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

NCT05227690
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Phase
Phase 2
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Recruitment status
Completed
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Participants
385
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Lead sponsor
AbbVie
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Start date
2022-06-30
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Number of sites
25
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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) (10 mg QD and 30 mg QD) in male and female participants who have schizophrenia and are experiencing an acute exacerbation of psychosis.
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Short title
A Trial of 10 and 30 mg Doses of CVL-231 (Emraclidine) in Participants With Schizophrenia
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Official title
A Phase 2, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of Two Fixed Doses (10 mg and 30 mg QD) of CVL-231 (Emraclidine) in Participants With Schizophrenia Experiencing an Acute Exacerbation of Psychosis
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Control arm
Placebo
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Registry reports results
Yes
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Listing at source
Listed
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Recruitment status
Completed
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Phase
Phase 2
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Study type
Interventional
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Completion date
2024-08-26
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First posted
2022-02-07
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Registry last updated
2025-09-17
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Primary completion date
2024-08-23
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Start date
2022-06-30
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Actual participants
385
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Participants
385
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Participant count basis
Actual
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Protocol amendments
4
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Number of sites
25
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
AbbVie
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05227690
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ClinicalTrials.gov ID
NCT05227690
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Double masking
Masked roles
Participants, Investigators
Sources for study design
clinicaltrials.gov

  1. Change From Baseline at Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total Score

    Timeframe: Baseline through Week 6

    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.

  1. Change From Baseline at Week 6 in the Clinical Global Impression - Severity (CGI-S Score)

    Timeframe: Baseline through Week 6

    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 was based on the following scale: 0 = not assessed; 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. Negative changes from Baseline indicate less mental illness.

  2. Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score

    Timeframe: Baseline; Weeks 1, 2, 3, 4, 5, and 6

    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.

  3. Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score

    Timeframe: Baseline; Weeks 1, 2, 3, 4, 5, and 6

    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 was based on the following scale: 0 = not assessed; 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. Negative changes from Baseline indicate less mental illness.

  4. Percentage of Responders at Week 6 (Responders Defined as ≥30% Reduction From Baseline in Positive and Negative Syndrome Scale [PANSS] Total Score)

    Timeframe: Baseline through Week 6

    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. A PANSS responder is defined as a participant with at least a 30% decrease in PANSS total score compared to Baseline at Week 6 visit or the early termination visit. If a participant discontinued and did not have an early termination visit, the participant's last assessment was considered.

  5. Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

    Timeframe: From first dose of study drug until 28 days following last dose of study drug (up to Week 10)

    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.

  6. Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs)

    Timeframe: Baseline; from first dose of study drug up to Week 6

    12-lead electrocardiogram (ECG) recordings were obtained after the participant had been supine and at rest for at least 3 minutes.

  7. Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments

    Timeframe: Baseline; from first dose of study drug up to Week 6

    Clinical laboratory tests were performed at scheduled study visits, and the investigator recorded any clinically significant changes.

  8. Number of Participants With Clinically Significant Changes in Vital Sign Measurements

    Timeframe: Baseline; from first dose of study drug up to Week 6

    Vital signs were obtained after the participant had been supine and at rest for 3 minutes and included temperature, systolic and diastolic blood pressure, respiratory rate, and heart rate. Participants' body weights were also measured and recorded.

  9. Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results

    Timeframe: Baseline; from first dose of study drug up to Week 6

    The number of participants with clinically significant changes in physical and neurological examination results was documented.

  10. Number of Participants With Suicide-Related Treatment-Emergent Events Assessed Using the Columbia Suicide-Severity Rating Scale (C-SSRS)

    Timeframe: Baseline; from first dose of study drug up to Week 6

    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).

  11. Change From Baseline in Simpson Angus Scale (SAS) Total Score

    Timeframe: Baseline; Weeks 3 and 6

    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. Negative changes from Baseline indicate an improvement in symptoms.

  12. Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Rating Score

    Timeframe: Baseline; Weeks 3 and 6

    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.

  13. Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Evaluation Score

    Timeframe: Baseline; Weeks 3 and 6

    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. Negative changes from Baseline indicate an improvement in symptoms.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Maximum age
65 Years
Healthy volunteers
No

  • 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.

  • 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.

Sources for eligibility
clinicaltrials.gov

  • Little Rock, ArkansasLittle Rock, United States
  • Anaheim, CaliforniaAnaheim, United States
  • Garden Grove, CaliforniaGarden Grove, United States
  • Lemon Grove, CaliforniaLemon Grove, United States
  • Montclair, CaliforniaMontclair, United States
  • Riverside, CaliforniaRiverside, United States
  • San Diego, CaliforniaSan Diego, United States
  • Hialeah, FloridaHialeah, United States
  • Hollywood, FloridaHollywood, United States
  • Mangonia Park, FloridaMangonia Park, United States
  • Oakland Park, FloridaOakland Park, United States
  • Atlanta, GeorgiaAtlanta, United States
  • Decatur, GeorgiaDecatur, United States
  • Shreveport, LouisianaShreveport, United States
  • Gaithersburg, MarylandGaithersburg, United States
  • Flowood, MississippiFlowood, United States
  • North Canton, OhioNorth Canton, United States
  • DeSoto, TexasDeSoto, United States
  • Houston, TexasHouston, United States
  • Irving, TexasIrving, United States
  • Richardson, TexasRichardson, United States
  • Stara ZagoraStara Zagora, Bulgaria
  • Veliko TarnovoVeliko Tarnovo, Bulgaria
  • Veliko Tarnovo, Veliko TarnovoVeliko Tarnovo, Bulgaria
  • Vratsa, VratsaVratsa, Bulgaria
Sources for sites
clinicaltrials.gov

Other registry identifiers

  • 2022-000580-52
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (2)