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

NCT04244175 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CVL-865-SZ-0012019-002576-14
• Study Type: interventional
• Target: 154
• Locations: 7 countries
• Sites: 76

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

Keywords

CVL-865; Anti-epileptic drugs (AEDs); Focal epilepsy; γ-aminobutyric acid (GABA); Partial seizure; PF-06372865; Darigabat

Outcome Measures

Primary Outcomes (1)

• Response Ratio (RRatio)

  Response Ratio (RRatio) is calculated as RRatio=(T-B)/(T+B) ×100, where T represents the focal onset seizure frequency rate per week in the Maintenance Phase and B represents the focal onset seizure frequency rate per week in the Baseline Period. The Response Ratio ranges between -100 and 100; negative values indicate reduction in seizure rate and positive values indicate increase in seizure rate during treatment.

  Baseline Period; Maintenance Phase Days 15 through 71

Secondary Outcomes (17)

• Percentage Change From Baseline in Focal Onset Seizure Frequency Per Week Over the Maintenance Phase

  Baseline Period; Maintenance Phase Days 15 through 71

• Percentage of Participants With 50 Percent (%) Responder Rate

  Baseline Period; Maintenance Phase Days 15 through 71

• Percentage of Seizure-free Participants During the Maintenance Phase

  Maintenance Phase Days 15 through 71

• Weekly Seizure Rate During the Maintenance Phase

  Maintenance Phase Weeks 1, 2, 3, 4, 5, 6, 7, 8

• Patient's Global Impression of Change (PGI-C) Score at Maintenance Phase Days 15, 43, and 71

  Maintenance Phase Days 15, 43, and 71

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

CVL-865 7.5 mg BID

EXPERIMENTAL

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.

Drug: CVL-865

CVL-865 25 mg BID

EXPERIMENTAL

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.

Drug: CVL-865

Interventions

Placebo DRUG

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

Placebo

CVL-865 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.

Also known as: Darigabat, PF-06372865

CVL-865 25 mg BID; CVL-865 7.5 mg BID

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• AbbVie: lead

Study Sites (76)

Little Rock, Arkansas

Little Rock, Arkansas, 72205, United States

Location

Downey, California

Downey, California, 90242, United States

Location

Loma Linda, California

Loma Linda, California, 92354, United States

Location

Valencia, California

Valencia, California, 91355, United States

Location

New Haven, Connecticut

New Haven, Connecticut, 06520, United States

Location

Altamonte Springs, Florida

Altamonte Springs, Florida, 32714, United States

Location

Gulf Breeze, Florida

Gulf Breeze, Florida, 32561-4458, United States

Location

Homestead, Florida

Homestead, Florida, 33032, United States

Location

Jacksonville, Florida

Jacksonville, Florida, 32224, United States

Location

Miami, Florida

Miami, Florida, 33136, United States

Location

Miami Lakes, Florida

Miami Lakes, Florida, 33016, United States

Location

Orlando, Florida

Orlando, Florida, 32806, United States

Location

Port Charlotte, Florida

Port Charlotte, Florida, 33952, United States

Location

Port Orange, Florida

Port Orange, Florida, 32127, United States

Location

Tampa, Florida

Tampa, Florida, 33606, United States

Location

Suwanee, Georgia,

Suwanee, Georgia, 30024, United States

Location

Honolulu, Hawaii

Honolulu, Hawaii, 96817, United States

Location

Lexington, Kentucky

Lexington, Kentucky, 40504, United States

Location

Scarborough, Maine

Scarborough, Maine, 04074, United States

Location

Baltimore, Maryland

Baltimore, Maryland, 21287, United States

Location

Bethesda, Maryland

Bethesda, Maryland, 20817, United States

Location

Boston, Massachusetts

Boston, Massachusetts, 02114, United States

Location

Chesterfield, Missouri

Chesterfield, Missouri, 63005, United States

Location

Saint Louis, Missouri

St Louis, Missouri, 63110, United States

Location

Hackensack, New Jersey

Hackensack, New Jersey, 07601, United States

Location

Mineola, New York

Mineola, New York, 11501, United States

Location

New York

New York, New York, 10021, United States

Location

Rochester, New York

Rochester, New York, 14642, United States

Location

Syracuse, New York

Syracuse, New York, 13210, United States

Location

Columbus, Ohio

Columbus, Ohio, 43221, United States

Location

Toledo, Ohio

Toledo, Ohio, 43614, United States

Location

Oklahoma City, Oklahoma

Oklahoma City, Oklahoma, 73112, United States

Location

Philadelphia, Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Philadelphia, Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

Location

Charleston, South Carolina

Charleston, South Carolina, 29425, United States

Location

Nashville, Tennessee

Nashville, Tennessee, 37232, United States

Location

Salt Lake City, Utah

Salt Lake City, Utah, 84108, United States

Location

Camperdown, New South Wales

Camperdown, New South Wales, 2050, Australia

Location

Randwick, New South Wales

Randwick, New South Wales, 2031, Australia

Location

Westmead, New South Wales

Westmead, New South Wales, 2145, Australia

Location

Herston, Queensland

Herston, Queensland, 4029, Australia

Location

South Brisbane, Queensland

South Brisbane, Queensland, 4101, Australia

Location

Fitzroy, Victoria

Fitzroy, Victoria, 3065, Australia

Location

Heidelberg, Victoria

Heidelberg, Victoria, 3084, Australia

Location

Melbourne, Victoria

Melbourne, Victoria, 3004, Australia

Location

Parkville, Victoria

Parkville, Victoria, 3050, Australia

Location

Bydgoszcz, Kujawsko-Pomorskie

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-163, Poland

Location

Kraków, Malopolskie

Krakow, Lesser Poland Voivodeship, 31-209, Poland

Location

Warszawa, Mazowieckie

Warsaw, Masovian Voivodeship, 02-119, Poland

Location

Gdańsk, Pomorskie

Gdansk, Pomeranian Voivodeship, 80-546, Poland

Location

Gdańsk, Pomorskie

Gdansk, Pomeranian Voivodeship, 80-803, Poland

Location

Wojnicz, Lskie

Wojnicz, Wojnicz Lskie, 40-650, Poland

Location

Białystok

Bialystok, 15-704, Poland

Location

Lublin

Lublin, 20-078, Poland

Location

Warszawa

Warsaw, 02-952, Poland

Location

Lodz

Lodz, Łódź Voivodeship, 90-752, Poland

Location

Kragujevac, Sumadija

Kragujevac, Sumadija, 34000, Serbia

Location

Neurology Department, Kragujevac

Kragujevac, Sumadija, 34000, Serbia

Location

Belgrade

Belgrade, 11000, Serbia

Location

Clinic of Neurology, Belgrade

Belgrade, 11000, Serbia

Location

Niš

Niš, 18000, Serbia

Location

Gwangjin-gu, Seoul

Gwangju, Seoul, 05030, South Korea

Location

Irwon-Ro Gangnam-gu., Seoul

Irwon-dong, Seoul, 06351, South Korea

Location

Malaga,

Málaga, Andalusia, 29010, Spain

Location

Barcelona, Catalunya

Barcelona, Catalonia, 08003, Spain

Location

Terrassa

Terrassa, Catalonia, 08222, Spain

Location

Navarra

Navarro, Navarre, 31008, Spain

Location

Barcelona

Barcelona, 8035, Spain

Location

Madrid

Madrid, 28027, Spain

Location

Madrid

Madrid, 28034, Spain

Location

Madrid

Madrid, 28040, Spain

Location

Sevilla

Seville, 41013, Spain

Location

Valencia

Valencia, 46026, Spain

Location

Uzhgorod

Uzhhorod, Uzhgorod, 88018, Ukraine

Location

Kyiv

Kyiv, 02091, Ukraine

Location

Lviv

Lviv, 79035, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 35965432 DERIVED

MeSH Terms

Conditions

Seizures; Epilepsies, Partial

Interventions

PF-06372865

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Epilepsy; Brain Diseases; Central Nervous System Diseases

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2020
• First Posted: January 28, 2020
• Study Start: January 27, 2020
• Primary Completion: May 21, 2024
• Study Completion: May 21, 2024
• Last Updated: May 30, 2025
• Results First Posted: May 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (37); AU (9); PL (10); ES (10); SE (5); UA (3); KR (2)