A Study to Assess Change in Disease Activity and Adverse Events of Oral Icalcaprant in Adult Participants With Major Depressive Disorder

A Phase 2, Multicenter, 6-Week, Double Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Icalcaprant in Subjects With Major Depressive Disorder

Major depressive disorder (MDD; depression) is a mood disorder that causes a continued feeling of sadness and loss of interest. It is a common and serious illness that can cause both emotional and physical symptoms such as feelings of sadness, irritability, not being able to focus on activities, tiredness, changes in eating habits, and aches and pains. This study will assess the changes in disease activity and adverse events of oral Icalcaprant in adult participants with major depressive disorder who are currently experiencing a major depressive episode (MDE).

Icalcaprant is an investigational drug being developed for the treatment of depressive episodes in adult participants with major depressive disorder. Participants are placed in 1 of 3 groups, called treatment arms. There is a 1 in 3 chance that a participant will be assigned to placebo treatment. Around 195 adult participant with major depressive disorder will be enrolled in approximately 35 sites in North America.

Participants will receive oral capsules of Icalcaprant or matching placebo once daily for 6 weeks, with a 30-day safety follow-up.

There may be a higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Icalcaprant; Drug: Placebo for Icalcaprant

• Study Type: Interventional
• Enrollment (Estimated): 195
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: ABBVIE CALL CENTER; Phone Number: 844-663-3742; Email: abbvieclinicaltrials@abbvie.com

Study Locations

• United States
  • Alabama
    • Dothan, Alabama, United States, 36303
      • Recruiting
      • Harmonex /ID# 277517
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Recruiting
      • Ima Clinical Research Phoenix (Alea) /ID# 277516
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Recruiting
      • Preferred Research Partner, Inc /ID# 279206
    • Little Rock, Arkansas, United States, 72211
      • Recruiting
      • Woodland International Research Group /ID# 277605
  • California
    • Anaheim, California, United States, 92805
      • Recruiting
      • Advanced Research Center /ID# 277537
    • Imperial, California, United States, 92251
      • Recruiting
      • Sun Valley Research Center /ID# 277513
    • Lemon Grove, California, United States, 91945
      • Recruiting
      • Synergy San Diego /ID# 277553
    • Long Beach, California, United States, 90807
      • Recruiting
      • Accellacare - Long Beach /ID# 279181
    • Sherman Oaks, California, United States, 91403
      • Recruiting
      • CenExel CNR /ID# 277533
    • Temecula, California, United States, 92591
      • Recruiting
      • Inland Psychiatric Medical Group Inc. /ID# 279275
    • Walnut Creek, California, United States, 94596
      • Recruiting
      • Sunwise Clinical Research /ID# 277555
  • Florida
    • Hollywood, Florida, United States, 33024
      • Recruiting
      • CenExel Hollywood FL /ID# 278200
    • Jacksonville, Florida, United States, 32256
      • Recruiting
      • Cns Healthcare - Jacksonville /ID# 277658
    • Miami, Florida, United States, 33125
      • Recruiting
      • GMI Florida - Central Miami Medical Institute /ID# 278218
    • Orlando, Florida, United States, 32801
      • Recruiting
      • Clinical Neuroscience Solutions - Orlando - East South Street /ID# 277558
    • Riverview, Florida, United States, 33578
      • Recruiting
      • EquiPath Health & Research Tampa Bay, LLC /ID# 279128
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Recruiting
      • Trialmed /ID# 277601
    • Norcross, Georgia, United States, 30092
      • Recruiting
      • Evergreen Clinical Trials - Norcross /ID# 279421
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Recruiting
      • Flourish Research - Great Lakes Clinical Trials /ID# 278201
    • Warrenville, Illinois, United States, 60555
      • Recruiting
      • Amr Conventions Research /ID# 277547
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Recruiting
      • Redbird Research /ID# 277485
  • New York
    • New York, New York, United States, 10036
      • Recruiting
      • Manhattan Behavioral Medicine /ID# 277910
    • New York, New York, United States, 10036
      • Recruiting
      • Ima Clinical Research - Manhattan /ID# 278212
  • Ohio
    • Avon Lake, Ohio, United States, 44012-1004
      • Recruiting
      • Quest Therapeutics of Avon /ID# 277550
    • Columbus, Ohio, United States, 43210-1250
      • Recruiting
      • OSU Psychiatry Department /ID# 277529
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
      • Recruiting
      • Sooner Clinical Research /ID# 277659
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Recruiting
      • CNS Healthcare - Memphis /ID# 278192
  • Texas
    • Austin, Texas, United States, 78754
      • Recruiting
      • Community Clinical Research - Austin - Cross Park Drive /ID# 277935
    • Austin, Texas, United States, 78737
      • Recruiting
      • Austin Clinical Trial Partners /ID# 279321
    • Bellaire, Texas, United States, 77401
      • Recruiting
      • Houston Clinical Trials - Bellaire /ID# 277551
    • Richardson, Texas, United States, 75080
      • Recruiting
      • Pillar Clinical Research - Richardson /ID# 276764
  • Washington
    • Bellevue, Washington, United States, 98007
      • Recruiting
      • Northwest Clinical Research Center /ID# 277484
    • Everett, Washington, United States, 98201
      • Recruiting
      • Core Clinical Research /ID# 277518

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants with a diagnosis of major depressive disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, text revision (DSM-5-TR) without psychotic features, confirmed by the Mini International Neuropsychiatric Interview (MINI) 7.0.
• Body Mass Index (BMI) is ≥ 18.0 to ≤ 35.0 kg/m^2
• Currently experiencing an major depressive episode (MDE) beginning at least 4 weeks prior to consent and not exceeding 6 months prior to Screening
• Normal physical examination findings, clinical laboratory test results, vital signs, and 12-lead ECG results at Visit 1 or abnormal results that are judged not clinically significant by the investigator and documented as such in the eCRF.

Exclusion Criteria:

• Has failed (no more than 25% response on Antidepressant Treatment History Questionnaire (ATRQ)) 3 or more antidepressant treatments during the current depressive episode despite an adequate dose (per ATRQ) and duration (at least 6 weeks).
• History of an allergic reaction or significant sensitivity to constituents of the study drug (and its excipients) and/or other products in the same class.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Icalcaprant Dose A; Participants will receive oral Icalcaprant dose A once daily for 6 weeks and attend a follow up visit 30 days following end of treatment.	Drug: Icalcaprant; Oral Capsules
Experimental: Icalcaprant Dose B; Participants will receive oral Icalcaprant dose B once daily for 6 weeks and attend a follow up visit 30 days following end of treatment.	Drug: Icalcaprant; Oral Capsules
Placebo Comparator: Placebo for Icalcaprant; Participants will receive oral placebo once daily for 6 weeks and attend a follow up visit 30 days following end of treatment.	Drug: Placebo for Icalcaprant; Oral Capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score.	Montgomery-Åsberg Depression Rating Scale (MADRS) The MADRS is a 10-item, clinician-rated scale that evaluates the participant's depressive symptomatology during the past week. Participants are to be rated on items assessing feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. Each item will be scored on a 7-point scale with a score of 0 reflecting no symptoms and a score of 6 reflecting symptoms of maximum severity.	Up to approximately 6 weeks
Number of Participants with Adverse Events (AEs)	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study.	Up to approximately 10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Clinical Global Impression (CGIS)	Change from Baseline in Clinical Global Impression (CGIS)-The CGIS is a single-item clinician-reported measure of severity of depression. Clinicians are asked to consider their total clinical experience with Participants with major depressive disorder (MDD) and assess how severely ill the participant has been during the past 7 days. Response options range from 1 to 7: 1 = normal to 7 = very severely ill.	Up to approximately 6 weeks

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: December 2, 2025
• First Submitted That Met QC Criteria: December 2, 2025
• First Posted (Actual): December 11, 2025

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Major Depressive Disorder; Icalcaprant
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: M25-987

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.
• IPD Sharing Time Frame: For details on when studies are available for sharing, visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No