E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gaucher disease type 3 |
De ziekte van Gaucher type 3 |
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E.1.1.1 | Medical condition in easily understood language |
Gaucher disease type 3 |
De ziekte van Gaucher type 3 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10027424 |
E.1.2 | Term | Metabolic and nutritional disorders congenital |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 |
Assess the potential efficacy of ambroxol in adults and children with GD3. |
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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 |
1) The patient or the parent(s) / legal guardian(s) must provide written informed consent before start of the study; 2) Male and female patients with documented deficiency of GCase activity and GBA genotype fitting GD3; 3) Male and female patients of all ages; 4) Able to travel to the study site; 5) Patients receive ERT with treatment ongoing at the time of enrollment;
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E.4 | Principal exclusion criteria |
1) The patient is transfusion dependent; 2) The patient has received an investigational product within 30 days prior to enrollment; 3) Known hypersensitivity reactions, intolerance or adverse reactions to ambroxol or to the inactive ingredients; 4) Pregnancy, because there are no sufficient data for the use of ambroxol in pregnant women (see Summary of Product Characteristics (SPC)); 5) The patient is lactating. Ambroxol crosses into the breast milk. As there is no adequate experience in humans to date, ambroxol should not be used in lactation in a study setting (see SPC); 6) The patient is unwilling or, in the investigator’s opinion, unable to adhere to the requirements of the study; 7) The patient is unable to swallow powder and has no other enteral access (e.g. gastrostomy); 8) Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in cerebrospinal fluid (CSF) Lyso-GL1, from GD3 patients receiving ambroxol |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
End of (interventional) periods |
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E.5.2 | Secondary end point(s) |
• Change in plasma Lyso-GL1, GL-1, chitotriosidase and Lyso-GM3, from GD3 patients receiving ambroxol; • Change in CSF GL-1 and Lyso-GM3, from GD3 patients receiving ambroxol; • Change in GCase activity in leukocytes, from GD3 patients receiving ambroxol; • Effect of ambroxol on functional/developmental outcomes using the Goal Attainment Scaling (GAS) in GD3 patients; • Effect of ambroxol on quality of life using the Pediatric Quality of Life Inventory (PedsQL) in GD3 patients; • Effect of ambroxol on ataxia using the Scale for the Assessment and Rating of Ataxia (SARA) in GD3 patients; • Effect of ambroxol on neuropsychological outcomes using the Attention Network Task (ANT) and/or Wechsler scale in GD3 patients; • If epilepsy: effect of ambroxol on seizure control using the Unified Myoclonus Rating Scale (UMRS) and a seizure log book in GD3 patients. * Bahavioural assessment (SDQ/SWAN) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
End of (interventional) periods |
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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 | No |
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) | Yes |
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 | No |
E.8.1.6 | Cross over | Yes |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 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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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 | 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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |