E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with genetically ascertained Unverricht-Lundborg disease (ULD). |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054894 |
E.1.2 | Term | Unverricht-Lundborg disease |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to compare the efficacy of brivaracetam 5 and 150mg/d in b.i.d. administration with placebo, on the symptom relief of action myoclonus in patients with ULD. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to compare the efficacy of brivaracetam 5 and 150mg/d in b.i.d. administration with placebo on the functional disability and on the symptom relief as evaluated by the Myoclonus Patient Questionnaire in patients with ULD. The secondary objectives are also to evaluate the dose/clinical response relationship, to assess the safety and tolerability of BRV in this patient population as well as to assess the effect of BRV on the global evaluation of the disease evolution (assessed by the investigator) of these ULD patients. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subjects with diagnosed 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 Myoclonus sum 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. |
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E.4 | Principal 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 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The least-square means of the percent reduction from baseline on the Action Myoclonus will be estimated at every post-randomization visit in each treatment arm. 95% confidence limits on the difference between the least-square means of the Action Myoclonus score at the scheduled end of the treatment phase (V7) will be presented. The population for primary efficacy analysis is the ITT population. The effect on the treatment difference because of concomitant use of Levetiracetam and/or Piracetam will be investigated through an interaction term with treatment and randomization stratum in the model. A descriptive analysis will be performed on the categorized percent reduction from baseline at end of treatment on the action myoclonus. The defined categories are <-25%, [-25% , 0[, [0 , 25%[ , [25% , 50%[ , [50% , 75%[ , [75% , 100%[ and 100%. If primary efficacy is proven for at least 1 dose of BRV, the following secondary endpoints will be tested for each of the doses of BRV. The testing scheme will be hierarchical, meaning that reaching statistical significance (on 5%) on at least one dose of BRV on a secondary endpoint is a necessary condition to continue testing on 5% significance level for the next secondary endpoint. • The Functional disability as per Section 5 of the UMRS (see Section 4.5.1). • The Myoclonus Patient Questionnaire (Section 1 of the UMRS). • Global Evaluation Scales (by investigator). • The Stimulus sensitivity (Section 3 of the UMRS). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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.8.3 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |