A Study of Two Fabrazyme (Agalsidase Beta) Dosing Regimens in Treatment-naïve, Male Pediatric Patients Without Severe Symptoms (FIELD)

Genzyme

Status and phase: Completed; Phase 3

Conditions: Fabry Disease

Treatments: Biological: Agalsidase beta

Study type: Interventional

Funder types: Industry

Identifiers

NCT00701415

EFC12821 (Other Identifier)

AGAL06207

2007-005668-28 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 31 patients

Sex: Male

Ages: 5 to 18 years old

Volunteers: No Healthy Volunteers

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^2. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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31 participants in 2 patient groups

Fabrazyme 0.5 mg/kg

Experimental group

Description:

Fabrazyme 0.5 mg/kg was administered every 2 weeks (up to 131 infusion) up to 260 weeks, the total infusion time was not less than 45 minutes. In case of significant progression of Fabry disease, the dose was increased to 1.0 mg/kg every 2 weeks.

Treatment:

Biological: Agalsidase beta

Biological: Agalsidase beta

Fabrazyme 1.0 mg/kg

Experimental group

Description:

Fabrazyme 1.0 mg/kg was administered every 4 weeks (up to 66 infusion) up to 260 weeks, the total infusion time was not less than 90 minutes. In case of significant progression of Fabry disease, the dose was increased to 1.0 mg/kg every 2 weeks.

Treatment:

Biological: Agalsidase beta

Biological: Agalsidase beta