E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of alpha-Mannosidosis |
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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 |
• Define effective dose based on evaluation of efficacy of rhLAMAN (Lamazym) from baseline on: The biochemical markers , The clinical parameters • To evaluate the long-term safety profile of rhLAMAN (Lamazym)
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E.2.2 | Secondary objectives of the trial |
• To determine the PK profile after repeated dose of rhLAMAN (Lamazym) in patients with alpha-Mannosidosis as measured by rhLAMAN levels in plasma |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The patient must have a confirmed diagnosis of alpha-Mannosidosis as defined by alpha-mannosidase activity < 10% of normal activity in blood leukocytes 2. The patient must have an age at the time of screening ≥ 5 year and ≤ 21 years 3. The patient must have physical ability to perform 6-minutes walk test (6MWT), 3 minute-stair climb test (3MSCT) and pulmonary lung function test (spirometry, body plethysmography). 4. The patient must have the ability to mentally cooperate in the cognitive and motor function tests 5. The patient must have the ability to hear and follow a request. Hearing aids can be worn. 6. Patient or patient’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) 7. The patient and his/her guardian(s) must have the ability to comply with the protocol
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E.4 | Principal exclusion criteria |
1. The patient cannot walk without support. 2. Presence of known chromosomal abnormality and syndromes affecting psychomotor development, other than alpha-Mannosidosis 3. History of bone marrow transplantation 4. Presence of known clinically significant cardiovascular, hepatic, pulmonary or renal disease or other medical conditions that, in the opinion of the Investigator, would preclude participation in the trial 5. Presence of an ECHO with abnormalities within half a year that, in the opinion of the Investigator, would preclude participation in the trial 6. Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the investigator, would preclude participation in the trial 7. Pregnancy 8. Psychosis within the last 3 months
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy endpoints, measured at interim (3 months) and 6 months evaluation: Change from baseline of Oligosaccharide in serum-, urine- and cerebrospinal fluid Change from baseline in cerebrospinal fluid neurodegeneration biomarkers Change from baseline of MRS (white matter and mannose level) Change from baseline of functional capacity (6MWT, 3MSC, BOT2, Gait) Change from baseline of cognitive development (Leiter R) Change from baseline of Pulmonary function (FVC) Change from baseline of Hearing Safety endpoints: Adverse events Vital signs Urinalysis Hematology and blood chemistry rhLAMAN antibody and inhibitory antibody
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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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 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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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 | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
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 |