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

Schizophrenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05227703
• Other study ID #: CVL-231-2002
• Status: Recruiting
• Phase: Phase 2
• Start date: June 30, 2022
• Est. completion date: December 2024

Study information

• Verified date: May 2024
• Source: Cerevel Therapeutics, LLC
• Contact: Cerevel Clinical Trial Support
• Email: cerevelclinicaltrials[@]cerevel.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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) (15 mg QD and 30 mg QD) in male and female participants who have schizophrenia and are experiencing an acute exacerbation of psychosis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 372
• Est. completion date: December 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

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.

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• CVL-231 15 mg
CVL-231 15 mg, oral (tablet), once per day for 6 weeks
• Required CVL-231 30 mg
CVL-231 30 mg, oral (tablet), once per day for 6 weeks
• Placebo
Matching placebo, oral (tablet), once per day for 6 weeks

Locations

Country	Name	City	State
Bulgaria	Burgas, Burgas	Burgas
Bulgaria	Lovech, Lovech	Lovech
Bulgaria	Pleven, Pleven	Pleven
Bulgaria	Plovdiv, Plovdiv	Plovdiv
Bulgaria	Sofia, Sofia	Sofia
Hungary	Budapest, Budapest	Budapest
Hungary	Gyor, Gyor-Moson-Sopron	Gyor	Gyor-Moson-Sopron
Hungary	Kalocsa, Bács-Kiskun	Kalocsa	Bács-Kiskun
United States	Atlanta, Georgia	Atlanta	Georgia
United States	Austin, Texas	Austin	Texas
United States	Bellflower, California	Bellflower	California
United States	Bentonville, Arkansas	Bentonville	Arkansas
United States	Berlin, New Jersey	Berlin	New Jersey
United States	Charlotte, North Carolina	Charlotte	North Carolina
United States	Chicago, Illinois	Chicago	Illinois
United States	Chicago, Illinois	Chicago	Illinois
United States	Homestead, Florida	Homestead	Florida
United States	La Habra, California	La Habra	California
United States	Marlton, New Jersey	Marlton	New Jersey
United States	Miami, Florida	Miami	Florida
United States	Miami Lakes, Florida	Miami Lakes	Florida
United States	Miami Springs, Florida	Miami Springs	Florida
United States	New Haven, Connecticut	New Haven	Connecticut
United States	Saint Louis, Missouri	Saint Louis	Missouri
United States	San Diego, California	San Diego	California
United States	Sherman Oaks, California	Sherman Oaks	California
United States	Torrance, California	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Cerevel Therapeutics, LLC

Countries where clinical trial is conducted

United States,  Bulgaria,  Hungary, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Primary	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. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.	Baseline through Week 6
Secondary	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 through Week 6
Secondary	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. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.	Baseline through Week 6
Secondary	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 through Week 6
Secondary	Percentage of responders at Week 6 (responders defined as =30% reduction from Baseline in PANSS total score)	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
Secondary	Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)	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
Secondary	Incidence of clinically significant changes in electrocardiogram (ECG) results	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
Secondary	Incidence of clinically significant changes in clinical laboratory results		Up to Week 6
Secondary	Incidence of clinically significant changes in vital sign measurements	Assessment of clinically significant changes in vital signs including temperature, systolic and diastolic blood pressure, and heart rate.	Up to Week 6
Secondary	Incidence of clinically significant changes in physical and neurological examination results		Up to Week 6
Secondary	Clinically significant findings in suicidality 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).	Up to Week 6
Secondary	Frequency of clinically significant findings in extrapyramidal symptoms evaluated using the Simpson Angus Scale (SAS)	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
Secondary	Frequency of clinically significant findings in extrapyramidal symptoms evaluated using the Barnes Akathisia Rating Scale (BARS)	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
Secondary	Frequency of clinically significant findings in extrapyramidal symptoms evaluated using the Abnormal Involuntary Movement Scale (AIMS)	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