E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10016016 |
E.1.2 | Term | Fabry's disease |
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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 objectives of this open-label study are to evaluate the efficacy (GL-3 clearance), pharmacokinetics (PK), and safety parameters (including immunogenicity) for 2 alternative dose regimens of Fabrazyme (0.5 mg/kg every 2 weeks [q2w] and 1.0 mg/kg every 4 weeks [q4w]) in treatment-naive male pediatric patients with Fabry disease without severe symptoms. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients who meet the following inclusion criteria will be eligible for enrollment in this study: 1. The patient and/or patient’s parent(s)/legal guardian(s) must provide written informed consent prior to any protocol-related procedures being performed. 2. The patient must have a confirmed diagnosis of Fabry disease as documented by leukocyte a-Galactosidase A (alpha-GAL) activity of <4 nmol/hr/mg leukocyte (preferred assay). If the leukocyte alpha-GAL activity assay is not possible the patient must have documented plasma alpha-GAL <1.5 nmol/hr/mL. (All results from Genzyme’s Clinical Specialty Laboratory [CSL]). 3. The patient must have evidence of globotriaosylceramide (GL-3) accumulation as documented by plasma GL-3 (>7.0 microg/mL) and/or urinary GL-3 (>0.03 mg GL-3/mmol creatinine) levels (by central analysis laboratories). 4. The patient must be male ≥5 and ≤18 years of age. |
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E.4 | Principal exclusion criteria |
Patients who meet any of the following exclusion criteria will not be eligible for enrollment in this study: 1. Patient has albuminuria (first morning void urinary albumin/creatinine ratio >30 mg/g on at least 2 out of 3 consecutive samples, each at least 1 week apart). 2. Patient has a GFRiohexol <90 L/min/1.73 m2. 3. Patient has documented evidence of stroke or transient ischemic attack (TIA), or if a brain magnetic resonance imaging (MRI) has been performed, bright lesions >2 mm on T2- or fluid attenuated inversion recovery- (FLAIR) weighted images within the white matter or the basal ganglia. 4. Patient has severe and recurrent acroparesthesia, judged by the physician as frequent (more than once a week) pain episodes for at least 3 months that influence daily activities, irrespective of medication. 5. Patient has an end-diastolic left ventricular posterior wall thickness (LVPWTd) and/or an end-diastolic interventricular septum thickness (IVSTd) ≥2 standard deviations (SD) compared to normal (based on body surface area [BSA] normal ranges from Kampmann, et al 2000) as read at the study site. 6. Patient has received prior treatment specific to Fabry Disease. 7. Patient has participated in a study employing an investigational drug within 30 days of the start of their participation in this study. 8. Patient has any medical condition or extenuating circumstance, which, in the opinion of the Study Investigator, could interfere with study compliance. 9. Patient has any medical condition or extenuating circumstance, for example diabetes mellitus, which, in the opinion of the Study Investigator, could interfere with the interpretation of study results. 10. Patient is on treatment with angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs). 11. Patient is allergic to iohexol/iodine. 12. Patient or parent(s)/legal guardian(s) is unwilling to comply with the requirements of the protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint: The primary efficacy endpoint will be histological evaluation of GL-3 inclusions in the superficial skin vascular endothelium conducted using light microscopy (LM) histochemistry during Screening or Day 1, Week 52/Year 1, Week 156/Year 3, and Week 260/Year 5. Secondary Efficacy Endpoints: The secondary efficacy endpoints will be the effect of Fabrazyme treatment on GL-3 clearance in plasma and urine collection measured at Screening and every 3 months for the first year (through Week 52/Year 1) and every 6 months thereafter. |
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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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 | 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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End of the trial (last patient out) is defined as the safety followup which takes place approximately 4 weeks (28 days) after the last visit of the patient. |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |