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

NCT04686786 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: CVL-865-SZ-0022019-004057-83
• Study Type: interventional
• Target: 105
• Locations: 7 countries
• Sites: 56

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.

Conditions

Seizures

Keywords

CVL-865; Anti-epileptic drugs (AEDs); PF-06372865; γ-aminobutyric acid (GABA); focal epilepsy; partial seizure

Outcome Measures

Primary Outcomes (6)

• 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

Study Arms (1)

CVL-865 25 mg

EXPERIMENTAL

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

Interventions

CVL-865 DRUG

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.

Also known as: PF-06372865

CVL-865 25 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AbbVie: lead

Study Sites (56)

Little Rock, Arkansas

Little Rock, Arkansas, 72205, United States

Location

New Haven, Connecticut

New Haven, Connecticut, 06519, United States

Location

Gulf Breeze, Florida

Gulf Breeze, Florida, 32561-4458, United States

Location

Jacksonville, Florida

Jacksonville, Florida, 32224, United States

Location

Miami Lakes, Florida

Miami Lakes, Florida, 33016, United States

Location

Orlando, Florida

Orlando, Florida, 32806, United States

Location

Port Charlotte, Florida

Port Charlotte, Florida, 33952, United States

Location

Tampa, Florida

Tampa, Florida, 33606, United States

Location

Honolulu, Hawaii

Honolulu, Hawaii, 96817, United States

Location

Lexington, Kentucky

Lexington, Kentucky, 40504, United States

Location

Scarborough, Maine

Scarborough, Maine, 04074, United States

Location

Baltimore, Maryland

Baltimore, Maryland, 21287, United States

Location

Bethesda, Maryland

Bethesda, Maryland, 20817, United States

Location

Boston, Massachusetts

Boston, Massachusetts, 02114, United States

Location

Chesterfield, Missouri

Chesterfield, Missouri, 63005, United States

Location

Saint Louis, Missouri

St Louis, Missouri, 63110, United States

Location

Hackensack, New Jersey

Hackensack, New Jersey, 07601, United States

Location

New York

New York, New York, 10021, United States

Location

Rochester, New York

Rochester, New York, 14642, United States

Location

Toledo, Ohio

Toledo, Ohio, 43614, United States

Location

Oklahoma City, Oklahoma

Oklahoma City, Oklahoma, 73112, United States

Location

Philadelphia, Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Philadelphia, Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

Location

Charleston, South Carolina

Charleston, South Carolina, 29425, United States

Location

Nashville, Tennessee

Nashville, Tennessee, 37232, United States

Location

Salt Lake City, Utah

Salt Lake City, Utah, 84132, United States

Location

Camperdown, New South Wales

Camperdown, New South Wales, 2050, Australia

Location

Randwick, New South Wales

Randwick, New South Wales, 2031, Australia

Location

Westmead, New South Wales

Westmead, New South Wales, 2145, Australia

Location

Herston, Queensland

Herston, Queensland, 4029, Australia

Location

Fitzroy, Victoria

Fitzroy, Victoria, 3065, Australia

Location

Heidelberg, Victoria

Heidelberg, Victoria, 3084, Australia

Location

Melbourne, Victoria

Melbourne, Victoria, 3004, Australia

Location

Parkville, Victoria

Parkville, Victoria, 3050, Australia

Location

Bydgoszcz, Kujawsko-Pomorskie

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-163, Poland

Location

Kraków, Malopolskie

Krakow, Lesser Poland Voivodeship, 31-209, Poland

Location

Gdańsk, Pomorskie

Gdansk, Pomeranian Voivodeship, 80-803, Poland

Location

Wojnicz, Lskie

Wojnicz, Wojnicz Lskie, 40-650, Poland

Location

Białystok

Bialystok, 15-704, Poland

Location

Warszawa

Warsaw, 02-952, Poland

Location

Lodz

Lodz, Łódź Voivodeship, 90-752, Poland

Location

Kragujevac, Sumadija

Kragujevac, Sumadija, 34000, Serbia

Location

Neurology Department, Kragujevac

Kragujevac, Sumadija, 34000, Serbia

Location

Gwangjin-gu, Seoul

Gwangju, Seoul, 05030, South Korea

Location

Irwon-Ro Gangnam-gu., Seoul

Irwon-dong, Seoul, 06351, South Korea

Location

Malaga,

Málaga, Andalusia, 29010, Spain

Location

Barcelona, Catalunya

Barcelona, Catalonia, 08003, Spain

Location

Barcelona, Catalonia

Barcelona, Catalonia, 08035, Spain

Location

Terrassa, Catalonia

Terrassa, Catalonia, 08222, Spain

Location

Madrid

Madrid, 28034, Spain

Location

Madrid

Madrid, 28040, Spain

Location

Sevilla

Seville, 41013, Spain

Location

Valencia

Valencia, 46026, Spain

Location

Uzhgorod

Uzhhorod, Uzhgorod, 88018, Ukraine

Location

Kyiv

Kyiv, 02091, Ukraine

Location

Lviv

Lviv, 79035, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 35965432 DERIVED

MeSH Terms

Conditions

Seizures; Epilepsies, Partial

Interventions

PF-06372865

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Epilepsy; Brain Diseases; Central Nervous System Diseases

Limitations and Caveats

This trial was closed early after CVL-865-SZ-001 (NCT04244175) did not meet its primary objective

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2020
• First Posted: December 29, 2020
• Study Start: December 8, 2020
• Primary Completion: December 5, 2024
• Study Completion: December 5, 2024
• Last Updated: December 11, 2025
• Results First Posted: December 11, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (26); PL (7); SE (2); AU (8); KR (2); ES (8); UA (3)