CompletedNCT00701415FIELDUpdated Jun 29, 2016Results posted

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

A Phase 3 interventional study of Agalsidase beta and Agalsidase beta in Fabry Disease, sponsored by Genzyme, a Sanofi Company. Completed at 12 sites in 9 countries. Open to male participants aged 5 Years to 18 Years. Per ClinicalTrials.gov, last updated 2016-06-29.

Sponsored by Genzyme, a Sanofi Company (part of Sanofi) · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 31
Allocation: Randomized
Ages: 5 Years to 18 Years
Sex: Male

Study 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.

Conditions studied

Fabry Disease

Browse trials for

Fabry Disease 246

Keywords

α-GAL, α-Galactosidase-A, r-hαGAL

In context

Fabry Disease

246 studies on the registry are indexed under Fabry Disease; 56 are open to participants now.

This study's enrollment of 31 is above the median of 22 across 108 interventional studies indexed under Fabry Disease.

Browse Fabry Disease studies →

Lead sponsor

Genzyme, a Sanofi Company is the lead sponsor of 308 studies on the registry; 5 are open to participants now.

Of its 25 completed or terminated interventional studies of FDA-regulated products, 19 (76%) have results posted.

First submitted before Genzyme became part of Sanofi.

Browse Genzyme studies →All Sanofi studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 5 Years to 18 Years
Sexes eligible: Male
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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.

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 31 participants (actual)

Study arms

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
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

Interventions

BiologicalAgalsidase beta
Powder for concentrate for solution for infusion 1.0 mg/kg/4 weeks
Also known as: Fabrazyme, Recombinant human α-galactosidase A (r-hαGAL)
BiologicalAgalsidase beta
Powder for concentrate for solution for infusion 0.5 mg/kg/2 weeks
Also known as: Fabrazyme, Recombinant human α-galactosidase A (r-hαGAL)

What researchers measure

Primary outcomes

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.
Time frame: Baseline, Week 52, Week 156 and Week 260

Secondary outcomes

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.
Time frame: Baseline, Week 12, 28, 40, 52, 80, 104, 132, 156, 184, 208, 236 and 260
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.
Time frame: Baseline, Week 12, 28, 40, 52, 80, 104, 132, 156, 184, 208, 236 and 260

Results

Posted Jun 29, 2016

Participant flow

The study was conducted at 12 sites in 9 countries. A total of 44 participants were screened between 17 June 2008 and 12 April 2010.

Participant flow — Overall Study
Milestone	Fabrazyme 0.5 mg/kg	Fabrazyme 1.0 mg/kg
Started	16	15
Completed	15	14
Not completed	1	1
Withdrew: Adverse event	0	1
Withdrew: Social/family issues and needle phobia	1	0

Outcome measures

PrimarySkin 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.

Time frame:: Baseline, Week 52, Week 156 and Week 260
Reported as:: Number · Percentage of participants

Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium
Percentage of participants	Fabrazyme 0.5 mg/kg	Fabrazyme 1.0 mg/kg
Zero (0) Skin GL-3 Score at Baseline	18.8	33.3
Zero (0) Skin GL-3 Score at Week 52	75	80
Zero (0) Skin GL-3 Score at Week 156	56.3	80
Zero (0) Skin GL-3 Score at Week 260	68.8	66.7
Mild (1) Skin GL-3 Score at Baseline	6.3	0
Mild (1) Skin GL-3 Score at Week 52	6.3	13.3
Mild (1) Skin GL-3 Score at Week 156	18.8	0
Mild (1) Skin GL-3 Score at Week 260	12.5	20
Moderate (2) Skin GL-3 Score at Baseline	75	66.7
Moderate (2) Skin GL-3 Score at Week 52	0	0
Moderate (2) Skin GL-3 Score at Week 156	6.3	13.3
Moderate (2) Skin GL-3 Score at Week 260	0	6.7
Severe (3) Skin GL-3 Score at Baseline	0	0
Severe (3) Skin GL-3 Score at Week 52	0	0
Severe (3) Skin GL-3 Score at Week 156	0	0
Severe (3) Skin GL-3 Score at Week 260	0	0
Missing Skin GL-3 Score at Baseline	0	0
Missing Skin GL-3 Score at Week 52	18.8	6.7
Missing Skin GL-3 Score at Week 156	18.8	6.7
Missing Skin GL-3 Score at Week 260	18.8	6.7

SecondaryPercent 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.

Time frame:: Baseline, Week 12, 28, 40, 52, 80, 104, 132, 156, 184, 208, 236 and 260
Reported as:: Mean · Percent change

Percent Change From Baseline in GL-3 Clearance From Plasma
Percent change	Fabrazyme 0.5 mg/kg	Fabrazyme 1.0 mg/kg
Week 12 (n=14, 11)	-52.37 ± 10.12	-52.74 ± 6.79
Week 28 (n=14, 14)	-49.06 ± 15.43	-47.55 ± 16.75
Week 40 (n=13, 14)	-52.01 ± 11.29	-50.82 ± 12.87
Week 52 (n=14, 14)	-52.29 ± 10.48	-45.87 ± 16.01
Week 80 (n=13, 14)	-52.91 ± 13.93	-48.93 ± 14.75
Week 104 (n=13, 14)	-51.08 ± 20.45	-39.92 ± 18.69
Week 132 (n=11, 14)	-61.39 ± 10.71	-52.97 ± 17.1
Week 156 (n=11, 14)	-48.72 ± 18.48	-44.83 ± 14.14
Week 184 (n=12, 14)	-53.62 ± 19.38	-49.08 ± 17.93
Week 208 (n=12, 14)	-48.83 ± 16.80	-46.09 ± 16.84
Week 236 (n=12, 14)	-56.44 ± 12.08	-47.25 ± 13.04
Week 260 (n=11, 14)	-59.95 ± 12.39	-46.34 ± 14.01

SecondaryPercent 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.

Time frame:: Baseline, Week 12, 28, 40, 52, 80, 104, 132, 156, 184, 208, 236 and 260
Reported as:: Mean · Percent change

Percent Change From Baseline in GL-3 Clearance From Urine
Percent change	Fabrazyme 0.5 mg/kg	Fabrazyme 1.0 mg/kg
Week 12 (n=15, 14)	-50.77 ± 64.59	-63.39 ± 38.81
Week 28 (n=15, 15)	-50.84 ± 100.61	-52.55 ± 58.59
Week 40 (n=15, 14)	-44.22 ± 105.03	-63.87 ± 24.41
Week 52 (n=15, 14)	-70.1 ± 41.4	-20.72 ± 156.1
Week 80 (n=14, 14)	-35.84 ± 102.31	35.22 ± 238.61
Week 104 (n=14, 14)	-21.92 ± 138.78	-56.39 ± 42.39
Week 132 (n=13, 14)	-48.79 ± 100.1	-45.61 ± 48.84
Week 156 (n=13, 14)	-65.57 ± 52.11	-28.92 ± 84.32
Week 184 (n=13, 14)	-76.54 ± 38.93	-10.5 ± 146.86
Week 208 (n=13, 14)	-60.94 ± 67.99	-50.93 ± 46.52
Week 236 (n=13, 14)	-69.08 ± 51.72	-40.09 ± 77.04
Week 260 (n=13, 14)	-57.59 ± 93.74	-28.27 ± 56.79

Adverse events

Collected over All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 264) regardless of seriousness or relationship to investigational product.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Fabrazyme 0.5 mg/kg	—	6/16 (37.5%)	16/16 (100%)
Fabrazyme 1.0 mg/kg	—	5/15 (33.3%)	15/15 (100%)

Most frequent serious events

Showing 10 of 21

Most frequent serious events
Event	Fabrazyme 0.5 mg/kg	Fabrazyme 1.0 mg/kg
GASTROINTESTINAL HAEMORRHAGEGastrointestinal disorders	0/16	1/15
MEDICAL DEVICE COMPLICATIONGeneral disorders	0/16	1/15
PYREXIAGeneral disorders	1/16	1/15
ERYSIPELASInfections and infestations	0/16	1/15
OTITIS MEDIAInfections and infestations	0/16	1/15
PNEUMONIAInfections and infestations	0/16	1/15
SEPSISInfections and infestations	0/16	1/15
TINEA PEDISInfections and infestations	0/16	1/15
PARAESTHESIANervous system disorders	1/16	1/15
TREMORNervous system disorders	0/16	1/15

Most frequent other events

Showing 10 of 246

Most frequent other events
Event	Fabrazyme 0.5 mg/kg	Fabrazyme 1.0 mg/kg
PYREXIAGeneral disorders	12/16	8/15
DIARRHOEAGastrointestinal disorders	10/16	8/15
ABDOMINAL PAINGastrointestinal disorders	9/16	6/15
NAUSEAGastrointestinal disorders	9/16	7/15
VOMITINGGastrointestinal disorders	9/16	7/15
ANGIOKERATOMASkin and subcutaneous tissue disorders	9/16	5/15
PAIN IN EXTREMITYMusculoskeletal and connective tissue disorders	8/16	5/15
HEADACHENervous system disorders	8/16	4/15
COUGHRespiratory, thoracic and mediastinal disorders	8/16	5/15
NASOPHARYNGITISInfections and infestations	7/16	5/15

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Fabrazyme 0.5 mg/kg	Fabrazyme 1.0 mg/kg	Total
Mean	11.2 ± 4	11.9 ± 4.5	11.5 ± 4.2

Sex: Female, Male
Sex: Female, Male(Participants)	Fabrazyme 0.5 mg/kg	Fabrazyme 1.0 mg/kg	Total
Female	0	0	0
Male	16	15	31

Study locations

12 sites

Decatur, Georgia, United States
Cincinnati, Ohio, United States
Seattle, Washington, United States
Buenos Aires, Argentina
Passo Fundo, Rio Grande do Sul, Brazil
Vancouver, British Columbia, Canada
Montreal, QC, Canada
Prague, Czechia
Amsterdam, Netherlands
Bergen, Norway
Warsaw, Poland
Cambridge, United Kingdom

References and documents

Publications

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. PubMed 25955246 ↗
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. PubMed 23531228 ↗

Timeline

Tracking since Sep 25, 2026

Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Sep 2008, a primary completion of Jun 2015 and a completion of Jun 2015. It does not say whether these dates are actual or estimated.

Results were first posted in Jun 2016, 1 year after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered: Jun 17, 2008
First posted: Jun 19, 2008
Start: Sep 2008
Primary completionActual: Jun 2015
CompletionActual: Jun 2015
Results first posted: Jun 29, 2016
Last update: Jun 29, 2016

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Jun 29, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00701415
Lead sponsor: Genzyme, a Sanofi Company
Responsible party: Sponsor
First posted: Jun 19, 2008
Start date: Sep 2008
Primary completion: Jun 2015
Completion: Jun 2015
Results posted: Jun 29, 2016
Last update: Jun 29, 2016

Study contacts

Medical Monitor

study director · Genzyme, a Sanofi Company

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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