Trial Outcomes & Findings for An Open-label Extension Trial of CVL-865 as Adjunctive Therapy in the Treatment of Focal Onset Seizures (NCT NCT04686786)
NCT ID: NCT04686786
Last Updated: 2025-12-11
Results Overview
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'.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
105 participants
Primary outcome timeframe
From first dose of study drug up to Week 61
Results posted on
2025-12-11
Participant Flow
Enrollment into the trial consisted of eligible participants who completed the Maintenance Phase of Trial CVL-865-SZ-001 (NCT04244175).
Participant milestones
| Measure |
CVL-865 25 mg
Participants received 25 milligrams (mg) CVL-865 tablets orally twice daily (BID).
|
|---|---|
|
Overall Study
STARTED
|
105
|
|
Overall Study
Received at Least 1 Dose of Investigational Medicinal Product (IMP)
|
105
|
|
Overall Study
COMPLETED
|
39
|
|
Overall Study
NOT COMPLETED
|
66
|
Reasons for withdrawal
| Measure |
CVL-865 25 mg
Participants received 25 milligrams (mg) CVL-865 tablets orally twice daily (BID).
|
|---|---|
|
Overall Study
Adverse Event
|
9
|
|
Overall Study
Death
|
1
|
|
Overall Study
Lack of Efficacy
|
25
|
|
Overall Study
Treatment with Prohibited Concomitant Medications
|
1
|
|
Overall Study
Study Terminated by Sponsor
|
14
|
|
Overall Study
Withdrawal by Subject
|
15
|
|
Overall Study
Other than specified
|
1
|
Baseline Characteristics
An Open-label Extension Trial of CVL-865 as Adjunctive Therapy in the Treatment of Focal Onset Seizures
Baseline characteristics by cohort
| Measure |
CVL-865 25 mg
n=105 Participants
Participants received 25 mg CVL-865 tablets orally BID.
|
|---|---|
|
Age, Continuous
|
41.5 years
STANDARD_DEVIATION 12.70 • n=9 Participants
|
|
Sex: Female, Male
Female
|
55 Participants
n=9 Participants
|
|
Sex: Female, Male
Male
|
50 Participants
n=9 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
16 Participants
n=9 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
87 Participants
n=9 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=9 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=9 Participants
|
|
Race (NIH/OMB)
Asian
|
5 Participants
n=9 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
4 Participants
n=9 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=9 Participants
|
|
Race (NIH/OMB)
White
|
90 Participants
n=9 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=9 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=9 Participants
|
PRIMARY outcome
Timeframe: From first dose of study drug up to Week 61Population: The Safety Set included all participants who received at least 1 dose of IMP.
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'.
Outcome measures
| Measure |
CVL-865 25 mg
n=105 Participants
Participants received 25 mg CVL-865 tablets orally BID.
|
|---|---|
|
Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Participants with TEAE
|
88 Participants
|
|
Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Participants with TESAE
|
11 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 57Population: The Safety Set included all participants who received at least 1 dose of IMP.
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)'.
Outcome measures
| Measure |
CVL-865 25 mg
n=105 Participants
Participants received 25 mg CVL-865 tablets orally BID.
|
|---|---|
|
Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECGs)
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 57Population: The Safety Set included all participants who received at least 1 dose of IMP.
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.
Outcome measures
| Measure |
CVL-865 25 mg
n=105 Participants
Participants received 25 mg CVL-865 tablets orally BID.
|
|---|---|
|
Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Measurements
|
2 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 57Population: The Safety Set included all participants who received at least 1 dose of IMP.
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.
Outcome measures
| Measure |
CVL-865 25 mg
n=105 Participants
Participants received 25 mg CVL-865 tablets orally BID.
|
|---|---|
|
Number of Participants With Clinically Significant Changes From Baseline in Physical and Neurological Examination Results
Number of participants with any clinically significant physical examination findings
|
5 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Physical and Neurological Examination Results
Number of participants with any clinically significant neurological examination findings
|
7 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 61Population: The Safety Set included all participants who received at least 1 dose of IMP.
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).
Outcome measures
| Measure |
CVL-865 25 mg
n=105 Participants
Participants received 25 mg CVL-865 tablets orally BID.
|
|---|---|
|
Suicidality Based on the Columbia Suicide-Severity Rating Scale (C-SSRS)
Suicidal Ideation: (1) Wish to be dead
|
6 Participants
|
|
Suicidality Based on the Columbia Suicide-Severity Rating Scale (C-SSRS)
Suicidal Ideation: (2) Non-specific active suicidal thoughts
|
5 Participants
|
|
Suicidality Based on the Columbia Suicide-Severity Rating Scale (C-SSRS)
Suicidal Ideation: (3) Active suicidal ideation with any methods (not plan) without intent to act
|
1 Participants
|
|
Suicidality Based on the Columbia Suicide-Severity Rating Scale (C-SSRS)
Suicidal Ideation: (4) Active suicidal ideation with some intent to act, without specific plan
|
2 Participants
|
|
Suicidality Based on the Columbia Suicide-Severity Rating Scale (C-SSRS)
Suicidal Ideation: (5) Active suicidal ideation with specific plan and intent
|
0 Participants
|
PRIMARY outcome
Timeframe: Week 57, Week 61Population: The Safety Set included all participants who received at least 1 dose of IMP. Here, "Overall Number of Participants Analyzed" is the number of participants evaluable for this outcome measure.
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.
Outcome measures
| Measure |
CVL-865 25 mg
n=83 Participants
Participants received 25 mg CVL-865 tablets orally BID.
|
|---|---|
|
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)
|
-1.4 score on a scale
Standard Deviation 8.45
|
Adverse Events
CVL-865 25 mg
Serious events: 11 serious events
Other events: 77 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
CVL-865 25 mg
n=105 participants at risk
Participants received 25 mg CVL-865 tablets orally BID.
|
|---|---|
|
Cardiac disorders
CARDIAC ARREST
|
0.95%
1/105 • Number of events 1 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
General disorders
NON-CARDIAC CHEST PAIN
|
0.95%
1/105 • Number of events 1 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Infections and infestations
DIVERTICULITIS INTESTINAL PERFORATED
|
0.95%
1/105 • Number of events 1 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Injury, poisoning and procedural complications
CRANIOFACIAL FRACTURE
|
0.95%
1/105 • Number of events 1 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Musculoskeletal and connective tissue disorders
CERVICAL SPINAL STENOSIS
|
0.95%
1/105 • Number of events 1 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL CHEST PAIN
|
0.95%
1/105 • Number of events 1 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Nervous system disorders
SEIZURE
|
1.9%
2/105 • Number of events 2 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Nervous system disorders
STATUS EPILEPTICUS
|
0.95%
1/105 • Number of events 1 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Psychiatric disorders
APATHY
|
0.95%
1/105 • Number of events 1 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Psychiatric disorders
DEPRESSION
|
0.95%
1/105 • Number of events 1 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Psychiatric disorders
SUICIDE ATTEMPT
|
0.95%
1/105 • Number of events 1 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
|
0.95%
1/105 • Number of events 1 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
Other adverse events
| Measure |
CVL-865 25 mg
n=105 participants at risk
Participants received 25 mg CVL-865 tablets orally BID.
|
|---|---|
|
Injury, poisoning and procedural complications
SKIN LACERATION
|
2.9%
3/105 • Number of events 4 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
2.9%
3/105 • Number of events 3 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
4.8%
5/105 • Number of events 5 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Investigations
NEUTROPHIL COUNT DECREASED
|
3.8%
4/105 • Number of events 4 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Investigations
WEIGHT DECREASED
|
3.8%
4/105 • Number of events 4 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Investigations
WEIGHT INCREASED
|
2.9%
3/105 • Number of events 3 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
5.7%
6/105 • Number of events 7 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
3.8%
4/105 • Number of events 5 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Nervous system disorders
ATAXIA
|
2.9%
3/105 • Number of events 3 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Nervous system disorders
BALANCE DISORDER
|
5.7%
6/105 • Number of events 6 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Nervous system disorders
DIZZINESS
|
11.4%
12/105 • Number of events 15 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Nervous system disorders
HEADACHE
|
16.2%
17/105 • Number of events 35 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Nervous system disorders
HYPOAESTHESIA
|
2.9%
3/105 • Number of events 3 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Nervous system disorders
SEIZURE
|
8.6%
9/105 • Number of events 11 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Nervous system disorders
SOMNOLENCE
|
19.0%
20/105 • Number of events 30 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Psychiatric disorders
ANXIETY
|
7.6%
8/105 • Number of events 8 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Psychiatric disorders
INSOMNIA
|
3.8%
4/105 • Number of events 4 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Psychiatric disorders
IRRITABILITY
|
3.8%
4/105 • Number of events 4 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
10.5%
11/105 • Number of events 15 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
8.6%
9/105 • Number of events 22 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
2.9%
3/105 • Number of events 4 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Gastrointestinal disorders
CONSTIPATION
|
2.9%
3/105 • Number of events 4 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Gastrointestinal disorders
DIARRHOEA
|
4.8%
5/105 • Number of events 5 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Gastrointestinal disorders
NAUSEA
|
4.8%
5/105 • Number of events 7 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Gastrointestinal disorders
VOMITING
|
4.8%
5/105 • Number of events 5 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
General disorders
FATIGUE
|
14.3%
15/105 • Number of events 16 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
General disorders
FEELING HOT
|
2.9%
3/105 • Number of events 3 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
General disorders
NON-CARDIAC CHEST PAIN
|
2.9%
3/105 • Number of events 5 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Infections and infestations
COVID-19
|
7.6%
8/105 • Number of events 8 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Infections and infestations
EAR INFECTION
|
2.9%
3/105 • Number of events 3 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Infections and infestations
INFLUENZA
|
2.9%
3/105 • Number of events 3 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Injury, poisoning and procedural complications
CONTUSION
|
2.9%
3/105 • Number of events 5 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Injury, poisoning and procedural complications
FALL
|
12.4%
13/105 • Number of events 16 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Injury, poisoning and procedural complications
FOOT FRACTURE
|
2.9%
3/105 • Number of events 3 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
|
Injury, poisoning and procedural complications
HEAD INJURY
|
2.9%
3/105 • Number of events 4 • 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.
The Safety Set included all participants who received at least 1 dose of IMP.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
- Publication restrictions are in place
Restriction type: OTHER