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

NCT07184619 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: NW-3509/022/III/2024
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Treatment-resistant Schizophrenia

Keywords

evenamide; treatment-resistant schizophrenia; antipsychotic; schizophrenia; TRS; add-on treatment

Outcome Measures

Primary Outcomes (2)

• Change from baseline to endpoint (Week 12) on the total score of the Positive and Negative Syndrome Scale (PANSS).

  Efficacy measured by the mean change from baseline to endpoint of Positive and Negative Syndrome Scale \[PANSS\] total score: a 30-item scale that was designed to assess various symptoms of schizophrenia each rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology).

  From Baseline to Week 12

• Incidence of treatment-emergent adverse events (TEAEs), AEs leading to discontinuation (ADOs), and serious AEs (SAEs).

  Safety and tolerability of a dose of evenamide of 15 mg bid, compared to placebo. The assessment of safety and tolerability will be based primarily on the incidence of treatment-emergent adverse events (TEAEs), AEs leading to discontinuation (ADOs), and serious AEs (SAEs).

  From Baseline to 30-day Safety Follow up (12 Weeks of treament + 30-day safety follow up)

Secondary Outcomes (5)

• Change from baseline to endpoint (Week 12) on the Clinical Global Impression - Severity of illness (CGI-S) score.

  From Baseline to Week 12

• Proportion of patients rated as 'improved' on the CGI-C at endpoint (Week 12).

  Week 12

• Change from baseline to endpoint (Week 12) on the Positive Symptoms sub-scale score of the PANSS.

  From Baseline to Week 12

• Change from baseline to endpoint (Week 12) on the Personal and Social Performance (PSP) scale.

  From Baseline to Week 12

• Change from baseline to endpoint (Week 12) on the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form scale (Q-LES-Q-SF).

  From Baseline to Week 12

Other Outcomes (5)

• Change from baseline to endpoint (Week 12) on the Negative Symptoms sub-scale score of the PANSS.

  From Baseline to Week 12.

• Change from baseline to endpoint (Week 12) on the Calgary Depression Scale for Schizophrenia (CDSS).

  From Baseline to Week 12

• Change from baseline to endpoint (Week 12) on the Global Assessment of Functioning (GAF) scale.

  From Baseline to Week 12.

Study Arms (2)

Evenamide 15 mg bid

EXPERIMENTAL

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

Drug: Evenamide 15 mg bid

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Evenamide 15 mg bid DRUG

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

Evenamide 15 mg bid

Placebo DRUG

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

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Newron Pharmaceuticals SPA: lead

Study Sites (5)

UCLA DGSOM, UCLA Health, UCLA Semel Institute

Los Angeles, California, 90095, United States

RECRUITING

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

Miami, Florida, 33136, United States

NOT YET RECRUITING

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

Atlanta, Georgia, 30322, United States

NOT YET RECRUITING

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

Baltimore, Maryland, 21224, United States

NOT YET RECRUITING

Manhattan Psychiatric Center, The Nathan Kline Institute for Psychiatric Research

New York, New York, 10035, United States

NOT YET RECRUITING

Related Publications (3)

• 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.

  PMID: 39708914 BACKGROUND

• 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.

  PMID: 39661380 BACKGROUND

• 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.

  PMID: 37349110 BACKGROUND

MeSH Terms

Conditions

Schizophrenia, Treatment-Resistant; Schizophrenia

Interventions

BID protein, human

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Ravi Anand, MD

  Newron Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Newron Pharmaceuticals

CONTACT

+39 02 610 3461; info@newron.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2025
• First Posted: September 22, 2025
• Study Start: January 23, 2026
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: January 28, 2026

Record last verified: 2026-01

Locations

US (5)