Long-term Safety and Tolerability Evaluation of Emraclidine in Adult Patients with Schizophrenia: A 52-week, Phase 2, Open-label Clinical Trial
- Trial ID
- 2024-511441-19-00
- Protocol
- CVL-231-2003
- Sponsor
- Cerevel Therapeutics LLC
Trial statistics
Objectives
The primary objective of this 52-week, Phase 2, open-label trial is to assess the long-term **safety** and **tolerability** of oral emraclidine in adult participants with **schizophrenia**. Evaluating the safety and tolerability of emraclidine is clinically relevant as it provides essential information on the potential risks and adverse effects associated with long-term use of this investigational drug in the treatment of schizophrenia. Understanding these aspects is crucial for determining the viability of emraclidine as a therapeutic option for patients with schizophrenia.
Participants
The clinical trial involves a total of **550 participants** diagnosed with **schizophrenia**, aiming to evaluate the long-term safety and tolerability of oral emraclidine. The study population includes both male and female participants aged 18 to 65 years. Participants were selected based on their completion of prior related trials or their stable condition on antipsychotic medication for at least three months in the year preceding the trial. The trial includes individuals who are outpatients, with hospitalization permitted only for psychosocial reasons unrelated to their psychiatric condition. Participants are required to reside in a stable living environment and demonstrate the ability to comply with trial protocols, including medication regimens and scheduled visits. The study population is characterized by a body mass index ranging from 18.0 to 40.0 kg/m² and a minimum body weight of 50 kg. The trial includes a vulnerable population, with participants capable of providing informed consent and adhering to contraception requirements during and after the trial period.
Plans and Procedures
The clinical trial is a **Phase 2**, open-label study designed to evaluate the long-term safety and tolerability of **emraclidine** in adult participants diagnosed with **schizophrenia**. The trial will span a duration of 52 weeks, with an additional 28-day follow-up period, making the total participant involvement approximately 56 weeks for rollover participants and 58 weeks for de novo participants. The study will include two groups: participants who have completed treatment in previous double-blind, placebo-controlled Phase 2 efficacy trials (CVL-231-2001 or CVL-231-2002), referred to as rollover participants, and de novo participants who have stable schizophrenia but were not part of the prior trials.
The trial will commence with a screening period of up to 15 days for de novo participants to assess eligibility based on inclusion criteria such as age, diagnosis, and stability on antipsychotic medication. Following the screening, eligible participants will enter the 52-week treatment period where they will receive oral emraclidine at a dose of 30 mg daily. The trial will be conducted on an outpatient basis, and participants will be required to attend scheduled visits to monitor treatment-emergent adverse events, changes in vital signs, body weight, and other clinical assessments.
Study visits will be structured to include an initial inclusion (screening) visit, regular follow-up visits throughout the treatment period, and an end-of-study visit. The primary endpoints focus on the safety profile of emraclidine, including the incidence of treatment-emergent adverse events and clinically significant changes in various health parameters. Participants may be withdrawn from the study if they fail to comply with protocol requirements, experience significant adverse events, or if the investigator deems it necessary for their safety. The trial aims to enroll approximately 850 participants to comprehensively assess the safety and tolerability of emraclidine in this population.
Treatment
The clinical trial involves the administration of **emraclidine**, an experimental medication, to evaluate its long-term safety and tolerability in adult participants with schizophrenia. **Emraclidine** is provided in the form of a **tablet** and is administered **orally**. The maximum daily dose of **emraclidine** is 30 mg, with a total maximum dose of 10,920 mg over the course of the 52-week treatment period. The active substance, **emraclidine**, is chemically synthesized and is also known by its sponsor product code, CVL-231. The chemical name for **emraclidine** is 1-(2,4-dimethyl-5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)-2-{1-[2-(trifluoromethyl)pyridin-4-yl]azetidin-3-yl}ethan-1-one. The medication is not formulated for pediatric use and is not classified as an orphan drug.
In addition to the experimental treatment, the study may include the use of standard-of-care therapy as deemed necessary by the clinical investigators. No placebo or active comparator treatment is specified in the trial protocol. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed regimen. The trial is designed to assess the safety profile of **emraclidine** over an extended period, providing valuable data on its tolerability in the target population.
Efficacy
The efficacy of the investigational product, **emraclidine**, in the clinical trial will be assessed through various primary endpoints. These include the evaluation of 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. Additionally, clinically significant findings in suicidality will be assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS), and extrapyramidal symptoms will be evaluated using the change from baseline in the Simpson-Angus Scale (SAS), Abnormal Involuntary Movement Scale (AIMS), and Barnes Akathisia Rating Scale (BARS) assessments.
The trial is designed as a 52-week, Phase 2, open-label study to evaluate the long-term safety and tolerability of oral emraclidine in adult participants with schizophrenia. The trial will be conducted on an outpatient basis, with participants being assessed at various timepoints throughout the study. The trial will include a 52-week treatment period and a 28-day follow-up period, with each participant participating for up to approximately 56 weeks (rollover participants) or 58 weeks (de novo participants). The assessments will be conducted using validated scales and laboratory tests to ensure the accuracy and reliability of the data collected.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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.
- 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
- "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 "
- "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 "
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Not Recruiting | 01 Apr 2024 | 236 |
 Hungary | Not Recruiting | 01 Apr 2024 | 64 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
EMRACLIDINE | Test | TABLET | ORAL | 30 | 52 | PRD11094870 |
EMRACLIDINE | Test | TABLET | ORAL | 30 | 52 | PRD11094868 |
EMRACLIDINE | Test | TABLET | ORAL | 30 | 52 | PRD11094867 |