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

AbbVie25 sites in 2 countries385 target enrollmentJune 30, 2022

ConditionsSchizophrenia

InterventionsPlacebo Emraclidine 10 mg Emraclidine 30 mg

Overview

Phase: Phase 2
Intervention: Placebo
Conditions: Schizophrenia
Sponsor: AbbVie
Enrollment: 385
Locations: 25
Primary Endpoint: Change From Baseline at Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total Score
Status: Completed
Last Updated: 7 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

Brief 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.

Registry

clinicaltrials.gov

Start Date

June 30, 2022

End Date

August 26, 2024

Last Updated

7 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

AbbVie

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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.

Exclusion Criteria

•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.

Arms & Interventions

Placebo

Participants received placebo tablets orally once daily (QD) through Day 45 of Week 6.

Intervention: Placebo

Emraclidine 10 mg, once daily (QD)

Participants received emraclidine 10 mg tablets orally once daily (QD) through Day 45 of Week 6.

Intervention: Emraclidine 10 mg

Emraclidine 30 mg, once daily (QD)

Participants received emraclidine 30 mg tablets orally once daily (QD) through Day 45 of Week 6.

Intervention: Emraclidine 30 mg

Outcomes

Primary Outcomes

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

Time Frame: 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.

Secondary Outcomes

Change From Baseline at Week 6 in the Clinical Global Impression - Severity (CGI-S Score)(Baseline through Week 6)
Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score(Baseline; Weeks 1, 2, 3, 4, 5, and 6)
Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score(Baseline; Weeks 1, 2, 3, 4, 5, and 6)
Percentage of Responders at Week 6 (Responders Defined as ≥30% Reduction From Baseline in Positive and Negative Syndrome Scale [PANSS] Total Score)(Baseline through Week 6)
Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments(Baseline; from first dose of study drug up to Week 6)
Number of Participants With Treatment Emergent Adverse Event (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 10))
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs)(Baseline; from first dose of study drug up to Week 6)
Number of Participants With Clinically Significant Changes in Vital Sign Measurements(Baseline; from first dose of study drug up to Week 6)
Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results(Baseline; from first dose of study drug up to Week 6)
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Rating Score(Baseline; Weeks 3 and 6)
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 6)
Change From Baseline in Simpson Angus Scale (SAS) Total Score(Baseline; Weeks 3 and 6)
Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Evaluation Score(Baseline; Weeks 3 and 6)