E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Focal Onset Seizures (FOS) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016843 |
E.1.2 | Term | Focal seizures |
E.1.2 | System Organ Class | 100000004852 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The study is designed to facilitate the selection of a suitable dose range of NBI-921352 for use in subsequent efficacy and safety studies in adult subjects with FOS. The study objectives are as follows: • To assess the safety and tolerability of NBI-921352 in adults with FOS taking concomitant background ASMs. • To characterize the PK and PK/pharmacodynamic (PD) relationship of NBI-921352 and determine the effect of NBI-921352 on plasma levels of background ASMs. • To assess the efficacy of NBI-921352 on FOS frequency and quality of life in adults with FOS taking concomitant background ASMs. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria: • Capable of providing consent and has completed the written informed consent.
• Male or female, 18 to 65 years of age, inclusive, with a body mass index <40 kg/m2.
• Diagnosis of focal onset epilepsy according to the International League Against Epilepsy (ILAE) Classification of Epilepsy (2017) at least 18 months before screening. Diagnosis must be confirmed using the central adjudication process.
• Documented seizure frequency in the baseline seizure diary
• History of uncontrolled seizures despite adequate treatment with at least 1 anti-seizure medication (ASM) for at least 18 months prior to screening. • Treatment with at least 1 but not more than 4 ASMs for at least 1 month before screening, during the baseline seizure diary data collection, and throughout the duration of the study.
• Female subjects of childbearing potential must agree to use contraception consistently from screening until the final study visit or 30 days after the last dose of study treatment, whichever is longer.
• Be able to keep accurate seizure diaries |
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E.4 | Principal exclusion criteria |
Subjects will be excluded from the study if they meet any of the following criteria: •History of epilepsy with only nonmotor seizures without an observable component, psychogenic nonepileptic seizures, or primary generalized seizures.
•Presence or previous history of developmental and/or epileptic encephalopathy.
•Presence of seizure types other than FOS.
•History of repetitive seizures within the 12-month period preceding study entry where the individual seizures cannot be counted.
•Status epilepticus within the last 12 months before enrollment.
•Any suicidal behavior or suicidal ideation of type 4 or type 5 in the 2 years before screening, a history of suicide attempt in the last 2 years, or more than 1 lifetime suicide attempt.
•History or presence of any significant medical or surgical condition, lab value, or concomitant medication that would place the subject at increased risk as determined by the investigator.
•A known history of clinically concerning cardiac arrhythmia (including long QT syndrome) or prolongation of screening (pre-treatment) QT interval corrected for heart rate.
•Currently taking disallowed medications listed in Section 7.1.1 or it is anticipated that the subject will require treatment with at least 1 of the disallowed concomitant medications during the study.
•Past use of vigabatrin without stable visual fields tested twice in the 12 months after the last dose of vigabatrin.
•Require use of rescue medication more than once per week. •Multiple drug allergies or a severe drug reaction to an ASM(s), including dermatological (eg, Stevens-Johnson syndrome), hematological, or organ toxicity reactions.
•An implanted responsive neurostimulator system (RNS). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary: • Number of participants with Serious Treatment-emergent Adverse Events ( TEAEs), TEAEs leading to discontinuation of study treatment, and fatal TEAEs • NBI-921352 PK/PD, including exposure-efficacy response relationship |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, Treatment Period: Day 1 to Week 11 |
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E.5.2 | Secondary end point(s) |
Secondary: • Percent change from baseline in monthly Focal onset seizure frequency during the treatment period • Percent change from baseline in monthly focal onset seizure frequency during the maintenance period • Clinical Global Impression of Change (CGIC) scores at Week 11 • Treatment response defined as ≥50% reduction in monthly (28 days) FOS frequency during the treatment period compared to the seizure baseline period.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline, Treatment Period: Day 1 to Week 11; Maintenance Period: Week 4 to Week 11 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
France |
Hungary |
Italy |
Spain |
United Kingdom |
Czechia |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 15 |