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

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

Official Title
-----------------
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

Conditions
-----------------
Schizophrenia

Intervention / Treatment
-----------------
* Drug: CVL-231 30 mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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. 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. Participants who have been stable on antipsychotic medication for at least one 3-month in the year prior to screening. Outpatient status at the time of signing the informed consent form informed consent form (ICF). Willing to discontinue all prohibited medications to meet protocol-required washouts prior to and during the trial period. Ability, in the investigator's opinion, 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 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. 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 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 C-SSRS and investigator's clinical assessment. Any condition that could possibly affect drug absorption, including, but not limited to bowel resections, bariatric weight loss surgery, gastric banding, and gastrectomy 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 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CVL-231 30 mg<br>Participants will receive CVL-231 30 milligrams (mg) tablet, once daily for 52 weeks. | Drug: CVL-231 30 mg<br>* Oral tablets<br>* Other names: Emraclidine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) |  | Up to Week 56 | 
| Number of Participants With Clinically Significant Changes in Vital Sign Values |  | Up to Week 52 | 
| Number of Participants With Clinically Significant Changes in Body Weight |  | Up to Week 52 | 
| Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results |  | Up to Week 52 | 
| Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values |  | Up to Week 52 | 
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Values |  | Up to Week 52 | 
| Number of Participants With Clinically Significant Changes in Metabolic Parameter Values |  | Up to Week 52 | 
| Number of Participants With Clinically Significant Change in Columbia Suicide Severity Rating Scale (C-SSRS) Score |  | Up to Week 52 | 
| Number of Participants With Change from Baseline in Extrapyramidal Symptoms Measured by the Simpson Angus Scale (SAS) Score |  | Baseline up to Week 52 | 
| Number of Participants With Change from Baseline in Extrapyramidal Symptoms Measured by the Abnormal Involuntary Movement Scale (AIMS) Score |  | Baseline up to Week 52 | 
| Number of Participants With Change from Baseline in Extrapyramidal Symptoms Measured by the Barnes Akathisia Rating Scale (BARS) Score |  | Baseline up to Week 52 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Schizophrenia Spectrum and Other Psychotic Disorders, Mental Disorders