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

• ClinicalTrials.gov Identifier: NCT00701415
• Recruitment Status: Completed
• First Posted: June 19, 2008
• Results First Posted: June 29, 2016
• Last Update Posted: June 29, 2016
• Sponsor: Genzyme, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Genzyme, a Sanofi Company )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Fabry Disease	Biological: Agalsidase beta	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: September 2008
• Actual Primary Completion Date: June 2015
• Actual Study Completion Date: June 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Fabrazyme 0.5 mg/kg; 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.	Biological: Agalsidase beta; Powder for concentrate for solution for infusion 1.0 mg/kg/4 weeks; Other Names: Fabrazyme; Recombinant human α-galactosidase A (r-hαGAL)
Experimental: Fabrazyme 1.0 mg/kg; 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.	Biological: Agalsidase beta; Powder for concentrate for solution for infusion 0.5 mg/kg/2 weeks; Other Names: Fabrazyme; Recombinant human α-galactosidase A (r-hαGAL)

Outcome Measures

Primary Outcome Measures :

1. 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 Outcome Measures :

1. Percent Change From Baseline in GL-3 Clearance From Plasma [ Time Frame: Baseline, Week 12, 28, 40, 52, 80, 104, 132, 156, 184, 208, 236 and 260 ]
   Plasma samples were assayed for GL-3 clearance using a validated tandem mass spectrometry with an upper limit of normal plasma GL-3 level of 7.0 μg/mL. Number of participants analyzed=participants with both baseline and post-baseline GL-3 plasma clearance assessment. Here 'n' signifies number of participants with available data for specified category.
2. Percent Change From Baseline in GL-3 Clearance From Urine [ Time Frame: Baseline, Week 12, 28, 40, 52, 80, 104, 132, 156, 184, 208, 236 and 260 ]
   Plasma samples were assayed for total urine GL-3 clearance using a validated tandem mass spectrometry with an upper limit of normal of <0.030 mg/mmoL of creatinine. Number of participants analyzed=participants with both baseline and post-baseline GL-3 urine clearance assessment. Here 'n' signifies number of participants with available data for specified category.

Eligibility Criteria

• Ages Eligible for Study: 5 Years to 18 Years (Child, Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Georgia

Decatur, Georgia, United States

United States, Ohio

Cincinnati, Ohio, United States

United States, Washington

Seattle, Washington, United States

Argentina

Buenos Aires, Argentina

Brazil

Passo Fundo, RS, Brazil

Canada, British Columbia

Vancouver, British Columbia, Canada

Canada

Montreal, QC, Canada

Czech Republic

Prague 2, Czech Republic

Netherlands

Amsterdam, Netherlands

Norway

Bergen, Norway

Poland

Warsaw, Poland

United Kingdom

Cambridge, United Kingdom

Sponsors and Collaborators

Genzyme, a Sanofi Company

Investigators

• Study Director: Medical Monitor; Genzyme, a Sanofi Company

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wijburg FA, Bénichou B, Bichet DG, Clarke LA, Dostalova G, Fainboim A, Fellgiebel A, Forcelini C, An Haack K, Hopkin RJ, Mauer M, Najafian B, Scott CR, Shankar SP, Thurberg BL, Tøndel C, Tylki-Szymańska A, Ramaswami U. Characterization of early disease status in treatment-naive male paediatric patients with Fabry disease enrolled in a randomized clinical trial. PLoS One. 2015 May 8;10(5):e0124987. doi: 10.1371/journal.pone.0124987. eCollection 2015.

Rombach SM, Smid BE, Bouwman MG, Linthorst GE, Dijkgraaf MG, Hollak CE. Long term enzyme replacement therapy for Fabry disease: effectiveness on kidney, heart and brain. Orphanet J Rare Dis. 2013 Mar 25;8:47. doi: 10.1186/1750-1172-8-47.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT00701415
• Other Study ID Numbers: AGAL06207; 2007-005668-28 ( EudraCT Number ); EFC12821 ( Other Identifier: Sanofi )
• First Posted: June 19, 2008
• Results First Posted: June 29, 2016
• Last Update Posted: June 29, 2016
• Last Verified: May 2016

Keywords provided by Sanofi ( Genzyme, a Sanofi Company ):

α-GAL, α-Galactosidase-A, r-hαGAL

Additional relevant MeSH terms:

Fabry Disease; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Lipid Metabolism Disorders