Clinical trial NCT05227703: A Trial of 15 and 30 mg Doses of CVL-231 (Emraclidine) in Participants With Schizophrenia
Official title: A Phase 2, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of Two Fixed Doses (15 mg and 30 mg QD) of CVL-231 (Emraclidine) in Participants With Schizophrenia Experiencing an Acute Exacerbation of Psychosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Keywords: Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2022-02-07
Enrollment: 391
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Placebo-controlled
Primary purpose: TREATMENT

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) (15 mg QD and 30 mg QD) in male and female participants who have schizophrenia and are experiencing an acute exacerbation of psychosis.


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.
* 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.

Primary outcomes:
measure: Change from Baseline at Week 6 in the Positive and Negative Syndrome Scale (PANSS) total score
timeFrame: Baseline through Week 6
Secondary outcomes:
measure: Change from Baseline at Week 6 in the Clinical Global Impression - Severity (CGI-S score)
timeFrame: Baseline through Week 6
measure: Change from Baseline at all time points in Positive and Negative Syndrome Scale (PANSS) total score
timeFrame: Baseline through Week 6
measure: Change from Baseline at all time points in the Clinical Global Impression - Severity (CGI-S) score
timeFrame: Baseline through Week 6
measure: Percentage of responders at Week 6 (responders defined as ≥30% reduction from Baseline in PANSS total score)
timeFrame: Baseline through Week 6
measure: Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to Week 10
measure: Incidence of clinically significant changes in electrocardiogram (ECG) results
timeFrame: Up to Week 6
measure: Incidence of clinically significant changes in clinical laboratory results
timeFrame: Up to Week 6
measure: Incidence of clinically significant changes in vital sign measurements
timeFrame: Up to Week 6
measure: Incidence of clinically significant changes in physical and neurological examination results
timeFrame: Up to Week 6
measure: Clinically significant findings in suicidality assessed using the Columbia Suicide-Severity Rating Scale (C-SSRS)
timeFrame: Up to Week 6
measure: Frequency of clinically significant findings in extrapyramidal symptoms evaluated using the Simpson Angus Scale (SAS)
timeFrame: Up to Week 6
measure: Frequency of clinically significant findings in extrapyramidal symptoms evaluated using the Barnes Akathisia Rating Scale (BARS)
timeFrame: Up to Week 6
measure: Frequency of clinically significant findings in extrapyramidal symptoms evaluated using the Abnormal Involuntary Movement Scale (AIMS)
timeFrame: Up to Week 6
Other outcomes:
measure: Clinical Global Impression - Improvement (CGI-I) score at Weeks 3 and 6
timeFrame: Time Frame: Week 3 and Week 6
measure: Change from Baseline at all time points in Positive and Negative Syndrome Scale (PANSS) positive, negative, and general psychopathology subscale scores
timeFrame: Every week from baseline through Week 6
measure: Change from Baseline at all time points in PANSS Marder Factor scores Change from Baseline at all time points in PANSS Marder Factor scores Change from Baseline at all time points in PANSS Marder Factor scores
timeFrame: Every week from baseline through Week 6
Locations:
city: Bentonville
country: United States
facility: Bentonville, Arkansas
state: Arkansas
city: Bellflower
country: United States
facility: Bellflower, California
state: California
city: La Habra
country: United States
facility: La Habra, California
state: California
city: San Diego
country: United States
facility: San Diego, California
state: California
city: Sherman Oaks
country: United States
facility: Sherman Oaks, California
state: California
city: Torrance
country: United States
facility: Torrance, California
state: California
city: New Haven
country: United States
facility: New Haven, Connecticut
state: Connecticut
city: Homestead
country: United States
facility: Homestead, Florida
state: Florida
city: Miami Lakes
country: United States
facility: Miami Lakes, Florida
state: Florida
city: Miami Springs
country: United States
facility: Miami Springs, Florida
state: Florida
city: Miami
country: United States
facility: Miami, Florida
state: Florida
city: Atlanta
country: United States
facility: Atlanta, Georgia
state: Georgia
city: Savannah
country: United States
facility: Savannah, Georgia
state: Georgia
city: Chicago
country: United States
facility: Chicago, Illinois
state: Illinois
city: Chicago
country: United States
facility: Chicago, Illinois
state: Illinois
city: Berlin
country: United States
facility: Berlin, New Jersey
state: New Jersey
city: Marlton
country: United States
facility: Marlton, New Jersey
state: New Jersey
city: Charlotte
country: United States
facility: Charlotte, North Carolina
state: North Carolina
city: Austin
country: United States
facility: Austin, Texas
state: Texas
city: Sofia
country: Bulgaria
facility: Sofia, Sofia-Grad
state: Sofia-Grad
city: Burgas
country: Bulgaria
facility: Burgas, Burgas
city: Pleven
country: Bulgaria
facility: Pleven, Pleven
city: Sofia
country: Bulgaria
facility: Sofia, Sofia
city: Kalocsa
country: Hungary
facility: Kalocsa, Bács-Kiskun
state: Bács-Kiskun
city: Győr
country: Hungary
facility: Győr, Győr-Moson-Sopron
state: Győr-Moson-Sopron
city: Budapest
country: Hungary
facility: Budapest, Budapest
Study officials:
affiliation: AbbVie
name: Julie Adams
role: STUDY_DIRECTOR
References: