Emraclidine for Schizophrenia

Recruiting at 26 trial locations

Overseen By Cerevel Clinical Trial Support

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AbbVie

Must not be taking: Antidepressants, Mood stabilizers

Disqualifiers: Substance use disorder, Cardiovascular, Diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

391 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called Emraclidine, given in two different doses daily. It aims to help people with schizophrenia who are having severe symptom flare-ups. The medication works by targeting specific parts of the brain to reduce symptoms like hallucinations and delusions.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications before and during the trial, as there is a required washout period (time without taking certain medications) specified in the protocol.

What data supports the effectiveness of the drug Emraclidine for treating schizophrenia?

Emraclidine is a new drug that targets M4 receptors in the brain, which may help with schizophrenia symptoms. While the main study focused on its safety, its unique action on brain receptors suggests potential benefits for treating schizophrenia. ^{1 2 3 4 5}

Is Emraclidine (CVL-231) safe for humans?

Emraclidine has been tested in a phase 1b trial for schizophrenia, where its safety and tolerability were evaluated in patients. This suggests that some safety data exists, but specific details on side effects or adverse reactions were not provided in the available research. ^{1 3 5 6 7}

How is the drug Emraclidine unique in treating schizophrenia?

Emraclidine is unique because it is a novel drug that specifically targets the M4 receptors in the brain, which are part of the cholinergic system, offering a different mechanism of action compared to traditional antipsychotics that primarily target dopamine receptors. ^{3 8 9 10 11}

Research Team

Julie Adams

Principal Investigator

AbbVie

Eligibility Criteria

This trial is for adults with schizophrenia who are moderately to severely ill, have had a recent worsening of symptoms, and meet specific health criteria. They must not be resistant to antipsychotic treatments or have certain other mental health conditions.

Inclusion Criteria

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

I understand the trial's nature and can follow its requirements.

Exclusion Criteria

I have not taken, nor will I need to take, any forbidden medications during the trial.

I do not have schizophrenia, but I might have anxiety due to it. I haven't had severe depression or manic episodes needing medication in the last month.

Risk for suicidal behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) and investigator's clinical assessment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 15 mg or 30 mg of CVL-231 or placebo daily for 6 weeks

6 weeks

Weekly visits for assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CVL-231 (Emraclidine)

Trial Overview The trial tests two doses (15 mg and 30 mg) of a drug called CVL-231 against a placebo in people with schizophrenia over six weeks to see if it's effective and safe for treating acute psychosis.

Participant Groups

Group I: CVL-231 30 mg, once daily (QD) Experimental Treatment 1 Intervention

Oral Dose

Group II: CVL-231 15 mg, once daily (QD) Experimental Treatment 1 Intervention

Oral Dose

Group III: Placebo, once daily (QD) Placebo Group 1 Intervention

Oral Dose

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Cerevel Therapeutics, LLC

Lead Sponsor

Trials

37

Recruited

5,500+

Findings from Research

Emerging treatments for schizophrenia, such as cannabidiol and lumateperone, aim to address a broader range of symptoms beyond just the positive symptoms typically targeted by existing antipsychotics, with some showing promise in treating negative and cognitive symptoms.

New long-acting injectable formulations like Aripiprazole Lauroxil and Perseris have been approved, providing rapid therapeutic levels without the need for initial oral treatment, which may improve adherence and reduce adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities. Krogmann, A., Peters, L., von Hardenberg, L., et al.[2020]

Current antipsychotic medications primarily target positive symptoms of schizophrenia but do not effectively address negative symptoms and cognitive dysfunction, highlighting a significant gap in treatment options.

Recent research suggests that enhancing NMDA receptor function may provide a new therapeutic approach, with several promising compounds emerging that could potentially treat all symptom areas of schizophrenia, as supported by both preclinical and clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of NMDA receptor function as a treatment for schizophrenia. Cioffi, CL.[2022]

Emraclidine, a selective M4 receptor modulator, was found to be safe and well-tolerated in a phase 1b trial involving 81 participants with schizophrenia, with no significant differences in adverse events compared to placebo.

The most common side effect was headache, and any increases in blood pressure and heart rate were modest and resolved over time, suggesting a favorable side-effect profile for further investigation as a treatment for schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emraclidine, a novel positive allosteric modulator of cholinergic M4 receptors, for the treatment of schizophrenia: a two-part, randomised, double-blind, placebo-controlled, phase 1b trial. Krystal, JH., Kane, JM., Correll, CU., et al.[2023]

Typical antipsychotic drugs primarily target D2 receptors but can cause significant side effects like extrapyramidal symptoms and increased prolactin levels, leading to poor patient compliance and higher relapse rates.

Atypical antipsychotics, such as olanzapine and sertindole, offer a better safety profile with fewer extrapyramidal effects and improved efficacy, making them a promising alternative for treating schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug treatments for schizophrenia - past, present and future. Rasmussen, JG.[2014]

Clozapine remains the only antipsychotic specifically approved for treatment-refractory schizophrenia, having undergone extensive testing in patients who did not respond to other medications.

Recent studies have begun to compare clozapine with newer atypical antipsychotics like risperidone and olanzapine, which are better tolerated but have shown varying success in patients with poor responses to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing treatment-resistant schizophrenia: evidence from randomized clinical trials. Citrome, L., Bilder, RM., Volavka, J.[2019]

Pimavanserin (Nuplazid) is specifically designed to treat hallucinations and delusions in patients with Parkinson's disease, showing promise in improving their quality of life.

Clinical studies have demonstrated that pimavanserin effectively reduces these symptoms without significantly impacting motor function, making it a safer alternative to traditional antipsychotics for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pimavanserin (Nuplazid): A Treatment for Hallucinations and Delusions Associated With Parkinson's Disease. Cruz, MP.[2022]

In a 4-week exploratory trial involving 12 patients with acute schizophrenia, EMD 57455 (panamesine) showed significant improvement in psychiatric symptoms, with 4 out of 7 completers classified as responders based on a 50% reduction in their BPRS scores.

While EMD 57455 demonstrated potential antipsychotic effects similar to atypical neuroleptics, it was not completely free of side effects, as two patients experienced extrapyramidal symptoms and one had restlessness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the sigma receptor ligand EMD 57445 (panamesine) in patients with schizophrenia: an open clinical trial. Huber, MT., Gotthardt, U., Schreiber, W., et al.[2012]

A combination of xanomeline and trospium showed improved tolerability and significant antipsychotic effects in a randomized study of 182 patients with acute psychosis, with a notable reduction in symptoms as measured by the PANSS score.

The study suggests that targeting the cholinergic system may offer a new treatment avenue for schizophrenia, as the combination therapy demonstrated superior efficacy in reducing both positive and negative symptoms compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Xanomeline-Trospium and Muscarinic Involvement in Schizophrenia. Kidambi, N., Elsayed, OH., El-Mallakh, RS.[2023]

SU-23397, a new hybrid molecule, shows promising antipsychotic activity in severely ill schizophrenic patients at doses ranging from 20 mg to 250 mg daily, despite the trial being uncontrolled.

However, the treatment was associated with some safety concerns, as seven out of ten subjects required antiparkinson medication, and two patients experienced premature ventricular contractions, indicating potential cardiac risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of antipsychotic activity of an unique agent: SU-23397. Mielke, EH., Gallant, DM., Bishop, G., et al.[2007]

References

1. United States pubmed.ncbi.nlm.nih.gov

Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Modulation of NMDA receptor function as a treatment for schizophrenia. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Emraclidine, a novel positive allosteric modulator of cholinergic M4 receptors, for the treatment of schizophrenia: a two-part, randomised, double-blind, placebo-controlled, phase 1b trial. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Refractory schizophrenia and atypical antipsychotics. [2017]

5. England pubmed.ncbi.nlm.nih.gov

Drug treatments for schizophrenia - past, present and future. [2014]

6. United States pubmed.ncbi.nlm.nih.gov

Managing treatment-resistant schizophrenia: evidence from randomized clinical trials. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Beyond the dopamine receptor: novel therapeutic targets for treating schizophrenia. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Pimavanserin (Nuplazid): A Treatment for Hallucinations and Delusions Associated With Parkinson's Disease. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the sigma receptor ligand EMD 57445 (panamesine) in patients with schizophrenia: an open clinical trial. [2012]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Xanomeline-Trospium and Muscarinic Involvement in Schizophrenia. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Assessment of antipsychotic activity of an unique agent: SU-23397. [2007]