Brivaracetam as add-on Treatment of Unverricht-Lundborg Disease (ULD) in Adolescents and Adults

Study Overview
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Brief Summary
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The study will compare the efficacy and safety of Brivaracetam with placebo in patients with Unverricht- Lundborg Disease (ULD).

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Study to Evaluate the Efficacy and Safety of Brivaracetam Used as Adjunctive Treatment for 12 Weeks in Adolescent and Adult Patients (≥ 16 Years) With Genetically Ascertained Unverricht-Lundborg Disease

Conditions
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Unverricht-Lundborg Disease

Intervention / Treatment
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* Other: Placebo
* Drug: BRV 2.5 mg
* Drug: BRV 25 mg
* Drug: BRV 50 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Subjects with diagnosed Unverricht-Lundborg disease (ULD) ascertained by appropriate genetic testing for a homozygous or compound heterozygous mutation in the CSTB gene- Subjects with moderate to severe myoclonus documented by an Action Myoclonussum score of ≥ 30 (evaluation by investigator)-Subjects currently being or having been treated with clonazepam up to the maximum recommended daily dose of 20 mg or up to their individual optimal dose as assessed by the investigator- Subjects currently being or having been treated with valproate up to the maximum recommended daily dose 60 mg/kg or serum levels of 100 mcg/ml or up to their individual optimal dose as specified by the investigator- Male/female subjects from 16 years onwards. Subjects under 18 years may only be included where legally permitted and ethically accepted Exclusion Criteria: - Subjects currently on felbamate or having been on felbamate within less than 18 months prior to Visit 1- Subjects currently treated with phenytoin or having been on phenytoin in the last month prior to Visit 1- Subjects currently on vigabatrine. Subjects having been on vigabatrine if no visual fields examination report available including standard static (Humphrey or Octopus) or cinetic perimetry (Goldman)- Subject taking any drug with possible central nervous system (CNS) effects- Subjects taking any drug that may significantly influence the metabolism of BRV (CYP2C or CYP3A potent inducers/inhibitors)- Known clinically significant acute or chronic illness or illness which may impair reliable participation in the trial, necessitate the use of medication not allowed by protocol or represent a safety risk in the Investigator's opinion- Subjects with history of severe adverse hematological reaction to any drug- Impaired hepatic function: ALAT/SGPT, ASAT/SGOT, alkaline phosphatase, GGT value of more than three times the upper limit of the reference range- History of suicide attempt during the last 5 years- Subject with suicidal ideations within the last year or at risk of suicide attempt unless cleared by written confirmation from a psychiatrist and approved by the UCB physician- Ongoing psychiatric disorder other than mild controlled disorder

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo Placebo twice a day (bid), 14 weeks (2 week Up-Titration Period + 12 week Maintenance Period) | Other: Placebo<br>* Pharmaceutical Form: Tablet Concentration: 2.5 mg, 25 mg and 50 mg Route of Administration: Oral use<br>|
| Experimental: Brivaracetam 5 mg/day<br>Brivaracetam (BRV) 5 mg/day 5 mg twice a day (bid) using 2.5 mg tablets for 12 weeks (after 2 week Up- Titration Period) | Drug: BRV 2.5 mg<br>* Pharmaceutical Form: Tablet Concentration: 2.5 mg Route of Administration: Oral use<br>* Other names: ucb34714;|
| Experimental: Brivaracetam 150 mg/day<br>Brivaracetam (BRV) 150 mg/day 150 mg twice a day (bid) using 25 mg and 50 mg tablets for 12 weeks (after 2 week Up-Titration Period) | Drug: BRV 25 mg<br>* Pharmaceutical Form: Tablet Concentration: 25 mg Route of Administration: Oral use<br>Drug: BRV 50 mg<br>* Pharmaceutical Form: Tablet Concentration: 50 mg Route of Administration: Oral use<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to the End of Treatment Period on the Action Myoclonus Score (Unified Myoclonus Rating Scale (UMRS) Section 4) | The range for Action Myoclonus Score (centrally read) is 0 (best) - 160 (worst). Percent change from Baseline = 100 X ((Baseline UMRS4 - Treatment UMRS4) / Baseline UMRS4). Baseline is defined as the last non-missing value prior to or on Randomization Visit. | From Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to the End of Treatment Period on the Functional Disability Score (Unified Myoclonus Rating Scale (UMRS) Section 5) | The range for Functional Disability Score is 0 (best) to 28 (worst). Percent change from Baseline = 100 X ((Baseline UMRS5 - Treatment UMRS5) / Baseline UMRS5). Baseline is defined as the last non-missing value prior to or on Randomization Visit. | Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit) | 
| Percent Change From Baseline to the End of Treatment Period on the Stimulus Sensitivity Score (Unified Myoclonus Rating Scale (UMRS) Section 3) | The range for Stimulus Sensitivity Score is 0 (best) to 17 (worst). Percent change from Baseline = 100 X ((Baseline UMRS3 - Treatment UMRS3) / Baseline UMRS3). Baseline is defined as the last non-missing value prior to or on Randomization Visit. | Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit) | 
| Percent Change From Baseline to the End of Treatment Period on the Myoclonus Patient Questionnaire (Unified Myoclonus Rating Scale (UMRS) Section 1) | The range for Myoclonus Patient Questionnaire is 0 (best) to 44 (worst). Percent change from Baseline = 100 X ((Baseline UMRS1 - Treatment UMRS1) / Baseline UMRS1). Baseline is defined as the last non-missing value prior to or on Randomization Visit. | Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit) | 
| Global Evaluation Score (Investigator) at the End of Treatment Period | The Global Evaluation Scale Score (Investigator) ranges from 1 (Marked worsening) to 7 (Marked improvement). | End of Treatment Period (Week 14 or Early Discontinuation Visit) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Unverricht-Lundborg Disease, Baltic Myoclonus, Progressive Myoclonic Epilepsies, Myoclonus, Brivaracetam