A Study to Assess Adverse Events and Change in Disease Activity of Oral Icalcaprant in Adult Participants With Bipolar I or II Disorder

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

Bipolar disorder is a severe chronic mood disorder that affects up to 4% of the adult population and 1.8% of the pediatric population in the United States. This study will assess how safe and effective Icalcaprant is in treating adult participants with bipolar I or II disorder.

Icalcaprant is an investigational drug being developed for the treatment of depressive episodes in adult participants with bipolar I or II 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 a placebo. Around 195 adult participants with bipolar I or II disorder will be enrolled in approximately 35 sites across the United States of America.

Participants will receive oral capsules of Icalcaprant or matching placebo once daily for 6 weeks, with a 4-week safety follow-up period.

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: Bipolar I Disorder; Bipolar II 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
    • Huntsville, Alabama, United States, 35801
      • Recruiting
      • University of Alabama - Huntsville Regional Medical Campus /ID# 272951
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Recruiting
      • Chandler Clinical Research Trials /ID# 274500
  • Arkansas
    • Bryant, Arkansas, United States, 72022
      • Recruiting
      • Sanro Clinical Research Group /ID# 279462
  • California
    • Anaheim, California, United States, 92805
      • Recruiting
      • Advanced Research Center /ID# 272828
    • Garden Grove, California, United States, 92845
      • Recruiting
      • Collaborative Neuroscience Research - Garden Grove /ID# 271917
    • Montclair, California, United States, 91763
      • Recruiting
      • Catalina Research Institute, LLC /ID# 272831
    • Oceanside, California, United States, 92056
      • Recruiting
      • Excell Research /ID# 272854
    • Orange, California, United States, 92868
      • Recruiting
      • Pacific Neuropsychiatric Specialists - Orange /ID# 273118
    • Sherman Oaks, California, United States, 91403
      • Recruiting
      • Schuster Medical Research Institute /ID# 272848
  • Florida
    • Hollywood, Florida, United States, 33024
      • Recruiting
      • CenExel Hollywood FL /ID# 273101
    • Largo, Florida, United States, 33777
      • Recruiting
      • Accel Research Sites Network - St. Pete /ID# 272962
    • Orlando, Florida, United States, 32814
      • Recruiting
      • Combined Research Orlando Phase I-IV /ID# 279458
    • Orlando, Florida, United States, 32803
      • Recruiting
      • Apg Research /ID# 272925
    • Pompano Beach, Florida, United States, 33060
      • Recruiting
      • Clinical Research Center Of Florida /ID# 278790
    • Saint Augustine, Florida, United States, 32086
      • Recruiting
      • St. Johns Center for Clinical Research - Saint Augustine Location /ID# 279465
    • West Palm Beach, Florida, United States, 33407
      • Recruiting
      • Neuroscience Institute - West Palm Beach /ID# 272922
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Recruiting
      • Georgia Psychiatric Consultants & Advanced Discovery Research /ID# 279438
  • Illinois
    • Chicago, Illinois, United States, 60641
      • Recruiting
      • Pillar Clinical Research - Chicago /ID# 272823
      • Contact: Site Coordinator; Phone Number: 2245347332
    • Warrenville, Illinois, United States, 60555
      • Recruiting
      • Amr Conventions Research /ID# 272867
  • Missouri
    • Saint Charles, Missouri, United States, 63304
      • Recruiting
      • St. Charles Psychiatric Associates /ID# 279239
  • New York
    • New York, New York, United States, 10036
      • Recruiting
      • Manhattan Behavioral Medicine /ID# 279769
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • University Of Cincinnati Medical Center /ID# 274160
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University /ID# 272954
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
      • Recruiting
      • Sooner Clinical Research /ID# 272856
  • Texas
    • Austin, Texas, United States, 78754
      • Recruiting
      • Community Clinical Research - Austin - Cross Park Drive /ID# 272940
    • Houston, Texas, United States, 77007
      • Recruiting
      • Elixia - Houston /ID# 279200
    • Missouri City, Texas, United States, 77459-5204
      • Recruiting
      • Mind Matters Psychiatry /ID# 273536
    • Richardson, Texas, United States, 75080
      • Recruiting
      • Pillar Clinical Research - Richardson /ID# 272821
    • The Woodlands, Texas, United States, 77381
      • Recruiting
      • Family Psychiatry Of The Woodlands /ID# 275177
  • Washington
    • Bellevue, Washington, United States, 98007
      • Recruiting
      • Northwest Clinical Research Center /ID# 272847
    • Everett, Washington, United States, 98201
      • Recruiting
      • Core Clinical Research /ID# 272955

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participants with a diagnosis of bipolar I or II according to the (Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) DSM-5-TR) without psychotic features, confirmed by the Mini International Neuropsychiatric Interview (MINI) 7.0.2, and currently experiencing an (major depressive episode) MDE beginning at least 4 weeks prior to consent and not exceeding 6 months prior to screening.
• Body Mass Index (BMI) is ≥ 18.0 to ≤ 35.0 kg/m^2.
• A condition of general good health, based upon the results of a medical history, physical examination, vital signs, laboratory profile and a 12-lead ECG.
• CGI-S-BP score of ≥ 4 for depression and overall bipolar illness at screening (Visit 1) and baseline (Visit 2).
• YMRS total score ≤ 12 at screening (Visit 1) and baseline (Visit 2).

• Participants on treatment with a single mood stabilizer (lithium, valproate, or lamotrigine), maintained at a stable dose for ≥ 28 days prior to screening. Current mood stabilizer dose must remain unchanged for the duration of the study.

  • If taking lithium or valproate, participant must have a therapeutic blood level at screening of lithium (0.8 - 1.2 mg/dL) or valproate (50 - 125 mg/dL).
  • If taking lamotrigine, participant must be taking a locally approved maintenance dose.

Exclusion Criteria:

• 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.
• History of or active medical conditions(s) that might interfere with the conduct of the study, confound the interpretation of the study results, or endanger the subject's well-being. This includes any unstable condition, history or evidence of malignancy (other than treated basal or squamous cell carcinoma), or any significant hematologic, endocrine, cardiovascular, respiratory, renal, hepatic, gastrointestinal, or neurological disorder (if there is a history of such disease but the condition has been stable for more than 1 year, does not require treatment with prohibited medications, and is judged by the investigator not to interfere with the participant's participation in the study, the participant may be included in the study).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Icalcaprant Dose A; Participants will receive oral Icalcaprant dose A once daily for 6 weeks and followed for 4 weeks.	Drug: Icalcaprant; Oral Capsules; Other Names: ABBV-1354; CVL-354
Experimental: Group 2: Icalcaprant Dose B; Participants will receive oral Icalcaprant dose B once daily for 6 weeks and followed for 4 weeks.	Drug: Icalcaprant; Oral Capsules; Other Names: ABBV-1354; CVL-354
Placebo Comparator: Group 3: Placebo for Icalcaprant; Participants will receive oral placebo for Icalcaprant daily for 6 weeks and followed for 4 weeks.	Drug: Placebo for Icalcaprant; Oral Capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline to Week 6 in the MADRS (Montgomery-Åsberg Depression Rating Scale) total score	MADRS is a depression rating scale consisting of 10 items representing the core symptoms of depressive illness, each rated 0 (no symptom) to 6 (severe symptom). Total score ranges from 0 (no depression) to 60 (severely depressed).	Up to approximately Week 6
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 to Week 6 in Clinician Global Impression of Severity - Bipolar Disorder (CGI-S-BP) score	Clinician Global Impression of Severity - Bipolar Disorder (CGI-S-BP) is a clinician-reported measure of severity of mania, depression, and overall bipolar disorder. Clinicians are asked to consider their total clinical experience with bipolar subjects and assess how severely ill has the participant been during the past 7 days. Response options range from 'Normal, not ill' to 'Very severely ill'.	Up to approximately Week 6

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): February 3, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: November 18, 2024
• First Submitted That Met QC Criteria: November 18, 2024
• First Posted (Actual): November 20, 2024

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: Bipolar Disorder; Bipolar I Disorder; Bipolar II Disorder; lcalcaprant; ABBV-1354; CVL-354
• Additional Relevant MeSH Terms: Bipolar and Related Disorders; Mental Disorders; Mood Disorders; Bipolar Disorder
• Other Study ID Numbers: M25-526

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.: Yes