A Randomized, Multicenter, Multinational, Phase 3B, Open-Label, Parallel-Group Study of Fabrazyme (agalsidase beta) in Treatment-Naive Male Pediatric Patients with Fabry Disease Without Severe Symptoms - FIELD (Fabrazyme: Intervening Early at a Lower Dose)
- Conditions
- Fabry diseaseMedDRA version: 9.1Level: LLTClassification code 10016016Term: Fabry's disease
- Registration Number
- EUCTR2007-005668-28-CZ
- Lead Sponsor
- Genzyme Europe BV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 45
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.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
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 mL/min/1.73 m2. In case of properly documented low protein intake, values as low as 80 mL/min/1.73 m2 may be acceptable, after consultation with the Medical Monitor.
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. The presence of any contra-indication mentioned in the labeling of Fabrazyme and/or iohexol (Omnipaque).
12. Patient or parent(s)/legal guardian(s) is unwilling to comply with the requirements of the protocol.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 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 (5 years to 18 years of age) with Fabry disease without severe symptoms.;Secondary Objective: ;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.
- Secondary Outcome Measures
Name Time Method