Back to resultsA Study of Two Fabrazyme (Agalsidase Beta) Dosing Regimens in Treatment-naïve, Male Pediatric Patients Without Severe Symptoms (FIELD)
Primary Purpose
Fabry Disease
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Agalsidase beta
Agalsidase beta
Sponsored by
About this trial
This is an interventional treatment trial for Fabry Disease focused on measuring α-GAL, α-Galactosidase-A, r-hαGAL
Eligibility 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Fabrazyme 0.5 mg/kg
Fabrazyme 1.0 mg/kg
Arm 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.
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.
Outcomes
Primary Outcome Measures
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium
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
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00701415
Brief Title
A Study of Two Fabrazyme (Agalsidase Beta) Dosing Regimens in Treatment-naïve, Male Pediatric Patients Without Severe Symptoms
Acronym
FIELD
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 Type
Interventional
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
September 2008 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genzyme, a Sanofi Company
4. Oversight
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fabry Disease
Keywords
α-GAL, α-Galactosidase-A, r-hαGAL
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
31 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fabrazyme 0.5 mg/kg
Arm Type
Experimental
Arm 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.
Arm Title
Fabrazyme 1.0 mg/kg
Arm Type
Experimental
Arm 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.
Intervention Type
Biological
Intervention Name(s)
Agalsidase beta
Other Intervention Name(s)
Fabrazyme, Recombinant human α-galactosidase A (r-hαGAL)
Intervention Description
Powder for concentrate for solution for infusion 1.0 mg/kg/4 weeks
Intervention Type
Biological
Intervention Name(s)
Agalsidase beta
Other Intervention Name(s)
Fabrazyme, Recombinant human α-galactosidase A (r-hαGAL)
Intervention Description
Powder for concentrate for solution for infusion 0.5 mg/kg/2 weeks
Primary Outcome Measure Information:
Title
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium
Description
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.
Time Frame
Baseline, Week 52, Week 156 and Week 260
Secondary Outcome Measure Information:
Title
Percent Change From Baseline in GL-3 Clearance From Plasma
Description
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.
Time Frame
Baseline, Week 12, 28, 40, 52, 80, 104, 132, 156, 184, 208, 236 and 260
Title
Percent Change From Baseline in GL-3 Clearance From Urine
Description
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.
Time Frame
Baseline, Week 12, 28, 40, 52, 80, 104, 132, 156, 184, 208, 236 and 260
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Genzyme, a Sanofi Company
Official's Role
Study Director
Facility Information:
City
Decatur
State/Province
Georgia
Country
United States
City
Cincinnati
State/Province
Ohio
Country
United States
City
Seattle
State/Province
Washington
Country
United States
City
Buenos Aires
Country
Argentina
City
Passo Fundo
State/Province
RS
Country
Brazil
City
Vancouver
State/Province
British Columbia
Country
Canada
City
Montreal, QC
Country
Canada
City
Prague 2
Country
Czech Republic
City
Amsterdam
Country
Netherlands
City
Bergen
Country
Norway
City
Warsaw
Country
Poland
City
Cambridge
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
25955246
Citation
Wijburg FA, Benichou 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, Tondel C, Tylki-Szymanska 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.
Results Reference
derived
PubMed Identifier
23531228
Citation
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.
Results Reference
derived
Learn more about this trial
A Study of Two Fabrazyme (Agalsidase Beta) Dosing Regimens in Treatment-naïve, Male Pediatric Patients Without Severe Symptoms
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