A Trial of 10, 15 and 30 mg Doses of CVL-231 (Emraclidine) in Participants With Schizophrenia

Phase 1

Conditions: Patients with schizophrenia who are experiencing an acute exacerbation of psychosis
MedDRA version: 20.0Level: HLGTClassification code 10039628Term: Schizophrenia and other psychotic disordersSystem Organ Class: 10037175 - Psychiatric disorders
MedDRA version: 20.0Level: PTClassification code 10039626Term: SchizophreniaSystem Organ Class: 10037175 - Psychiatric disorders
Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]

Registration Number: EUCTR2022-001151-16-HU

Lead Sponsor: Cerevel Therapeutics, LLC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 850

Inclusion Criteria

Rollover Participants
1. Completed 6 weeks of post-randomization treatment in Trial CVL-231-2001 or CVL-231-2002 and who, in the opinion of the investigator, could potentially benefit from treatment with emraclidine for schizophrenia.
2. Outpatient status at last day of treatment period (Day 45) of the preceding double-blind trial (CVL-231-2001 or CVL-231-2002) defined as follows:
• Ability to be discharged from the hospital on Day 45 of Trial CVL-231-2001 or CVL-231-2002
• Hospitalization for psychosocial reasons (eg, homelessness or need for shelter that is unrelated to the participant’s underlying psychiatric condition) will be considered outpatient status
• Participants remaining in hospital at Day 45 of Trial CVL-231-2001 or CVL-231-2002 (for other than psychosocial reasons) will be permitted to enroll in Trial CVL-231-2003 at Day 45 of the double-blind trial if they are planned to be discharged from the hospital before the Week 1 visit of Trial CVL-231-2003
• Participants not discharged by the Week 1 visit of Trial CVL-231-2003 must be withdrawn
3. Agree to comply with the following contraception requirements during the trial and for 7 days after the last dose of IMP:
• Sexually active men must agree to use a condom during treatment and until the end of relevant systemic exposure in women of childbearing potential (ie, 7 days after the last dose of IMP)
• Sexually active women of childbearing potential must use acceptable (at minimum) contraception as defined in Section 10.4.1.1 of the Protocol
In addition, male participants should not donate sperm for a minimum of 7 days following the last dose of IMP.
4. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in Section 10.1.3. of the Protocol
5. Ability, in the opinion of the investigator, to understand the nature of the trial, participate in trial visits, and comply with protocol requirements, including the prescribed dosage regimens, scheduled visits, laboratory tests, outcomes measures, and other trial procedures.

De Novo Participants
6. Male and female participants, ages 18 to 65 years, inclusive, at the time of signing the ICF.
7. Primary diagnosis of schizophrenia per DSM-5, as confirmed by the MINI for Psychotic Disorders version 7.0.2.
8. Participants who have been stable on antipsychotic medication for at least one 3-month period in the year prior to screening (received the same medication or group of medications for at least 3 consecutive months in the prior year and demonstrated stability of symptoms on the antipsychotic medication).
9. Outpatient status at the time of signing the ICF. Hospitalization for psychosocial reasons (eg, homelessness or need for shelter that is unrelated to the participant’s underlying psychiatric condition) will be considered outpatient status. Participants may be hospitalized for not more than 14 days during the conversion to emraclidine with the approval of the medical monitor but must be discharged from the hospital before the Week 1 visit.
10. Scores as follows (normal to mild symptoms) at the time of signing the ICF and Baseline (Day 1):
• All individual items of the SAS <2
• All individual items (Items 1-7) of the AIMS <2
• Clinical global assessment item of the BARS <3
11. Willing to discontinue all prohibited medications to meet protocol-required washouts prior to and during the trial period.
12. Resides in a stable living environment as demonstrated by the

Exclusion Criteria

Rollover Participants
1.Participants who had a clinically significant medical, surgical, psychiatric, or laboratory/ECG abnormality during conduct of the previous double-blind trial that could compromise either participant safety or the results of the trial
2.Yes” responses for suicidal ideation item 4 and 5 or any of the suicidal behavior items on the C-SSRS at any time point during the prior double-blind trial
3.Likely to require prohibited concomitant therapy during the trial
4.Positive pregnancy test result prior to receiving IMP
5.Orthostatic hypotension or Systolic blood pressure =140 mmHg and/or diastolic blood pressure =90 mmHg at the Week 6 Visit (Day 45) of preceding double-blind trial
6.Considering or scheduled to undergo any surgical procedure during the trial
De Novo Participants
7.Current DSM-5 diagnosis other than schizophrenia
8. Schizophrenia considered resistant/refractory to antipsychotic treatment by history or history of response to clozapine treatment only or failure to respond to clozapine treatment for schizophrenia
9.History of tardive dyskinesia or extrapyramidal symptoms that required medication within 6 months prior to signing the ICF
10.Current or past history of significant pulmonary, gastrointestinal, renal, hepatic, metabolic, genitourinary, endocrine, malignancy, hematological, immunological, neurological, or psychiatric disease that could compromise either participant safety or the results of the trial
11.Current or past history of significant cardiovascular disease
12.Active central nervous system infection, demyelinating disease, degenerative neurological disease, intellectual disability, brain tumor, prior hospitalization for severe head trauma, seizures, 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
13.Diagnosis of moderate to severe substance or alcohol-use disorder as per DSM-5 criteria within 12 months prior to signing the ICF
14.Yes” responses for suicidal ideation item 4 and 5 or any of the suicidal behavior items on the C-SSRS (within the past 6 months)
15.Any condition or surgery that could possibly affect drug absorption
16.Have recently been diagnosed with and hospitalized for COVID-19 within 6 months prior to signing the ICF or test positive for SARS-CoV-2 within 30 days prior to signing the ICF
17.Use of prohibited medications prior to randomization within the required wash-out period or likely to require prohibited concomitant therapy during the trial
18.Transcranial magnetic stimulation or electroconvulsive therapy within 90 days of signing the ICF
19.Positive result for HIV antibody, HBV surface antigen, HBV core antibody, or HCV antibody at Screening
20.Positive drug screen or a positive test for alcohol
21. AST or ALT =2 × ULN or total bilirubin >1.5 × ULN at the Screening Visit, confirmed by a single repeat measurement
22.Positive pregnancy test result prior to receiving IMP
23.12-lead ECG demonstrating any of the following at the Screening Visit and at Baseline:
• QTcF interval >450 ms
• QRS interval >120 ms (unless right bundle branch block)
• PR interval >200 ms
• LVH with ST depressions and/or T wave inversions in leads with relatively tall R waves
• Type 2 second-degree or third-degree atrioventricular block
• Heart rate <45 bpm or >100 bpm
• Abnormal ECG changes
• Abnormal heart rhythm
24.Orthostatic hypotension or Systolic blood pressure =140 mmHg and/or diastol

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the long-term safety and tolerability of oral emraclidine in adult participants with schizophrenia;Secondary Objective: Not applicable;Primary end point(s): • Treatment-emergent adverse events<br>• Clinically significant changes in vital sign measurements, body weight, physical and neurological examination results, ECG assessments, clinical laboratory assessments, and metabolic parameters<br>• Clinically significant findings in suicidality assessed using the C-SSRS<br>• Extrapyramidal symptoms evaluated using the change from Baseline in SAS, AIMS, and BARS assessments;Timepoint(s) of evaluation of this end point: Week 52

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Not applicable;Timepoint(s) of evaluation of this end point: Not applicable

Related Trials