A Study of Aticaprant in Adult and Elderly Participants With Major Depressive Disorder (MDD)

Depressive Disorder, Major Clinical Trial

— VENTURA-LT  

Official title:

An Open-label, Long-term, Safety and Efficacy Study of Aticaprant as Adjunctive Therapy in Adult and Elderly Participants With Major Depressive Disorder (MDD)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05518149
• Other study ID #: CR109218
• Secondary ID: 2022-000430-4267
• Status: Recruiting
• Phase: Phase 3
• Start date: September 22, 2022
• Est. completion date: October 22, 2025

Study information

• Verified date: April 2024
• Source: Janssen Research & Development, LLC
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the long-term safety and tolerability of aticaprant administered as adjunctive therapy to a current antidepressant (selective serotonin reuptake inhibitor [SSRI] or serotonin and norepinephrine reuptake inhibitor [SNRI]) in all participants with major depressive disorder (MDD).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 840
• Est. completion date: October 22, 2025
• Est. primary completion date: October 22, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

Inclusion Criteria:

Transferred-entry participants:

-Participants must have completed the double blind (DB) (expand DB) Treatment Phase of Study 67953964MDD3001 or Study 67953964MDD3002 without early treatment discontinuation or switch in the oral selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) in the parent study

Direct-entry participants:

• Have a Hamilton Depression Rating Scale (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
• 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
• Must be an outpatient at open-label treatment phase baseline
• 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) Direct-entry and Transferred-entry Participants: -Participants should not take any prohibited medication or food supplements Exclusion Criteria:

Transferred-entry Participants:

• Participant has been non-compliant with the study intervention administration in the DB Treatment Phase in either of Studies 67953964MDD3001 or 67953964MDD3002 (that is, have missed either 4 or more consecutive doses of study intervention or a total of 8 or more doses during the DB Treatment Phase)
• Participant has any condition or situation/circumstance for which, in the opinion of the investigator, participation would not be in the best interest of the participant (example, compromise the well-being) or that could prevent, limit, or confound the protocol specified assessments

Direct-entry Participants:

• Employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator
• Has a history or evidence of clinically meaningful noncompliance with current antidepressant therapy
• Known allergies, hypersensitivity, or intolerance to aticaprant or any of its excipients

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major

Intervention

Drug:
• Aticaprant
Aticaprant 10 mg tablet will be administered orally.

Locations

Country	Name	City	State
Argentina	INSA Instituto de Neurociencias San Agustín	Buenos Aires
Argentina	CENydET - Centro Neurobiologico y de Stress Traumatico	Ciudad Autonoma Buenos Aires
Argentina	Hospital Italiano de Buenos Aires	Ciudad Autonoma de Buenos Aires
Argentina	CEN Consultorios Especializados en Neurociencias	Cordoba
Argentina	Centro Medico Luquez	Cordoba
Argentina	CENPIA	La Plata
Argentina	Clinica Privada de Salud Mental Santa Teresa de Ávila	La Plata
Argentina	C I A P Centro de investigacion y Asistencia en Psiquiatria	Rosario
Argentina	Instituto Medico de La Fundacion Estudios Clinicos	Rosario
Argentina	Clinica Mayo de UMCB	San Miguel de Tucuman
Australia	Peninsula Therapeutic & Research Group	Frankston
Australia	Albert Road Clinic	Melbourne
Belgium	Anima	Alken
Belgium	Vitaz	Sint Niklaas
Brazil	Universidade Federal do Ceara Hospital Universitario Walter Cantidio	Fortaleza
Brazil	Ruschel Medicina e Pesquisa Clínica Ltda	Rio de Janeiro
Brazil	BR Trials	Sao Paulo
Bulgaria	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	Ruse
Bulgaria	DCC 'Sv. Vrach and Sv. Sv. Kuzma and Damyan', OOD	Sofia
Bulgaria	Medical Center St. Naum	Sofia
Bulgaria	MHC - Sofia, EOOD	Sofia
Bulgaria	Diagnostic Consulting Center Mladost - M Varna	Varna
Bulgaria	Mental Health Center - Veliko Tarnovo EOOD	Veliko Tarnovo
China	Beijing Anding Hospital of Capital Medical University	Beijing
Czechia	Psychiatricka ambulance, MUDr. Marta Holanova	Brno
Czechia	Neuroterapie KH, s.r.o.	Kutna Hora
Czechia	A-Shine s.r.o.	Plzen
Czechia	Praglandia s r o	Prague 5
Czechia	AD71 s.r.o.	Praha 10
Czechia	Clintrial s r o	Praha 10
Czechia	Medical Services Prague s.r.o.	Praha 6
Czechia	NeuropsychiatrieHK, s.r.o.	Praha 6
Czechia	Institut Neuropsychiatricke pece	Praha 8
France	Cabinet Medical des Drs Prizac-Desbonnet Scottez	Douai
France	CHU de Nantes hotel Dieu	Nantes
Hungary	Semmelweis Egyetem	Budapest
Hungary	PsychoTech Kft	Pecs
Italy	AUSL LE di Lecce	Lecce
Italy	Ospedale San Raffaele	Milano
Italy	Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria alle Scotte	Siena
Korea, Republic of	Korea University Ansan Hospital	Gyeonggi-do
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Kyung Hee University Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Poland	Mlynowamed Specjalistyczny Psychiatryczny Gabinet Lekarski Joanna Lazarczyk	Bialystok
Poland	Clinsante Osrodek Badan Klinicznych	Bydgoszcz
Poland	Centrum Badan Klinicznych PI-House sp. z o.o.	Gdansk
Poland	Centrum Medyczne Care Clinic Katowice	Katowice
Poland	Specjalistyczna Indywidualna Praktyka Lekarska	Lodz
Poland	Filip Rybakowski Specjalistyczna Praktyka Lekarska	Poznan
Poland	Indywidualna Specjalistyczna Praktyka Lekarska Agnieszka Remlinger Molenda	Suchy Las
Poland	Specjalistyczny Gabinet Psychiatryczny Kowalkowski Gerard	Torun
Slovakia	Psychomed-Svatosavsky, s.r.o.	Banska Bystrica
Slovakia	Nemocnica s poliklinikou Prievidza so sidlom v Bojniciach	Bojnice
Slovakia	Epamed sro	Koshice
Slovakia	Liptovska Nemocnica S Poliklinikou Mudr. Ivana Stodolu	Liptovsky Mikulas
Slovakia	Psychiatricka Ambulancia Psycholine S.R.O.	Rimavska Sobota
Slovakia	Crystal Comfort s.r.o.	Vranov nad Toplou
South Africa	Cape Town Clinical Research Centre	Cape Town
South Africa	Gert Bosch Pretoria South Africa	Pretoria
South Africa	Somerset West Clinical Research Unit	Strand
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Institucion Hosp Hestia Palau	Barcelona
Spain	Hosp. Univ. La Paz	Madrid
Spain	Corporacio Sanitari Parc Tauli	Sabadell
Sweden	Sahlgrenska Universitetssjukhuset	Goteborg
Sweden	ProbarE i Lund AB	Lund
Sweden	ProbarE i Stockholm AB	Stockholm
Sweden	Studieenheten Akademiskt Specialistcentrum Stockholm	Stockholm
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Taipei Medical University	Taipei City
United States	Lehigh Center for Clinical Research	Allentown	Pennsylvania
United States	Advanced Research Center Inc	Anaheim	California
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Research Network America	Berwyn	Illinois
United States	University of Alabama at Birmingham - The Kirklin Clinic	Birmingham	Alabama
United States	Erie County Medical Center	Buffalo	New York
United States	New Hope Clinical Research	Charlotte	North Carolina
United States	Chicago Research Center	Chicago	Illinois
United States	Patient Priority Clinical Sites LLC	Cincinnati	Ohio
United States	Innovative Research of West Florida, Incorporated	Clearwater	Florida
United States	Vertex Research Group, Inc	Clermont	Florida
United States	Alpine Research Organization	Clinton	Utah
United States	MCB Clinical Research Centers, LLC	Colorado Springs	Colorado
United States	Wexner Medical Center at the Ohio State University	Columbus	Ohio
United States	CNS Clinical Research Group	Coral Springs	Florida
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Midwest Clinical Research Center	Dayton	Ohio
United States	Conrad Clinical Research	Edmond	Oklahoma
United States	Revive Research Institute	Elgin	Illinois
United States	University of Connecticut Health Center	Farmington	Connecticut
United States	Gulfcoast Medical Research Center	Fort Myers	Florida
United States	North Texas Clinical Trials	Fort Worth	Texas
United States	Sarkis Clinical Trials	Gainesville	Florida
United States	CBH Health	Gaithersburg	Maryland
United States	Behavioral Research Specialists LLC	Glendale	California
United States	Amedica Research Institute Inc	Hialeah	Florida
United States	Galiz Research	Hialeah	Florida
United States	New Life Medical Research Center, Inc.	Hialeah	Florida
United States	Premier Psychiatric Research Institute, LLC	Lincoln	Nebraska
United States	Asclepes Research	Long Beach	California
United States	Suburban Research Associates	Media	Pennsylvania
United States	ActivMed Practices and Research	Methuen	Massachusetts
United States	A Plus Research	Miami	Florida
United States	Ezy Medical Research	Miami	Florida
United States	Felicidad Medical Research	Miami	Florida
United States	Florida Research Center Inc.	Miami	Florida
United States	Global Medical Institutes	Miami	Florida
United States	LCC Medical Research Institute, Inc	Miami	Florida
United States	Pharmax Research Clinic Inc	Miami	Florida
United States	Vital Care Research	Miami	Florida
United States	Meridian International Research	Miami Gardens	Florida
United States	University of Miami	Miami Lakes	Florida
United States	Clinical Trials of America	Monroe	Louisiana
United States	Monroe Biomedical Research	Monroe	North Carolina
United States	Bioscience Research LLC	Mount Kisco	New York
United States	Cedar Psychiatry	Murray	Utah
United States	Fieve Clinical Research, Inc.	New York	New York
United States	Manhattan Behavioral Medicine	New York	New York
United States	Bravo Health Care Center	North Bay Village	Florida
United States	Psychiatric Care and Research Center (PCRC)	O'Fallon	Missouri
United States	Excell Research Inc	Oceanside	California
United States	K2 Medical Research	Ocoee	Florida
United States	Paradigm Research Professionals, LLC	Oklahoma City	Oklahoma
United States	Sooner Clinical Research	Oklahoma City	Oklahoma
United States	Medical Research Group of Central Florida	Orange City	Florida
United States	Combined Research Orlando	Orlando	Florida
United States	University of Pennsylvania - Perelman School of Medicine	Philadelphia	Pennsylvania
United States	CDC Research Institute LLC	Port Saint Lucie	Florida
United States	Prospective Research Innovations Inc	Rancho Cucamonga	California
United States	Finger Lakes Clinical Research	Rochester	New York
United States	Midwest Research Group	Saint Charles	Missouri
United States	Syrentis Clinical Research	Santa Ana	California
United States	CMB Clinical Trials	Santee	California
United States	California Neuroscience Research	Sherman Oaks	California
United States	Viking Clinical Research Ltd	Temecula	California
United States	SW Biomedical Research LLC	Tucson	Arizona
United States	University of Arizona	Tucson	Arizona
United States	Next Level Clinical Trials, LLC	West Covina	California

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  China,  Czechia,  France,  Hungary,  Italy,  Korea, Republic of,  Poland,  Slovakia,  South Africa,  Spain,  Sweden,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events (AEs)	An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have causal relationship with the intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product.	Up to Week 54
Primary	Number of Participants with Adverse Events of Special Interest (AESI)	AEs considered to be of special interest are as Pruritus and Diarrhea.	Up to Week 54
Primary	Number of Participants with Change from Baseline in Vital Signs Abnormalities	Vital signs include body weight, temperature, pulse/heart rate, respiratory rate, pulse oximetry and blood pressure (systolic and diastolic) values.	Up to Week 54
Primary	Number of Participants with Abnormal Body Weight	Participants will be weighed at approximately the same time of day on the same scale, wearing lightweight clothing without shoes; they will be instructed to empty their bladders before being weighed.	Up to Week 54
Primary	Number of Participants with Abnormal Body Mass Index (BMI)	A BMI between 18.5 and 25 kilogram per meter square (kg/m^2) indicates a normal weight.	Up to Week 54
Primary	Percentage of Participants with Suicidal Ideation or Suicidal Behavior based on the Columbia-Suicide Severity Rating Scale (C-SSRS)	C-SSRS is semi structured clinician-administered questionnaire designed to solicit the occurrence, severity, and frequency of suicide-related ideation and behaviors. The maximum score assigned for each participant will also be summarized into one of three categories: no suicidal ideation or behavior (0), suicidal ideation (1-5), suicidal behavior (6-10). Total score ranges from 1 to 10. Higher scores indicate greater severity.	Up to Week 54
Primary	Number of Participants with Abnormalities in Clinical Laboratory parameters	Number of participants with abnormalities in clinical laboratory parameters will be reported.	Up to Week 54
Primary	Number of Participants with Abnormalities in Electrocardiogram (ECG)	Number of participants with abnormalities in ECG will be reported.	Up to Week 54
Primary	Withdrawal Symptoms Assessment Using the Physician Withdrawal Checklist (PWC-20)	Withdrawal symptoms are assessed using the PWC-20. The PWC-20 is a simple and accurate method used to assess potential withdrawal symptoms following cessation of treatment. The PWC-20 is a reliable and sensitive instrument for the assessment of discontinuation symptoms.	Up to Week 54
Primary	Number of participants with Clinically Relevant Sexual Dysfunction Over Time as Measured by the Arizona Sexual Experiences Scale (ASEX) Score	The ASEX is a participant-reported five-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Each of the 5 items is rated on a 6-point scale, ranging from 1 to 6. Total score ranges from 5 to 30, with the higher scores indicating more sexual dysfunction.	Up to Week 54
Secondary	Change from Baseline in the Montgomery-asberg Depression Rating Scale (MADRS) Total Score Over Time	Change from baseline in MADRS total score over time will be reported. The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.	Baseline up to Week 54
Secondary	Change from Baseline in the Participant Health Questionnaire, 9-Item (PHQ-9) Total Score over Time	Change from baseline in PHQ-9 total score over time will be reported. The 9-item PHQ-9 scale scores each of the 9 symptom domains of the Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-5) diagnostic criteria for recurrent or single episode major depressive disorder (MDD) criteria and used both as a screening tool and a measure of response to treatment for depression. 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.	Baseline up to Week 54
Secondary	Change from Baseline in Dimensional Anhedonia Rating Scale (DARS) Total Score Over Time	Change from baseline in DARS total score over time will be reported. The DARS is a 17-item self-report questionnaire that is designed to assess anhedonia in MDD, and particularly to increase scale generalizability while maintaining specificity. Respondents provide their own examples of rewarding experiences across the domains of hobbies, social activities, food/drink, and sensory experience. Participants answer a set of standardized questions about desire, motivation, effort and consummatory pleasure with a recall period of "right now" for the examples provided. The instrument is scored as a total sum of all items (range 0-68) with higher scores reflecting increased motivation, effort and pleasure (that is, less anhedonia).	Baseline up to Week 54
Secondary	Change from Baseline in the Clinical Global Impression-Severity (CGI-S) Total Score Over Time	Change from baseline in the CGI-S total score over time will be reported. The CGI-S evaluates the severity of psychopathology on a scale of 0 to 7. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill participants. The CGI-S permits a global evaluation of the participant's condition at a given time.	Baseline up to Week 54
Secondary	Percentage of Participants with Greater than or Equal to (>=) 50 percent (%) Reduction from Baseline in the MADRS Total Score Over Time	Percentage of participants with >=50% reduction from baseline in the MADRS total score over time will be reported. The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.	Week 54
Secondary	Percentage of Participants with Remission of Depressive Symptoms Over Time	Percentage of participants with remission of depressive symptoms over time, defined as a MADRS total score less than or equal to (<=) 10 will be reported. The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.	Week 54