What side effects are associated with this type of intervention?

Common treatments for seizures, particularly those involving GABAergic agents like gabapentin, pregabalin, and topiramate, often have side effects such as dizziness, fatigue, somnolence, and cognitive dysfunction. Gabapentin and pregabalin can cause dizziness, sleepiness, and gait unsteadiness, while topiramate is associated with cognitive issues, paresthesia, headache, and mood problems. These side effects can vary in intensity and may limit the tolerability of these medications for some patients.

What prior FDA approvals exist?

Several drugs have been FDA-approved for the treatment of seizures, particularly those that act on the GABA-A receptor as positive allosteric modulators. Benzodiazepines such as diazepam and clonazepam are well-known examples that enhance the effect of GABA at the GABA-A receptor, providing anticonvulsant effects. Additionally, felbamate has been approved for the treatment of partial seizures, demonstrating significant efficacy in clinical trials. These treatments share a similar mechanism of action to CVL-865, which is currently being studied as an adjunctive therapy for drug-resistant focal onset seizures.

What other types of research exist?

Promising novel alternatives to CVL-865 for seizure patients include WIN 55,212-2, a cannabinoid receptor agonist, which has shown significant anticonvulsant properties. Additionally, (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl]butanamide (ucb 34714) has demonstrated potent antiepileptic activity and is progressing through clinical trials. These alternatives have shown efficacy in recent studies and could be considered for treatment in 2024.

← Back to Search

CVL-865 for Seizures

Phase 2

Waitlist Available

Research Sponsored by Cerevel Therapeutics, LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants with a diagnosis of epilepsy with focal onset, as defined in the International League Against Epilepsy (ILAE) Classification of Seizures, focal aware, focal impaired awareness, and focal to bilateral tonic-clonic seizures for at least 2 years prior to signing the Informed Consent Form (ICF)

Participants must have a body mass index (BMI) of 17.5 to 40.0 kilogram per meter square (kg/m^2) and a total body weight greater than (>) 50 kilograms (kg) [110 pounds (lbs)]

Must not have

Use of prohibited medications as listed in the protocol in the absence of appropriate washout phase or the likelihood of requiring treatment during the study period with drugs not permitted by the study protocol

Participants with difficulty swallowing

Timeline

Screening 3 weeks

Treatment Varies

Follow Up day 15, day 43, day 71, day 92 and/or early termination (et)

Summary

This trial is testing a new medication called CVL-865 for people whose seizures are not controlled by current treatments. The medication works by balancing brain activity to help reduce seizures. CVL-865 is one of the newer antiepileptic drugs with a novel mode of action compared to more established treatments.

Who is the study for?

This trial is for adults with drug-resistant focal onset seizures, who've tried at least two anti-epileptic drugs without success and are currently on 1 to 3 stable AEDs. They must have had a minimum of eight seizures in the last eight weeks and been diagnosed with epilepsy for at least two years. Participants need a BMI between 17.5 to 40 kg/m^2 and weigh over 50 kg.

What is being tested?

The study tests CVL-865 as an additional treatment against placebo in people with focal onset seizures that don't respond well to other medications. The goal is to see if CVL-865 can reduce seizure frequency safely and tolerably.

What are the potential side effects?

While specific side effects of CVL-865 aren't listed, common ones for seizure medications include dizziness, fatigue, nausea, mood changes, or skin rashes. Safety will be closely monitored throughout the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have been diagnosed with focal epilepsy for at least 2 years.

Select...

My BMI is between 17.5 and 40, and I weigh more than 110 lbs.

Select...

I've had 4 or more seizures a month for the last 3 months.

Select...

My brain scans showed no worsening abnormalities when my epilepsy was diagnosed.

Select...

I've had at least 8 seizures in the last 8 weeks without a 3-week break.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am not currently using, nor likely to use, any medications not allowed by the study.

Select...

I have trouble swallowing.

Select...

I have had frequent seizures in the last year that couldn't be counted.

Select...

I have had a severe seizure episode within the last 5 years.

Select...

I have a type of epilepsy that might be genetic, including Lennox-Gastaut Syndrome.

Select...

I am not pregnant or breastfeeding.

Select...

I am taking medication that is sensitive to certain proteins.

Select...

I do not have any significant ongoing health issues affecting my heart, lungs, stomach, kidneys, liver, blood, immune system, or brain.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ day 15, day 43, day 71, day 92 and/or early termination (et)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~day 15, day 43, day 71, day 92 and/or early termination (et)

This trial's timeline: 3 weeks for screening, Varies for treatment, and day 15, day 43, day 71, day 92 and/or early termination (et) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Response Ratio (RRatio)

Secondary study objectives

Change From Baseline in Clinical Global Impression-Improvement Scale (CGI-I) Score at Day 15, 43 and 71

Change From Baseline in Focal Onset Seizure Frequency per Week over the Maintenance Phase

Change from Baseline in Clinical Global Impression-Severity of Symptoms Scale (CGI-S) Score at Day 15, 43 and 71

+13 more

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: Low Dose: CVL-865 7.5 mgExperimental Treatment1 Intervention

Participants will receive CVL-865 tablets orally BID up to the maximum dose of 7.5 mg until Day 92 during the treatment period.

Group II: High Dose: CVL-865 25 mgExperimental Treatment1 Intervention

Participants will receive CVL-865 tablets orally twice daily (BID) up to the maximum dose of 25 milligrams (mg) until Day 92 during the treatment period.

Group III: PlaceboPlacebo Group1 Intervention

Participants will receive a placebo matched to CVL-865 tablets orally BID until Day 92 during the treatment period.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

CVL-865

2020

Completed Phase 2

~160

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for seizures work by stabilizing neuronal activity through various mechanisms. These include enhancing inhibitory neurotransmission via the GABAergic system, reducing excitatory neurotransmission, and modulating ion channels to stabilize neuronal membranes. CVL-865, a GABA-A receptor positive allosteric modulator, specifically enhances the effect of GABA, the primary inhibitory neurotransmitter, thereby reducing neuronal excitability and preventing seizures. Understanding these mechanisms is important for selecting the most effective treatment tailored to the patient's specific type of seizures and their response to therapy.

[How do antiepileptic drugs work?].New antiepileptic drugs.