An Open-label Extension Trial of CVL-865 as Adjunctive Therapy in the Treatment of Focal Onset Seizures

Study Overview
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Brief Summary
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The purpose of this study is to assess the long-term safety and tolerability of CVL-865 as adjunctive therapy in participants with focal onset seizures.

Official Title
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A 57-Week, Multicenter, Active-treatment, Open-label Extension Trial of CVL-865 as Adjunctive Therapy in Adults With Drug-Resistant Focal Onset Seizures

Conditions
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Seizures

Intervention / Treatment
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* Drug: CVL-865


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who completed treatment in Trial CVL-865-SZ-001 (NCT04244175) A female participant of childbearing potential who is sexually active with a nonsterilized male partner must agree to use a highly effective method of contraception from signing of informed consent through 30 days post last dose A male participant with a pregnant or a nonpregnant partner of childbearing potential must agree to use a condom during treatment and until the end of relevant systemic exposure in the male participant for 94 days following the last dose with the investigational medicinal product (IMP) Participants who are capable of giving signed informed consent Participants who are able, in the opinion of the investigator, to understand the nature of the trial and comply with protocol requirements, including the prescribed dosage regimens, scheduled visits, laboratory tests, and other trial procedures Exclusion Criteria: Participants who, in the opinion of the investigator, medical monitor, or sponsor, should not participate in the trial Participants who, in the judgment of the investigator, experienced poor tolerability to the IMP during the double-blind trial or whose safety assessments resulted in new concerns that would suggest that the participant may not be appropriate for 57 weeks of treatment with CVL-865 in an extension trial Participants who experienced status epilepticus during Trial CVL-865-SZ-001 Participants who have demonstrated substantial noncompliance to trial procedures in Trial CVL-865-SZ-001, based on the investigator's judgment, would not be eligible for this trial Participants who answer yes on the C-SSRS Suicidal Ideation Item 4 or Item 5 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan, or Active Suicidal Ideation with Specific Plan and Intent), or participants who answer yes on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior), or participants who, in the opinion of the investigator, present a serious risk of suicide Participants with any of the following abnormalities in clinical laboratory tests at Visit 1, as assessed by the central laboratory and confirmed by a single repeat measurement, if deemed necessary (Females: Hemoglobin <11 gram per deciliter (g/dL); Males: hemoglobin <12 g/dL; White blood cell (WBC) count <3.0 x 10 power 9 per liter (10^9/L); Neutrophil count <2.0 x 10^9/L; Platelet count <150 × 10^9/L) Participants who would be likely to require the use of prohibited concomitant medications during the trial Female participants who have a positive pregnancy test result

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CVL-865 25 mg<br>Participants will receive CVL-865 tablets orally twice daily (BID) up to the maximum dose of 25 milligrams (mg) until Week 57 during the treatment period. | Drug: CVL-865<br>* Participants will receive 25 mg CVL-865 tablets orally BID during the treatment period. The dose may be decreased to 17.5 mg BID for tolerability.<br>* Other names: PF-06372865;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs will include abuse-related adverse events (AEs) and AEs related to medication handling irregularities (MHIs). The number of Participants With TEAEs and TESAEs will be assessed. | From first dose of study drug up to Week 61 (follow up period) | 
| Number of Participants with Clinically Significant Changes in Electrocardiogram (ECGs) | 12-lead ECGs recordings will be obtained after the participant has been supine and at rest for at least 5 minutes. | Baseline up to Week 57 or early termination (ET) | 
| Number of Participants with Clinically Significant Changes in Vital Sign Measurements | Vital signs will be measured with the participant in a sitting/semi-recumbent position after 5 minutes rest and will include temperature, systolic and diastolic blood pressure, and heart rate. | Baseline up to Week 57 or early termination (ET) | 
| Number of Participants with Clinically Significant Changes in Physical and Neurological Examination Results | Number of participants with clinically significant changes in physical and neurological examination results will be assessed. | Baseline up to Week 57 or early termination (ET) | 
| Number of Participants With Positive Response to Columbia Suicide-Severity Rating Scale (C-SSRS) | The C-SSRS rates an individual's degree of suicidal ideation (SI) on a scale, ranging from wish to be dead to active suicidal ideation with specific plan and intent. The scale identifies SI severity and intensity, which may be indicative of an individual's intent to commit suicide. C-SSRS SI severity subscale ranges from 0 (no SI) to 5 (active SI with plan and intent). | Baseline up to Week 61 (follow up period) | 
| Number of Participants with Positive Response to Modified Clinical Institute Withdrawal Assessment - Benzodiazepines (mCIWA-B) | The modified Clinical Institute Withdrawal Assessment - Benzodiazepines (mCIWA-B) is a sensitive instrument to measure withdrawal under conditions where there is a taper of medication (rather than abrupt discontinuation). It consists of 17-items that monitor the type and severity of BZD withdrawal symptoms such as irritability, fatigue, appetite, and sleeplessness. The total score ranges from 1 to 68 with higher scores indicating more severe withdrawal. | Week 54 up to Week 61 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CVL-865, Anti-epileptic drugs (AEDs), PF-06372865, γ-aminobutyric acid (GABA), focal epilepsy, partial seizure