Emraclidine for Schizophrenia

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called Emraclidine (also known as CVL-231) for individuals with schizophrenia experiencing a sudden increase in symptoms. The study will compare two doses of the treatment against a placebo (a pill with no active medicine) to determine its effectiveness in reducing psychotic episodes. Suitable candidates for this trial include those diagnosed with schizophrenia for over two years and currently experiencing worsening symptoms. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in schizophrenia treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Emraclidine, also known as CVL-231, is generally safe for people. In earlier studies, its safety profile matched that of other trials, indicating it usually doesn't cause serious side effects. The most common side effects were mild, such as headaches and dizziness, similar to those from other schizophrenia medications. Additionally, studies found that Emraclidine is safe for long-term use, as demonstrated in research conducted over extended periods. This information reassures that the treatment has undergone safety testing before reaching this stage of research. ^{1 2 3 4 5}

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

Researchers are excited about Emraclidine for schizophrenia because it targets the condition differently than current treatments. Most schizophrenia medications focus on dopamine pathways, but Emraclidine works by modulating muscarinic acetylcholine receptors, potentially offering a new approach to managing symptoms. This unique mechanism could mean fewer side effects compared to traditional antipsychotics, which often cause significant issues like weight gain or movement disorders. Additionally, Emraclidine's once-daily oral dosing makes it user-friendly, possibly improving adherence and overall patient outcomes.

What evidence suggests that Emraclidine might be an effective treatment for schizophrenia?

Research has shown that emraclidine might help reduce symptoms of schizophrenia. In earlier studies, patients taking emraclidine had lower PANSS scores, indicating symptom improvement. In this trial, participants will receive either a 15 mg or 30 mg dose of emraclidine, or a placebo. Emraclidine affects certain parts of the brain, called M4 receptors, which may help reduce psychotic symptoms. It aims to do this without causing some common side effects of other treatments, such as movement problems. Overall, early results suggest that emraclidine could be a helpful option for managing schizophrenia symptoms. ^{1 2 3 6 7}

Who Is on the Research Team?

Julie Adams

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05227690

A Trial of 10 and 30 mg Doses of CVL-231 (Emraclidine) in ... A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms. Baseline through Week 6. Secondary Outcome Measures ...

2. news.abbvie.com news.abbvie.com/2024-11-11-AbbVie-Provides-Update-on-Phase-2-Results-for-Emraclidine-in-Schizophrenia

AbbVie Provides Update on Phase 2 Results for ... It is hypothesized that by selectively targeting M4 receptors, emraclidine has the potential to reduce psychotic symptoms without interfering ...

3. horizonscandb.pcori.org horizonscandb.pcori.org/report/topics/835

Emraclidine (CVL-231) to treat acute psychosis in ... Although these drugs are effective in reducing core symptoms of schizophrenia, undesirable adverse effects, such as tardive dyskinesia (a disorder causing ...

4. abbvieclinicaltrials.com abbvieclinicaltrials.com/study/?id=CVL-231-2003

A Study to Evaluate Safety and Tolerability of CVL-231 ... The primary purpose of this study is to assess the long-term safety and tolerability of oral emraclidine in adult participants with schizophrenia.

5. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(22)01990-0/abstract

Emraclidine, a novel positive allosteric modulator of ... Emraclidine is a novel, brain-penetrant, highly selective M4 receptor positive allosteric modulator in development for the treatment of schizophrenia.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36528376/

Emraclidine, a novel positive allosteric modulator of ... Emraclidine is a novel, brain-penetrant, highly selective M4 receptor positive allosteric modulator in development for the treatment of schizophrenia.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05443724?tab=table

A Study to Evaluate Safety and Tolerability of CVL-231 ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...