E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), is a rare autosomal dominant disorder characterized by recurrent strokes starting in mid-adulthood and leading in some to severe motor disability with pseudobulbar palsy and dementia of the subcortical type |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10008804 |
E.1.2 | Term | Chromosomal abnormalities and abnormal gene carriers |
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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 study objective is to determine whether chronic administration of 6R-BH4 for 24 months to CADASIL patients results in improved endothelial function, as assessed by FMD, when compared to placebo. |
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E.2.2 | Secondary objectives of the trial |
Secondary study objectives are to determine differences between the two treatment arms in terms of tolerability, occurrence of new strokes or deaths, and progression of disability, as assessed by specific scales: Barthel index, Rankin scale, NIHSS |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
- Age > 30 and ≤ 65 years - Diagnosis of CADASIL confirmed by the identification of a mutation in the Notch3 gene - Informed consent |
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E.4 | Principal exclusion criteria |
- Dementia (DSM-IV criteria) with a SIDAM score <33 - Autoimmune disorders - Pregnancy, nursing or childbearing potential not on adequate contraception - Myocardial infarction, cerebral vascular accident, or pulmonary embolism during the 3 months prior to Screening. - Severe uncontrolled hypertension (BP >180 mmHg systolic and /or 110 mmHg diastolic). - Hypotension at Screening, defined as seated resting BP values of < 100 mmHg systolic or < 55 mmHg diastolic, or as symptomatic (orthostatic) hypotension - Serum creatinine >2.5 mg/dL or hepatic enzymes >2X normal - Pacemakers, implantable cardioverter defibrillators or metallic implants not compatible with MRI scanning - Concomitant treatment with methotrexate, levodopa, phosphodiesterase-3 (milrinone) or phosphodiesterase -5 inhibitors (sildenafil, taladafil, vardenafil) , pentoxyfylline, nitrate/nitrite-based vasodilators, L-arginine, or dietary supplements containing L-arginine or gingko biloba within 30 days prior to Screening, or anticipated need for treatment with any of these agents during the course of the study. - Participation in other drug trials within the last 30 days before start for the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in endothelial function by FMD assessment after 24-month treatment with 6R-BH4 or placebo |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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 | 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.8.3 |
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.8.5 | The trial involves multiple Member States | No |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |