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NCT07184619PHASE3Recruiting

Evenamide, a Glutamate Release Modulator, as Add-On to Standard of Care in Subjects With Documented Treatment-Resistant Schizophrenia

Newron Pharmaceuticals SPA

Start Date

1/23/2026

Completion Date

12/31/2026

Summary

This is a prospective, 12-week, randomized, double-blind, placebo-controlled study, designed to evaluate the efficacy, safety, and tolerability of a dose of evenamide of 15 mg bid, compared to placebo, as add-on treatment in patients with documented treatment-resistant schizophrenia (TRS) who have prospectively demonstrated inadequate response to their current stable therapeutic dose of an antipsychotic(s). Approximately 400 patients will be randomized equally (1:1) to each of the two treatment groups in this study.

Eligibility Criteria

Age Range: 18 years to No maximum

Key Inclusion Criteria: * Age - 18 years, or older. * If female, the subject has a negative pregnancy test at the screening visit and at baseline, is not lactating, and agrees to use adequate contraception, unless not of childbearing potential. * Meets current DSM-5-TR criteria for schizophrenia. * Has shown treatment-resistance to antipsychotics as per TRRIP working group definition (Howes et al., 2017). * Currently receiving "standard of care" therapy of a minimal recommended therapeutic dose of one or more antipsychotic(s). * Has a Clinical Global Impression - Severity of disease (CGI-S) rating of "mildly ill" to "among the most extremly ill" at baseline. * Has a BPRS total score ≥ 45 at screening and baseline. * Has a PANSS total score ≥ 70 at baseline. * Has a Global Assessment of Functioning (GAF) scale total score ≤ 50. * Adherence to prescribed antipsychotic treatment. * Patient has provided written informed consent prior to participating in the study. Key Exclusion Criteria: * Current DSM-5-TR diagnosis of schizophreniform disorder, schizoaffective disorder, or other primary psychiatric diagnosis, such as bipolar disorder or major depressive disorder * History (within three months of study entry) or current diagnosis of "Substance Use Disorder" as defined by the DSM-5-TR criteria. * Severity of current episode of psychosis requires that the patient be hospitalized to stabilize the severity of his/her psychotic symptoms. However, these patients may qualify for the study provided their antipsychotic dose has been stable for 6 weeks prior to screening. * History or current diagnosis of other psychiatric or behavioral disorders. * Known suicidal risk, or a suicide attempt within the past 2 years. * History of neuroleptic malignant syndrome or priapism. * Disease/medical condition of any type that may impact the patient's safety or interfere with any of the study evaluations. * History or current diagnosis of epilepsy or seizure disorder, or occurrence of a seizure within the past year, or repeated drug-induced seizures.

Interventions

DRUG

Evenamide 15 mg bid

DRUG

Placebo

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Conditions

Treatment-resistant Schizophrenia

Locations

UCLA DGSOM, UCLA Health, UCLA Semel Institute

Los Angeles, California 90095

United States

University of Miami, Miller School of Medicine; Jackson Behavioral Health Hospital

Miami, Florida 33136

United States

Grady Behavioral Health Center, -Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine

Atlanta, Georgia 30322

United States

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine

Baltimore, Maryland 21224

United States

Manhattan Psychiatric Center, The Nathan Kline Institute for Psychiatric Research

New York, New York 10035

United States

Help Hospital

Vijayawada, Andhra Pradesh 520002

India

Gauhati Medical College and Hospital

Guwahati, Assam 781032

India

Masina Hospital Trust

Mumbai, Maharashtra 400027

India

New Manak Healthcare Hospital

Navi Mumbai, Maharashtra 400706

India

Ahana Hospitals LLP

Madurai, Tamil Nadu 625020

India

Udyan Health Care

Lucknow, Uttar Pradesh 226012

India

Seth Sukhlal Karnani Memorial Hospital

Kolkata, West Bengal 700025

India

Hospital Tuanku Fauziah

Kangar, 01000

Malaysia

Sentosa Hospital

Kuching, 93250

Malaysia

Sultan Abdul Halim Hospital

Sungai Petani, 08000

Malaysia