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

NCT05550532 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: CR10923067953964MDD30022022-000461-41
• Study Type: interventional
• Target: 444
• Locations: 14 countries
• Sites: 131

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).

Conditions

Anhedonia; Depressive Disorder, Major

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Change From Baseline to Day 43 in Dimensional Anhedonia Rating Scale (DARS) Total Score

  Baseline (Day 1) to Day 43

• Change From Baseline Over Time in MADRS Total Score

  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

  At Day 43

• Percentage of Participants With Remission of Depressive Symptoms Based on MADRS Total Score at Day 43

  At Day 43

• Change From Baseline to Day 43 in Patient Health Questionnaire, 9-Item (PHQ-9) Total Score

  Baseline (Day 1) to Day 43

Study Arms (2)

Aticaprant

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Aticaprant DRUG

Aticaprant tablet will be administered orally.

Also known as: JNJ-67953964

Aticaprant

Placebo OTHER

Placebo tablet will be administered orally.

Placebo

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (131)

University of Alabama at Birmingham

Birmingham, Alabama, 35205, United States

Location

Sunwise Clinical Research

Lafayette, California, 94549, United States

Location

Pacific Neuropsychiatric Specialists

Orange, California, 92868, United States

Location

Prospective Research Innovations Inc

Rancho Cucamonga, California, 91730, United States

Location

University of California San Diego Medical Center

San Diego, California, 92103, United States

Location

CMB Clinical Trials

Santee, California, 92071, United States

Location

California Neuroscience Research

Sherman Oaks, California, 91403, United States

Location

Pacific Clinical Research Medical Group

Upland, California, 91786, United States

Location

Next Level Clinical Trials, LLC

West Covina, California, 91790, United States

Location

MCB Clinical Research Centers LLC

Colorado Springs, Colorado, 80910, United States

Location

CNS Clinical Research Group

Coral Springs, Florida, 33067, United States

Location

Sarkis Clinical Trials

Gainesville, Florida, 32607, United States

Location

New Life Medical Research Center, Inc.

Hialeah, Florida, 33012, United States

Location

K2 Medical Research

Maitland, Florida, 32751, United States

Location

Vital Care Research

Miami, Florida, 33122, United States

Location

Global Medical Institutes

Miami, Florida, 33125, United States

Location

LCC Medical Research Institute Inc

Miami, Florida, 33126, United States

Location

Florida Research Center Inc.

Miami, Florida, 33174, United States

Location

Ezy Medical Research

Miami, Florida, 33175, United States

Location

Felicidad Medical Research

Miami, Florida, 33184, United States

Location

Bravo Health Care Center

North Bay Village, Florida, 33141, United States

Location

APG Research LLC

Orlando, Florida, 32803, United States

Location

Combined Research Orlando

Orlando, Florida, 32803, United States

Location

Quantum Laboratories

Pompano Beach, Florida, 33064, United States

Location

CDC Research Institute LLC

Port Saint Lucie, Florida, 34952, United States

Location

Psychiatric Medicine Associates

Skokie, Illinois, 60076, United States

Location

Tandem Clinical Research

Marrero, Louisiana, 70072, United States

Location

CBH Health

Gaithersburg, Maryland, 20877, United States

Location

Michigan Clinical Research Institute

Ann Arbor, Michigan, 48105, United States

Location

Revive Research Institute

Farmington Hills, Michigan, 48334, United States

Location

Midwest Research Group

Saint Charles, Missouri, 63304, United States

Location

Premier Psychiatric Research Institute, LLC

Lincoln, Nebraska, 68526, United States

Location

Erie County Medical Center

Buffalo, New York, 14215, United States

Location

Manhattan Behavioral Medicine

New York, New York, 10036, United States

Location

New Hope Clinical Research

Charlotte, North Carolina, 28211, United States

Location

Monroe Biomedical Research

Monroe, North Carolina, 28112, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Wexner Medical Center at the Ohio State University

Columbus, Ohio, 43221, United States

Location

Conrad Clinical Research

Edmond, Oklahoma, 73013, United States

Location

Sooner Clinical Research

Oklahoma City, Oklahoma, 73112, United States

Location

Paradigm Research Professionals, LLC

Oklahoma City, Oklahoma, 73118, United States

Location

Lehigh Center for Clinical Research LLC

Allentown, Pennsylvania, 18103, United States

Location

Global Medical Institutes

Moosic, Pennsylvania, 18507, United States

Location

Clinical Trials of South Carolina

Charleston, South Carolina, 29406, United States

Location

Donald J Garcia Jr MD PA

Austin, Texas, 78737, United States

Location

Relaro Medical Trials

Dallas, Texas, 75243, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75247-9119, United States

Location

R and H Clinical Research

Stafford, Texas, 77477, United States

Location

Cedar Psychiatry

Murray, Utah, 84107, United States

Location

Northwest Clinical Research Center

Bellevue, Washington, 98007, United States

Location

Core Clinical Research

Everett, Washington, 98201, United States

Location

Fundacion para el Estudio y Tratamiento de las Enfermedades Mentales

Buenos Aires, C1133AAH, Argentina

Location

CEN Consultorios Especializados en Neurociencias

Córdoba, 5000FJF, Argentina

Location

Instituto Medico DAMIC

Córdoba, X5003DCE, Argentina

Location

Centro Medico Luquez

Córdoba, X5006IKK, Argentina

Location

INSA Instituto de Neurociencias San Agustín

La Plata, 1900, Argentina

Location

Clinica Privada de Salud Mental Santa Teresa de Ávila

La Plata, Thanks, Argentina

Location

C I A P Centro de investigacion y Asistencia en Psiquiatria

Rosario, 2000, Argentina

Location

Clinica Mayo de UMCB

San Miguel de Tucumán, 4000, Argentina

Location

Clinica El Jardin

Santiago del Estero, 4200, Argentina

Location

Trial Tech Tecnologia em Pesquisas com Medicamentos

Curitiba, 80240-280, Brazil

Location

Associacao Hospitalar Moinhos de Vento

Porto Alegre, 90035-001, Brazil

Location

MHC - Sofia, EOOD

Sofia, 1202, Bulgaria

Location

DCC 'Sv. Vrach and Sv. Sv. Kuzma and Damyan', OOD

Sofia, 1408, Bulgaria

Location

Medical Center Hera EOOD

Sofia, 1510, Bulgaria

Location

Medical Center Intermedica, OOD

Sofia, 1680, Bulgaria

Location

Diagnostic Consulting Center Mladost - M Varna

Varna, 9020, Bulgaria

Location

Alpha Recherche Clinique

Québec, Quebec, G2J 0C4, Canada

Location

DIEX Recherche Sherbrooke Inc

Sherbrooke, Quebec, J1L 0H8, Canada

Location

Hebei Mental Health Center

Baoding, 071000, China

Location

Beijing Anding Hospital of Capital Medical University

Beijing, 100088, China

Location

Beijing Huilongguan Hospital

Beijing, 100096, China

Location

Peking University Sixth Hospital

Beijing, 100191, China

Location

The second Xiangya Hospital of Central South University

Changsha, 410011, China

Location

West China Hospital Sichuan University

Chengdu, 610041, China

Location

Guangdong Provincial People's Hospital

Guangzhou, 510060, China

Location

Huzhou third people's Hospital

Huzhou, 313000, China

Location

Shanghai Mental Health Center

Shanghai, 200030, China

Location

Tongji Hospital of Tongji University

Shanghai, 200065, China

Location

The First Hospital of Hebei Medical University

Shijiazhuang, 050031, China

Location

Suzhou Guangji Hospital

Suzhou, 215003, China

Location

Tianjin Anding Hospital

Tianjin, 300222, China

Location

Wuhan Mental Health Center

Wuhan, 430000, China

Location

Wuhu Hospital of Beijing Anding hospital

Wuhu, 242407, China

Location

XiAn Mental Healthcare Center

Xi'an, 710061, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, 450052, China

Location

Psychiatricka ambulance, MUDr. Marta Holanova

Brno, 61500, Czechia

Location

Neuroterapie KH S R O

Kutná Hora, 284 01, Czechia

Location

Medical Services Prague S R O

Prague, 16000, Czechia

Location

Institut Neuropsychiatricke pece

Prague, 186 00, Czechia

Location

CHU de Brest - Hopital de la Cavale Blanche

Bohars, 29820, France

Location

CHU Clermont-Ferrand - Hopital Gabriel Montpied

Clermont-Ferrand, 63000, France

Location

Cabinet Medical des Drs Prizac-Desbonnet Scottez

Douai, 59500, France

Location

CHU de Nantes hotel Dieu

Nantes, 44093, France

Location

Hopital Sainte Anne

Paris, 75674, France

Location

CHRU de Tours Clinique Psychiatrique Universitaire

Tours, 37044, France

Location

Clinsante Osrodek Badan Klinicznych

Bydgoszcz, 85 794, Poland

Location

Centrum Medyczne Care Clinic Katowice

Katowice, 40568, Poland

Location

Filip Rybakowski Specjalistyczna Praktyka Lekarska

Poznan, 60-744, Poland

Location

Indywidualna Specjalistyczna Praktyka Lekarska Agnieszka Remlinger Molenda

Suchy Las, 62-002, Poland

Location

Psychomed-Svatosavsky, s.r.o.

Banská Bystrica, 97401, Slovakia

Location

Nemocnica s poliklinikou Prievidza so sidlom v Bojniciach

Bojnice, 97201, Slovakia

Location

Psychiatricka Ambulancia Mentum S.R.O.

Bratislava, 82007, Slovakia

Location

Epamed sro

Košice, 040 11, Slovakia

Location

Univerzitna nemocnica L. Pasteura Kosice

Košice, 04190, Slovakia

Location

Liptovska Nemocnica S Poliklinikou Mudr. Ivana Stodolu

Liptovský Mikuláš, 03123, Slovakia

Location

Psychiatricka Ambulancia Psycholine S.R.O.

Rimavská Sobota, 97901, Slovakia

Location

Crystal Comfort s.r.o.

Vranov nad Topľou, 9301, Slovakia

Location

Cape Town Clinical Research Centre

Cape Town, 7530, South Africa

Location

Gert Bosch Pretoria South Africa

Pretoria, 181, South Africa

Location

Somerset West Clinical Research Unit

Strand, 7140, South Africa

Location

Bucheon St. Mary's Hospital

Bucheon-si, 14647, South Korea

Location

Inje University Haeundae Paik Hospital

Busan, 48108, South Korea

Location

CHA University ilsan Medical Center

Goyang, 10414, South Korea

Location

Korea University Ansan Hospital

Gyeonggi-do, 15355, South Korea

Location

KyungHee University Hospital

Seoul, 02447, South Korea

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

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

Seoul, 07345, South Korea

Location

Seoul National University Hospital

Seoul, 3080, South Korea

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Taipei Medical University

Taipei, 110, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Cheng Hsin General Hospital

Taipei, 112, Taiwan

Location

University of Sussex

Brighton, BN1 9RY, United Kingdom

Location

Royal Edinburgh Hospital

Edinburgh, EH10 5HF, United Kingdom

Location

Institute of Psychiatry

London, SE5 8AF, United Kingdom

Location

Renfrewshire CMHT

Paisley, PA1 1JS, United Kingdom

Location

Moorgreen Hospital

Southampton, SO30 3JB, United Kingdom

Location

Crisis Resolution and Home Treatment Team

Wigan and Leigh, WN7 1YN, United Kingdom

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Anhedonia

Interventions

Aticaprant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Executive Medical Director
• Organization: Janssen Research and Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2022
• First Posted: September 22, 2022
• Study Start: December 6, 2022
• Primary Completion: November 8, 2024
• Study Completion: November 13, 2024
• Last Updated: February 13, 2026
• Results First Posted: January 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

CA (2); GB (6); CN (17); FR (6); SL (8); ZA (3); US (51); BU (5); CZ (4); BR (2); PL (4); KR (10); TW (4); AR (9)