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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT00701415
First received: June 17, 2008
Last updated: May 20, 2016
Last verified: May 2016
  Purpose
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 Intervention Phase
Fabry Disease
Biological: Agalsidase beta
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium [ Time Frame: Baseline, Week 52, Week 156 and Week 260 ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 31
Study Start Date: September 2008
Study Completion Date: June 2015
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   5 Years to 18 Years   (Child, Adult)
Genders 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00701415

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):
Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT00701415     History of Changes
Other Study ID Numbers: AGAL06207  2007-005668-28  EFC12821 
Study First Received: June 17, 2008
Results First Received: May 20, 2016
Last Updated: May 20, 2016
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Brazil: National Health Surveillance Agency
Canada: Ministry of Health & Long Term Care, Ontario
Netherlands: Medicines Evaluation Board (MEB)
Norway: Norwegian Medicines Agency (NoMA)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products (CBEK)
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Sanofi:
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

ClinicalTrials.gov processed this record on August 30, 2016