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

Depressive Disorder, Major Clinical Trial

— VENTURA-2  

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: NCT05550532
• Other study ID #: CR109230
• Secondary ID: 2022-000461-4167
• Status: Recruiting
• Phase: Phase 3
• Start date: December 6, 2022
• Est. completion date: October 31, 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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 710
• Est. completion date: October 31, 2024
• Est. primary completion date: October 17, 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 (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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Aticaprant
Aticaprant tablet will be administered orally.

Other:
• Placebo
Placebo tablet will be administered orally.

Locations

Country	Name	City	State
Argentina	Fundacion para el Estudio y Tratamiento de las Enfermedades Mentales	Ciudad Autonoma de Buenos Aires
Argentina	CEN Consultorios Especializados en Neurociencias	Cordoba
Argentina	Centro Medico Luquez	Cordoba
Argentina	Instituto Medico DAMIC	Cordoba
Argentina	Clinica Privada de Salud Mental Santa Teresa de Ávila	La Plata
Argentina	INSA Instituto de Neurociencias San Agustín	La Plata
Argentina	C I A P Centro de investigacion y Asistencia en Psiquiatria	Rosario
Argentina	Clinica Mayo de UMCB	San Miguel de Tucuman
Argentina	Clinica El Jardin	Santiago del Estero
Brazil	Trial Tech Tecnologia em Pesquisas com Medicamentos	Curitiba
Brazil	Associacao Hospitalar Moinhos de Vento	Porto Alegre
Bulgaria	DCC 'Sv. Vrach and Sv. Sv. Kuzma and Damyan', OOD	Sofia
Bulgaria	Medical Center Hera EOOD	Sofia
Bulgaria	Medical Center Intermedica, OOD	Sofia
Bulgaria	MHC - Sofia, EOOD	Sofia
Bulgaria	Diagnostic Consulting Center Mladost - M Varna	Varna
Canada	Alpha Recherche Clinique	Quebec
Canada	DIEX Recherche Sherbrooke Inc	Sherbrooke	Quebec
China	Hebei Mental Health Center	Baoding
China	Beijing Anding Hospital of Capital Medical University	Beijing
China	Beijing Huilongguan Hospital	Beijing
China	Peking University Sixth Hospital	Beijing
China	The second Xiangya Hospital of Central South University	Changsha
China	West China Hospital Sichuan University	Chengdu
China	Guangdong Provincial People's Hospital	Guangzhou
China	Huzhou third people's Hospital	Hu Zhou
China	Shanghai Mental Health Center	Shanghai
China	Tongji Hospital of Tongji University	Shanghai
China	The First Hospital of Hebei Medical University	Shijiazhuang
China	Tianjin Anding Hospital	Tianjin
China	Wuhan Mental Health Center	Wuhan
China	XiAn Mental Healthcare Center	XI An
Czechia	Psychiatricka ambulance, MUDr. Marta Holanova	Brno
Czechia	Neuroterapie KH s r o	Kutna Hora
Czechia	Medical Services Prague s.r.o.	Praha 6
Czechia	Institut Neuropsychiatricke pece	Praha 8
France	CHU de Brest - Hopital de la Cavale Blanche	Bohars
France	CHU Clermont-Ferrand - Hopital Gabriel Montpied	Clermont Ferrand
France	Cabinet Medical des Drs Prizac-Desbonnet Scottez	Douai
France	CHU de Nantes hotel Dieu	Nantes
France	Hopital Sainte Anne	Paris
France	CHRU de Tours Clinique Psychiatrique Universitaire	Tours cedex 9
Korea, Republic of	Bucheon St. Mary's Hospital	Bucheon-si
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	Korea University Ansan Hospital	Gyeonggi-do
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	KyungHee University Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	The Catholic University of Korea Yeouido St. Mary's Hospital	Seoul
Poland	Clinsante Osrodek Badan Klinicznych	Bydgoszcz
Poland	Centrum Medyczne Care Clinic Katowice	Katowice
Poland	Filip Rybakowski Specjalistyczna Praktyka Lekarska	Poznan
Poland	Indywidualna Specjalistyczna Praktyka Lekarska Agnieszka Remlinger Molenda	Suchy Las
Slovakia	Psychomed-Svatosavsky, s.r.o.	Banska Bystrica
Slovakia	Nemocnica s poliklinikou Prievidza so sidlom v Bojniciach	Bojnice
Slovakia	Psychiatricka Ambulancia Mentum S.R.O.	Bratislava
Slovakia	Epamed sro	Koshice
Slovakia	Univerzitna nemocnica L. Pasteura Kosice	Kosice
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
Taiwan	China Medical University Hospital	Taichung
Taiwan	Cheng Hsin General Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Taipei Medical University	Taipei City
United Kingdom	University of Sussex	Brighton
United Kingdom	Renfrewshire CMHT	Paisley
United Kingdom	Moorgreen Hospital	Southampton
United States	Lehigh Center for Clinical Research	Allentown	Pennsylvania
United States	Michigan Clinical Research Institute	Ann Arbor	Michigan
United States	Donald J Garcia Jr MD PA	Austin	Texas
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Erie County Medical Center	Buffalo	New York
United States	New Hope Clinical Research	Charlotte	North Carolina
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	Relaro Medical Trials	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Conrad Clinical Research	Edmond	Oklahoma
United States	Core Clinical Research	Everett	Washington
United States	Revive Research Institute	Farmington Hills	Michigan
United States	Sarkis Clinical Trials	Gainesville	Florida
United States	CBH Health	Gaithersburg	Maryland
United States	Sunwise Clinical Research	Lafayette	California
United States	Premier Psychiatric Research Institute, LLC	Lincoln	Nebraska
United States	K2 Medical Research	Maitland	Florida
United States	Tandem Clinical Research	Marrero	Louisiana
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	Vital Care Research	Miami	Florida
United States	Monroe Biomedical Research	Monroe	North Carolina
United States	Global Medical Institutes	Moosic	Pennsylvania
United States	Cedar Psychiatry	Murray	Utah
United States	Manhattan Behavioral Medicine	New York	New York
United States	Bravo Health Care Center	North Bay Village	Florida
United States	Paradigm Research Professionals, LLC	Oklahoma City	Oklahoma
United States	Sooner Clinical Research	Oklahoma City	Oklahoma
United States	Pacific Neuropsychiatric Specialists	Orange	California
United States	APG Research LLC	Orlando	Florida
United States	Combined Research Orlando	Orlando	Florida
United States	Quantum Laboratories	Pompano Beach	Florida
United States	CDC Research Institute LLC	Port Saint Lucie	Florida
United States	Prospective Research Innovations Inc	Rancho Cucamonga	California
United States	Midwest Research Group	Saint Charles	Missouri
United States	University of California San Diego Medical Center	San Diego	California
United States	CMB Clinical Trials	Santee	California
United States	California Neuroscience Research	Sherman Oaks	California
United States	Psychiatric Medicine Associates	Skokie	Illinois
United States	R and H Clinical Research	Stafford	Texas
United States	Pacific Clinical Research Medical Group	Upland	California
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,  Brazil,  Bulgaria,  Canada,  China,  Czechia,  France,  Korea, Republic of,  Poland,  Slovakia,  South Africa,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Montgomery-Asberg 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 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 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 as Assessed by MADRS Total Score	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 at Day 43 as Assessed by MADRS Total Score	Percentage of participants with remission of depressive symptoms, defined as a MADRS total score of 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 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. The 9-item PHQ-9 scale scores each of the 9 symptom domains of the 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.	Day 43
Secondary	Change From Baseline Over Time in the Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form - Ability to Participate in Social Roles and Activities 8a (PROMIS-APS 8a)	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