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

Phase 2

Completed

• Conditions: Seizures
• Interventions: Drug: CVL-865

• Registration Number: NCT04686786
• Lead Sponsor: AbbVie

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-12-08
• Study First Submitted: 2020-12-23
• Study First Submitted QC: 2020-12-23
• Study First Posted: 2020-12-29
• Primary Completion: 2024-12-05
• Study Completion: 2024-12-05
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-02
• Last Update Posted: 2025-04-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 105

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CVL-865 25 mg	CVL-865	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants with Positive Response to Modified Clinical Institute Withdrawal Assessment - Benzodiazepines (mCIWA-B)	Week 54 up to Week 61	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.
Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	From first dose of study drug up to Week 61 (follow up period)	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.
Number of Participants with Clinically Significant Changes in Electrocardiogram (ECGs)	Baseline up to Week 57 or early termination (ET)	12-lead ECGs recordings will be obtained after the participant has been supine and at rest for at least 5 minutes.
Number of Participants with Clinically Significant Changes in Physical and Neurological Examination Results	Baseline up to Week 57 or early termination (ET)	Number of participants with clinically significant changes in physical and neurological examination results will be assessed.
Number of Participants with Clinically Significant Changes in Vital Sign Measurements	Baseline up to Week 57 or early termination (ET)	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.
Number of Participants With Positive Response to Columbia Suicide-Severity Rating Scale (C-SSRS)	Baseline up to Week 61 (follow up period)	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).

Trial Locations

Locations (54)

Little Rock, Arkansas; 🇺🇸 Little Rock, Arkansas, United States

Jacksonville, Florida; 🇺🇸 Jacksonville, Florida, United States

Lexington, Kentucky; 🇺🇸 Lexington, Kentucky, United States

Scarborough, Maine; 🇺🇸 Scarborough, Maine, United States

Baltimore, Maryland; 🇺🇸 Baltimore, Maryland, United States

Toledo, Ohio; 🇺🇸 Toledo, Ohio, United States

Saint Louis, Missouri; 🇺🇸 Saint Louis, Missouri, United States

Hackensack, New Jersey; 🇺🇸 Hackensack, New Jersey, United States

Randwick, New South Wales; 🇦🇺 Randwick, New South Wales, Australia

Westmead, New South Wales; 🇦🇺 Westmead, New South Wales, Australia

Herston, Queensland; 🇦🇺 Herston, Queensland, Australia

Fitzroy, Victoria; 🇦🇺 Fitzroy, Victoria, Australia

Melbourne, Victoria; 🇦🇺 Melbourne, Victoria, Australia

Parkville, Victoria; 🇦🇺 Parkville, Victoria, Australia

Gwangjin-gu, Seoul; 🇰🇷 Gwangju, Seoul, Korea, Republic of

Lodz; 🇵🇱 Łódź, Lodz, Poland

Kraków, Malopolskie; 🇵🇱 Kraków, Malopolskie, Poland

Wojnicz, Lskie; 🇵🇱 Wojnicz, Wojnicz Lskie, Poland

Philadelphia, Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Warszawa; 🇵🇱 Warszawa, Poland

Kragujevac, Sumadija; 🇷🇸 Kragujevac, Sumadija, Serbia

Neurology Department, Kragujevac; 🇷🇸 Kragujevac, Sumadija, Serbia

Malaga,; 🇪🇸 Málaga, Andalusia, Spain

Terrassa, Catalonia; 🇪🇸 Terrassa, Catalonia, Spain

Uzhgorod; 🇺🇦 Úzhgorod, Uzhgorod, Ukraine

Kyiv; 🇺🇦 Kyiv, Ukraine

Nashville, Tennessee; 🇺🇸 Nashville, Tennessee, United States

Salt Lake City, Utah; 🇺🇸 Salt Lake City, Utah, United States

New York; 🇺🇸 New York, New York, United States

Valencia; 🇪🇸 Valencia, Spain

Madrid; 🇪🇸 Madrid, Spain

Honolulu, Hawaii; 🇺🇸 Honolulu, Hawaii, United States

Chesterfield, Missouri; 🇺🇸 Chesterfield, Missouri, United States

Rochester, New York; 🇺🇸 Rochester, New York, United States

Oklahoma City, Oklahoma; 🇺🇸 Oklahoma City, Oklahoma, United States

Camperdown, New South Wales; 🇦🇺 Camperdown, New South Wales, Australia

Heidelberg, Victoria; 🇦🇺 Heidelberg, Victoria, Australia

Irwon-Ro Gangnam-gu., Seoul; 🇰🇷 Irwon-dong, Seoul, Korea, Republic of

Białystok; 🇵🇱 Białystok, Poland

Barcelona, Catalunya; 🇪🇸 Barcelona, Catalonia, Spain

Barcelona, Catalonia; 🇪🇸 Barcelona, Catalonia, Spain

Sevilla; 🇪🇸 Sevilla, Spain

Lviv; 🇺🇦 Lviv, Ukraine

New Haven, Connecticut; 🇺🇸 New Haven, Connecticut, United States

Orlando, Florida; 🇺🇸 Orlando, Florida, United States

Tampa, Florida; 🇺🇸 Tampa, Florida, United States

Bethesda, Maryland; 🇺🇸 Bethesda, Maryland, United States

Boston, Massachusetts; 🇺🇸 Boston, Massachusetts, United States

Charleston, South Carolina; 🇺🇸 Charleston, South Carolina, United States

Miami Lakes, Florida; 🇺🇸 Miami Lakes, Florida, United States

Gdańsk, Pomorskie; 🇵🇱 Gdańsk, Pomorskie, Poland

Gulf Breeze, Florida; 🇺🇸 Gulf Breeze, Florida, United States

Port Charlotte, Florida; 🇺🇸 Port Charlotte, Florida, United States

Bydgoszcz, Kujawsko-Pomorskie; 🇵🇱 Bydgoszcz, Kujawsko-Pomorskie, Poland