Overview
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 participants who have schizophrenia and are experiencing an acute exacerbation of psychosis.
Eligibility
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.