A Trial of 15 and 30 mg Doses of CVL-231 (Emraclidine) in Participants With Schizophrenia

A Phase 2, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of Two Fixed Doses (15 mg and 30 mg QD) of CVL-231 (Emraclidine) in Participants With Schizophrenia Experiencing an Acute Exacerbation of Psychosis

This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group, 6-week trial to evaluate the efficacy, safety, and tolerability of 2 fixed doses of CVL-231 (Emraclidine) (15 mg QD and 30 mg QD) in male and female adult participants who have schizophrenia and are experiencing an acute exacerbation of psychosis.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Emraclidine 15 mg; Drug: Emraclidine 30 mg; Drug: Placebo

Detailed Description

The trial included up to a 15-day Screening Period (up to a maximum of 21 days allowed with approval of the medical monitor), a 45-day Inpatient Treatment Period, and a 28-day Follow-up Period. Each participant participated in the trial for up to approximately 13 weeks.

• Study Type: Interventional
• Enrollment (Actual): 391
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Burgas, Bulgaria, 8000
    • Burgas, Burgas
  • Pleven, Bulgaria, 5800
    • Pleven, Pleven
  • Sofia, Bulgaria, 1282
    • Sofia, Sofia
  • Sofia-Grad
    • Sofia, Sofia-Grad, Bulgaria, 1431
      • Sofia, Sofia-Grad
• Hungary
  • Budapest, Hungary, 1083
    • Budapest, Budapest
  • Bács-Kiskun county
    • Kalocsa, Bács-Kiskun county, Hungary, 6300
      • Kalocsa, Bács-Kiskun
  • Győr-Moson-Sopron
    • Győr, Győr-Moson-Sopron, Hungary, 9024
      • Győr, Győr-Moson-Sopron
• United States
  • Arkansas
    • Bentonville, Arkansas, United States, 72712-3873
      • Bentonville, Arkansas
  • California
    • Bellflower, California, United States, 90706-7079
      • Bellflower, California
    • La Habra, California, United States, 90631-3842
      • La Habra, California
    • San Diego, California, United States, 92103-2209
      • San Diego, California
    • Sherman Oaks, California, United States, 91403-1747
      • Sherman Oaks, California
    • Torrance, California, United States, 90504-4432
      • Torrance, California
  • Connecticut
    • New Haven, Connecticut, United States, 06519-1109
      • New Haven, Connecticut
  • Florida
    • Homestead, Florida, United States, 33032-8187
      • Homestead, Florida
    • Miami, Florida, United States, 33122-1335
      • Miami, Florida
    • Miami Lakes, Florida, United States, 33016-1553
      • Miami Lakes, Florida
    • Miami Springs, Florida, United States, 33166-7225
      • Miami Springs, Florida
  • Georgia
    • Atlanta, Georgia, United States, 30331-2012
      • Atlanta, Georgia
    • Savannah, Georgia, United States, 31405-5701
      • Savannah, Georgia
  • Illinois
    • Chicago, Illinois, United States, 60640-5017
      • Chicago, Illinois
    • Chicago, Illinois, United States, 60641
      • Chicago, Illinois
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Berlin, New Jersey
    • Marlton, New Jersey, United States, 08053
      • Marlton, New Jersey
  • North Carolina
    • Charlotte, North Carolina, United States, 28211-4849
      • Charlotte, North Carolina
  • Texas
    • Austin, Texas, United States, 78754-5122
      • Austin, Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Primary diagnosis of schizophrenia per DSM-5, as confirmed by the MINI for Psychotic Disorders.
• CGI-S ≥4 (moderately to severely ill) at the time of signing the ICF and Baseline.
• PANSS Total Score between 85 and 120, inclusive, at the time of signing the ICF and at Baseline.
• Experiencing an acute exacerbation or relapse of psychotic symptoms, with onset less than 60 days prior to signing the ICF.
• Willing to discontinue all prohibited medications to meet protocol-required washouts prior to and during the trial period.
• Body mass index of 18.0 to 40.0 kg/m2 and a total body weight ≥50 kg (110 lbs).
• Ability, in the opinion of the investigator, to understand the nature of the trial, participate in trial visits, and comply with protocol requirements.

Exclusion Criteria:

• 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.

• Any of the following:

  • Schizophrenia 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

• Any of the following regarding history of schizophrenia:

  • Time from initial onset of schizophrenia <2 years based on prior records or participant self-report
  • Presenting with an initial diagnosis of schizophrenia
  • Presenting for the first time with an acute psychotic episode requiring treatment
• Reduction (improvement) in PANSS total score of ≥20% between Screening and Baseline.
• 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.
• 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 course of the trial that may confound the interpretation of the trial results
• 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.
• Risk for suicidal behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) and investigator's clinical assessment.
• Any condition that could possibly affect drug absorption.
• Use of prohibited medications prior to randomization within the required wash-out period or likely to require prohibited concomitant therapy during the trial.
• Clinically significant abnormal findings on the physical examination, medical history review, ECG, or clinical laboratory results at screening.
• Positive pregnancy test result prior to receiving 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 IMP are also excluded.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CVL-231 15 mg, once daily (QD); Oral Dose	Drug: Emraclidine 15 mg; Emraclidine 15 mg, oral (tablet), once per day (QD) for 6 weeks; Other Names: CVL-231; ABBV-1231
Experimental: CVL-231 30 mg, once daily (QD); Oral Dose	Drug: Emraclidine 30 mg; Emraclidine 30 mg, oral (tablet), QD for 6 weeks; Other Names: CVL-231; ABBV-1231
Placebo Comparator: Placebo, once daily (QD); Oral Dose	Drug: Placebo; Matching placebo, oral (tablet), QD for 6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline at Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total Score	The PANSS measures symptom severity of participants with schizophrenia and contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale with a total minimum score of 30 and a maximum score of 210. Baseline was defined as the last value obtained prior to initiation of investigational medicinal product (IMP). Change from baseline for a given endpoint was defined as the value on a given Study Day (Time Point) minus the Baseline Value. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.	Baseline through Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	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 10)
Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments	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 6
Number of Participants With Clinically Significant Changes in Vital Sign Measurements	Vital signs were obtained after the participant had been supine and at rest for 3 minutes and included temperature, systolic and diastolic blood pressure, respiratory rate, and heart rate. Participants' body weights were also measured and recorded.	Baseline; from first dose of study drug up to Week 6
Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results	The number of participants with clinically significant changes in physical and neurological examination results was documented.	Baseline; from first dose of study drug up to Week 6
Number of Participants With Suicide-Related Treatment-Emergent Events Assessed Using the Columbia Suicide-Severity Rating Scale (C-SSRS)	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 6
Change From Baseline at Week 6 in the Clinical Global Impression - Severity (CGI-S Score)	The CGI-S captures clinician's response to: "Considering your total clinical experience, how mentally ill is the participant at this time?" The clinician's answer rated on the following 7-point scale: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill participants. Baseline was defined as the last value obtained prior to initiation of investigational medicinal product (IMP). 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 less mental illness.	Baseline through Week 6
Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score	The PANSS measures symptom severity of participants with schizophrenia and contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale with a total minimum score of 30 and a maximum score of 210. Baseline was defined as the last value obtained prior to initiation of investigational medicinal product (IMP). Change from baseline for a given endpoint was defined as the value on a given Study Day (Time Point) minus the Baseline Value. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.	Baseline; Weeks 1, 2, 3, 4, 5, and 6
Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score	The CGI-S captures clinician's response to: "Considering your total clinical experience, how mentally ill is the participant at this time?" The clinician's answer rated on the following 7-point scale: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill participants. Baseline was defined as the last value obtained prior to initiation of Emraclidine. 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 less mental illness.	Baseline; Weeks 1, 2, 3, 4, 5, and 6
Percentage of Responders at Week 6 (Responders Defined as ≥30% Reduction From Baseline in PANSS Total Score)	The PANSS measures symptom severity of participants with schizophrenia and contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale with a total minimum score of 30 and a maximum score of 210. A PANSS responder is defined as a participant with at least a 30% change in PANSS total score compared to baseline at Week 6 or the early termination visit. If a subject discontinued and did not have an early termination visit, the subject's last assessment was considered.	Baseline through Week 6
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs)	Assessment of clinically significant changes in electrocardiogram measures measured by 12-lead ECG recording after the participant has been supine and at rest for at least 3 minutes.	Baseline; from first dose of study drug up to Week 6
Change From Baseline in Simpson Angus Scale (SAS) Total Score	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 3 and 6
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Rating Score	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 3 and 6
Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Evaluation Score	The BARS consists of 4 items related to akathisia: The first 3 items are rated on a 4-point scale, with a score of 0 representing absence of symptoms and a score of 3 representing a severe condition. The fourth item, reported here, is the Global Clinical Evaluation Score. The Global Clinical Evaluation Score is evaluated using a 6-point scale, with a score of 0 representing the absence of symptoms and a score of 5 representing severe akathisia. A negative change from baseline indicates an improvement in symptoms.	Baseline; Weeks 3 and 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression - Improvement (CGI-I) score at Weeks 3 and 6	The CGI-I captures clinician's response to: "Rate total improvement whether or not, in your judgment, it is due entirely to drug treatment. Compared to his/her condition at admission to the project (screening) how much has he /she changed? 0 = Not assessed 1 = Very much improved 2 = Much improved 3 = Minimally improved 4 = No change 5 = Minimally worse 6 = Much worse 7 = Very much worse	Time Frame: Week 3 and Week 6
Change from Baseline at all time points in Positive and Negative Syndrome Scale (PANSS) positive, negative, and general psychopathology subscale scores	The PANSS measures symptom severity of participants with schizophrenia and contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale with a total minimum score of 30 and a maximum score of 210. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.	Every week from baseline through Week 6
Change from Baseline at all time points in PANSS Marder Factor scores Change from Baseline at all time points in PANSS Marder Factor scores Change from Baseline at all time points in PANSS Marder Factor scores	The Negative Marder Factor score is calculated as the sum of the rating assigned to each of the 7 applicable Marder factor items, and ranges from 7 to 49 with a higher score indicating greater severity of symptoms.	Every week from baseline through Week 6

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: Julie Adams, AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2022
• Primary Completion (Actual): August 15, 2024
• Study Completion (Actual): September 11, 2024

Study Registration Dates

• First Submitted: January 27, 2022
• First Submitted That Met QC Criteria: January 27, 2022
• First Posted (Actual): February 7, 2022

Study Record Updates

• Last Update Posted (Estimated): October 28, 2025
• Last Update Submitted That Met QC Criteria: October 14, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Schizophrenia; Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia; Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders
• Other Study ID Numbers: CVL-231-2002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No