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

NCT ID: NCT05550532

Last Updated: 2026-01-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 444 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-06
• Study Completion Date: 2024-11-13

Brief 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).

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.

Conditions

Depressive Disorder, Major; Anhedonia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Aticaprant

Intervention Type: DRUG

Aticaprant tablet will be administered orally.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo tablet will be administered orally.

Interventions

Aticaprant

Aticaprant tablet will be administered orally.

Intervention Type: DRUG

Placebo

Placebo tablet will be administered orally.

Intervention Type: OTHER

Other Intervention Names

JNJ-67953964

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Sunwise Clinical Research

Lafayette, California, United States

Pacific Neuropsychiatric Specialists

Orange, California, United States

Prospective Research Innovations Inc

Rancho Cucamonga, California, 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

Pacific Clinical Research Medical Group

Upland, California, United States

Next Level Clinical Trials, LLC

West Covina, California, United States

MCB Clinical Research Centers LLC

Colorado Springs, Colorado, United States

CNS Clinical Research Group

Coral Springs, Florida, United States

Sarkis Clinical Trials

Gainesville, Florida, United States

New Life Medical Research Center, Inc.

Hialeah, Florida, United States

K2 Medical Research

Maitland, Florida, United States

Vital Care Research

Miami, Florida, United States

Global Medical Institutes

Miami, Florida, United States

LCC Medical Research Institute Inc

Miami, Florida, United States

Florida Research Center Inc.

Miami, Florida, United States

Ezy Medical Research

Miami, Florida, United States

Felicidad Medical Research

Miami, Florida, United States

Bravo Health Care Center

North Bay Village, Florida, 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

Psychiatric Medicine Associates

Skokie, Illinois, United States

Tandem Clinical Research

Marrero, Louisiana, United States

CBH Health

Gaithersburg, Maryland, United States

Michigan Clinical Research Institute

Ann Arbor, Michigan, United States

Revive Research Institute

Farmington Hills, Michigan, United States

Midwest Research Group

Saint Charles, Missouri, United States

Premier Psychiatric Research Institute, LLC

Lincoln, Nebraska, United States

Erie County Medical Center

Buffalo, New York, United States

Manhattan Behavioral Medicine

New York, New York, United States

New Hope Clinical Research

Charlotte, North Carolina, United States

Monroe Biomedical Research

Monroe, North Carolina, United States

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Wexner Medical Center at the Ohio State University

Columbus, Ohio, United States

Conrad Clinical Research

Edmond, Oklahoma, United States

Sooner Clinical Research

Oklahoma City, Oklahoma, United States

Paradigm Research Professionals, LLC

Oklahoma City, Oklahoma, United States

Lehigh Center for Clinical Research LLC

Allentown, Pennsylvania, United States

Global Medical Institutes

Moosic, Pennsylvania, United States

Clinical Trials of South Carolina

Charleston, South Carolina, United States

Donald J Garcia Jr MD PA

Austin, Texas, United States

Relaro Medical Trials

Dallas, Texas, United States

UT Southwestern Medical Center

Dallas, Texas, United States

R and H Clinical Research

Stafford, Texas, United States

Cedar Psychiatry

Murray, Utah, United States

Northwest Clinical Research Center

Bellevue, Washington, United States

Core Clinical Research

Everett, Washington, United States

Fundacion para el Estudio y Tratamiento de las Enfermedades Mentales

Buenos Aires, , Argentina

CEN Consultorios Especializados en Neurociencias

Córdoba, , Argentina

Instituto Medico DAMIC

Córdoba, , Argentina

Centro Medico Luquez

Córdoba, , Argentina

INSA Instituto de Neurociencias San Agustín

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

Clinica Mayo de UMCB

San Miguel de Tucumán, , Argentina

Clinica El Jardin

Santiago del Estero, , Argentina

Trial Tech Tecnologia em Pesquisas com Medicamentos

Curitiba, , Brazil

Associacao Hospitalar Moinhos de Vento

Porto Alegre, , Brazil

CEMEC - Centro Multidisciplinar de Estudos Clínicos

São Bernardo do Campo, , Brazil

MHC - Sofia, EOOD

Sofia, , 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

Diagnostic Consulting Center Mladost - M Varna

Varna, , Bulgaria

Alpha Recherche Clinique

Québec, Quebec, Canada

DIEX Recherche Sherbrooke Inc

Sherbrooke, Quebec, Canada

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

Huzhou, , China

Shanghai Mental Health Center

Shanghai, , China

Tongji Hospital of Tongji University

Shanghai, , China

The First Hospital of Hebei Medical University

Shijiazhuang, , China

Suzhou Guangji Hospital

Suzhou, , China

Tianjin Anding Hospital

Tianjin, , China

Wuhan Mental Health Center

Wuhan, , China

Wuhu Hospital of Beijing Anding hospital

Wuhu, , China

XiAn Mental Healthcare Center

Xi'an, , China

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, , China

Psychiatricka ambulance, MUDr. Marta Holanova

Brno, , Czechia

Neuroterapie KH S R O

Kutná Hora, , Czechia

Medical Services Prague S R O

Prague, , Czechia

Institut Neuropsychiatricke pece

Prague, , Czechia

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, , France

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, , Poland

Psychomed-Svatosavsky, s.r.o.

Banská Bystrica, , Slovakia

Nemocnica s poliklinikou Prievidza so sidlom v Bojniciach

Bojnice, , Slovakia

Psychiatricka Ambulancia Mentum S.R.O.

Bratislava, , Slovakia

Epamed sro

Košice, , Slovakia

Univerzitna nemocnica L. Pasteura Kosice

Košice, , Slovakia

Liptovska Nemocnica S Poliklinikou Mudr. Ivana Stodolu

Liptovský Mikuláš, , Slovakia

Psychiatricka Ambulancia Psycholine S.R.O.

Rimavská Sobota, , Slovakia

Crystal Comfort s.r.o.

Vranov nad Topľou, , Slovakia

Cape Town Clinical Research Centre

Cape Town, , South Africa

Gert Bosch Pretoria South Africa

Pretoria, , South Africa

Somerset West Clinical Research Unit

Strand, , South Africa

Bucheon St. Mary's Hospital

Bucheon-si, , South Korea

Inje University Haeundae Paik Hospital

Busan, , South Korea

CHA University ilsan Medical Center

Goyang, , South Korea

Korea University Ansan Hospital

Gyeonggi-do, , South Korea

KyungHee University Hospital

Seoul, , South Korea

Korea University Anam Hospital

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

The Catholic University of Korea Yeouido St. Mary's Hospital

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

China Medical University Hospital

Taichung, , Taiwan

Taipei Medical University

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Cheng Hsin General Hospital

Taipei, , Taiwan

University of Sussex

Brighton, , United Kingdom

Royal Edinburgh Hospital

Edinburgh, , United Kingdom

Institute of Psychiatry

London, , United Kingdom

Renfrewshire CMHT

Paisley, , United Kingdom

Moorgreen Hospital

Southampton, , United Kingdom

Crisis Resolution and Home Treatment Team

Wigan and Leigh, , United Kingdom

Countries

United States; Argentina; Brazil; Bulgaria; Canada; China; Czechia; France; Poland; Slovakia; South Africa; South Korea; Taiwan; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

67953964MDD3002

Identifier Type: OTHER

Identifier Source: secondary_id

2022-000461-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR109230

Identifier Type: -

Identifier Source: org_study_id