A Trial of 10 and 30 mg Doses of CVL-231 (Emraclidine) in Participants With Schizophrenia

Phase 2

Completed

• Conditions: Schizophrenia
• Interventions: Drug: CVL-231 10 mg; Drug: Required CVL-231 30 mg; Drug: Placebo

• Registration Number: NCT05227690
• Lead Sponsor: AbbVie

Brief Summary

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) (10 mg QD and 30 mg QD) in male and female participants who have schizophrenia and are experiencing an acute exacerbation of psychosis.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-01-27
• Study First Submitted QC: 2022-01-27
• Study First Posted: 2022-02-07
• Study Start: 2022-06-30
• Primary Completion: 2024-08-23
• Study Completion: 2024-08-26
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-24
• Last Update Posted: 2025-04-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 385

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CVL-231 10 mg, once daily (QD)	CVL-231 10 mg	Oral Dose
CVL-231 30 mg, once daily (QD)	Required CVL-231 30 mg	Oral Dose
Placebo, once daily (QD)	Placebo	Oral Dose

Primary Outcome Measures

Name	Time	Method
Change from Baseline at Week 6 in the Positive and Negative Syndrome Scale (PANSS) total score	Baseline through Week 6	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.

Secondary Outcome Measures

Name	Time	Method
Change from Baseline at all time points in the Clinical Global Impression - Severity (CGI-S) score	Baseline through Week 6	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.
Change from Baseline at Week 6 in the Clinical Global Impression - Severity (CGI-S score)	Baseline through Week 6	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.
Incidence of clinically significant changes in vital sign measurements	Up to Week 6	Assessment of clinically significant changes in vital signs including temperature, systolic and diastolic blood pressure, and heart rate.
Frequency of clinically significant findings in extrapyramidal symptoms evaluated using the Barnes Akathisia Rating Scale (BARS)	Up to Week 6	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 global clinical evaluation is made on a 6-point scale, with a score of 0 representing absence of symptom and a score of 5 representing severe akathisia.
Frequency of clinically significant findings in extrapyramidal symptoms evaluated using the Abnormal Involuntary Movement Scale (AIMS)	Up to Week 6	The AIMS assessment consists of 10 items describing symptoms of dyskinesia. 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 subject's dental status.
Change from Baseline at all time points in Positive and Negative Syndrome Scale (PANSS) total score	Baseline through Week 6	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.
Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)	Up to Week 10	Any AE occurring following the start of treatment or occurring before treatment but increasing in severity afterward will be counted as treatment-emergent AE (TEAE)
Incidence of clinically significant changes in clinical laboratory results	Up to Week 6
Clinically significant findings in suicidality assessed using the Columbia Suicide-Severity Rating Scale (C-SSRS)	Up to Week 6	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).
Percentage of responders at Week 6 (responders defined as ≥30% reduction from Baseline in PANSS total score)	Baseline through Week 6	A PANSS responder is defined as a participant with at least a 30% change in PANSS total score compared to baseline at Week 6.
Incidence of clinically significant changes in physical and neurological examination results	Up to Week 6
Incidence of clinically significant changes in electrocardiogram (ECG) results	Up to Week 6	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
Frequency of clinically significant findings in extrapyramidal symptoms evaluated using the Simpson Angus Scale (SAS)	Up to Week 6	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.

Trial Locations

Locations (25)

Oakland Park, Florida; 🇺🇸 Oakland Park, Florida, United States

DeSoto, Texas; 🇺🇸 DeSoto, Texas, United States

Richardson, Texas; 🇺🇸 Richardson, Texas, United States

Little Rock, Arkansas; 🇺🇸 Little Rock, Arkansas, United States

Garden Grove, California; 🇺🇸 Garden Grove, California, United States

Montclair, California; 🇺🇸 Montclair, California, United States

Anaheim, California; 🇺🇸 Anaheim, California, United States

Lemon Grove, California; 🇺🇸 Lemon Grove, California, United States

Stara Zagora; 🇧🇬 Stara Zagora, Bulgaria

Houston, Texas; 🇺🇸 Houston, Texas, United States

Irving, Texas; 🇺🇸 Irving, Texas, United States

San Diego, California; 🇺🇸 San Diego, California, United States

Riverside, California; 🇺🇸 Riverside, California, United States

Hialeah, Florida; 🇺🇸 Hialeah, Florida, United States

Atlanta, Georgia; 🇺🇸 Atlanta, Georgia, United States

Hollywood, Florida; 🇺🇸 Hollywood, Florida, United States

Mangonia Park, Florida; 🇺🇸 Mangonia Park, Florida, United States

Shreveport, Louisiana; 🇺🇸 Shreveport, Louisiana, United States

Decatur, Georgia; 🇺🇸 Decatur, Georgia, United States

Gaithersburg, Maryland; 🇺🇸 Gaithersburg, Maryland, United States

North Canton, Ohio; 🇺🇸 North Canton, Ohio, United States

Veliko Tarnovo; 🇧🇬 Veliko Tarnovo, Bulgaria

Flowood, Mississippi; 🇺🇸 Flowood, Mississippi, United States

Veliko Tarnovo, Veliko Tarnovo; 🇧🇬 Veliko Tarnovo, Bulgaria

Vratsa, Vratsa; 🇧🇬 Vratsa, Bulgaria