A Study to Evaluate Safety and Tolerability of CVL-231 (Emraclidine) in Adult Participants With Schizophrenia

August 19, 2026 updated by: AbbVie

A 52-week, Phase 2, Open-label Trial to Evaluate the Long-term Safety and Tolerability of CVL-231 (Emraclidine) in Adult Participants With Schizophrenia

The primary purpose of this study is to assess the long-term safety and tolerability of oral emraclidine in adult participants with schizophrenia.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

698

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bulgaria
      • Pazardzhik, Bulgaria, 4400
        • Pazardzhik, Pazardzhik
      • Pleven, Bulgaria, 5800
        • Pleven, Pleven
      • Sliven, Bulgaria, 8800
        • Sliven, Sliven
      • Stara Zagora, Bulgaria, 6003
        • Stara Zagora, Stara Zagora
      • Varna, Bulgaria, 9000
        • Varna, Varna
      • Veliko Tarnovo, Bulgaria, 5000
        • Veliko Tarnovo, Veliko Tarnovo
      • Vratsa, Bulgaria, 3000
        • Vratsa, Vratsa
    • Sofia-Grad
      • Sofia, Sofia-Grad, Bulgaria, 1431
        • Sofia, Sofia-Grad
      • Sofia, Sofia-Grad, Bulgaria, 1202
        • Sofia, Sofia-Grad
      • Sofia, Sofia-Grad, Bulgaria, 1407
        • Sofia, Sofia-Grad
      • Sofia, Sofia-Grad, Bulgaria, 1510
        • Sofia, Sofia-Grad
      • Sofia, Sofia-Grad, Bulgaria, 1606
        • Sofia, Sofia-Grad
      • Sofia, Sofia-Grad, Bulgaria, 1680
        • Sofia, Sofia-Grad
  • Hungary
    • Bács-Kiskun county
      • Kalocsa, Bács-Kiskun county, Hungary, 6300
        • Kalocsa, Bács-Kiskun
    • Győr-Moson-Sopron
      • Győr, Győr-Moson-Sopron, Hungary, 9024
        • Gyor, Gyor-Moson-Sopron
  • Puerto Rico
      • San Juan, Puerto Rico, 918
        • San Juan, Puerto Rico
      • San Juan, Puerto Rico, 926
        • San Juan, Puerto Rico
  • Ukraine
      • Kropyvnytskyi, Ukraine, 25491
        • Kropyvnytskyi, Kropyvnytskyi
      • Kyiv, Ukraine, 04080
        • Kyiv, Kyïv
      • Smila, Ukraine, 20708
        • Smila, Smila
      • Vinnytsia, Ukraine, 21018
        • Vinnytsia, Vinnytsia
    • Ivano-Frankivsk Oblast
      • Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine, 76011
        • Ivano Frankivsk, Ivano Frankivsk
    • Lviv Oblast
      • Lviv, Lviv Oblast, Ukraine, 79021
        • Lviv, L'vivs'ka Oblast
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85012-2707
        • Phoenix, Arizona
    • Arkansas
      • Bryant, Arkansas, United States, 72022-9252
        • Bryant, Arkansas
      • Little Rock, Arkansas, United States, 72211-3702
        • Little Rock, Arkansas
    • California
      • Anaheim, California, United States, 92805-5854
        • Anaheim, California
      • Bellflower, California, United States, 90706-7079
        • Bellflower, California
      • Culver City, California, United States, 90230-6632
        • Culver City, California
      • Garden Grove, California, United States, 92845-2506
        • Garden Grove, California
      • La Habra, California, United States, 90631-3842
        • La Habra, California
      • Lemon Grove, California, United States, 91945-2956
        • Lemon Grove, California
      • Montclair, California, United States, 91763-2231
        • Montclair, California
      • Orange, California, United States, 92868-4447
        • Orange,California
      • Pico Rivera, California, United States, 90660-4920
        • Pico Rivera, California
      • Riverside, California, United States, 92506-3237
        • Riverside, California
      • San Diego, California, United States, 92103-2209
        • San Diego, California
      • San Diego, California, United States, 92123
        • San Diego, California
      • San Diego, California, United States, 92121
        • San Diego, California
      • Sherman Oaks, California, United States, 91403-1747
        • Sherman Oaks, California
      • Torrance, California, United States, 90502-4432
        • Torrance, California
      • Walnut Creek, California, United States, 94549
        • Walnut Creek, California
    • Connecticut
      • New Haven, Connecticut, United States, 06519-1109
        • New Haven, Connecticut
    • Florida
      • Bonita Springs, Florida, United States, 34134-4154
        • Bonita Springs,Florida
      • Fort Myers, Florida, United States, 33901-3711
        • Fort Myers, Florida
      • Hialeah, Florida, United States, 33012-4648
        • Hialeah, Florida
      • Hialeah, Florida, United States, 33016-1814
        • Hialeah, Florida
      • Miami, Florida, United States, 33155
        • Miami, Florida
      • Miami, Florida, United States, 33122-1335
        • Miami, Florida
      • Miami, Florida, United States, 33125-5114
        • Miami, Florida
      • Miami Lakes, Florida, United States, 33016-1553
        • Miami Lakes, Florida
      • Miami Lakes, Florida, United States, 33016
        • Miami Lakes, Florida
      • Miami Springs, Florida, United States, 33166-7225
        • Miami Springs, Florida
      • Oakland Park, Florida, United States, 33334-4135
        • Oakland Park, Florida
      • West Palm Beach, Florida, United States, 33407-2015
        • West Palm Beach, Florida
    • Georgia
      • Atlanta, Georgia, United States, 30331
        • Atlanta, Georgia
      • Atlanta, Georgia, United States, 30328-4018
        • Atlanta, Georgia
      • Atlanta, Georgia, United States, 30318-3102
        • Atlanta, Georgia
      • Decatur, Georgia, United States, 30030-3438
        • Decatur, Georgia
      • Savannah, Georgia, United States, 31405-5702
        • Savannah,Georgia
    • Illinois
      • Berwyn, Illinois, United States, 60402-2248
        • Berwyn, Illinois
      • Chicago, Illinois, United States, 60640-5017
        • Chicago, Illinois
      • Chicago, Illinois, United States, 60611-3478
        • Chicago, Illinois
      • Chicago, Illinois, United States, 60622-1702
        • Chicago, Illinois
      • Chicago, Illinois, United States, 60623
        • Chicago, Illinois
      • Chicago, Illinois, United States, 60641-4023
        • Chicago, Illinois
    • Louisiana
      • Marrero, Louisiana, United States, 70072-3083
        • Marrero, Louisiana
      • Shreveport, Louisiana, United States, 71101-4603
        • Shreveport, Louisiana
    • Maryland
      • Gaithersburg, Maryland, United States, 20877-1409
        • Gaithersburg, Maryland
    • Mississippi
      • Flowood, Mississippi, United States, 39232-8016
        • Flowood, Mississippi
    • Nevada
      • Las Vegas, Nevada, United States, 89102-1972
        • Las Vegas, Nevada
    • New Jersey
      • Berlin, New Jersey, United States, 08009
        • Berlin, New Jersey
    • New York
      • Cedarhurst, New York, United States, 11516-1905
        • Cedarhurst, New York
      • New York, New York, United States, 10036-4811
        • New York, New York
      • Staten Island, New York, United States, 10314-1607
        • Staten Island, New York
    • North Carolina
      • Charlotte, North Carolina, United States, 28211-4849
        • Charlotte, North Carolina
    • Ohio
      • North Canton, Ohio, United States, 44718-2567
        • North Canton, Ohio
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73102-1018
        • Oklahoma City, Oklahoma
    • Tennessee
      • Franklin, Tennessee, United States, 37067-5967
        • Franklin,Tennessee
    • Texas
      • Austin, Texas, United States, 78754-5122
        • Austin, Texas
      • DeSoto, Texas, United States, 75115-2066
        • DeSoto, Texas
      • Houston, Texas, United States, 77043
        • Houston, Texas
      • Houston, Texas, United States, 77074
        • Houston, Texas
      • Plano, Texas, United States, 75093-0010
        • Plano, Texas
      • Richardson, Texas, United States, 75080-3764
        • Richardson, Texas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Completed 6 weeks of post-randomization treatment in Trial CVL-231-2001 (NCT05227690) or CVL-231-2002 (NCT05227703) and who, in the opinion of the investigator, could potentially benefit from treatment with emraclidine for schizophrenia.
  2. Primary diagnosis of schizophrenia per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), as confirmed by the Mini International Neuropsychiatric Interview (MINI) for Psychotic Disorders.
  3. Participants who have been stable on antipsychotic medication for at least one 3-month in the year prior to screening.
  4. Outpatient status at the time of signing the informed consent form informed consent form (ICF).
  5. Willing to discontinue all prohibited medications to meet protocol-required washouts prior to and during the trial period.
  6. Ability, in the investigator's opinion, to understand the nature of the trial, participate in trial visits, and comply with protocol requirements.

Exclusion Criteria:

  1. Current DSM-5 diagnosis other than schizophrenia (note: anxiety symptoms secondary to schizophrenia are allowed.

    • Acute depressive symptoms within 30 days prior to signing the ICF that require treatment with an antidepressant are exclusory.
    • Acute manic symptoms within 30 days prior to signing the ICF that require treatment with a mood stabilizer are exclusory.

  2. Any of the following:

    • Schizophrenia is considered resistant/refractory to antipsychotic treatment by history (failure to respond to 2 or more courses of adequate pharmacological treatment defined as an adequate dose per label and a treatment duration of at least 4 weeks).
    • History of response to clozapine treatment only or failure to respond to clozapine treatment.
  3. Current or past history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, genitourinary, endocrine (including diabetes mellitus), malignancy (except for basal cell carcinoma of the skin and cervical carcinoma in situ, at the discretion of the investigator), hematological, immunological, neurological, or psychiatric disease that, in the opinion of the investigator or medical monitor, could compromise either participant safety or the results of the trial.
  4. Active central nervous system infection, demyelinating disease, degenerative neurological disease, brain tumor, prior hospitalization for severe head trauma, seizures (excluding febrile seizures in childhood), or any central nervous system disease deemed to be progressive during the trial that may confound the interpretation of the trial results
  5. Diagnosis of moderate to severe substance or alcohol use disorder (excluding nicotine or caffeine) as per DSM-5 criteria within 12 months prior to signing the ICF.
  6. Risk for suicidal behavior as assessed by the C-SSRS and investigator's clinical assessment.
  7. Any condition that could possibly affect drug absorption, including, but not limited to bowel resections, bariatric weight loss surgery, gastric banding, and gastrectomy
  8. Use of prohibited medications prior to randomization within the required wash-out period or likely to require prohibited concomitant therapy during the trial.
  9. Clinically significant abnormal findings on the physical examination, medical history review, ECG, or clinical laboratory results at screening.
  10. Positive pregnancy test result prior to receiving investigational medicinal product (IMP).

Note: female participants who are pregnant, breastfeeding, or planning to become pregnant during IMP treatment or within 7 days after the last dose of the IMP are also excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CVL-231-2001/2002 Active Rollover
Participants who completed treatment with emraclidine in one of the double-blind, placebo-controlled Phase 2 efficacy trials (CVL-231-2001; NCT05227690 or CVL-231-2002; NCT05227703) were denoted as "active rollover" participants. They received emraclidine 30 mg tablets orally once daily (QD) for 52 weeks in this study.
Drug: Emraclidine 30 mg
Emraclidine 30 mg, oral (tablet), once per day for 52 weeks
Other Names:
  • CVL-231
  • ABBV-1231
Experimental: CVL-231-2001/2002 Placebo Rollover
Participants who completed treatment with placebo for emraclidine in one of the double-blind, placebo-controlled Phase 2 efficacy trials (CVL-231-2001; NCT05227690 or CVL-231-2002; NCT05227703) were denoted as "placebo rollover" participants. They received emraclidine 30 mg tablets orally once daily (QD) for 52 weeks in this study.
Drug: Emraclidine 30 mg
Emraclidine 30 mg, oral (tablet), once per day for 52 weeks
Other Names:
  • CVL-231
  • ABBV-1231
Experimental: De Novo
Participants with stable schizophrenia who were not enrolled in one of the prior Phase 2 efficacy trials were denoted as "de novo" participants. They received emraclidine 30 mg tablets orally once daily (QD) for 52 weeks in this study.
Drug: Emraclidine 30 mg
Emraclidine 30 mg, oral (tablet), once per day for 52 weeks
Other Names:
  • CVL-231
  • ABBV-1231

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Time Frame: From first dose of study drug until 28 days following last dose of study drug (up to Week 56)
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 drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.
From first dose of study drug until 28 days following last dose of study drug (up to Week 56)
Number of Participants With Out-of-Range Vital Signs Occurring Post-Baseline
Time Frame: Baseline; from first dose of study drug up to Week 52
Vital signs were obtained after the participant had been supine and at rest for 3 minutes and included systolic and diastolic blood pressure, heart rate, temperature, and respiratory rate.
Baseline; from first dose of study drug up to Week 52
Number of Participants With Clinically Significant Changes in Body Weight
Time Frame: Baseline; from first dose of study drug up to Week 52
Participants' body weights were measured and recorded.
Baseline; from first dose of study drug up to Week 52
Number of Participants With Post-Baseline Clinically Significant Physical Examinations and Neurological Examinations
Time Frame: Baseline; from first dose of study drug up to Week 52
The number of participants with clinically significant changes in physical and neurological examination results post-treatment was documented.
Baseline; from first dose of study drug up to Week 52
Number of Participants With Clinically Significant Post-Baseline Changes in Electrocardiogram (ECG) Values
Time Frame: Baseline; from first dose of study drug up to Week 52
12-lead electrocardiogram (ECG) recordings were obtained after the participant had been supine and at rest for at least 3 minutes.
Baseline; from first dose of study drug up to Week 52
Number of Participants With Clinically Significant Changes in Clinical Laboratory Values
Time Frame: Baseline; from first dose of study drug up to Week 52
Clinical laboratory tests were performed at scheduled study visits, and the investigator recorded any clinically significant changes.
Baseline; from first dose of study drug up to Week 52
Number of Participants With Clinically Significant Changes in Metabolic Parameter Values
Time Frame: Baseline; from first dose of study drug up to Week 52
Clinical laboratory tests were performed at scheduled study visits, and the investigator recorded any clinically significant changes in metabolic parameter values.
Baseline; from first dose of study drug up to Week 52
Number of Participants With Suicide-Related Treatment-Emergent Events Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)
Time Frame: Baseline; from first dose of study drug up to Week 52
The C-SSRS rates an individual's degree of suicidal ideation (SI) on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent." The scale identifies SI severity and intensity, which may be indicative of an individual's intent to commit suicide. C-SSRS SI severity subscale ranges from 0 (no SI) to 5 (active SI with plan and intent).
Baseline; from first dose of study drug up to Week 52
Change From Baseline in Simpson Angus Scale (SAS) Total Score
Time Frame: Baseline; Weeks 4, 8, 12, 20, 26, 32, 38, 44, and 52
The SAS consists of a list of 10 symptoms of parkinsonism. Each item is rated on a 5-point scale, with a score of 0 representing absence of symptoms and a score of 4 representing a severe condition. The SAS total score is the sum of the scores for all 10 items. Baseline was defined as the last value obtained prior to initiation of study drug. Change from baseline for a given endpoint was defined as the value on a given Study Day (Time Point) minus the Baseline Value. Negative changes from Baseline indicate an improvement in symptoms.
Baseline; Weeks 4, 8, 12, 20, 26, 32, 38, 44, and 52
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Rating Score
Time Frame: Baseline; Weeks 4, 8, 12, 20, 26, 32, 38, 44, and 52

The Abnormal Involuntary Movement Scale assessment consists of 10 items describing symptoms of dyskinesia. Facial and oral movements (items 1-4), extremity movements (items 5 and 6), and trunk movements (item 7) are observed unobtrusively while the participant is at rest, and the investigator also makes global judgments on the participant's dyskinesias (items 8-10). Each item is rated on a 5-point scale, with a score of 0 representing absence of symptoms (for item 10, no awareness), and a score of 4 indicating a severe condition (for item 10, awareness, severe distress). In addition, the AIMS includes 2 yes/no questions that address the participant's dental status.

The AIMS Movement Rating Score is defined as the sum of individual scores from items 1-7, ranging from 0 to 28. A lower score indicates less severe or absent abnormal movements. A negative change in the mean from Baseline indicates improvement in the severity of abnormal involuntary movements.
Baseline; Weeks 4, 8, 12, 20, 26, 32, 38, 44, and 52
Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Evaluation Score
Time Frame: Baseline; Weeks 4, 8, 12, 20, 26, 32, 38, 44, and 52
The BARS consists of 4 items related to akathisia. The fourth item, reported here, is the Global Clinical Evaluation Score. The Global Clinical Evaluation Score is evaluated using a 6-point scale, ranging from 0 to 5, with 0 representing absence of symptoms and a score of 5 representing severe akathisia. A negative change from baseline indicates an improvement in symptoms.
Baseline; Weeks 4, 8, 12, 20, 26, 32, 38, 44, and 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AbbVie

Investigators

  • Study Director: ABBVIE INC., AbbVie

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2022

Primary Completion (Actual)

June 25, 2025

Study Completion (Actual)

June 25, 2025

Study Registration Dates

First Submitted

June 29, 2022

First Submitted That Met QC Criteria

June 29, 2022

First Posted (Actual)

July 5, 2022

Study Record Updates

Last Update Posted (Actual)

August 21, 2026

Last Update Submitted That Met QC Criteria

August 19, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CVL-231-2003
  • 2022-001151-16 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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