E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with congenital venous malformations (CVM) |
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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 |
To compare the systemic exposure to ethanol with the two test products. |
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E.2.2 | Secondary objectives of the trial |
- To compare the systemic (cardiopulmonary, hematological, metabolic) and local outcome of the two test products. - To compare the embolosclerosing activity of L0122 gel and absolute ethanol on size reduction of CVM. - To compare the clinical efficacy (patient benefit) of the two test products. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Patients of both sexes, of at least 12 years of age, -For women of childbearing potential, negative pregnancy test at baseline, -Patients with one clinically and radiologically (MRI) documented lesion diagnosed as CVM (pure or predominant), -Patients for which an embolosclerotherapy by the percutaneous route is indicated as first line therapy of the test lesion, or for which previous treatments (i.e. surgery, embolosclerotherapy, laser) have been unsuccessful or insufficient, -Patients with CVM lesional size of at least 12 cm3 (maximum craniocaudal dimension X mean dimension of 3 transverse equispaced measurements X mean dimension of 3 deepness equispaced measurements dimension) at MRI, -Patients with focal or multifocal CVM lesion, i.e. with one or several well-interconnecting venous spaces and well-defined margins, -Patients or parents able to follow study instructions and attend study visits, -Written informed consent from the patients or parents.
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E.4 | Principal exclusion criteria |
-Patients under 12 years of age, -Pregnant women, nursing mothers and women of childbearing potential with no reliable contraception from more than 2 months, -Women of childbearing potential with a positive pregnancy test at baseline, -Patients with CVM of non venous predominance, -Patients with CVM that are not reachable by the percutaneous route, -Patients with extensive superficial skin CVM (i.e. with high risk of skin necrosis), -Patients with a test lesion adjacent to major nerves (e.g. facial nerve in the parotid region, intramuscular regions adjacent to major nerves), -Patients with facial CVM or bone involvement, -Patients with small CVM lesion (<12 cm3 at MRI), -Patients requiring more than 1 ml/Kg body weight (b.w.) in USA or more than 0.5 ml/Kg b.w. in france, or more than 30 mL of absolute ethanol to infuse, -Patients with a known allergy to one of the components of the test products, -Patients with a suspected allergy to iodinated products, -Patients with abnormal clotting parameters (platelets, partial thromboplastin, prothrombin time), -Patients with an active inflammatory episode of the test lesion (i.e. acute or subacute swelling of the test lesion), -Patients with complex malformations (e.g. Klippel-Trenaunay syndrome, Blue Rubber Bled Nevus syndrome, Muco-cutaneous familial venous malformations, Mafucci’s syndrome), -Patients in which a surgery, laser therapy or embolosclerotherapy of the test lesion has been performed within the last 12 weeks prior to study entry, -Asthmatic patients who require daily medications, -Patients with a non treated or non stabilized cardiac disease, -Patients with a suspected right-left shunt, -Patients with an intercurrent condition or a concomitant treatment which may interfere with a good conduct or the evaluation parameters of the study, -Patients who participated in a study within the 12 weeks prior to study entry, -Patients or parents who are not able or willing to follow the study instructions, -Patients or parents who refuse to give written informed consent. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacokinetic parameter (primary study parameter): Cmax The parameter will be determined by plasma monitoring of ethanol just before infusion, then 5 mn, 10 mn, 20 mn, 40 mn, 60 mn, 90 mn, 120 mn after infusion at the first site, and every 60 mn onwards until ethanolemia becomes undetectable.
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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 | 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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | 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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Provided in the protocol. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |