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

Seizures Clinical Trial

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04686786
• Other study ID #: CVL-865-SZ-002
• Secondary ID: 2019-004057-83
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: December 8, 2020
• Est. completion date: June 2025

Study information

• Verified date: February 2024
• Source: Cerevel Therapeutics, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 120
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Seizures

Intervention

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.

Locations

Country	Name	City	State
Australia	Camperdown, New South Wales	Camperdown	New South Wales
Australia	Fitzroy, Victoria	Fitzroy	Victoria
Australia	Heidelberg, Victoria	Heidelberg	Victoria
Australia	Herston, Queensland	Herston	Queensland
Australia	Melbourne, Victoria	Melbourne	Victoria
Australia	Parkville, Victoria	Parkville	Victoria
Australia	Randwick, New South Wales	Randwick	New South Wales
Australia	Westmead, New South Wales	Westmead	New South Wales
Poland	Bydgoszcz, Kujawsko-Pomorskie	Bydgoszcz	Kujawsko-Pomorskie
Poland	Gdansk, Pomorskie	Gdansk	Pomorskie
Poland	Wojnicz, Lskie	Wojnicz	Wojnicz Lskie
Spain	Barcelona, Catalonia	Barcelona	Catalonia
Spain	Barcelona, Catalunya	Barcelona	Catalonia
Spain	Madrid	Madrid
Spain	Madrid	Madrid
Spain	Malaga,	Málaga	Andalusia
Spain	Sevilla	Sevilla
Spain	Terrassa, Catalonia	Terrassa	Catalonia
Spain	Valencia	Valencia
Ukraine	Lviv	Lviv
Ukraine	Uzhgorod	Úzhgorod	Uzhgorod
United States	Baltimore, Maryland	Baltimore	Maryland
United States	Bethesda, Maryland	Bethesda	Maryland
United States	Boston, Massachusetts	Boston	Massachusetts
United States	Charleston, South Carolina	Charleston	South Carolina
United States	Gulf Breeze, Florida	Gulf Breeze	Florida
United States	Hackensack, New Jersey	Hackensack	New Jersey
United States	Honolulu, Hawaii	Honolulu	Hawaii
United States	Jacksonville, Florida	Jacksonville	Florida
United States	Lexington, Kentucky	Lexington	Kentucky
United States	Nashville, Tennessee	Nashville	Tennessee
United States	New Haven, Connecticut	New Haven	Connecticut
United States	New York	New York	New York
United States	Oklahoma City, Oklahoma	Oklahoma City	Oklahoma
United States	Orlando, Florida	Orlando	Florida
United States	Philadelphia, Pennsylvania	Philadelphia	Pennsylvania
United States	Philadelphia, Pennsylvania	Philadelphia	Pennsylvania
United States	Port Charlotte, Florida	Port Charlotte	Florida
United States	Rochester, New York	Rochester	New York
United States	Saint Louis, Missouri	Saint Louis	Missouri
United States	Salt Lake City, Utah	Salt Lake City	Utah
United States	Scarborough, Maine	Scarborough	Maine
United States	Tampa, Florida	Tampa	Florida
United States	Toledo, Ohio	Toledo	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Cerevel Therapeutics, LLC

Countries where clinical trial is conducted

United States,  Australia,  Poland,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	TEAEs will include abuse-related adverse events (AEs) and AEs related to medication handling irregularities (MHIs). The number of Participants With TEAEs and TESAEs will be assessed.	From first dose of study drug up to Week 61 (follow up period)
Primary	Number of Participants with Clinically Significant Changes in Electrocardiogram (ECGs)	12-lead ECGs recordings will be obtained after the participant has been supine and at rest for at least 5 minutes.	Baseline up to Week 57 or early termination (ET)
Primary	Number of Participants with Clinically Significant Changes in Vital Sign Measurements	Vital signs will be measured with the participant in a sitting/semi-recumbent position after 5 minutes rest and will include temperature, systolic and diastolic blood pressure, and heart rate.	Baseline up to Week 57 or early termination (ET)
Primary	Number of Participants with Clinically Significant Changes in Physical and Neurological Examination Results	Number of participants with clinically significant changes in physical and neurological examination results will be assessed.	Baseline up to Week 57 or early termination (ET)
Primary	Number of Participants With Positive Response to 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 (follow up period)
Primary	Number of Participants with Positive Response to Modified Clinical Institute Withdrawal Assessment - Benzodiazepines (mCIWA-B)	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 BZD withdrawal symptoms such as irritability, fatigue, appetite, and sleeplessness. The total score ranges from 1 to 68 with higher scores indicating more severe withdrawal.	Week 54 up to Week 61