A Trial of 15 and 30 mg Doses of CVL-231 (Emraclidine) in Participants With Schizophrenia

NCT05227703 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CVL-231-2002
• Study Type: interventional
• Target: 391
• Locations: 3 countries
• Sites: 26

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 adult participants who have schizophrenia and are experiencing an acute exacerbation of psychosis.

Conditions

Schizophrenia

Keywords

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Outcome Measures

Primary Outcomes (1)

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

  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. Baseline was defined as the last value obtained prior to initiation of investigational medicinal product (IMP). Change from baseline for a given endpoint was defined as the value on a given Study Day (Time Point) minus the Baseline Value. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.

  Baseline through Week 6

Secondary Outcomes (13)

• 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 PANSS Total Score)

  Baseline through 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)

Study Arms (3)

CVL-231 15 mg, once daily (QD)

EXPERIMENTAL

Oral Dose

Drug: Emraclidine 15 mg

CVL-231 30 mg, once daily (QD)

EXPERIMENTAL

Oral Dose

Drug: Emraclidine 30 mg

Placebo, once daily (QD)

PLACEBO COMPARATOR

Oral Dose

Drug: Placebo

Interventions

Emraclidine 15 mg DRUG

Emraclidine 15 mg, oral (tablet), once per day (QD) for 6 weeks

Also known as: CVL-231, ABBV-1231

CVL-231 15 mg, once daily (QD)

Emraclidine 30 mg DRUG

Emraclidine 30 mg, oral (tablet), QD for 6 weeks

Also known as: CVL-231, ABBV-1231

CVL-231 30 mg, once daily (QD)

Placebo DRUG

Matching placebo, oral (tablet), QD for 6 weeks

Placebo, once daily (QD)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (26)

Bentonville, Arkansas

Bentonville, Arkansas, 72712-3873, United States

Location

Bellflower, California

Bellflower, California, 90706-7079, United States

Location

La Habra, California

La Habra, California, 90631-3842, United States

Location

San Diego, California

San Diego, California, 92103-2209, United States

Location

Sherman Oaks, California

Sherman Oaks, California, 91403-1747, United States

Location

Torrance, California

Torrance, California, 90504-4432, United States

Location

New Haven, Connecticut

New Haven, Connecticut, 06519-1109, United States

Location

Homestead, Florida

Homestead, Florida, 33032-8187, United States

Location

Miami, Florida

Miami, Florida, 33122-1335, United States

Location

Miami Lakes, Florida

Miami Lakes, Florida, 33016-1553, United States

Location

Miami Springs, Florida

Miami Springs, Florida, 33166-7225, United States

Location

Atlanta, Georgia

Atlanta, Georgia, 30331-2012, United States

Location

Savannah, Georgia

Savannah, Georgia, 31405-5701, United States

Location

Chicago, Illinois

Chicago, Illinois, 60640-5017, United States

Location

Chicago, Illinois

Chicago, Illinois, 60641, United States

Location

Berlin, New Jersey

Berlin, New Jersey, 08009, United States

Location

Marlton, New Jersey

Marlton, New Jersey, 08053, United States

Location

Charlotte, North Carolina

Charlotte, North Carolina, 28211-4849, United States

Location

Austin, Texas

Austin, Texas, 78754-5122, United States

Location

Sofia, Sofia-Grad

Sofia, Sofia-Grad, 1431, Bulgaria

Location

Burgas, Burgas

Burgas, 8000, Bulgaria

Location

Pleven, Pleven

Pleven, 5800, Bulgaria

Location

Sofia, Sofia

Sofia, 1282, Bulgaria

Location

Kalocsa, Bács-Kiskun

Kalocsa, Bács-Kiskun county, 6300, Hungary

Location

Győr, Győr-Moson-Sopron

Győr, Győr-Moson-Sopron, 9024, Hungary

Location

Budapest, Budapest

Budapest, 1083, Hungary

Location

MeSH Terms

Conditions

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• Julie Adams

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Placebo-controlled

Study Record Dates

• First Submitted: January 27, 2022
• First Posted: February 7, 2022
• Study Start: July 5, 2022
• Primary Completion: August 15, 2024
• Study Completion: September 11, 2024
• Last Updated: October 28, 2025
• Results First Posted: October 28, 2025

Record last verified: 2025-10

Locations

BU (4); HU (3); US (19)