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

Depressive Disorder, Major Clinical Trial

— VENTURA-1  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05455684
• Other study ID #: CR109217
• Secondary ID: 2022-000439-2267
• Status: Recruiting
• Phase: Phase 3
• Start date: June 22, 2022
• Est. completion date: October 1, 2024

Study information

• Verified date: June 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 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 538
• Est. completion date: October 1, 2024
• Est. primary completion date: September 18, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

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

Related Conditions & MeSH terms

• Anhedonia
• Depression
• Depressive Disorder
• Depressive Disorder, Major

Intervention

Drug:
• Aticaprant
Aticaprant will be administered orally as tablets.

Other:
• Placebo
Placebo will be administered orally as tablets.

Locations

Country	Name	City	State
Argentina	CENydET - Centro Neurobiologico y de Stress Traumatico	Ciudad Autonoma Buenos Aires
Argentina	CIPREC	Ciudad Autonoma de Buenos Aires
Argentina	Hospital Italiano	Ciudad Autonoma de Buenos Aires
Argentina	STAT Research S.A.	Ciudad Autonoma de Buenos Aires
Argentina	Resolution	Ciudad de Mendoza
Argentina	Fundacion Lennox	Cordoba
Argentina	CENPIA	La Plata
Argentina	Instituto Medico de La Fundacion Estudios Clinicos	Rosario
Australia	Peninsula Therapeutic & Research Group	Frankston
Australia	Albert Road Clinic	Melbourne
Australia	The Alfred Hospital	Melbourne
Belgium	Anima	Alken
Belgium	C.H.U. Brugmann	Bruxelles
Belgium	Pz Duffel	Duffel
Belgium	Vitaz	Sint Niklaas
Brazil	Universidade Federal do Ceara Hospital Universitario Walter Cantidio	Fortaleza
Brazil	Instituto Goiano de Neuropsiquiatria	Goiania
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	Sao Jose do Rio Preto
Brazil	BR Trials	Sao Paulo
Brazil	CPQuali Pesquisa Clinica LTDA ME	São 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	Medical Center St. Naum	Sofia
Bulgaria	Mental Health Center - Veliko Tarnovo EOOD	Veliko Tarnovo
Czechia	Narodni ustav dusevniho zdravi	Klecany
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	NeuropsychiatrieHK, s.r.o.	Praha 6
Czechia	Psychiatricka ordinace	Usti nad Labem
Hungary	Obudai Egeszsegugyi Centrum Kft	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Bugat Pal Korhaz	Gyongyos
Hungary	Dr Mathe es Tarsa Bt	Kalocsa
Hungary	PsychoTech Kft	Pecs
Hungary	Tolna Megyei Balassa Janos Korhaz	Szekszárd
Italy	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	ASST Fatebenefratelli Sacco	Milano
Italy	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico	Milano
Italy	Ospedale San Raffaele	Milano
Italy	Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria alle Scotte	Siena
Poland	Gabinet Lekarski Psychiatryczny Ireneusz Kaczorowski	Belchatow
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
Portugal	Hospital de Braga	Braga
Portugal	Fund. Champalimaud	Lisboa
Portugal	Hospital CUF Inf. Santo	Lisboa
Spain	Hosp Clinic de Barcelona	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Institucion Hosp Hestia Palau	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
Sweden	Sahlgrenska Universitetssjukhuset	Goteborg
Sweden	ProbarE i Lund AB	Lund
Sweden	ProbarE i Stockholm AB	Stockholm
Sweden	Studieenheten Akademiskt Specialistcentrum Stockholm	Stockholm
United States	Advanced Research Center Inc	Anaheim	California
United States	West Houston Clinical Research Service	Bellaire	Texas
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Research Network America	Berwyn	Illinois
United States	Montefiore Medical Center PRIME	Bronx	New York
United States	University of Virginia	Charlottesville	Virginia
United States	Chicago Research Center	Chicago	Illinois
United States	Patient Priority Clinical Sites LLC	Cincinnati	Ohio
United States	University of Cincinnati Medical Center	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	Proscience Research Group	Culver City	California
United States	Midwest Clinical Research Center	Dayton	Ohio
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	Bay Area Clinical Services	Friendswood	Texas
United States	Charak Center for Health and Wellness	Garfield Heights	Ohio
United States	Behavioral Research Specialists LLC	Glendale	California
United States	Amedica Research Institute Inc	Hialeah	Florida
United States	Convenient Medical Center	Hialeah	Florida
United States	Galiz Research	Hialeah	Florida
United States	New Life Medical Research Center, Inc.	Hialeah	Florida
United States	Clinical Trial Network - Houston	Houston	Texas
United States	University of Kansas Medical Center Research Institute	Kansas City	Kansas
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	Pharmax Research Clinic Inc	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	Bioscience Research LLC	Mount Kisco	New York
United States	Fieve Clinical Research Inc	New York	New York
United States	Psychiatric Care and Research Center (PCRC)	O'Fallon	Missouri
United States	Excell Research Inc	Oceanside	California
United States	Medical Research Group of Central Florida	Orange City	Florida
United States	University of Pennsylvania - Perelman School of Medicine	Philadelphia	Pennsylvania
United States	Finger Lakes Clinical Research	Rochester	New York
United States	Syrentis Clinical Research	Santa Ana	California
United States	USF, Department of Psychiatry and Behavioral Neurosciences	Tampa	Florida
United States	Viking Clinical Research Ltd	Temecula	California
United States	SW Biomedical Research LLC	Tucson	Arizona
United States	University of Arizona	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Czechia,  Hungary,  Italy,  Poland,  Portugal,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score to Day 43	Change from baseline in MADRS total score to Day 43 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 possible score of 60. Higher scores represent a more severe condition.	Baseline to Day 43
Secondary	Change from Baseline in Dimensional Anhedonia Rating Scale (DARS) Total Score to Day 43	Change from baseline in DARS total score to Day 43 will be reported. DARS is a 17-item self-report questionnaire that is designed to assess anhedonia in major depressive disorder (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 to Day 43
Secondary	Change from Baseline in 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 possible score of 60. Higher scores represent a more severe condition.	Baseline up to Day 57
Secondary	Percentage of Responders on Depressive Symptoms Scale from Baseline to Day 43	Percentage of responders on depressive symptoms scale, defined as a greater than or equal to (>=) 50 percent (%) improvement in MADRS total score from baseline to Day 43 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 possible score of 60. Higher scores represent a more severe condition.	Baseline to Day 43
Secondary	Percentage of Participants with Remission of Depressive Symptoms Defined as a MADRS Total Score <=10 at Day 43	Percentage of participants with remission of depressive symptoms, defined as a MADRS total score less than or equal to (<=) 10 at Day 43 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 possible score of 60. Higher scores represent a more severe condition.	Day 43
Secondary	Change from Baseline in Patient Health Questionnaire, 9-Item (PHQ-9) Total Score to Day 43	Change from baseline in PHQ-9 total score to Day 43 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) MDD criteria and it is 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 to Day 43
Secondary	Change from Baseline in DARS Total Score Over Time	Change from baseline in DARS total score over time will be reported. DARS is a 17-item self-report questionnaire that was 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 on 0 (not at all) to 4 (very much) and the total score is calculated as a sum of all items (range 0-68) with higher scores reflecting increased motivation, effort, and pleasure (that is, less anhedonia).	Baseline up to Day 57
Secondary	Change from Baseline in the PHQ-9 Anhedonia-specific Item (PHQ-9, item 1) Over Time	Change from baseline in the PHQ-9 Anhedonia-specific item (PHQ-9, item 1) 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) MDD criteria and it is 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 Day 57
Secondary	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) at Day 43 will be reported.	Day 43
Secondary	Change from Baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) Short Form-Ability to Participate in Social Roles and Activities - 8a (PROMIS-APS 8a) Over Time	The PROMIS-APS 8a includes items selected from the PROMIS item bank to provide an assessment of the current degree of involvement in one's usual social roles, activities, and responsibilities, including work, family, friends, and leisure. The 8-item short form will be used in this study, and responses to every item are in a 5-point ordinal scale ranging from 1 = "Always" to 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 (SD) of 10.	Baseline up to Day 57
Secondary	Change from Baseline over Time in the Work Productivity and Activity Impairment (WPAI:D)	The WPAI:D questionnaire is a validated short instrument that assesses impairment in work and other regular activities over the past 7 days. The WPAI questionnaire assesses 4 separate measures: absenteeism (that is , the proportion of work time missed due to MDD), presenteeism (that is, the degree of impairment while working due to MDD), work productivity loss (ie, overall work impairment due to MDD/absenteeism plus presenteeism), and activity impairment (that is, the degree of impairment of regular, nonwork activity due to MDD). The WPAI outcomes are expressed as impairment percentages, with higher values indicating greater impairment and less productivity, that is, worse outcomes.	Baseline up to Day 43