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

Primary Purpose

Seizures

Status
Enrolling by invitation
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
CVL-865
Sponsored by
Cerevel Therapeutics, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Seizures focused on measuring CVL-865, Anti-epileptic drugs (AEDs), PF-06372865, γ-aminobutyric acid (GABA), focal epilepsy, partial seizure

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Gulf Breeze, Florida
  • Jacksonville, Florida
  • Orlando, Florida
  • Port Charlotte, Florida
  • Tampa, Florida
  • Honolulu, Hawaii
  • Lexington, Kentucky
  • Scarborough, Maine
  • Baltimore, Maryland
  • Bethesda, Maryland
  • Boston, Massachusetts
  • Saint Louis, Missouri
  • Hackensack, New Jersey
  • New York
  • Rochester, New York
  • Toledo, Ohio
  • Oklahoma City, Oklahoma
  • Philadelphia, Pennsylvania
  • Charleston, South Carolina
  • Nashville, Tennessee
  • Salt Lake City, Utah
  • Camperdown, New South Wales
  • Randwick, New South Wales
  • Westmead, New South Wales
  • Herston, Queensland
  • Fitzroy, Victoria
  • Heidelberg, Victoria
  • Melbourne, Victoria
  • Parkville, Victoria
  • Bydgoszcz, Kujawsko-Pomorskie
  • Gdańsk, Pomorskie
  • Wojnicz, Lskie
  • Malaga,
  • Barcelona, Catalunya
  • Barcelona, Catalonia
  • Terrassa, Catalonia
  • Madrid
  • Madrid
  • Sevilla
  • Valencia

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CVL-865 25 mg

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.
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.
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.
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).
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.

Secondary Outcome Measures

Full Information

First Posted
December 23, 2020
Last Updated
August 22, 2023
Sponsor
Cerevel Therapeutics, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT04686786
Brief Title
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

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
December 8, 2020 (Actual)
Primary Completion Date
June 2025 (Anticipated)
Study Completion Date
June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cerevel Therapeutics, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Seizures
Keywords
CVL-865, Anti-epileptic drugs (AEDs), PF-06372865, γ-aminobutyric acid (GABA), focal epilepsy, partial seizure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CVL-865 25 mg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
CVL-865
Other Intervention Name(s)
PF-06372865
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Description
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.
Time Frame
From first dose of study drug up to Week 61 (follow up period)
Title
Number of Participants with Clinically Significant Changes in Electrocardiogram (ECGs)
Description
12-lead ECGs recordings will be obtained after the participant has been supine and at rest for at least 5 minutes.
Time Frame
Baseline up to Week 57 or early termination (ET)
Title
Number of Participants with Clinically Significant Changes in Vital Sign Measurements
Description
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.
Time Frame
Baseline up to Week 57 or early termination (ET)
Title
Number of Participants with Clinically Significant Changes in Physical and Neurological Examination Results
Description
Number of participants with clinically significant changes in physical and neurological examination results will be assessed.
Time Frame
Baseline up to Week 57 or early termination (ET)
Title
Number of Participants With Positive Response to Columbia Suicide-Severity Rating Scale (C-SSRS)
Description
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).
Time Frame
Baseline up to Week 61 (follow up period)
Title
Number of Participants with Positive Response to Modified Clinical Institute Withdrawal Assessment - Benzodiazepines (mCIWA-B)
Description
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.
Time Frame
Week 54 up to Week 61

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eliza Hueda
Organizational Affiliation
Cerevel Therapeutics, LLC
Official's Role
Study Director
Facility Information:
Facility Name
Gulf Breeze, Florida
City
Gulf Breeze
State/Province
Florida
ZIP/Postal Code
32561-4458
Country
United States
Facility Name
Jacksonville, Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Orlando, Florida
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Port Charlotte, Florida
City
Port Charlotte
State/Province
Florida
ZIP/Postal Code
33952
Country
United States
Facility Name
Tampa, Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
Honolulu, Hawaii
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96817
Country
United States
Facility Name
Lexington, Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40504
Country
United States
Facility Name
Scarborough, Maine
City
Scarborough
State/Province
Maine
ZIP/Postal Code
04074
Country
United States
Facility Name
Baltimore, Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Bethesda, Maryland
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
Boston, Massachusetts
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Saint Louis, Missouri
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Hackensack, New Jersey
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
New York
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Rochester, New York
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Toledo, Ohio
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43614
Country
United States
Facility Name
Oklahoma City, Oklahoma
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
Philadelphia, Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Charleston, South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Nashville, Tennessee
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Salt Lake City, Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Camperdown, New South Wales
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
Randwick, New South Wales
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
Westmead, New South Wales
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Herston, Queensland
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Fitzroy, Victoria
City
Fitzroy
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
Facility Name
Heidelberg, Victoria
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
Melbourne, Victoria
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Parkville, Victoria
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
Bydgoszcz, Kujawsko-Pomorskie
City
Bydgoszcz
State/Province
Kujawsko-Pomorskie
ZIP/Postal Code
85-163
Country
Poland
Facility Name
Gdańsk, Pomorskie
City
Gdańsk
State/Province
Pomorskie
ZIP/Postal Code
80-803
Country
Poland
Facility Name
Wojnicz, Lskie
City
Wojnicz
State/Province
Wojnicz Lskie
ZIP/Postal Code
40-650
Country
Poland
Facility Name
Malaga,
City
Málaga
State/Province
Andalusia
ZIP/Postal Code
29010
Country
Spain
Facility Name
Barcelona, Catalunya
City
Barcelona
State/Province
Catalonia
ZIP/Postal Code
08003
Country
Spain
Facility Name
Barcelona, Catalonia
City
Barcelona
State/Province
Catalonia
ZIP/Postal Code
08035
Country
Spain
Facility Name
Terrassa, Catalonia
City
Terrassa
State/Province
Catalonia
ZIP/Postal Code
08222
Country
Spain
Facility Name
Madrid
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Madrid
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Sevilla
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Valencia
City
Valencia
ZIP/Postal Code
46026
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35965432
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.
Results Reference
derived

Learn more about this trial

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

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