A Trial of the Efficacy and Safety of CVL-865 as Adjunctive Therapy in the Treatment of Focal Onset Seizures

NCT ID: NCT04244175

Last Updated: 2025-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 154 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-27
• Study Completion Date: 2024-05-21

Brief Summary

The goal of this clinical trial is to learn if CVL-865, when taken regularly with other anti-seizure medicines, works to prevent seizures in adults with drug-resistant focal onset seizures. It will also learn about the safety of CVL-865.

The main question it aims to answer is whether CVL-865, when taken regularly with other anti-seizure medicines, lowers the number of seizures in those with a diagnosis of epilepsy with drug-resistant focal onset seizures.

This study has an 8-week Screening/Baseline Period, a 13-week Treatment Period (including a 2-week Titration Phase, an 8-week Maintenance Phase, and a 3-week Taper Phase), and a 4-week Safety Follow-Up Period.

Participants will take CVL-865 or a placebo twice a day during the 10-13 week Treatment Period, visit the clinic every few weeks for checkups, tests, and surveys, and fill out an e-Diary.

Conditions

Seizures

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Participants received a placebo matched to CVL-865 tablets orally twice a day (BID) during the 2-week Titration Phase, the 8-week Maintenance Phase, and the 3-week Taper Phase.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants received CVL-865 matched placebo tablets orally twice a day (BID) during the Treatment Period.

CVL-865 7.5 mg BID

CVL-865 tablets were administered orally as 2.5 mg twice a day (BID) for 1 week followed by 5 mg BID for another week during the Titration Phase, and then 7.5 mg BID during the 8-week Maintenance Phase. For participants not enrolling into the open-label extension trial, following the Maintenance Phase the dose was gradually decreased over a 3-week Taper Phase.

Group Type: EXPERIMENTAL

CVL-865

Intervention Type: DRUG

Participants received CVL-865 tablets orally twice a day (BID) up to the maximum dose of 7.5 mg BID or 25 mg BID during the Treatment Period.

CVL-865 25 mg BID

CVL-865 tablets were administered orally as 5 mg twice a day (BID) for 1 week followed by 12.5 mg for another week during the Titration Phase, and then 25 mg BID during the 8-week Maintenance Phase. For participants not enrolling into the open-label extension trial, following the Maintenance Phase the dose was gradually decreased over a 3-week Taper Phase.

Group Type: EXPERIMENTAL

CVL-865

Intervention Type: DRUG

Participants received CVL-865 tablets orally twice a day (BID) up to the maximum dose of 7.5 mg BID or 25 mg BID during the Treatment Period.

Interventions

Placebo

Participants received CVL-865 matched placebo tablets orally twice a day (BID) during the Treatment Period.

Intervention Type: DRUG

CVL-865

Participants received CVL-865 tablets orally twice a day (BID) up to the maximum dose of 7.5 mg BID or 25 mg BID during the Treatment Period.

Intervention Type: DRUG

Other Intervention Names

Darigabat; PF-06372865

Eligibility Criteria

Inclusion Criteria

• Participants with a diagnosis of epilepsy with focal onset, as defined in the International League Against Epilepsy (ILAE) Classification of Seizures, focal aware (except participants with only focal aware seizures without a motor component), 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 history of an average of 4 or more spontaneous and observable focal onset, as defined in the ILAE Classification of Seizures, focal aware (except participants with only focal aware seizures without a motor component), focal impaired awareness, and focal to bilateral tonic-clonic seizures per 28-day period for at least 3 months (84 days) prior to signing the ICF
• Participants who have tried and failed at least 2 appropriate Anti- epileptic drugs (AEDs) in the past and also currently taking 1 to 3 permitted AEDs at a stable dose for 4 Weeks prior to the Screening Visit
• Participants with a minimum of 8 focal onset, focal aware, focal impaired awareness, or focal to bilateral tonic-clonic seizures during the 8 week baseline period with no 21-day period free of any of these seizure types
• Participants must have had magnetic resonance imaging or contrast enhance computed tomography scan of the brain that demonstrated no progressive structural central nervous system abnormality at the time of the diagnosis of epilepsy
• 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)]
• Women of childbearing potential must agree to use an effective method of contraception from signing of informed consent throughout the duration of the study and for 30 days post last dose
• Male must agree to use condom during treatment and until the end of relevant systemic exposure in the male participant for 94 days following the last dose with Investigational Manufacturing Product (IMP)

Exclusion Criteria

• Participants with (genetic) idiopathic generalized epilepsies or combined generalized and focal epilepsies, including a history of Lennox-Gastaut Syndrome
• Participants with a history of seizures over the past 12 months that occur at such a high frequency they cannot be counted (eg, repetitive seizures, cluster seizures)
• Participants with a history of psychogenic non-epileptic seizures within the year prior to signing the ICF
• Participants with a history of status epilepticus within 5 years prior to signing the ICF
• Participants with a history of neurosurgery for seizures less than 1 year prior to signing the ICF, or radiosurgery less than 2 years prior to signing the ICF
• Participants with a current history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, hematological, immunological, or neurological (excluding focal onset epilepsy) disease
• Participants who test positive for human immunodeficiency virus (HIV), hepatitis B and/or or hepatitis C infection
• Participants with a 12-lead ECG demonstrating : QT interval corrected for heart rate using Fridericia's formula >450 milliseconds (msec) (average of 3 ECGs obtained at the Screening Visit); QRS interval >120 msec at the Screening Visit assessed by central reader
• Participants with abnormal laboratory test results which includes (Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) elevated to >2 × Upper limit of normal range (ULN); Total bilirubin greater than or equal to (>=)1.5 × ULN; 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
• 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 taking any drug that is a sensitive P-glycoprotein (P-gp) and Breast cancer resistance protein (BCRP) substrate
• Female participants who are breastfeeding and/or who have a positive pregnancy test result prior to receiving IMP
• Participants who are known to be allergic or hypersensitive to the IMP or any of its components
• Participants who have participated in any clinical trial within 60 days prior to signing the ICF or who have participated in more than 2 clinical trials within the year prior to signing the ICF
• Participants with difficulty swallowing
• Participants who answer "Yes" on the C-SSRS Suicidal Ideation Item 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) and whose most recent episode meeting criteria for this C-SSRS Item 4 occurred within the last 6 months, OR Subjects who answer "Yes" on the C-SSRS Suicidal Ideation Item 5 (Active Suicidal Ideation with Specific Plan and Intent) and whose most recent episode meeting criteria for this CSSRS Item 5 occurred within the last 6 months OR Subjects who answer "Yes" on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) and whose most recent episode meeting criteria for any of these 5 C-SSRS Suicidal Behavior Items occurred in the last 2 years

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ABBVIE INC.

Role: STUDY_DIRECTOR

AbbVie

Locations

Little Rock, Arkansas

Little Rock, Arkansas, United States

Downey, California

Downey, California, United States

Loma Linda, California

Loma Linda, California, United States

Valencia, California

Valencia, California, United States

New Haven, Connecticut

New Haven, Connecticut, United States

Altamonte Springs, Florida

Altamonte Springs, Florida, United States

Gulf Breeze, Florida

Gulf Breeze, Florida, United States

Homestead, Florida

Homestead, Florida, United States

Jacksonville, Florida

Jacksonville, Florida, United States

Miami, Florida

Miami, Florida, United States

Miami Lakes, Florida

Miami Lakes, Florida, United States

Orlando, Florida

Orlando, Florida, United States

Port Charlotte, Florida

Port Charlotte, Florida, United States

Port Orange, Florida

Port Orange, Florida, United States

Tampa, Florida

Tampa, Florida, United States

Suwanee, Georgia,

Suwanee, Georgia, United States

Honolulu, Hawaii

Honolulu, Hawaii, United States

Lexington, Kentucky

Lexington, Kentucky, United States

Scarborough, Maine

Scarborough, Maine, United States

Baltimore, Maryland

Baltimore, Maryland, United States

Bethesda, Maryland

Bethesda, Maryland, United States

Boston, Massachusetts

Boston, Massachusetts, United States

Chesterfield, Missouri

Chesterfield, Missouri, United States

Saint Louis, Missouri

St Louis, Missouri, United States

Hackensack, New Jersey

Hackensack, New Jersey, United States

Mineola, New York

Mineola, New York, United States

New York

New York, New York, United States

Rochester, New York

Rochester, New York, United States

Syracuse, New York

Syracuse, New York, United States

Columbus, Ohio

Columbus, Ohio, United States

Toledo, Ohio

Toledo, Ohio, United States

Oklahoma City, Oklahoma

Oklahoma City, Oklahoma, United States

Philadelphia, Pennsylvania

Philadelphia, Pennsylvania, United States

Philadelphia, Pennsylvania

Philadelphia, Pennsylvania, United States

Charleston, South Carolina

Charleston, South Carolina, United States

Nashville, Tennessee

Nashville, Tennessee, United States

Salt Lake City, Utah

Salt Lake City, Utah, United States

Camperdown, New South Wales

Camperdown, New South Wales, Australia

Randwick, New South Wales

Randwick, New South Wales, Australia

Westmead, New South Wales

Westmead, New South Wales, Australia

Herston, Queensland

Herston, Queensland, Australia

South Brisbane, Queensland

South Brisbane, Queensland, Australia

Fitzroy, Victoria

Fitzroy, Victoria, Australia

Heidelberg, Victoria

Heidelberg, Victoria, Australia

Melbourne, Victoria

Melbourne, Victoria, Australia

Parkville, Victoria

Parkville, Victoria, Australia

Bydgoszcz, Kujawsko-Pomorskie

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Kraków, Malopolskie

Krakow, Lesser Poland Voivodeship, Poland

Warszawa, Mazowieckie

Warsaw, Masovian Voivodeship, Poland

Gdańsk, Pomorskie

Gdansk, Pomeranian Voivodeship, Poland

Gdańsk, Pomorskie

Gdansk, Pomeranian Voivodeship, Poland

Wojnicz, Lskie

Wojnicz, Wojnicz Lskie, Poland

Białystok

Bialystok, , Poland

Lublin

Lublin, , Poland

Warszawa

Warsaw, , Poland

Lodz

Lodz, Łódź Voivodeship, Poland

Kragujevac, Sumadija

Kragujevac, Sumadija, Serbia

Neurology Department, Kragujevac

Kragujevac, Sumadija, Serbia

Belgrade

Belgrade, , Serbia

Clinic of Neurology, Belgrade

Belgrade, , Serbia

Niš

Niš, , Serbia

Gwangjin-gu, Seoul

Gwangju, Seoul, South Korea

Irwon-Ro Gangnam-gu., Seoul

Irwon-dong, Seoul, South Korea

Malaga,

Málaga, Andalusia, Spain

Barcelona, Catalunya

Barcelona, Catalonia, Spain

Terrassa

Terrassa, Catalonia, Spain

Navarra

Navarro, Navarre, Spain

Barcelona

Barcelona, , Spain

Madrid

Madrid, , Spain

Madrid

Madrid, , Spain

Madrid

Madrid, , Spain

Sevilla

Seville, , Spain

Valencia

Valencia, , Spain

Uzhgorod

Uzhhorod, Uzhgorod, Ukraine

Kyiv

Kyiv, , Ukraine

Lviv

Lviv, , Ukraine

Countries

United States; Australia; Poland; Serbia; South Korea; Spain; Ukraine

References

Gurrell R, Iredale P, Evrard A, Duveau V, Ruggiero C, Roucard C. Pronounced antiseizure activity of the subtype-selective GABAA positive allosteric modulator darigabat in a mouse model of drug-resistant focal epilepsy. CNS Neurosci Ther. 2022 Nov;28(11):1875-1882. doi: 10.1111/cns.13927. Epub 2022 Aug 14.

Reference Type: DERIVED

PMID: 35965432 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-002576-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CVL-865-SZ-001

Identifier Type: -

Identifier Source: org_study_id