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

NCT ID: NCT07184619

Last Updated: 2025-10-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-10-15

Study Completion Date

2026-09-01

Brief Summary

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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.

Detailed Description

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Conditions

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Treatment-resistant Schizophrenia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Evenamide 15 mg bid

Evenamide capsules 15 mg bid for a total of 12 weeks of add-on treatment

Group Type EXPERIMENTAL

Evenamide 15 mg bid

Intervention Type DRUG

Evenamide capsules 15 mg bid for a total of 12 weeks of add-on treatment

Placebo

Matching placebo capsules bid for a total of 12 weeks of add-on treatment

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Matching placebo capsules bid for a total of 12 weeks of add-on treatment

Interventions

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Evenamide 15 mg bid

Evenamide capsules 15 mg bid for a total of 12 weeks of add-on treatment

Intervention Type DRUG

Placebo

Matching placebo capsules bid for a total of 12 weeks of add-on treatment

Intervention Type DRUG

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Newron Pharmaceuticals SPA

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ravi Anand, MD

Role: STUDY_DIRECTOR

Newron Pharmaceuticals

Locations

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UCLA DGSOM, UCLA Health, UCLA Semel Institute

Los Angeles, California, United States

Site Status

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

Miami, Florida, United States

Site Status

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

Atlanta, Georgia, United States

Site Status

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

Baltimore, Maryland, United States

Site Status

Manhattan Psychiatric Center, The Nathan Kline Institute for Psychiatric Research

New York, New York, United States

Site Status

Countries

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United States

Central Contacts

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Newron Pharmaceuticals

Role: CONTACT

+39 02 610 3461

Facility Contacts

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Site contact

Role: primary

310-478-3711 ext. 44932

Site contact

Role: primary

305-243-6489

Site contact

Role: primary

404-616-4444

Site contact

Role: primary

410-343-9434

Site contact

Role: primary

212-866-2690

References

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Anand R, Turolla A, Chinellato G, Sansi F, Roy A, Hartman R. Efficacy and safety of evenamide, a glutamate modulator, added to a second-generation antipsychotic in inadequately/poorly responding patients with chronic schizophrenia: Results from a randomized, double-blind, placebo-controlled, phase 3, international clinical trial. Neuropharmacology. 2025 Mar 15;266:110275. doi: 10.1016/j.neuropharm.2024.110275. Epub 2024 Dec 19.

Reference Type BACKGROUND
PMID: 39708914 (View on PubMed)

Anand R, Turolla A, Chinellato G, Roy A, Hartman RD. Therapeutic Effect of Evenamide, a Glutamate Inhibitor, in Patients With Treatment-Resistant Schizophrenia (TRS): Final, 1-Year Results From a Phase 2, Open-Label, Rater-Blinded, Randomized, International Clinical Trial. Int J Neuropsychopharmacol. 2024 Dec 28;28(1):pyae061. doi: 10.1093/ijnp/pyae061.

Reference Type BACKGROUND
PMID: 39661380 (View on PubMed)

Anand R, Turolla A, Chinellato G, Roy A, Hartman RD. Phase 2 Results Indicate Evenamide, A Selective Modulator of Glutamate Release, Is Associated With Clinically Important Long-Term Efficacy When Added to an Antipsychotic in Patients With Treatment-Resistant Schizophrenia. Int J Neuropsychopharmacol. 2023 Aug 29;26(8):523-528. doi: 10.1093/ijnp/pyad035.

Reference Type BACKGROUND
PMID: 37349110 (View on PubMed)

Other Identifiers

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NW-3509/022/III/2024

Identifier Type: -

Identifier Source: org_study_id

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