E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
epilepsy in tuberous sclerosis complex (TSC) |
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E.1.1.1 | Medical condition in easily understood language |
epilepsy in tuberous sclerosis complex (TSC) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
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 clinical part of EPISTOP project is to identify the clinical and molecular biomarkers of epileptogenesis in a prospective clinical study of patients with TSC.
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E.2.2 | Secondary objectives of the trial |
Secondary objective of the clinical part of EPISTOP is to compare the effects of standard antiepileptic treatment in patients diagnosed as having epilepsy after clinical seizures vs after electroencephalographic epileptiform discharges, in a randomized trial in TSC patients. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-male or female infants with a definite diagnosis of TSC (Roach criteria; Roach 1998 or DNA confirmed),
-age up to 4 months at the moment of enrolment,
-no clinical seizures seen by caregivers or on baseline videoEEG recording,
-written informed consent of caregivers. It is possible to give consent for the observational part of the study only. In this case, the child will not enter the randomized part of the study |
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E.4 | Principal exclusion criteria |
-any type of seizures observed till baseline visit,
-antiepileptic treatment at or prior to study entry,
-contraindications to MRI,
-any severe and/or uncontrolled medical condition that is considered by the investigator as possibly affecting the EPISTOP analyses or procedures.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint of the study is the collection of a set of molecular and clinical biomarkers in full analysis set of patients, including all TSC infants participating in the study and the control subjects. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
vEEG will be performed every 4 weeks (± 1 week) in the children under the age of 6 months, then every 6 weeks (± 1 week) in children under 12 months, and every 8 weeks (± 1 week) thereafter.
MRI will be performed at baseline (unless patient had an MRI performed within 1 month before baseline visit and an additional scan cannot be performed without general anaesthesia) and then as clinically indicated, but not later than at the age of 2 years.
Neuropsychological assessment using a specially designed targeted battery of test will be performed every 6 months.
Blood samples will be collected at study entry, at the onset of epileptiform discharges on vEEG or at the age of 6 months, whichever is applicable, at the onset of clinical seizures and at the end of follow-up (age 2 years) |
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E.5.2 | Secondary end point(s) |
Key secondary endpoint is better efficacy of antiepileptic treatment in patients diagnosed as epileptic after electroencephalographic epileptiform discharges in comparison to patients diagnosed as having epilepsy after the onset of clinical seizures. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The parameters of efficacy assessment include: the distribution of seizure free patients, proportion of patients with drug resistant seizures, proportion of patients with normalized EEG, the neuropsychological outcome recognized as the results in a battery of tests performed at the age of 24 months. |
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Different time points for epilepsy diagnosis |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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Last visit of the last subject |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |