Schizophrenia
Conditions
Keywords
Schizophrenia Spectrum and Other Psychotic Disorders, Mental Disorders
Brief summary
The primary purpose of this study is to assess the long-term safety and tolerability of oral emraclidine in adult participants with schizophrenia.
Interventions
Emraclidine 30 mg, oral (tablet), once per day for 52 weeks
Sponsors
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Completed 6 weeks of post-randomization treatment in Trial CVL-231-2001 (NCT05227690) or CVL-231-2002 (NCT05227703) and who, in the opinion of the investigator, could potentially benefit from treatment with emraclidine for schizophrenia. 2. Primary diagnosis of schizophrenia per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), as confirmed by the Mini International Neuropsychiatric Interview (MINI) for Psychotic Disorders. 3. Participants who have been stable on antipsychotic medication for at least one 3-month in the year prior to screening. 4. Outpatient status at the time of signing the informed consent form informed consent form (ICF). 5. Willing to discontinue all prohibited medications to meet protocol-required washouts prior to and during the trial period. 6. Ability, in the investigator's opinion, to understand the nature of the trial, participate in trial visits, and comply with protocol requirements.
Exclusion criteria
1. 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. 2. Any of the following: * Schizophrenia is 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. 3. 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. 4. 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 trial that may confound the interpretation of the trial results 5. 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. 6. Risk for suicidal behavior as assessed by the C-SSRS and investigator's clinical assessment. 7. Any condition that could possibly affect drug absorption, including, but not limited to bowel resections, bariatric weight loss surgery, gastric banding, and gastrectomy 8. Use of prohibited medications prior to randomization within the required wash-out period or likely to require prohibited concomitant therapy during the trial. 9. Clinically significant abnormal findings on the physical examination, medical history review, ECG, or clinical laboratory results at screening. 10. Positive pregnancy test result prior to receiving investigational medicinal product (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 the IMP are also excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | From first dose of study drug until 28 days following last dose of study drug (up to Week 56) | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug. |
| Number of Participants With Out-of-Range Vital Signs Occurring Post-Baseline | Baseline; from first dose of study drug up to Week 52 | Vital signs were obtained after the participant had been supine and at rest for 3 minutes and included systolic and diastolic blood pressure, heart rate, temperature, and respiratory rate. |
| Number of Participants With Clinically Significant Changes in Body Weight | Baseline; from first dose of study drug up to Week 52 | Participants' body weights were measured and recorded. |
| Number of Participants With Post-Baseline Clinically Significant Physical Examinations and Neurological Examinations | Baseline; from first dose of study drug up to Week 52 | The number of participants with clinically significant changes in physical and neurological examination results post-treatment was documented. |
| Number of Participants With Clinically Significant Post-Baseline Changes in Electrocardiogram (ECG) Values | Baseline; from first dose of study drug up to Week 52 | 12-lead electrocardiogram (ECG) recordings were obtained after the participant had been supine and at rest for at least 3 minutes. |
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Values | Baseline; from first dose of study drug up to Week 52 | Clinical laboratory tests were performed at scheduled study visits, and the investigator recorded any clinically significant changes. |
| Number of Participants With Clinically Significant Changes in Metabolic Parameter Values | Baseline; from first dose of study drug up to Week 52 | Clinical laboratory tests were performed at scheduled study visits, and the investigator recorded any clinically significant changes in metabolic parameter values. |
| Number of Participants With Suicide-Related Treatment-Emergent Events Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) | Baseline; from first dose of study drug up to Week 52 | 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). |
| Change From Baseline in Simpson Angus Scale (SAS) Total Score | Baseline; Weeks 4, 8, 12, 20, 26, 32, 38, 44, and 52 | 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. Baseline was defined as the last value obtained prior to initiation of study drug. Change from baseline for a given endpoint was defined as the value on a given Study Day (Time Point) minus the Baseline Value. Negative changes from Baseline indicate an improvement in symptoms. |
| Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Rating Score | Baseline; Weeks 4, 8, 12, 20, 26, 32, 38, 44, and 52 | The Abnormal Involuntary Movement Scale assessment consists of 10 items describing symptoms of dyskinesia. Facial and oral movements (items 1-4), extremity movements (items 5 and 6), and trunk movements (item 7) are observed unobtrusively while the participant is at rest, and the investigator also makes global judgments on the participant's dyskinesias (items 8-10). 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 participant's dental status. The AIMS Movement Rating Score is defined as the sum of individual scores from items 1-7, ranging from 0 to 28. A lower score indicates less severe or absent abnormal movements. A negative change in the mean from Baseline indicates improvement in the severity of abnormal involuntary movements. |
| Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Evaluation Score | Baseline; Weeks 4, 8, 12, 20, 26, 32, 38, 44, and 52 | The BARS consists of 4 items related to akathisia. The fourth item, reported here, is the Global Clinical Evaluation Score. The Global Clinical Evaluation Score is evaluated using a 6-point scale, ranging from 0 to 5, with 0 representing absence of symptoms and a score of 5 representing severe akathisia. A negative change from baseline indicates an improvement in symptoms. |
Countries
Bulgaria, Hungary, Puerto Rico, Ukraine, United States
Contacts
STUDY_DIRECTORABBVIE INC.
AbbVie
Participant flow
Recruitment details
Two groups of participants were included in the study: rollover (who completed treatment in the double-blind, placebo-controlled, Phase 2 efficacy Study CVL-231-2001 or Study CVL-231-2002) and de novo participants (who had stable schizophrenia and were not enrolled in either Phase 2 efficacy study). The study included an up to 15-day Screening Period (de novo participants only), a 52-week Treatment Period, and a 28-day Follow-up Period.
Pre-assignment details
The Intent-to-treat (ITT) population included all participants who were enrolled in this trial and was used for the Participant Flow, Demographic and Baseline Characteristics, and safety analysis. The Safety Analysis Set included all participants who received at least 1 dose of emraclidine in Study CVL-231-2003 and was used for efficacy evaluations.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 45.0 years STANDARD_DEVIATION 11.96 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 431 Participants |
| Sex: Female, Male Female | 220 Participants |
| Sex: Female, Male Male | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 97 | 0 / 49 | 2 / 552 |
| other Total, other adverse events | 24 / 97 | 21 / 49 | 212 / 552 |
| serious Total, serious adverse events | 7 / 97 | 2 / 49 | 35 / 552 |
Outcome results
None listed