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

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

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.

Study Overview

• Status: Terminated
• Conditions: Seizures
• Intervention / Treatment: Drug: CVL-865

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Camperdown, New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Randwick, New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Westmead, New South Wales
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Herston, Queensland
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Fitzroy, Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Heidelberg, Victoria
    • Melbourne, Victoria, Australia, 3004
      • Melbourne, Victoria
    • Parkville, Victoria, Australia, 3050
      • Parkville, Victoria
• Poland
  • Bialystok, Poland, 15-704
    • Białystok
  • Warsaw, Poland, 02-952
    • Warszawa
  • Kuyavian-Pomeranian Voivodeship
    • Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland, 85-163
      • Bydgoszcz, Kujawsko-Pomorskie
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 31-209
      • Kraków, Malopolskie
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-803
      • Gdańsk, Pomorskie
  • Wojnicz Lskie
    • Wojnicz, Wojnicz Lskie, Poland, 40-650
      • Wojnicz, Lskie
  • Łódź Voivodeship
    • Lodz, Łódź Voivodeship, Poland, 90-752
      • Lodz
• Serbia
  • Sumadija
    • Kragujevac, Sumadija, Serbia, 34000
      • Kragujevac, Sumadija
    • Kragujevac, Sumadija, Serbia, 34000
      • Neurology Department, Kragujevac
• South Korea
  • Seoul
    • Gwangju, Seoul, South Korea, 05030
      • Gwangjin-gu, Seoul
    • Irwon-dong, Seoul, South Korea, 06351
      • Irwon-Ro Gangnam-gu., Seoul
• Spain
  • Madrid, Spain, 28034
    • Madrid
  • Madrid, Spain, 28040
    • Madrid
  • Seville, Spain, 41013
    • Sevilla
  • Valencia, Spain, 46026
    • Valencia
  • Andalusia
    • Málaga, Andalusia, Spain, 29010
      • Malaga,
  • Catalonia
    • Barcelona, Catalonia, Spain, 08003
      • Barcelona, Catalunya
    • Barcelona, Catalonia, Spain, 08035
      • Barcelona, Catalonia
    • Terrassa, Catalonia, Spain, 08222
      • Terrassa, Catalonia
• Ukraine
  • Kyiv, Ukraine, 02091
    • Kyiv
  • Lviv, Ukraine, 79035
    • Lviv
  • Uzhgorod
    • Uzhhorod, Uzhgorod, Ukraine, 88018
      • Uzhgorod
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Little Rock, Arkansas
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • New Haven, Connecticut
  • Florida
    • Gulf Breeze, Florida, United States, 32561-4458
      • Gulf Breeze, Florida
    • Jacksonville, Florida, United States, 32224
      • Jacksonville, Florida
    • Miami Lakes, Florida, United States, 33016
      • Miami Lakes, Florida
    • Orlando, Florida, United States, 32806
      • Orlando, Florida
    • Port Charlotte, Florida, United States, 33952
      • Port Charlotte, Florida
    • Tampa, Florida, United States, 33606
      • Tampa, Florida
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Honolulu, Hawaii
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Lexington, Kentucky
  • Maine
    • Scarborough, Maine, United States, 04074
      • Scarborough, Maine
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Baltimore, Maryland
    • Bethesda, Maryland, United States, 20817
      • Bethesda, Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Boston, Massachusetts
  • Missouri
    • Chesterfield, Missouri, United States, 63005
      • Chesterfield, Missouri
    • St Louis, Missouri, United States, 63110
      • Saint Louis, Missouri
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack, New Jersey
  • New York
    • New York, New York, United States, 10021
      • New York
    • Rochester, New York, United States, 14642
      • Rochester, New York
  • Ohio
    • Toledo, Ohio, United States, 43614
      • Toledo, Ohio
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Oklahoma City, Oklahoma
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Philadelphia, Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Philadelphia, Pennsylvania
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Charleston, South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Nashville, Tennessee
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Salt Lake City, Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CVL-865 25 mg; 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; 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.; Other Names: PF-06372865

What is the study measuring?

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)	A TEAE was defined as an AE that started after the first dose of IMP in the open-label trial or a previously reported AE that increased in intensity, became serious, trial drug-related, or resulted in death, discontinuation, interruption, of reduction of IMP after the first dose of IMP in the open-label trial. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of serious and non-serious AEs regardless of causality is located in the 'Reported Adverse Events module'.	From first dose of study drug up to Week 61
Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECGs)	12-lead ECGs recordings were obtained after the participant had been supine and at rest for at least 5 minutes. The number of participants with significant abnormalities is reported by 'change from baseline in QT interval as corrected for heart rate by Fridericia's formula (QTcF)'.	Baseline up to Week 57
Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Measurements	Vital signs were measured with the participant in a sitting/semi-recumbent position after 5 minutes rest and included temperature, systolic and diastolic blood pressure, and heart rate.	Baseline up to Week 57
Number of Participants With Clinically Significant Changes From Baseline in Physical and Neurological Examination Results	A complete physical examination consisted of measurement of weight and a review of the following body systems: head, ears, eyes, nose, mouth, skin, heart, lungs, lymph nodes, and gastrointestinal, genitourinary, and musculoskeletal systems. A full neurological examination included an assessment of the participant's mental status (level of consciousness, orientation, speech, memory, etc), cranial nerves, motor (muscle appearance, tone, strength, and reflexes), sensation (including Romberg sign), coordination, and gait. Reported here is the number of participants with clinically significant changes in physical or neurological examination results.	Baseline up to Week 57
Suicidality Based on the 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
Change From End of Treatment in Modified Clinical Institute Withdrawal Assessment - Benzodiazepines (mCIWA-B) Score at the End of Post-treatment Follow-up (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 benzodiazepine withdrawal symptoms such as irritability, fatigue, appetite, and sleeplessness. The total score ranges from 1 (no withdrawal) to 68 (extreme withdrawal) with higher scores indicating more severe withdrawal.	Week 57, Week 61

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2020
• Primary Completion (Actual): December 5, 2024
• Study Completion (Actual): December 5, 2024

Study Registration Dates

• First Submitted: December 23, 2020
• First Submitted That Met QC Criteria: December 23, 2020
• First Posted (Actual): December 29, 2020

Study Record Updates

• Last Update Posted (Actual): December 11, 2025
• Last Update Submitted That Met QC Criteria: November 26, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: partial seizure; CVL-865; Anti-epileptic drugs (AEDs); γ-aminobutyric acid (GABA); PF-06372865; focal epilepsy
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Seizures; Epilepsies, Partial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; GABA Modulators; GABA Agents; PF-06372865
• Other Study ID Numbers: CVL-865-SZ-002; 2019-004057-83 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No