Emraclidine for Schizophrenia

Recruiting at 75 trial locations

Overseen By Cerevel Clinical Trial Support

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Cerevel Therapeutics, LLC

Must be taking: Antipsychotics

Must not be taking: Antidepressants, Mood stabilizers

Disqualifiers: Substance use disorder, Cardiovascular, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

850 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new pill called CVL-231 (also known as Emraclidine) to determine its safety and tolerability for people with schizophrenia over an extended period. Schizophrenia affects thinking, feeling, and behavior, often causing hallucinations or delusions. The trial seeks participants who have remained stable on their medication for at least three months in the past year. Those who participated in specific previous studies and could benefit from this treatment are ideal candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications before and during the study, as there is a washout period (time without taking certain medications) specified. You should discuss with the trial team which of your current medications are considered prohibited.

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

Research has shown that emraclidine, also known as CVL-231, has promising safety results from earlier studies. In a recent study, most participants tolerated emraclidine well, experiencing no severe side effects. The safety results mirrored those in previous studies, which is encouraging.

Emraclidine targets specific pathways in the brain, potentially reducing unwanted effects. Overall, current research supports the potential safety of emraclidine for treating schizophrenia, but further studies are needed to confirm these findings. ^{1 2 3 4 5}

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

Unlike the standard treatments for schizophrenia, which often include antipsychotics that target dopamine receptors, CVL-231 offers a fresh approach by focusing on the muscarinic acetylcholine receptor M4. This new mechanism of action could potentially lead to fewer side effects typically associated with dopaminergic pathways, such as weight gain and movement disorders. Researchers are particularly excited about CVL-231 because it may provide effective symptom relief while improving the overall quality of life for individuals with schizophrenia.

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

Research shows that emraclidine, also known as CVL-231, may improve symptoms of schizophrenia. Studies have found that it can reduce the PANSS score, which measures symptoms of schizophrenia, indicating it may lessen delusions and hallucinations. Emraclidine likely works by influencing brain chemicals, particularly by increasing M4 activity, which helps control dopamine levels linked to psychosis. Previous trials demonstrated its potential as a promising treatment for people with schizophrenia. These findings offer hope that emraclidine can effectively manage symptoms for those living with this condition. ^{1 6 7 8 9}

Who Is on the Research Team?

Erica Koenig, PhD

Principal Investigator

Cerevel Therapeutics, LLC

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with schizophrenia who can understand the study and follow its procedures. It's not for those whose only response to treatment has been clozapine, or have progressive brain diseases, severe head trauma history, seizures (except childhood febrile seizures), or a high risk of suicide.

Inclusion Criteria

You have been diagnosed with Schizophrenia

Do you have a Body Mass Index (BMI) between 18 - 40 kg/m

Are you currently taking Antipsychotic medication?

Exclusion Criteria

Have you been diagnosed with Major Depressive Disorder or PTSD or Obsessive-Compulsive Disorder?

Have you been diagnosed with Bipolar Disorder?

Have you been diagnosed with Schizoaffective Disorder?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CVL-231 30 mg tablet once daily

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CVL-231

Trial Overview The study is testing the long-term safety and how well people can tolerate CVL-231 (Emraclidine) at a dose of 30 mg. Emraclidine is taken orally by participants with schizophrenia to evaluate its effects over an extended period.

How Is the Trial Designed?

Group I: CVL-231 30 mg Experimental Treatment 1 Intervention

Participants will receive CVL-231 30 milligrams (mg) tablet, once daily for 52 weeks.

Who Is Running the Clinical Trial?

Cerevel Therapeutics, LLC

Lead Sponsor

Trials

37

Recruited

5,500+

Published Research Related to This Trial

Novel antipsychotic medications like cariprazine, brexpiprazole, and brilaroxazine have shown effectiveness in treating acute relapse of schizophrenia, while lumateperone also helps with asocial and depressive symptoms.

Many of these new treatments, such as pimavanserin and ulotaront, demonstrate promise in improving both positive and negative symptoms of schizophrenia, and they generally have favorable side-effect profiles compared to traditional antipsychotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New and emerging treatments for schizophrenia: a narrative review of their pharmacology, efficacy and side effect profile relative to established antipsychotics. Lobo, MC., Whitehurst, TS., Kaar, SJ., et al.[2023]

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]

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]

Brexpiprazole is effective for treating schizophrenia, with a response rate of 45.5% compared to 31.0% for placebo, and a number needed to treat (NNT) of 7, indicating it is a beneficial option for patients.

It is also well tolerated, with lower discontinuation rates due to adverse events compared to placebo, and while akathisia was the most common side effect, its occurrence was not significantly higher than in the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexpiprazole for schizophrenia and as adjunct for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antipsychotic - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Citrome, L.[2022]

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]

In a study involving five neuroleptic-free schizophrenic patients, treatment with EMD 57445 (panamesine) showed a high occupancy of D(2)-like dopamine receptors, similar to typical antipsychotic medications.

The findings suggest that the antipsychotic effects of EMD 57445 may be primarily due to its metabolite EMD 59983's strong binding to dopamine receptors rather than its sigma receptor affinity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Occupancy of striatal D(2)-like dopamine receptors after treatment with the sigma ligand EMD 57445, a putative atypical antipsychotic. Gründer, G., Müller, MJ., Andreas, J., et al.[2019]

Atypical antipsychotics are significantly associated with major adverse cardio- and cerebrovascular events (MACCE), with a reporting odds ratio of 2.46, indicating a higher risk compared to typical antipsychotics.

Antipsychotics that have a high affinity for certain receptors, such as Adrenergic alfa-1 and Serotoninergic 5-HT2A, as well as those with a higher risk of metabolic side effects, are linked to an increased risk of MACCE, suggesting that these receptor interactions may contribute to cardiovascular risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The association between receptor binding affinity and metabolic side effect profile of antipsychotics and major cardio- and cerebrovascular events: A case/non-case study using VigiBase. Aguiar, JP., Alves da Costa, F., Egberts, T., et al.[2021]

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]

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]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT05227703

NCT05227703 | A Trial of 15 and 30 mg Doses of CVL-231 ... A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms. Baseline through Week 6. Secondary Outcome Measures ...

3. abbvieclinicaltrials.com abbvieclinicaltrials.com/study/?id=CVL-231-2002

A Trial of 15 and 30 mg Doses of CVL-231 (Emraclidine) in ... A Trial of 15 and 30 mg Doses of CVL-231 (Emraclidine) in Participants With Schizophrenia ... This is a Phase 2, multicenter, randomized, double-blind, placebo- ...

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

Emraclidine (CVL-231) to treat acute psychosis in ... Emraclidine is thought to produce antipsychotic effects by upregulating M4 activity, which prevents acetylcholine release and indirectly modulates dopamine ...

5. delveinsight.com delveinsight.com/blog/cvl-231-for-schizophrenia-treatment

CVL-231 Phase Ib Trial Result | SIRS 2024 These findings underscore the potential of emraclidine as a promising treatment option for individuals with schizophrenia, offering hope for ...

6. 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.

7. 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.

8. 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 ... In the EMPOWER trials, emraclidine was well-tolerated with a safety profile comparable to that observed in the Phase 1b trial. The most ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0140673622019900

Emraclidine, a novel positive allosteric modulator of ... This two-part, phase 1b study was designed to assess the safety and tolerability of emraclidine, a novel, highly selective M4 muscarinic ...