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

Plain English Summary

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 is a Phase 3 clinical trial sponsored by Janssen Research & Development, LLC studying Depressive Disorder, Major, Anhedonia. Tests Aticaprant as an adjunctive therapy for major depressive disorder with moderate-to-severe anhedonia and inadequate response to current antidepressants. For adults aged 18 and older with major depressive disorder who have not responded well to previous antidepressant treatments. Participation involves taking daily medication for 43 days and attending regular clinic visits. Alternative treatments include other antidepressants or psychotherapy. The trial aims to enroll 513 participants.

Official 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).

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible participants must be medically stable, have a severe depressive episode, and have had an inadequate response to at least one antidepressant. Participants must be 18 years or older and have had their first depressive episode before age 55. Exclusion criteria include a history of severe substance use disorder, seizures, or suicidal ideation. Participants must be currently receiving an approved SSRI or SNRI for their depression. This trial is studying Depressive Disorder, Major, Anhedonia, so participants generally need a confirmed diagnosis.

What They're Measuring

Improvement in depressive symptoms is measured by changes in the Montgomery-Asberg Depression Rating Scale (MADRS) total score. The specific primary outcome measures are: Change From Baseline to Day 43 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Baseline (Day 1) to Day 43). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a significant treatment gap for patients with major depressive disorder who have not responded to previous treatments. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Depressive Disorder, Major, Anhedonia, where improved treatment options are needed.

Investor Insight

The large market size and unmet need for effective treatments make this trial an attractive investment opportunity. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 513 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if you have had an inadequate response to at least one antidepressant and if you meet the eligibility criteria. Daily participation involves taking a tablet and attending clinic visits for assessments. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: DOUBLE
• Enrollment: 513 participants

Interventions

• DRUG: Aticaprant — Aticaprant will be administered orally as tablets.
• OTHER: Placebo — Placebo will be administered orally as tablets.

Primary Outcomes

• Change From Baseline to Day 43 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Baseline (Day 1) to Day 43)

Secondary Outcomes

• 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), Days 15, 29 and 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)

Full 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 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

Trial Locations

• SW Biomedical Research LLC, Tucson, Arizona, United States
• University of Arizona, Tucson, Arizona, United States
• Advanced Research Center Inc, Anaheim, California, United States
• Proscience Research Group, Culver City, California, United States
• Behavioral Research Specialists LLC, Glendale, California, United States
• Asclepes Research, Long Beach, California, United States
• Excell Research Inc, Oceanside, California, United States
• Syrentis Clinical Research, Santa Ana, California, United States
• Viking Clinical Research Ltd, Temecula, California, United States
• University of Connecticut Health Center, Farmington, Connecticut, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Major Depressive Disorder
• Anhedonia
• Antidepressant Treatment Failure
• Selective Serotonin Reuptake Inhibitors (SSRIs)
• Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
• Psychotherapy
• Electroconvulsive Therapy
• Vagal Nerve Stimulation
• Deep Brain Stimulation

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