Clinical trial NCT04686786: An Open-label Extension Trial of CVL-865 as Adjunctive Therapy in the Treatment of Focal Onset Seizures
Official title: A 57-Week, Multicenter, Active-treatment, Open-label Extension Trial of CVL-865 as Adjunctive Therapy in Adults With Drug-Resistant Focal Onset Seizures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Seizures
Keywords: CVL-865
Anti-epileptic drugs (AEDs)
PF-06372865
γ-aminobutyric acid (GABA)
focal epilepsy
partial seizure
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2020-12-29
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: From first dose of study drug up to Week 61 (follow up period)
measure: Number of Participants with Clinically Significant Changes in Electrocardiogram (ECGs)
timeFrame: Baseline up to Week 57 or early termination (ET)
measure: Number of Participants with Clinically Significant Changes in Vital Sign Measurements
timeFrame: Baseline up to Week 57 or early termination (ET)
measure: Number of Participants with Clinically Significant Changes in Physical and Neurological Examination Results
timeFrame: Baseline up to Week 57 or early termination (ET)
measure: Number of Participants With Positive Response to Columbia Suicide-Severity Rating Scale (C-SSRS)
timeFrame: Baseline up to Week 61 (follow up period)
measure: Number of Participants with Positive Response to Modified Clinical Institute Withdrawal Assessment - Benzodiazepines (mCIWA-B)
timeFrame: Week 54 up to Week 61
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Little Rock, Arkansas
state: Arkansas
city: New Haven
country: United States
facility: New Haven, Connecticut
state: Connecticut
city: Gulf Breeze
country: United States
facility: Gulf Breeze, Florida
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville, Florida
state: Florida
city: Miami Lakes
country: United States
facility: Miami Lakes, Florida
state: Florida
city: Orlando
country: United States
facility: Orlando, Florida
state: Florida
city: Port Charlotte
country: United States
facility: Port Charlotte, Florida
state: Florida
city: Tampa
country: United States
facility: Tampa, Florida
state: Florida
city: Honolulu
country: United States
facility: Honolulu, Hawaii
state: Hawaii
city: Lexington
country: United States
facility: Lexington, Kentucky
state: Kentucky
city: Scarborough
country: United States
facility: Scarborough, Maine
state: Maine
city: Baltimore
country: United States
facility: Baltimore, Maryland
state: Maryland
city: Bethesda
country: United States
facility: Bethesda, Maryland
state: Maryland
city: Boston
country: United States
facility: Boston, Massachusetts
state: Massachusetts
city: Chesterfield
country: United States
facility: Chesterfield, Missouri
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis, Missouri
state: Missouri
city: Hackensack
country: United States
facility: Hackensack, New Jersey
state: New Jersey
city: New York
country: United States
facility: New York
state: New York
city: Rochester
country: United States
facility: Rochester, New York
state: New York
city: Toledo
country: United States
facility: Toledo, Ohio
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma City, Oklahoma
state: Oklahoma
city: Philadelphia
country: United States
facility: Philadelphia, Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia, Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston, South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Nashville, Tennessee
state: Tennessee
city: Salt Lake City
country: United States
facility: Salt Lake City, Utah
state: Utah
city: Camperdown
country: Australia
facility: Camperdown, New South Wales
state: New South Wales
city: Randwick
country: Australia
facility: Randwick, New South Wales
state: New South Wales
city: Westmead
country: Australia
facility: Westmead, New South Wales
state: New South Wales
city: Herston
country: Australia
facility: Herston, Queensland
state: Queensland
city: Fitzroy
country: Australia
facility: Fitzroy, Victoria
state: Victoria
city: Heidelberg
country: Australia
facility: Heidelberg, Victoria
state: Victoria
city: Melbourne
country: Australia
facility: Melbourne, Victoria
state: Victoria
city: Parkville
country: Australia
facility: Parkville, Victoria
state: Victoria
city: Gwangju
country: Korea, Republic of
facility: Gwangjin-gu, Seoul
state: Seoul
city: Irwon-dong
country: Korea, Republic of
facility: Irwon-Ro Gangnam-gu., Seoul
state: Seoul
city: Bydgoszcz
country: Poland
facility: Bydgoszcz, Kujawsko-Pomorskie
state: Kujawsko-Pomorskie
city: Łódź
country: Poland
facility: Lodz
state: Lodz
city: Kraków
country: Poland
facility: Kraków, Malopolskie
state: Malopolskie
city: Gdańsk
country: Poland
facility: Gdańsk, Pomorskie
state: Pomorskie
city: Wojnicz
country: Poland
facility: Wojnicz, Lskie
state: Wojnicz Lskie
city: Białystok
country: Poland
facility: Białystok
city: Warszawa
country: Poland
facility: Warszawa
city: Kragujevac
country: Serbia
facility: Kragujevac, Sumadija
state: Sumadija
city: Kragujevac
country: Serbia
facility: Neurology Department, Kragujevac
state: Sumadija
city: Málaga
country: Spain
facility: Malaga,
state: Andalusia
city: Barcelona
country: Spain
facility: Barcelona, Catalunya
state: Catalonia
city: Barcelona
country: Spain
facility: Barcelona, Catalonia
state: Catalonia
city: Terrassa
country: Spain
facility: Terrassa, Catalonia
state: Catalonia
city: Madrid
country: Spain
facility: Madrid
city: Madrid
country: Spain
facility: Madrid
city: Sevilla
country: Spain
facility: Sevilla
city: Valencia
country: Spain
facility: Valencia
city: Úzhgorod
country: Ukraine
facility: Uzhgorod
state: Uzhgorod
city: Kyiv
country: Ukraine
facility: Kyiv
city: Lviv
country: Ukraine
facility: Lviv
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References:
citation: 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.