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NCT04686786

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

Terminated Phase 2 Results posted Last updated 11 December 2025
What this trial tests

Phase 2 trial testing CVL-865 in Seizures in 105 participants. Terminated before completion.

Timeline
8 December 2020
Primary endpoint
5 December 2024
5 December 2024

Quick facts

Lead sponsorAbbVie
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment105
Start date8 December 2020
Primary completion5 December 2024
Estimated completion5 December 2024
Sites56 locations across Ukraine, Serbia, Poland, South Korea, Australia, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

AbbVie — full company profile →

Who can join

Adults 18 to 75, any sex, with Seizures. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) Primary · From first dose of study drug up to Week 61

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 requi

Participants with TEAE
GroupValue95% CI
CVL-865 25 mg88
Participants with TESAE
GroupValue95% CI
CVL-865 25 mg11
Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECGs) Primary · Baseline up to Week 57

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)'.

GroupValue95% CI
CVL-865 25 mg0
Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Measurements Primary · Baseline up to Week 57

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.

GroupValue95% CI
CVL-865 25 mg2
Number of Participants With Clinically Significant Changes From Baseline in Physical and Neurological Examination Results Primary · Baseline up to Week 57

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 chan

Number of participants with any clinically significant physical examination findings
GroupValue95% CI
CVL-865 25 mg5
Number of participants with any clinically significant neurological examination findings
GroupValue95% CI
CVL-865 25 mg7
Suicidality Based on the Columbia Suicide-Severity Rating Scale (C-SSRS) Primary · Baseline up to Week 61

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).

Suicidal Ideation: (1) Wish to be dead
GroupValue95% CI
CVL-865 25 mg6
Suicidal Ideation: (2) Non-specific active suicidal thoughts
GroupValue95% CI
CVL-865 25 mg5
Suicidal Ideation: (3) Active suicidal ideation with any methods (not plan) without intent to act
GroupValue95% CI
CVL-865 25 mg1
Suicidal Ideation: (4) Active suicidal ideation with some intent to act, without specific plan
GroupValue95% CI
CVL-865 25 mg2
Suicidal Ideation: (5) Active suicidal ideation with specific plan and intent
GroupValue95% CI
CVL-865 25 mg0
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) Primary · Week 57, 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.

GroupValue95% CI
CVL-865 25 mg-1.4± 8.45

Adverse events — posted to ClinicalTrials.gov

Time frame: All-cause mortality and adverse event tables include events reported from the start of safety data collection to the end of the study. The median time on follow-up was 260 days.. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

CVL-865 25 mg
Serious: 11/105 (10%)
Deaths: 1/105

Serious adverse events (12 terms)

ReactionSystemCVL-865 25 mg
SEIZURENervous system disorders
CARDIAC ARRESTCardiac disorders
NON-CARDIAC CHEST PAINGeneral disorders
DIVERTICULITIS INTESTINAL PERFORATEDInfections and infestations
CRANIOFACIAL FRACTUREInjury, poisoning and procedural complications
CERVICAL SPINAL STENOSISMusculoskeletal and connective tissue disorders
MUSCULOSKELETAL CHEST PAINMusculoskeletal and connective tissue disorders
STATUS EPILEPTICUSNervous system disorders
APATHYPsychiatric disorders
DEPRESSIONPsychiatric disorders
SUICIDE ATTEMPTPsychiatric disorders
PULMONARY EMBOLISMRespiratory, thoracic and mediastinal disorders
Other adverse events (35 terms — click to expand)

ReactionSystemCVL-865 25 mg
SOMNOLENCENervous system disorders
HEADACHENervous system disorders
FATIGUEGeneral disorders
FALLInjury, poisoning and procedural complications
DIZZINESSNervous system disorders
NEUTROPENIABlood and lymphatic system disorders
THROMBOCYTOPENIABlood and lymphatic system disorders
SEIZURENervous system disorders
COVID-19Infections and infestations
ANXIETYPsychiatric disorders
ARTHRALGIAMusculoskeletal and connective tissue disorders
BALANCE DISORDERNervous system disorders
DIARRHOEAGastrointestinal disorders
NAUSEAGastrointestinal disorders
VOMITINGGastrointestinal disorders
ASPARTATE AMINOTRANSFERASE INCREASEDInvestigations
NEUTROPHIL COUNT DECREASEDInvestigations
WEIGHT DECREASEDInvestigations
BACK PAINMusculoskeletal and connective tissue disorders
INSOMNIAPsychiatric disorders
IRRITABILITYPsychiatric disorders
ABDOMINAL PAINGastrointestinal disorders
CONSTIPATIONGastrointestinal disorders
FEELING HOTGeneral disorders
NON-CARDIAC CHEST PAINGeneral disorders
EAR INFECTIONInfections and infestations
INFLUENZAInfections and infestations
CONTUSIONInjury, poisoning and procedural complications
FOOT FRACTUREInjury, poisoning and procedural complications
HEAD INJURYInjury, poisoning and procedural complications
SKIN LACERATIONInjury, poisoning and procedural complications
ALANINE AMINOTRANSFERASE INCREASEDInvestigations
WEIGHT INCREASEDInvestigations
ATAXIANervous system disorders
HYPOAESTHESIANervous system disorders

Most-reported serious reactions: SEIZURE, CARDIAC ARREST, NON-CARDIAC CHEST PAIN, DIVERTICULITIS INTESTINAL PERFORATED, CRANIOFACIAL FRACTURE, CERVICAL SPINAL STENOSIS, MUSCULOSKELETAL CHEST PAIN, STATUS EPILEPTICUS.

Data from ClinicalTrials.gov NCT04686786 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Pronounced antiseizure activity of the subtype-selective GABA<sub>A</sub> positive allosteric modulator darigabat in a mouse model of drug-resistant focal epilepsy.
    Gurrell R, Iredale P, Evrard A, Duveau V, et al · · 2022 · cited 11× · PMID 35965432 · DOI 10.1111/cns.13927

Verify or expand the search:

Other trials of CVL-865

Trials testing the same drug.

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Other AbbVie trials

Trials by the same sponsor.

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