A 52-week, Open-label Trial of CVL-231 in Adult Participants With Schizophrenia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cerevel Therapeutics LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

8 Mar 2023 → 25 Jun 2025

Decision date (initial)

2024-03-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Cerevel Therapeutics, LLC

External identifiers

EU CT number

2024-511441-19-00

EudraCT number

2022-001151-16

ClinicalTrials.gov

NCT05443724

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

To assess the long-term safety and tolerability of oral emraclidine in adult participants with schizophrenia

Conditions and MedDRA coding

Schizophrenia

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Rollover Participants 1. Completed 6 weeks of post-randomization treatment in Trial CVL-2312001 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-2312001 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the Week 1 visit of Trial CVL-231-2003 • Participants not discharged by the Week 1 visit of Trial CVL-231-2003 must be withdrawn 3.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 women of childbearing potential must use acceptable (at minimum) contraception as defined in Section 10.4.1.1 of the Protocol. 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.
2. 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 protocolrequired washouts prior to and during the trial period. 12. Resides in a stable living environment as demonstrated by the ability to provide contact information for themselves and/or family/friend/caregiver. 13. Agree to comply with the following contraception requirements during the trial and for 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 14. Body mass index of 18.0 to 40.0 kg/m2 and a total body weight ≥50 kg (110 lbs). 15. 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 16. 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.

Exclusion criteria 2

1. "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 doubleblind 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. This criterion has been removed effective protocol version 3.0. 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, or HCV antibody with detectable viral RNA levels at Screening "
2. "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 diastolic blood pressure ≥90 mmHg at the Screening Visit and/or at Baseline 25.Any other abnormal safety findings unless, based on the investigator's judgment, the findings are not medically significant and would not impact the safety of the participant or the interpretation of the trial results. The medical monitor should be contacted to discuss individual cases, as needed 26.Considering or scheduled to undergo any surgical procedure during the trial 27.Any other condition that would preclude IMP administration or trial participation 28.Known allergy or hypersensitivity to emraclidine, closely related compounds, or any of its specified ingredients 29.Received IMP in a prior clinical trial of emraclidine, with the exception of Trial CVL-231-1005 30.History of participation in any clinical trial involving an IMP as defined by the following: • Current enrollment in another interventional trial , with the exception of a trial with a long-term follow-up period where dosing occurred more than 12 months prior to signing the ICF for this trial • Enrollment in more than 2 interventional trials within 12 months prior to signing the ICF 31.Anyone who should not participate in the trial in the opinion of the sponsor, investigator, or medical monitor, eg, participants who would be considered a risk for violent or destructive behavior 32.Employee of the investigator, clinic, or sponsor with direct involvement in the proposed trial or other trials under the direction of the investigator or clinic, as well as family members of the employee or investigator "

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. "• Treatment-emergent adverse events • Clinically significant changes in vital sign measurements, body weight, physical and neurological examination results, ECG assessments, clinical laboratory assessments, and metabolic parameters • Clinically significant findings in suicidality assessed using the C-SSRS • Extrapyramidal symptoms evaluated using the change from Baseline in SAS, AIMS, and BARS assessments "

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cerevel Therapeutics LLC

Sponsor organisation

Cerevel Therapeutics LLC

Address

222 Jacobs Street Suite 200

City

Cambridge

Postcode

02141-2297

Country

United States

Scientific contact point

Organisation

Cerevel Therapeutics LLC

Contact name

Abbvie Inc.

Public contact point

Organisation

Cerevel Therapeutics LLC

Contact name

Manager, Global Regulatory Strategy, Neuroscience

Third parties 7

Locations

2 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 33 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications