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

March 12, 2024 updated by: Cerevel Therapeutics, LLC

A Phase 2, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of Two Fixed Doses (10 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) (10 mg QD and 30 mg QD) in male and female participants who have schizophrenia and are experiencing an acute exacerbation of psychosis.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

372

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 Contact

Study Locations

  • Bulgaria
      • Razgrad, Bulgaria, 7200
        • Recruiting
        • Razgrad
      • Stara Zagora, Bulgaria, 6003
        • Recruiting
        • Stara Zagora
      • Veliko Tarnovo, Bulgaria, 5000
        • Recruiting
        • Veliko Tarnovo
        • Contact:
      • Veliko Tarnovo, Bulgaria, 5047
        • Terminated
        • Veliko Tarnovo, Veliko Tarnovo
      • Vratsa, Bulgaria, 3000
  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72211-3702
        • Recruiting
        • Little Rock, Arkansas
        • Contact:
    • California
      • Anaheim, California, United States, 92805-5854
        • Recruiting
        • Anaheim, California
      • Garden Grove, California, United States, 92845-2506
      • Lemon Grove, California, United States, 91945-2956
        • Recruiting
        • Lemon Grove, California
      • Montclair, California, United States, 91763-2231
        • Recruiting
        • Montclair, California
        • Contact:
      • Riverside, California, United States, 92506-3257
        • Recruiting
        • Riverside, California
        • Contact:
      • San Diego, California, United States, 92123
        • Recruiting
        • San Diego, California
    • Florida
      • Hialeah, Florida, United States, 33012-4648
        • Recruiting
        • Hialeah, Florida
      • Hollywood, Florida, United States, 33021-5414
        • Recruiting
        • Hollywood, Florida
      • Miami, Florida, United States, 33155
        • Withdrawn
        • Miami, Florida
      • Oakland Park, Florida, United States, 33334-4135
        • Active, not recruiting
        • Oakland Park, Florida
    • Georgia
      • Atlanta, Georgia, United States, 30328-4018
      • Decatur, Georgia, United States, 30030-3438
    • Louisiana
      • Shreveport, Louisiana, United States, 71101-4603
    • Maryland
      • Gaithersburg, Maryland, United States, 20877-1409
        • Recruiting
        • Gaithersburg, Maryland
        • Contact:
    • Mississippi
      • Flowood, Mississippi, United States, 39232-8016
    • Ohio
      • North Canton, Ohio, United States, 44720
        • Recruiting
        • North Canton, Ohio
        • Contact:
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73112-8766
    • Texas
      • DeSoto, Texas, United States, 75115-2092
        • Recruiting
        • DeSoto, Texas
      • Richardson, Texas, United States, 75080
        • Recruiting
        • Richardson, Texas
        • Contact:

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:

  • 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

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CVL-231 30 mg, once daily (QD)
Oral Dose
Drug: Required CVL-231 30 mg
CVL-231 30 mg, oral (tablet), once per day for 6 weeks
Placebo Comparator: Placebo, once daily (QD)
Oral Dose
Drug: Placebo
Matching placebo, oral (tablet), once per day for 6 weeks
Experimental: CVL-231 10 mg, once daily (QD)
Oral Dose
Drug: CVL-231 10 mg
CVL-231 10 mg, oral (tablet), once per day 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
Time Frame: 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.
Baseline through Week 6

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline at Week 6 in the Clinical Global Impression - Severity (CGI-S score)
Time Frame: 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.
Baseline through Week 6
Change from Baseline at all time points in Positive and Negative Syndrome Scale (PANSS) total score
Time Frame: 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.
Baseline through Week 6
Change from Baseline at all time points in the Clinical Global Impression - Severity (CGI-S) score
Time Frame: 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.
Baseline through Week 6
Percentage of responders at Week 6 (responders defined as ≥30% reduction from Baseline in PANSS total score)
Time Frame: 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.
Baseline through Week 6
Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)
Time Frame: 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)
Up to Week 10
Incidence of clinically significant changes in electrocardiogram (ECG) results
Time Frame: 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
Up to Week 6
Incidence of clinically significant changes in clinical laboratory results
Time Frame: Up to Week 6
Up to Week 6
Incidence of clinically significant changes in vital sign measurements
Time Frame: Up to Week 6
Assessment of clinically significant changes in vital signs including temperature, systolic and diastolic blood pressure, and heart rate.
Up to Week 6
Incidence of clinically significant changes in physical and neurological examination results
Time Frame: Up to Week 6
Up to Week 6
Clinically significant findings in suicidality assessed using the Columbia Suicide-Severity Rating Scale (C-SSRS)
Time Frame: 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).
Up to Week 6
Frequency of clinically significant findings in extrapyramidal symptoms evaluated using the Simpson Angus Scale (SAS)
Time Frame: 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.
Up to Week 6
Frequency of clinically significant findings in extrapyramidal symptoms evaluated using the Barnes Akathisia Rating Scale (BARS)
Time Frame: 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.
Up to Week 6
Frequency of clinically significant findings in extrapyramidal symptoms evaluated using the Abnormal Involuntary Movement Scale (AIMS)
Time Frame: 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.
Up to Week 6

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Global Impression - Improvement (CGI-I) score at Weeks 3 and 6
Time Frame: Time Frame: Week 3 and Week 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
Time Frame: Every week from 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.
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
Time Frame: Every week from baseline through Week 6
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

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

Sponsor

Cerevel Therapeutics, LLC

Investigators

  • Study Director: Erica Koenig, PhD, Cerevel Therapeutics, LLC

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)

June 30, 2022

Primary Completion (Estimated)

November 1, 2024

Study Completion (Estimated)

December 1, 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 (Actual)

March 13, 2024

Last Update Submitted That Met QC Criteria

March 12, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CVL-231-2001

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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