Mental Santa Teresa de Ávila
  • Rosario, Argentina, 2000
    • C I A P Centro de investigacion y Asistencia en Psiquiatria
  • San Miguel de Tucumán, Argentina, 4000
    • Clinica Mayo de UMCB
  • Santiago del Estero, Argentina, 4200
    • Clinica El Jardin
• Brazil
  • Curitiba, Brazil, 80240-280
    • Trial Tech Tecnologia em Pesquisas com Medicamentos
  • Porto Alegre, Brazil, 90035-001
    • Associação Hospitalar Moinhos de Vento
• Bulgaria
  • Sofia, Bulgaria, 1510
    • Medical Center Hera Eood
  • Sofia, Bulgaria, 1202
    • MHC - Sofia, EOOD
  • Sofia, Bulgaria, 1408
    • DCC 'Sv. Vrach and Sv. Sv. Kuzma and Damyan', OOD
  • Sofia, Bulgaria, 1680
    • Medical Center Intermedica, OOD
  • Varna, Bulgaria, 9020
    • Diagnostic Consulting Center Mladost - M Varna
• Canada
  • Quebec
    • Québec, Quebec, Canada, G2J 0C4
      • ALPHA Recherche Clinique
    • Sherbrooke, Quebec, Canada, J1L 0H8
      • Diex Recherche Sherbrooke Inc
• China
  • Baoding, China, 071000
    • Hebei Mental Health Center
  • Beijing, China, 100096
    • Beijing HuiLongGuan Hospital
  • Beijing, China, 100191
    • Peking University Sixth Hospital
  • Beijing, China, 100088
    • Beijing Anding Hospital of Capital Medical University
  • Changsha, China, 410011
    • The Second Xiangya Hospital of Central South University
  • Chengdu, China, 610041
    • West China Hospital Sichuan University
  • Guangzhou, China, 510060
    • Guangdong Provincial People's Hospital
  • Huzhou, China, 313000
    • Huzhou third people's Hospital
  • Shanghai, China, 200030
    • Shanghai Mental Health Center
  • Shanghai, China, 200065
    • Tongji Hospital of Tongji University
  • Shijiazhuang, China, 050031
    • The First Hospital of Hebei Medical University
  • Suzhou, China, 215003
    • Suzhou Guangji Hospital
  • Tianjin, China, 300222
    • Tianjin Anding Hospital
  • Wuhan, China, 430000
    • Wuhan Mental Health Center
  • Wuhu, China, 242407
    • Wuhu Hospital of Beijing Anding hospital
  • Xi'an, China, 710061
    • XiAn Mental Healthcare Center
  • Zhengzhou, China, 450052
    • the First Affiliated Hospital of Zhengzhou University
• Czechia
  • Brno, Czechia, 61500
    • Psychiatricka ambulance, MUDr. Marta Holanova
  • Kutná Hora, Czechia, 284 01
    • Neuroterapie KH S R O
  • Prague, Czechia, 16000
    • Medical Services Prague S R O
  • Prague, Czechia, 186 00
    • Institut neuropsychiatricke pece
• France
  • Bohars, France, 29820
    • CHU de Brest - Hopital de la Cavale Blanche
  • Clermont-Ferrand, France, 63000
    • CHU Clermont-Ferrand - Hôpital Gabriel Montpied
  • Douai, France, 59500
    • Cabinet Medical des Drs Prizac-Desbonnet Scottez
  • Nantes, France, 44093
    • CHU de Nantes hotel Dieu
  • Paris, France, 75674
    • Hopital Sainte Anne
  • Tours, France, 37044
    • CHRU de Tours Clinique Psychiatrique Universitaire
• Poland
  • Bydgoszcz, Poland, 85 794
    • Clinsante Osrodek Badan Klinicznych
  • Katowice, Poland, 40568
    • Centrum Medyczne Care Clinic Katowice
  • Poznan, Poland, 60-744
    • Filip Rybakowski Specjalistyczna Praktyka Lekarska
  • Suchy Las, Poland, 62-002
    • Indywidualna Specjalistyczna Praktyka Lekarska Agnieszka Remlinger Molenda
• Slovakia
  • Banská Bystrica, Slovakia, 97401
    • Psychomed-Svatosavsky, s.r.o.
  • Bojnice, Slovakia, 97201
    • Nemocnica s poliklinikou Prievidza so sidlom v Bojniciach
  • Bratislava, Slovakia, 82007
    • Psychiatricka Ambulancia Mentum S.R.O.
  • Košice, Slovakia, 040 11
    • Epamed sro
  • Košice, Slovakia, 04190
    • Univerzitna nemocnica L. Pasteura Kosice
  • Liptovský Mikuláš, Slovakia, 03123
    • Liptovska Nemocnica S Poliklinikou Mudr. Ivana Stodolu
  • Rimavská Sobota, Slovakia, 97901
    • Psychiatricka Ambulancia Psycholine S.R.O.
  • Vranov nad Topľou, Slovakia, 9301
    • Crystal Comfort s.r.o.
• South Africa
  • Cape Town, South Africa, 7530
    • Cape Town Clinical Research Centre
  • Pretoria, South Africa, 181
    • Gert Bosch Pretoria South Africa
  • Strand, South Africa, 7140
    • Somerset West Clinical Research Unit
• South Korea
  • Bucheon-si, South Korea, 14647
    • Bucheon St. Mary's Hospital
  • Busan, South Korea, 48108
    • Inje University Haeundae Paik Hospital
  • Goyang, South Korea, 10414
    • CHA University ilsan Medical Center
  • Gyeonggi-do, South Korea, 15355
    • Korea University Ansan Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 3080
    • Seoul National University Hospital
  • Seoul, South Korea, 02841
    • Korea University Anam Hospital
  • Seoul, South Korea, 02447
    • KyungHee University Hospital
  • Seoul, South Korea, 07345
    • The Catholic University of Korea Yeouido St. Mary's Hospital
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 110
    • Taipei Medical University
  • Taipei, Taiwan, 112
    • Cheng Hsin General Hospital
• United Kingdom
  • Brighton, United Kingdom, BN1 9RY
    • University of Sussex
  • Edinburgh, United Kingdom, EH10 5HF
    • Royal Edinburgh Hospital
  • London, United Kingdom, SE5 8AF
    • Institute of Psychiatry
  • Paisley, United Kingdom, PA1 1JS
    • Renfrewshire CMHT
  • Southampton, United Kingdom, SO30 3JB
    • Moorgreen Hospital
  • Wigan and Leigh, United Kingdom, WN7 1YN
    • Crisis Resolution and Home Treatment Team
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • University of Alabama at Birmingham
  • California
    • Lafayette, California, United States, 94549
      • Sunwise Clinical Research
    • Orange, California, United States, 92868
      • Pacific Neuropsychiatric Specialists
    • Rancho Cucamonga, California, United States, 91730
      • Prospective Research Innovations Inc
    • San Diego, California, United States, 92103
      • University of California San Diego Medical Center
    • Santee, California, United States, 92071
      • CMB Clinical Trials
    • Sherman Oaks, California, United States, 91403
      • California Neuroscience Research
    • Upland, California, United States, 91786
      • Pacific Clinical Research Medical Group
    • West Covina, California, United States, 91790
      • Next Level Clinical Trials, LLC
  • Colorado
    • Colorado Springs, Colorado, United States, 80910
      • MCB Clinical Research Centers LLC
  • Florida
    • Coral Springs, Florida, United States, 33067
      • CNS Clinical Research Group
    • Gainesville, Florida, United States, 32607
      • Sarkis Clinical Trials
    • Hialeah, Florida, United States, 33012
      • New Life Medical Research Center, Inc.
    • Maitland, Florida, United States, 32751
      • K2 Medical Research
    • Miami, Florida, United States, 33125
      • Global Medical Institutes
    • Miami, Florida, United States, 33175
      • Ezy Medical Research
    • Miami, Florida, United States, 33174
      • Florida Research Center Inc.
    • Miami, Florida, United States, 33184
      • Felicidad Medical Research
    • Miami, Florida, United States, 33122
      • Vital Care Research
    • Miami, Florida, United States, 33126
      • LCC Medical Research Institute Inc
    • North Bay Village, Florida, United States, 33141
      • Bravo Health Care Center
    • Orlando, Florida, United States, 32803
      • APG Research LLC
    • Orlando, Florida, United States, 32803
      • Combined Research Orlando
    • Pompano Beach, Florida, United States, 33064
      • Quantum Laboratories
    • Port Saint Lucie, Florida, United States, 34952
      • CDC Research Institute LLC
  • Illinois
    • Skokie, Illinois, United States, 60076
      • Psychiatric Medicine Associates
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research
  • Maryland
    • Gaithersburg, Maryland, United States, 20877
      • CBH Health
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • Michigan Clinical Research Institute
    • Farmington Hills, Michigan, United States, 48334
      • Revive Research Institute
  • Missouri
    • Saint Charles, Missouri, United States, 63304
      • Midwest Research GRoup
  • Nebraska
    • Lincoln, Nebraska, United States, 68526
      • Premier Psychiatric Research Institute, LLC
  • New York
    • Buffalo, New York, United States, 14215
      • Erie County Medical Center
    • New York, New York, United States, 10036
      • Manhattan Behavioral Medicine
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • New Hope Clinical Research
    • Monroe, North Carolina, United States, 28112
      • Monroe Biomedical Research
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43221
      • Wexner Medical Center at the Ohio State University
  • Oklahoma
    • Edmond, Oklahoma, United States, 73013
      • Conrad Clinical Research
    • Oklahoma City, Oklahoma, United States, 73112
      • Sooner Clinical Research
    • Oklahoma City, Oklahoma, United States, 73118
      • Paradigm Research Professionals, LLC
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Center for Clinical Research LLC
    • Moosic, Pennsylvania, United States, 18507
      • Global Medical Institutes
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Clinical Trials of South Carolina
  • Texas
    • Austin, Texas, United States, 78737
      • Donald J Garcia Jr MD PA
    • Dallas, Texas, United States, 75243
      • Relaro Medical Trials
    • Dallas, Texas, United States, 75247-9119
      • UT Southwestern Medical Center
    • Stafford, Texas, United States, 77477
      • R and H Clinical Research
  • Utah
    • Murray, Utah, United States, 84107
      • Cedar Psychiatry
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
    • Everett, Washington, United States, 98201
      • Core Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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
Experimental: Aticaprant; Participants will receive Aticaprant 10 milligrams (mg) tablet orally, once daily for 42 days during double-blind (DB) treatment phase in addition to their current antidepressant selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) therapy. Participants who will complete the DB treatment phase (Day 43) may be eligible to participate in a separate 52-week open-label long-term safety study 67953964MDD3003.	Drug: Aticaprant; Aticaprant tablet will be administered orally.; Other Names: JNJ-67953964
Placebo Comparator: Placebo; Participants will receive matching placebo tablet orally, once daily for 42 days during DB treatment phase in addition to their current antidepressant SSRI/SNRI therapy. Participants who will complete the DB treatment phase (Day 43) may be eligible to participate in a separate 52-week open-label long-term safety study 67953964MDD3003.	Other: Placebo; Placebo tablet will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Day 43 in Patient Health Questionnaire, 9-Item (PHQ-9) Total Score	Change from baseline to Day 43 in PHQ-9 total score is reported. The PHQ-9 is a 9-item, participant reported outcome measure to assess depressive symptoms. The scale scores each of the 9 symptom domains of the Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-5) MDD criteria. Each item is rated on a 4 point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms. The severity of the PHQ-9 is categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19) and severe (20-27). Negative changes in PHQ-9 total score indicate improvement.	Baseline (Day 1) to Day 43
Change From Baseline Over Time in DARS Total Score	Change from baseline over time in DARS total score is reported. The DARS is a 17-item self-report questionnaire that is designed to assess anhedonia in MDD across the 4 domains: hobbies, social activities, food/drink, and sensory experience. The DARS scale measures desire, motivation, effort, and consummatory pleasure. The DARS is rated on a 5-point Likert scale (0=not at all, 1=slightly, 2=moderately, 3=mostly, 4=very much) and responses are summed to generate the total score (range of 0 to 68). A lower total score is indicative of greater anhedonia. Positive changes in DARS total score indicate improvement.	Baseline (Day 1), Days 15, 29, and 43
Percentage of Participants With a Score Less Than (<) 2 in the PHQ-9 Anhedonia-specific Item (PHQ-9, Item 1) at Day 43	Percentage of participants with a score <2 in the PHQ-9 anhedonia-specific item (PHQ-9, item 1 is little interest or pleasure in doing things) at Day 43 is reported. The PHQ-9 is a 9-item, participant reported outcome measure to assess depressive symptoms. The scale scores each of the 9 symptom domains of the Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-5) MDD criteria. Each item is rated on a 4 point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms. The severity of the PHQ-9 is categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19) and severe (20-27).	At Day 43
Change From Baseline to Day 43 in Dimensional Anhedonia Rating Scale (DARS) Total Score	The DARS is a 17-item self-report questionnaire that is designed to assess anhedonia in MDD across the 4 domains: hobbies, social activities, food/drink, and sensory experience. The DARS scale measures desire, motivation, effort, and consummatory pleasure. The DARS is rated on a 5-point Likert scale (0=not at all, 1=slightly, 2=moderately, 3=mostly, 4=very much) and responses are summed to generate the total score (range of 0 to 68). A lower total score is indicative of greater anhedonia. Positive changes in DARS total score indicate improvement.	Baseline (Day 1) to Day 43
Change From Baseline Over Time in MADRS Total Score	Change from baseline over time in MADRS total score is reported. 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), Day 15, Day 29, and Day 43
Percentage of Participants Who Achieved Response on Depressive Symptoms Scale Based on MADRS Total Score at Day 43	Percentage of participants who achieved response on depressive symptoms scale based on MADRS total score at Day 43 are reported. Responders are defined as participants with a >=50 percent (%) improvement in the MADRS total score from baseline to a given timepoint. 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.	At Day 43
Percentage of Participants With Remission of Depressive Symptoms Based on MADRS Total Score at Day 43	Percentage of participants with remission of depressive symptoms based on MADRS total score at Day 43 is reported. Participant is defined as a remitter at a given time point if the MADRS total score is less than or equal to (<=)10 at that time point. 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.	At Day 43
Change From Baseline Over Time in the PHQ-9 Anhedonia-specific Item (PHQ-9, Item 1)	Change from baseline over time in the PHQ-9 anhedonia-specific item (PHQ-9, item 1 is little interest or pleasure in doing things) is reported. The PHQ-9 is a 9-item, participant reported outcome measure to assess depressive symptoms. The scale scores each of the 9 symptom domains of the Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-5) MDD criteria. Each item is rated on a 4 point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms. The severity of the PHQ-9 is categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19) and severe (20-27). PHQ-9, item 1 score ranged from 0-3. Higher score indicates more severe disease. Negative change in PHQ-9, item 1 score indicates improvement.	Baseline (Day 1), Day 15, Day 29, and Day 43
Change From Baseline Over Time in Patient Reported Outcomes Measurement Information System Short Form - Ability to Participate in Social Roles and Activities - 8a (PROMIS-APS 8a)	Change from baseline over time in the PROMIS-APS 8a is reported. This 8-item measure assesses participants' ability to participate in social roles and activities. The items measures the degree of involvement in social roles, activities, and responsibilities, including work, family, friends, and leisure. Each item is rated on a 5-point ordinal scale including 1=always, 2=usually, 3=sometimes, 4=rarely and 5=never, with higher scores indicating better social functioning. The total scores of PROMIS-APS 8a are scaled on a T-score metric with a mean of 50 and a standard deviation of 10. PROMIS-APS 8a total score ranges from 8 to 40 and T-score ranges from 25.9 to 65.4, a higher score indicates better social functioning. Positive change in score indicates improvement.	Baseline (Day 1), Days 15, 29, and 43
DB Treatment Phase: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)	Percentage of participants with TEAEs during DB treatment phase are reported. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAE is defined as any AE occurring at or after the initial administration of study intervention through the end of DB phase.	From start of treatment (Day 1) up to Day 43
Follow-up (FU) Phase: Percentage of Participants With AEs	Percentage of participants with AEs during FU phase are reported. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention.	From Day 44 up to Day 57

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Recruitment website to the ct.gov page of Ventura-2 (NCT05550532)

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2022
• Primary Completion (Actual): November 8, 2024
• Study Completion (Actual): November 13, 2024

Study Registration Dates

• First Submitted: September 20, 2022
• First Submitted That Met QC Criteria: September 20, 2022
• First Posted (Actual): September 22, 2022

Study Record Updates

• Last Update Posted (Actual): February 13, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: February 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: CR109230; 2022-000461-41 (EudraCT Number); 67953964MDD3002 (Other Identifier: Janssen Research & Development, LLC)

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