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 (VENTURA-1)

• ClinicalTrials.gov Identifier: NCT05455684
• Recruitment Status: Recruiting
• First Posted: July 13, 2022
• Last Update Posted: April 24, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: July 10, 2022
• First Posted Date: July 13, 2022
• Last Update Posted Date: April 24, 2024
• Actual Study Start Date: June 22, 2022
• Estimated Primary Completion Date: September 18, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 10, 2022)

Change from Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score to Day 43 [ Time Frame: Baseline 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 22, 2023)

• Change from Baseline in Dimensional Anhedonia Rating Scale (DARS) Total Score to Day 43 [ Time Frame: Baseline 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).
• Change from Baseline in MADRS Total Score over Time [ Time Frame: Baseline up to Day 57 ]
  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.
• Percentage of Responders on Depressive Symptoms Scale from Baseline to Day 43 [ Time Frame: 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.
• Percentage of Participants with Remission of Depressive Symptoms Defined as a MADRS Total Score <=10 at Day 43 [ Time Frame: 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.
• Change from Baseline in Patient Health Questionnaire, 9-Item (PHQ-9) Total Score to Day 43 [ Time Frame: Baseline 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.
• Change from Baseline in DARS Total Score Over Time [ Time Frame: Baseline up to Day 57 ]
  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).
• Change from Baseline in the PHQ-9 Anhedonia-specific Item (PHQ-9, item 1) Over Time [ Time Frame: Baseline up to Day 57 ]
  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.
• Percentage of Participants with a Score Less than (<) 2 in the PHQ-9 Anhedonia-specific Item (PHQ-9, Item 1) at Day 43 [ Time Frame: 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.
• 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 [ Time Frame: Baseline up to Day 57 ]
  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.
• Change from Baseline over Time in the Work Productivity and Activity Impairment (WPAI:D) [ Time Frame: Baseline up to Day 43 ]
  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.

Original Secondary Outcome Measures (submitted: July 10, 2022)

• Change from Baseline in Dimensional Anhedonia Rating Scale (DARS) Total Score to Day 43 [ Time Frame: Baseline 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).
• Change from Baseline in MADRS Total Score over Time [ Time Frame: Baseline up to Day 57 ]
  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.
• Percentage of Responders on Depressive Symptoms Scale from Baseline to Day 43 [ Time Frame: 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.
• Percentage of Participants with Remission of Depressive Symptoms Defined as a MADRS Total Score <=12 at Day 43 [ Time Frame: Day 43 ]
  Percentage of participants with remission of depressive symptoms, defined as a MADRS total score less than or equal to (<=) 12 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.
• Change from Baseline in Patient Health Questionnaire, 9-Item (PHQ-9) Total Score to Day 43 [ Time Frame: Baseline 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.
• Change from Baseline in DARS Total Score Over Time [ Time Frame: Baseline up to Day 57 ]
  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).
• Change from Baseline in the PHQ-9 Anhedonia-specific Item (PHQ-9, item 1) Over Time [ Time Frame: Baseline up to Day 57 ]
  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.
• Percentage of Participants with a Score Less than (<) 2 in the PHQ-9 Anhedonia-specific Item (PHQ-9, Item 1) at Day 43 [ Time Frame: 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.
• Change from Baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) Social Functioning Short Form 8a Total Score Over Time [ Time Frame: Baseline up to Day 57 ]
  The PROMIS Social Functioning Short Form Version 8a includes items selected from the PROMIS social functioning 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 social functioning short form are scaled on a T-score metric with a mean of 50 and a standard deviation (SD) of 10.
• Change from Baseline over Time in the Work Productivity and Activity Impairment (WPAI:D) [ Time Frame: Baseline up to Day 43 ]
  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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• 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 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Depressive Disorder, Major
• Anhedonia

Intervention

• Drug: Aticaprant
  Aticaprant will be administered orally as tablets.
  Other Name: JNJ-67953964
• Other: Placebo
  Placebo will be administered orally as tablets.

Study Arms

• Experimental: Aticaprant
  Participants will receive aticaprant tablets orally once daily for 42 days during double-blind treatment phase in addition to the current antidepressant selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) therapy. Participants who will complete the double-blind treatment phase (Day 43) may be eligible to participate in a separate 52-week open-label long-term safety study (67953964MDD3003).
  Intervention: Drug: Aticaprant
• Placebo Comparator: Placebo
  Participants will receive matching placebo orally once daily for 42 days during double-blind treatment phase in addition to their current antidepressant (SSRI/SNRI) therapy. Participants who will complete the double-blind treatment phase (Day 43) may be eligible to participate in a separate 52-week open-label long-term safety study (67953964MDD3003).
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 6, 2022): 538
• Original Estimated Enrollment (submitted: July 10, 2022): 592
• Estimated Study Completion Date: October 1, 2024
• Estimated Primary Completion Date: September 18, 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 74 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Contact; 844-434-4210; Participate-In-This-Study@its.jnj.com

• Listed Location Countries: Argentina, Australia, Belgium, Brazil, Bulgaria, Czechia, Hungary, Italy, Poland, Portugal, Spain, Sweden, United States
• Removed Location Countries: Korea, Republic of

Administrative Information

• NCT Number: NCT05455684
• Other Study ID Numbers: CR109217; 2022-000439-22 ( EudraCT Number ); 67953964MDD3001 ( Other Identifier: Janssen Research & Development, LLC )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
• URL: https://www.janssen.com/clinical-trials/transparency

• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: April 2024