E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metachromatic Leukodystrophy (MLD) in late infantile patients |
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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 | LLT |
E.1.2 | Classification code | 10024381 |
E.1.2 | Term | Leukodystrophy |
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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 overall objective is to evaluate efficacy and safety of rhASA treatment in patients with late infantile MLD and high residual level of voluntary function. Determination of the optimal dose will be elucidated |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must meet the following criteria to be enrolled in the study: 1. Subject’s legally authorized guardian(s) must provide signed, informed consent prior to performing any study-related activities (trial-related activities are any procedures that would not have been performed during normal management of the subject). 2. The patient must have a confirmed diagnosis of MLD as defined by: · ASA activity < 10 nmol/h/mg in leukocytes · Presence of confirmed pathogenetic mutations in the ARSA gene or elevated sulfatide in urine 3. The patient must have an age at the time of screening ≥ 1 year and < 6 years. 4. GMFM raw score ³ 60 at baseline (assessed not more than 4 weeks prior to first dosing). 5. The patient must have had onset of symptoms before the age of 4 years. 6. The subject and his/her guardian(s) must have the ability to comply with the clinical protocol. 7. The patients’ medical record must document that the legal guardian(s) has had independent counseling or a consultation regarding stem cell transplantation in order to assure that the guardian(s) is fully informed regarding the risks and benefits of this alternative.
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E.4 | Principal exclusion criteria |
Patients will be excluded from this study if they do not meet the specific inclusion criteria, or if any of the following criteria apply: 1. Spasticity so severe to inhibit transportation 2. Known multiple sulfatase deficiency 3. Presence of major congenital abnormality 4. Presence of known chromosomal abnormality and syndromes affecting psychomotor development 5. History of stem cell transplantation 6. Presence of known clinically significant cardiovascular, hepatic, pulmonary or renal disease or other medical condition that, in the opinion of the Investigator, would preclude participation in the trial 7. Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the trial 8. Use of any investigational product other than rhASA within 30 days prior to study enrolment or currently enrolled in another study which involves clinical investigations. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Relative change in GMFM after 26 weeks of treatment Absolute change in Mullen’s Scale of Early Learning after 26 weeks of treatment.
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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 | Yes |
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 | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | 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 | No |
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 | 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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Last patient last visit (week 52) |
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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 | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial days | 0 |