Highly Drug-resistant Focal Epilepsy
Conditions
Keywords
UCB0942, Treatment-resistant focal epilepsy, Partial seizures, Seizure therapy
Brief summary
This study is to assess the efficacy, safety, and tolerability of the investigational drug UCB0942in adult subjects with drug-resistant focal epilepsy across multiple centers in Europe.
Detailed description
The study will include a Screening Visit, a Prospective Outpatient Baseline Period (2 to 3 weeks), an Inpatient Period (3 weeks), an Outpatient Period (8 weeks of treatment and 2 weeks of taper), and a Safety Follow-Up Period (4 weeks). The total study duration after screening will be 19 to 20 weeks. Approximately 6 months after the last visit subjects will be asked to return for an additional visit.
Interventions
DRUGUCB0942
Active substance: UCB0942 Pharmaceutical form: Film-coated tablet Concentration: 200 mg Route of Administration: Oral use
DRUGPlacebo
Pharmaceutical form: Film-coated tablet Route of administration: Oral use
Sponsors
PRA Health Sciences
UCB Biopharma S.P.R.L.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is an adult (18 years of age or more) * Subject is able to understand the study and the ICF as assessed by the Investigator. Subjects with known mental retardation (defined as IQ below 70) are not eligible to participate. Subject and/or caregiver is considered reliable and capable of adhering to the protocol (eg, able to understand and complete diaries), visit schedule, and the medication intake scheme as instructed according to the judgment of the Investigator * Subject fulfills ILAE (1989) criteria for focal epilepsy; clinical semiology should be described and fulfill criteria for focal seizures; there will have been an electroencephalogram (EEG) reading compatible with focal epilepsy in the last 5 years; the subject has no seizures that are not focal by the new ILAE criteria; a brain MRI (magnetic resonance imaging) or head CT (computed tomography) to be performed before randomization, if no such scan was performed in the last 5 years, and a report is available. If a scan was performed within the last 5 years but the epilepsy has not been stable since the last scan, a new scan should be obtained * Subject has failed to achieve seizure control with ≥4 appropriately chosen Antiepileptic Drug (AED) regimens of adequate dose and duration, including the current treatment, as documented in medical records and per Investigator assessment of patient report * Subject is currently treated with a stable dose of at least 1 AED for the 4 weeks prior to the Screening Visit (Visit 1) and throughout the duration of the Treatment Period with or without additional concurrent vagus nerve stimulation (VNS) or other neurostimulation treatments. The VNS must have been in place for at least 12 months with constant settings for at least 3 months and the battery life of unit anticipated to extend for the duration of study prior to the Screening Visit and throughout the duration of the study * During the 4 weeks prior to Screening (Historical Baseline Period), subject must report to have had an average of at least 4 spontaneous and observable focal seizures per week (focal seizures refers to partial-onset seizures of type IA1, IB, and IC, but does not include type IA2, IA3, or IA4 seizures), and cannot have had any seizure-free period longer than 3 days (based on Investigator assessment of subject report and seizure diaries if available). The cut-off seizure frequency (4 seizures per week) and maximum seizure-free interval (3 days) must be maintained during the 2-week Prospective Outpatient Baseline Period * Female subjects of nonchildbearing potential (premenarcheal, postmenopausal for at least 2 years, bilateral oophorectomy or tubal ligation, and complete hysterectomy) are eligible. Female subjects of childbearing potential are eligible if they use medically accepted contraceptive methods. Oral or depot contraceptive treatment with at least ethinylestradiol 30 μg per intake used with an additional barrier contraception method, monogamous relationship with vasectomized or female partner, or double-barrier contraception are acceptable methods. The subject must understand the consequences and potential risks of inadequately protected sexual activity, be educated about and understand the proper use of contraceptive methods, and undertake to inform the Investigator of any potential change in status. Abstinence will be considered as an acceptable method of contraception if the Investigator can document that the subject agrees to be compliant when it is in line with the preferred and usual lifestyle of the subject * Male subjects confirm that during the study period and for a period of 3 months after the final dose, when having sexual intercourse with a woman of childbearing potential, he will use a barrier contraceptive (eg, condom) and that the respective partner will use an additional contraceptive method
Exclusion criteria
* Subject has participated in another study of an investigational medication (or medical device) within the last 30 days or is currently participating in another study of an investigational medication (or a medical device) * Subject has a known hypersensitivity to any components of UCB0942 formulation or to similar drugs (LEV, BRV, or benzodiazepines), or a history of drug or other allergy that, in the opinion of the Investigator or UCB Study Physician, contraindicates her/his participation * Subject has a current or past psychiatric condition that, in the opinion of the Investigator, could compromise his/her safety or ability to participate in this study including a history of schizophrenia, schizoaffective disorder, bipolar disorder, or severe unipolar depression. The presence of potential psychiatric
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 75 % Responder Rate During the 2-week Inpatient Period | During the 2-week Inpatient Period | The 75% responder rate is defined as the percentage of subjects with a 75 % or greater reduction in focal seizure frequency during the 2-week Inpatient Period compared with the Baseline Period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Percent Change in Weekly Focal Seizure Frequency During the Outpatient Maintenance Period | During the Outpatient Maintenance Period (8 weeks) | A negative value in median percent change reflects a reduction from Baseline. |
| Median Percent Change in Weekly Focal Seizure Frequency During the On-UCB0942 Overall Period | During the On-UCB0942 Overall Period (approximately 11 weeks) | A negative value in median percent change reflects a reduction from Baseline. |
| Seizure-free Rate (All Seizures) During the 2-week Inpatient Period | During the 2-week Inpatient Period | Seizure-free rate is reported as the percentage of seizure-free participants during the 2-week Inpatient Period. |
| Seizure-free Rate (All Seizures) During the Last 4 Weeks of the Outpatient Maintenance Period | During the last 4 weeks of the Outpatient Maintenance Period | Seizure-free rate is reported as the percentage of seizure-free participants during the last 4 weeks of the Outpatient Maintenance Period. |
| Seizure-free Rate (All Seizures) During the On-UCB0942 Overall Period | During the On-UCB0942 Overall Period (approximately 11 weeks) | Seizure-free rate is reported as the percentage of seizure-free participants during the On-UCB0942 Overall Period. |
| Median Percent Change in Weekly Focal Seizure Frequency During the 2-week Inpatient Period | During the 2-week Inpatient Period | A negative value in median percent change reflects a reduction from Baseline. |
| 75 % Responder Rate During the On-UCB0942 Overall Period | During the On-UCB0942 Overall Period (approximately 11 weeks) | The 75 % responder rate is defined as the percentage of subjects who achieve a 75 % or greater reduction in focal seizure frequency. |
| Percentage of Seizure Free Days (All Seizures) During the 2-week Inpatient Period | During the 2-week Inpatient Period | For the active group, the 2-week Inpatient Period refers to the last 2 weeks of the Inpatient Period, while for the Placebo group, it refers to the first 2 weeks of the Inpatient Period. |
| Percentage of Seizure-free Days (All Seizures) During the Outpatient Maintenance Period | During the Outpatient Maintenance Period (8 weeks) | — |
| Number of Patients Reporting at Least One Serious Adverse Event (SAE) During the Course of the Study | All study duration (approximately 19 to 20 weeks) | Number of subjects experiencing at least one serious adverse event (reported by the subject and/or caregiver or observed by the Investigator or inpatient staff). |
| Number of Subject Withdrawals Due to Adverse Events (AEs) During the Course of the Study | All study duration (approximately 19 to 20 weeks) | Number of subjects who withdrew from the study due adverse event (reported by the subject and/or caregiver or observed by the Investigator or inpatient staff). |
| 75 % Responder Rate During the Last 4 Weeks of the Outpatient Maintenance Period | During the last 4 weeks of the Outpatient Maintenance Period | The 75 % responder rate is defined as the percentage of subjects who achieve a 75 % or greater reduction in focal seizure frequency. |
Countries
Belgium, Bulgaria, Germany, Hungary, Netherlands, Spain
Participant flow
Recruitment details
Enrollment started in August 2015 and concluded in July 2017.
Pre-assignment details
Participant Flow refers to the Randomized Set.
Participants by arm
| Arm | Count |
|---|---|
| Placebo/UCB0942 After 2-week in the Inpatient Period, Placebo subjects received the experimental medicine (UCB0942). | 27 |
| UCB0942/UCB0942 Subjects received UCB0942. | 28 |
| Total Title | 55 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | AE, non-fatal | 0 | 1 |
| Overall Study | Hepatitis Positivity | 0 | 1 |
| Overall Study | Lack of Efficacy | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo/UCB0942 | UCB0942/UCB0942 | Total Title |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 28 Participants | 55 Participants |
| Age, Continuous | 35.2 years STANDARD_DEVIATION 8.7 | 36.2 years STANDARD_DEVIATION 11.4 | 35.7 years STANDARD_DEVIATION 10.1 |
| BMI (kg/m^2) | 25.66 kg/m^2 STANDARD_DEVIATION 4.82 | 27.20 kg/m^2 STANDARD_DEVIATION 4.32 | 26.45 kg/m^2 STANDARD_DEVIATION 4.59 |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 26 Participants | 25 Participants | 51 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 27 Participants | 25 Participants | 52 Participants |
| Sex: Female, Male Female | 14 Participants | 15 Participants | 29 Participants |
| Sex: Female, Male Male | 13 Participants | 13 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 28 |
| other Total, other adverse events | 26 / 27 | 27 / 28 |
| serious Total, serious adverse events | 0 / 27 | 2 / 28 |
Outcome results
Primary
75 % Responder Rate During the 2-week Inpatient Period
The 75% responder rate is defined as the percentage of subjects with a 75 % or greater reduction in focal seizure frequency during the 2-week Inpatient Period compared with the Baseline Period.
Time frame: During the 2-week Inpatient Period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/UCB0942 (FAS) | 75 % Responder Rate During the 2-week Inpatient Period | 11.1 percentage of participants |
| UCB0942/UCB0942 (FAS) | 75 % Responder Rate During the 2-week Inpatient Period | 30.8 percentage of participants |
p-value: =0.067995% CI: [0.9, 19.06]Regression, Logistic
Secondary
75 % Responder Rate During the Last 4 Weeks of the Outpatient Maintenance Period
The 75 % responder rate is defined as the percentage of subjects who achieve a 75 % or greater reduction in focal seizure frequency.
Time frame: During the last 4 weeks of the Outpatient Maintenance Period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/UCB0942 (FAS) | 75 % Responder Rate During the Last 4 Weeks of the Outpatient Maintenance Period | 33.3 percentage of participants |
| UCB0942/UCB0942 (FAS) | 75 % Responder Rate During the Last 4 Weeks of the Outpatient Maintenance Period | 29.2 percentage of participants |
Secondary
75 % Responder Rate During the On-UCB0942 Overall Period
The 75 % responder rate is defined as the percentage of subjects who achieve a 75 % or greater reduction in focal seizure frequency.
Time frame: During the On-UCB0942 Overall Period (approximately 11 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/UCB0942 (FAS) | 75 % Responder Rate During the On-UCB0942 Overall Period | 25.9 percentage of participants |
| UCB0942/UCB0942 (FAS) | 75 % Responder Rate During the On-UCB0942 Overall Period | 25.9 percentage of participants |
Secondary
Median Percent Change in Weekly Focal Seizure Frequency During the 2-week Inpatient Period
A negative value in median percent change reflects a reduction from Baseline.
Time frame: During the 2-week Inpatient Period
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo/UCB0942 (FAS) | Median Percent Change in Weekly Focal Seizure Frequency During the 2-week Inpatient Period | -12.5 percentage of change |
| UCB0942/UCB0942 (FAS) | Median Percent Change in Weekly Focal Seizure Frequency During the 2-week Inpatient Period | -53.68 percentage of change |
Secondary
Median Percent Change in Weekly Focal Seizure Frequency During the On-UCB0942 Overall Period
A negative value in median percent change reflects a reduction from Baseline.
Time frame: During the On-UCB0942 Overall Period (approximately 11 weeks)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo/UCB0942 (FAS) | Median Percent Change in Weekly Focal Seizure Frequency During the On-UCB0942 Overall Period | -53.85 percentage of change |
| UCB0942/UCB0942 (FAS) | Median Percent Change in Weekly Focal Seizure Frequency During the On-UCB0942 Overall Period | -29.87 percentage of change |
Secondary
Median Percent Change in Weekly Focal Seizure Frequency During the Outpatient Maintenance Period
A negative value in median percent change reflects a reduction from Baseline.
Time frame: During the Outpatient Maintenance Period (8 weeks)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo/UCB0942 (FAS) | Median Percent Change in Weekly Focal Seizure Frequency During the Outpatient Maintenance Period | -57.94 percentage of change |
| UCB0942/UCB0942 (FAS) | Median Percent Change in Weekly Focal Seizure Frequency During the Outpatient Maintenance Period | -26.32 percentage of change |
Secondary
Number of Patients Reporting at Least One Serious Adverse Event (SAE) During the Course of the Study
Number of subjects experiencing at least one serious adverse event (reported by the subject and/or caregiver or observed by the Investigator or inpatient staff).
Time frame: All study duration (approximately 19 to 20 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/UCB0942 (FAS) | Number of Patients Reporting at Least One Serious Adverse Event (SAE) During the Course of the Study | 0 Participants |
| UCB0942/UCB0942 (FAS) | Number of Patients Reporting at Least One Serious Adverse Event (SAE) During the Course of the Study | 2 Participants |
Secondary
Number of Subject Withdrawals Due to Adverse Events (AEs) During the Course of the Study
Number of subjects who withdrew from the study due adverse event (reported by the subject and/or caregiver or observed by the Investigator or inpatient staff).
Time frame: All study duration (approximately 19 to 20 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/UCB0942 (FAS) | Number of Subject Withdrawals Due to Adverse Events (AEs) During the Course of the Study | 0 Participants |
| UCB0942/UCB0942 (FAS) | Number of Subject Withdrawals Due to Adverse Events (AEs) During the Course of the Study | 1 Participants |
Secondary
Percentage of Seizure Free Days (All Seizures) During the 2-week Inpatient Period
For the active group, the 2-week Inpatient Period refers to the last 2 weeks of the Inpatient Period, while for the Placebo group, it refers to the first 2 weeks of the Inpatient Period.
Time frame: During the 2-week Inpatient Period
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo/UCB0942 (FAS) | Percentage of Seizure Free Days (All Seizures) During the 2-week Inpatient Period | 21.43 percentage of days |
| UCB0942/UCB0942 (FAS) | Percentage of Seizure Free Days (All Seizures) During the 2-week Inpatient Period | 57.14 percentage of days |
Secondary
Percentage of Seizure-free Days (All Seizures) During the Outpatient Maintenance Period
Time frame: During the Outpatient Maintenance Period (8 weeks)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo/UCB0942 (FAS) | Percentage of Seizure-free Days (All Seizures) During the Outpatient Maintenance Period | 51.79 percentage of days |
| UCB0942/UCB0942 (FAS) | Percentage of Seizure-free Days (All Seizures) During the Outpatient Maintenance Period | 51.35 percentage of days |
Secondary
Seizure-free Rate (All Seizures) During the 2-week Inpatient Period
Seizure-free rate is reported as the percentage of seizure-free participants during the 2-week Inpatient Period.
Time frame: During the 2-week Inpatient Period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/UCB0942 (FAS) | Seizure-free Rate (All Seizures) During the 2-week Inpatient Period | 3.7 percentage of particpants |
| UCB0942/UCB0942 (FAS) | Seizure-free Rate (All Seizures) During the 2-week Inpatient Period | 7.4 percentage of particpants |
Secondary
Seizure-free Rate (All Seizures) During the Last 4 Weeks of the Outpatient Maintenance Period
Seizure-free rate is reported as the percentage of seizure-free participants during the last 4 weeks of the Outpatient Maintenance Period.
Time frame: During the last 4 weeks of the Outpatient Maintenance Period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/UCB0942 (FAS) | Seizure-free Rate (All Seizures) During the Last 4 Weeks of the Outpatient Maintenance Period | 0 percentage of participants |
| UCB0942/UCB0942 (FAS) | Seizure-free Rate (All Seizures) During the Last 4 Weeks of the Outpatient Maintenance Period | 0 percentage of participants |
Secondary
Seizure-free Rate (All Seizures) During the On-UCB0942 Overall Period
Seizure-free rate is reported as the percentage of seizure-free participants during the On-UCB0942 Overall Period.
Time frame: During the On-UCB0942 Overall Period (approximately 11 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/UCB0942 (FAS) | Seizure-free Rate (All Seizures) During the On-UCB0942 Overall Period | 0 percentage of participants |
| UCB0942/UCB0942 (FAS) | Seizure-free Rate (All Seizures) During the On-UCB0942 Overall Period | 0 percentage of participants |