NCT00701415CompletedPhase 3
A Randomized, Multicenter, Multinational, Phase 3B, Open-Label, Parallel-Group Study of Fabrazyme (Agalsidase Beta) in Treatment-Naïve Male Pediatric Patients With Fabry Disease Without Severe Symptoms
Genzyme, a Sanofi Company12 sites in 9 countries31 target enrollmentStarted: September 1, 2008Last updated:
Conditions
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 31
- Locations
- 12
- Primary Endpoint
- Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium
Study Overview
Brief Summary
The purpose of this study was to determine whether 2 alternative dosing regimens of Fabrazyme (Agalsidase beta) (1.0 mg/kg every 4 weeks or 0.5 mg/kg every 2 weeks) were effective in treatment-naïve pediatric participants without severe symptoms. Participants were to be treated for 5 years.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 5 Years to 18 Years (Child, Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •The participant and/or participant's parent(s)/legal guardian(s) must provide written informed assent/consent prior to any protocol-related procedures being performed.
- •The participant must had a confirmed diagnosis of Fabry disease as documented by leukocyte α-Galactosidase A (αGAL) activity of <4 nmol/hr/mg leukocyte (preferred assay; resulted from a central laboratory). If the leukocyte αGAL activity assay was difficult to obtain, the participant might be enrolled based on documented plasma αGAL <1.5 nmol/hr/mL, with the agreement of the Medical Monitor (resulted from a central laboratory).
- •The participant must had evidence of globotriaosylceramide (GL-3) accumulation as documented by plasma GL-3 (>7.0 µg/mL) or urinary GL-3 (>0.3 mg GL-3/mmol creatinine) levels (results from a central laboratory).
- •The participant must be male ≥5 and ≤18 years of age.
Exclusion Criteria
- •Participant had 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).
- •Participant had a Glomerular Filtration Rate (GFR) by iohexol <90 L/min/1.73m^
- •In case of properly documented low protein intake, values as low as 80 mL/min/1.73 m^2 might be acceptable, after consultation with the Medical Monitor.
- •Participant had documented evidence of stroke or transient ischemic attack (TIA), or if a brain magnetic resonance imaging (MRI) had been performed, bright lesions >2 mm on T2- or fluid attenuated inversion recovery (FLAIR)- weighted images within the white matter or the basal ganglia.
- •Participant had severe and recurrent acroparesthesia, judged by the physician as frequent (more than once a week) pain episodes for at least 3 months that influenced daily activities, irrespective of medication.
- •Participant had 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.
- •Participant had received prior treatment specific to Fabry Disease.
- •Participant had participated in a study employing an investigational drug within 30 days of the start of their participation in this study.
- •Participant had any medical condition or extenuating circumstance, which in the opinion of the Study Investigator, could interfere with study compliance.
- •Participant had 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.
- •Participant was on treatment with angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs).
- •Participant had any contra-indication mentioned in the labeling of Fabrazyme and/or iohexol (Omnipaque).
- •Participant or parent(s)/legal guardian(s) was unwilling to comply with the requirements of the protocol.
Outcomes
Primary Outcomes
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium
Time Frame: Baseline, Week 52, Week 156 and Week 260
Skin biopsies were taken at Baseline, Week 52, Week 156 and Week 260 or early withdrawal and analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Each biopsy was scored for GL-3 accumulation on a severity score-scale of none, mild, moderate, severe (0-1-2-3). Scores are categorized as normal (score = 0) or abnormal (score = 1, 2 or 3). Data was summarized in terms of number of participants with none/trace, mild, moderate and severe biopsy scores.
Secondary Outcomes
- Percent Change From Baseline in GL-3 Clearance From Urine(Baseline, Week 12, 28, 40, 52, 80, 104, 132, 156, 184, 208, 236 and 260)
- Percent Change From Baseline in GL-3 Clearance From Plasma(Baseline, Week 12, 28, 40, 52, 80, 104, 132, 156, 184, 208, 236 and 260)
Investigators
Study Sites (12)
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