Evenamide for Treatment-Resistant Schizophrenia

(ENIGMA-TRS 2 Trial)

Not yet recruiting at 4 trial locations

Overseen By Newron Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Newron Pharmaceuticals SPA

Must be taking: Antipsychotics

Disqualifiers: Substance use disorder, Suicidal risk, Epilepsy, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an add-on treatment called Evenamide for individuals with treatment-resistant schizophrenia, a condition where standard antipsychotic medications prove insufficient. The study aims to determine if Evenamide can improve symptoms when added to a patient's current medication routine. Participants will receive either Evenamide or a placebo (a pill with no active drug) for 12 weeks. Individuals diagnosed with schizophrenia who continue to experience symptoms despite taking their medication might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not require you to stop your current medications. In fact, you need to continue your current antipsychotic treatment as part of the study.

Is there any evidence suggesting that evenamide is likely to be safe for humans?

Research has shown that evenamide is generally well-tolerated by people with treatment-resistant schizophrenia. In one study, patients took evenamide alongside their regular treatment for up to a year, and researchers found it safe with no major safety issues. Another study, lasting six weeks, also showed that patients managed the treatment well without significant side effects. These studies suggest that evenamide could be a safe option for those seeking new treatments for schizophrenia. However, individual experiences can differ, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for schizophrenia?

Evenamide is unique because it targets sodium channels in the brain, which is different from most schizophrenia treatments that focus on dopamine pathways. This novel mechanism of action could offer an effective option for those with treatment-resistant schizophrenia, who don't respond well to standard antipsychotics like risperidone or olanzapine. Researchers are excited about Evenamide because it may address symptoms that current medications can't, potentially improving quality of life for patients who have limited options.

What evidence suggests that evenamide might be an effective treatment for treatment-resistant schizophrenia?

Research has shown that evenamide, one of the treatments tested in this trial, can significantly aid individuals with treatment-resistant schizophrenia when added to current antipsychotic treatments. Studies found that about 70% of patients experienced a clear reduction in symptoms. In another study, around half of the patients no longer met the criteria for schizophrenia after using evenamide for one year. This treatment works by affecting glutamate, a brain chemical linked to schizophrenia. Overall, evenamide appears to be a promising additional therapy for improving symptoms in patients who haven't responded well to other treatments. Participants in this trial will receive either evenamide or a placebo as an add-on treatment. ^{3 4 6 7 8}

Who Is on the Research Team?

Ravi Anand, MD

Principal Investigator

Newron Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for outpatients with treatment-resistant schizophrenia, which means their current antipsychotic medications aren't working well enough. They must be stable on their current meds and able to take a new pill twice daily.

Inclusion Criteria

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

Exclusion Criteria

History (within three months of study entry) or current diagnosis of 'Substance Use Disorder' as defined by the DSM-5-TR criteria

History or current diagnosis of other psychiatric or behavioral disorders

Known suicidal risk, or a suicide attempt within the past 2 years

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either evenamide or placebo, given twice a day for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Evenamide

Trial Overview The study is testing Evenamide, thought to help with schizophrenia by affecting glutamate release in the brain. Participants will either get Evenamide or a placebo without knowing which one, alongside their usual medication for 12 weeks.

How Is the Trial Designed?

Group I: Evenamide 15 mg bid Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Newron Pharmaceuticals SPA

Lead Sponsor

Trials

21

Recruited

5,700+

Citations

1. newron.com newron.com/news-and-media/regulatory-news/newron-reports-exceptional-one-year-results-study-01415-evenamide

Newron reports exceptional one-year results of study 014/ ... -Review of the efficacy data indicated that treatment with evenamide resulted in approximately 50% of patients at one-year no longer meeting any ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39661380/

Therapeutic Effect of Evenamide, a Glutamate Inhibitor, in ... Overall, treatment with evenamide showed a gradual, sustained, and clinically important improvement up to 1 year in all efficacy measures.

3. academic.oup.com academic.oup.com/ijnp/article/28/1/pyae061/7921168

Therapeutic Effect of Evenamide, a Glutamate Inhibitor, in ... The results from a pilot, 1-year, randomized, open-label, add-on treatment study in treatment-resistant schizophrenia (TRS) with evenamide, a

4. psychiatrictimes.com psychiatrictimes.com/view/evenamide-new-results-show-70-of-patients-saw-reduction-treatment-resistant-schizophrenia-severity

Evenamide: New Results Show 70% of Patients Saw ... New study results show evenamide as an add-on to antipsychotics for treatment-resistant schizophrenia significantly reduced disease severity.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07184619

Evenamide, a Glutamate Release Modulator, as Add-On to ... This is a prospective, 12-week, randomized, double-blind, placebo-controlled study, designed to evaluate the efficacy, safety, and tolerability of a dose of ...

6. newron.com newron.com/news-and-media/regulatory-news/newron-present-data-and-updates-its-clinical-program-evaluating

Newron to present data and updates on its clinical program ... Newron to present data and updates on its clinical program evaluating evenamide as an add-on treatment for schizophrenia at the 2025 World ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10464926/

Phase 2 Results Indicate Evenamide, A Selective ... Results from a pilot, 6-week, randomized, open-label, rater-blinded study, with 46-week extension, indicate very good tolerability with exceptional, clinically ...

8. newron.com newron.com/news-and-media/regulatory-news/newron-present-new-analyses-and-updates-its-clinical-program

Newron to present new analyses from and updates on its ... Treatment-resistance to antipsychotics is observed in about 30% of patients with schizophrenia, and clozapine, the most potent second-generation ...