Trial Outcomes & Findings for A Study of Two Fabrazyme (Agalsidase Beta) Dosing Regimens in Treatment-naïve, Male Pediatric Patients Without Severe Symptoms (NCT NCT00701415)

Last Updated: 2016-06-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

31 participants

Primary outcome timeframe

Baseline, Week 52, Week 156 and Week 260

Results posted on

2016-06-29

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.

Of 44 screened participants, 31 were randomized in 1:1 ratio to fabrazyme 0.5 mg/kg and fabrazyme 1.0 mg/kg within each age stratum (5 to ≤11 years \[children\] and 12 to ≤18 years \[adolescents\]). 13 participants were screen failure due to failure to meet inclusion criteria or withdrawal of consent prior to all screening assessments being completed.

Participant milestones

Participant milestones
Measure	Fabrazyme 0.5 mg/kg Fabrazyme 0.5 mg/kg was administered every 2 weeks (up to 131 infusions) 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 Fabrazyme 1.0 mg/kg was administered every 4 weeks (up to 66 infusions) 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.
Overall Study STARTED	16	15
Overall Study COMPLETED	15	14
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Fabrazyme 0.5 mg/kg Fabrazyme 0.5 mg/kg was administered every 2 weeks (up to 131 infusions) 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 Fabrazyme 1.0 mg/kg was administered every 4 weeks (up to 66 infusions) 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.
Overall Study Adverse Event	0	1
Overall Study Social/family issues and needle phobia	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fabrazyme 0.5 mg/kg n=16 Participants 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 n=15 Participants 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.	Total n=31 Participants Total of all reporting groups
Age, Continuous	11.2 years STANDARD_DEVIATION 4 • n=5 Participants	11.9 years STANDARD_DEVIATION 4.5 • n=7 Participants	11.5 years STANDARD_DEVIATION 4.2 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	15 Participants n=7 Participants	31 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 52, Week 156 and Week 260

Population: Analysis was performed on Full analysis set (FAS), which included all randomized participants who received at least 1 infusion of study treatment.

Outcome measures

Outcome measures
Measure	Fabrazyme 0.5 mg/kg n=16 Participants Fabrazyme 0.5 mg/kg was administered every 2 weeks (up to 131 infusions) 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 n=15 Participants Fabrazyme 1.0 mg/kg was administered every 4 weeks (up to 66 infusions) 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.
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium Zero (0) Skin GL-3 Score at Week 156	56.3 Percentage of participants	80 Percentage of participants
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium Mild (1) Skin GL-3 Score at Week 52	6.3 Percentage of participants	13.3 Percentage of participants
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium Moderate (2) Skin GL-3 Score at Baseline	75 Percentage of participants	66.7 Percentage of participants
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium Moderate (2) Skin GL-3 Score at Week 156	6.3 Percentage of participants	13.3 Percentage of participants
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium Missing Skin GL-3 Score at Baseline	0 Percentage of participants	0 Percentage of participants
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium Missing Skin GL-3 Score at Week 52	18.8 Percentage of participants	6.7 Percentage of participants
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium Zero (0) Skin GL-3 Score at Baseline	18.8 Percentage of participants	33.3 Percentage of participants
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium Zero (0) Skin GL-3 Score at Week 52	75 Percentage of participants	80 Percentage of participants
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium Zero (0) Skin GL-3 Score at Week 260	68.8 Percentage of participants	66.7 Percentage of participants
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium Mild (1) Skin GL-3 Score at Baseline	6.3 Percentage of participants	0 Percentage of participants
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium Mild (1) Skin GL-3 Score at Week 156	18.8 Percentage of participants	0 Percentage of participants
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium Mild (1) Skin GL-3 Score at Week 260	12.5 Percentage of participants	20 Percentage of participants
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium Moderate (2) Skin GL-3 Score at Week 52	0 Percentage of participants	0 Percentage of participants
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium Moderate (2) Skin GL-3 Score at Week 260	0 Percentage of participants	6.7 Percentage of participants
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium Severe (3) Skin GL-3 Score at Baseline	0 Percentage of participants	0 Percentage of participants
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium Severe (3) Skin GL-3 Score at Week 52	0 Percentage of participants	0 Percentage of participants
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium Severe (3) Skin GL-3 Score at Week 156	0 Percentage of participants	0 Percentage of participants
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium Severe (3) Skin GL-3 Score at Week 260	0 Percentage of participants	0 Percentage of participants
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium Missing Skin GL-3 Score at Week 156	18.8 Percentage of participants	6.7 Percentage of participants
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium Missing Skin GL-3 Score at Week 260	18.8 Percentage of participants	6.7 Percentage of participants

SECONDARY outcome

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

Population: Analysis was performed on FAS.

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.

Outcome measures

Outcome measures
Measure	Fabrazyme 0.5 mg/kg n=14 Participants Fabrazyme 0.5 mg/kg was administered every 2 weeks (up to 131 infusions) 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 n=14 Participants Fabrazyme 1.0 mg/kg was administered every 4 weeks (up to 66 infusions) 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.
Percent Change From Baseline in GL-3 Clearance From Plasma Week 40 (n=13, 14)	-52.01 Percent change Standard Deviation 11.29	-50.82 Percent change Standard Deviation 12.87
Percent Change From Baseline in GL-3 Clearance From Plasma Week 12 (n=14, 11)	-52.37 Percent change Standard Deviation 10.12	-52.74 Percent change Standard Deviation 6.79
Percent Change From Baseline in GL-3 Clearance From Plasma Week 28 (n=14, 14)	-49.06 Percent change Standard Deviation 15.43	-47.55 Percent change Standard Deviation 16.75
Percent Change From Baseline in GL-3 Clearance From Plasma Week 52 (n=14, 14)	-52.29 Percent change Standard Deviation 10.48	-45.87 Percent change Standard Deviation 16.01
Percent Change From Baseline in GL-3 Clearance From Plasma Week 80 (n=13, 14)	-52.91 Percent change Standard Deviation 13.93	-48.93 Percent change Standard Deviation 14.75
Percent Change From Baseline in GL-3 Clearance From Plasma Week 104 (n=13, 14)	-51.08 Percent change Standard Deviation 20.45	-39.92 Percent change Standard Deviation 18.69
Percent Change From Baseline in GL-3 Clearance From Plasma Week 132 (n=11, 14)	-61.39 Percent change Standard Deviation 10.71	-52.97 Percent change Standard Deviation 17.1
Percent Change From Baseline in GL-3 Clearance From Plasma Week 156 (n=11, 14)	-48.72 Percent change Standard Deviation 18.48	-44.83 Percent change Standard Deviation 14.14
Percent Change From Baseline in GL-3 Clearance From Plasma Week 184 (n=12, 14)	-53.62 Percent change Standard Deviation 19.38	-49.08 Percent change Standard Deviation 17.93
Percent Change From Baseline in GL-3 Clearance From Plasma Week 208 (n=12, 14)	-48.83 Percent change Standard Deviation 16.80	-46.09 Percent change Standard Deviation 16.84
Percent Change From Baseline in GL-3 Clearance From Plasma Week 236 (n=12, 14)	-56.44 Percent change Standard Deviation 12.08	-47.25 Percent change Standard Deviation 13.04
Percent Change From Baseline in GL-3 Clearance From Plasma Week 260 (n=11, 14)	-59.95 Percent change Standard Deviation 12.39	-46.34 Percent change Standard Deviation 14.01

SECONDARY outcome

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

Population: Analysis was performed on FAS.

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.

Outcome measures

Outcome measures
Measure	Fabrazyme 0.5 mg/kg n=15 Participants Fabrazyme 0.5 mg/kg was administered every 2 weeks (up to 131 infusions) 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 n=15 Participants Fabrazyme 1.0 mg/kg was administered every 4 weeks (up to 66 infusions) 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.
Percent Change From Baseline in GL-3 Clearance From Urine Week 40 (n=15, 14)	-44.22 Percent change Standard Deviation 105.03	-63.87 Percent change Standard Deviation 24.41
Percent Change From Baseline in GL-3 Clearance From Urine Week 104 (n=14, 14)	-21.92 Percent change Standard Deviation 138.78	-56.39 Percent change Standard Deviation 42.39
Percent Change From Baseline in GL-3 Clearance From Urine Week 236 (n=13, 14)	-69.08 Percent change Standard Deviation 51.72	-40.09 Percent change Standard Deviation 77.04
Percent Change From Baseline in GL-3 Clearance From Urine Week 260 (n=13, 14)	-57.59 Percent change Standard Deviation 93.74	-28.27 Percent change Standard Deviation 56.79
Percent Change From Baseline in GL-3 Clearance From Urine Week 12 (n=15, 14)	-50.77 Percent change Standard Deviation 64.59	-63.39 Percent change Standard Deviation 38.81
Percent Change From Baseline in GL-3 Clearance From Urine Week 28 (n=15, 15)	-50.84 Percent change Standard Deviation 100.61	-52.55 Percent change Standard Deviation 58.59
Percent Change From Baseline in GL-3 Clearance From Urine Week 52 (n=15, 14)	-70.1 Percent change Standard Deviation 41.4	-20.72 Percent change Standard Deviation 156.1
Percent Change From Baseline in GL-3 Clearance From Urine Week 80 (n=14, 14)	-35.84 Percent change Standard Deviation 102.31	35.22 Percent change Standard Deviation 238.61
Percent Change From Baseline in GL-3 Clearance From Urine Week 132 (n=13, 14)	-48.79 Percent change Standard Deviation 100.1	-45.61 Percent change Standard Deviation 48.84
Percent Change From Baseline in GL-3 Clearance From Urine Week 156 (n=13, 14)	-65.57 Percent change Standard Deviation 52.11	-28.92 Percent change Standard Deviation 84.32
Percent Change From Baseline in GL-3 Clearance From Urine Week 184 (n=13, 14)	-76.54 Percent change Standard Deviation 38.93	-10.5 Percent change Standard Deviation 146.86
Percent Change From Baseline in GL-3 Clearance From Urine Week 208 (n=13, 14)	-60.94 Percent change Standard Deviation 67.99	-50.93 Percent change Standard Deviation 46.52

Adverse Events

Fabrazyme 0.5 mg/kg

Serious events: 6 serious events

Other events: 16 other events

Deaths: 0 deaths

Fabrazyme 1.0 mg/kg

Serious events: 5 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Fabrazyme 0.5 mg/kg n=16 participants at risk 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 n=15 participants at risk 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.
Gastrointestinal disorders GASTROINTESTINAL HAEMORRHAGE	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
General disorders MEDICAL DEVICE COMPLICATION	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
General disorders PYREXIA	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Infections and infestations CELLULITIS	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	0.00% 0/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Infections and infestations ERYSIPELAS	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Infections and infestations OTITIS MEDIA	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Infections and infestations PNEUMONIA	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Infections and infestations SEPSIS	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Infections and infestations TINEA PEDIS	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Injury, poisoning and procedural complications MULTIPLE INJURIES	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	0.00% 0/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Injury, poisoning and procedural complications OVERDOSE	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	0.00% 0/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Investigations BODY MASS INDEX DECREASED	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	0.00% 0/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Nervous system disorders PARAESTHESIA	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Nervous system disorders TREMOR	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Psychiatric disorders SUICIDAL IDEATION	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	0.00% 0/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Renal and urinary disorders MICROALBUMINURIA	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Respiratory, thoracic and mediastinal disorders COUGH	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Skin and subcutaneous tissue disorders DERMATITIS	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Surgical and medical procedures CENTRAL VENOUS CATHETERISATION	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	0.00% 0/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Surgical and medical procedures ELECTIVE SURGERY	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	0.00% 0/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
General disorders CHILLS	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	0.00% 0/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.

Other adverse events
Measure	Fabrazyme 0.5 mg/kg n=16 participants at risk 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 n=15 participants at risk 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.
Blood and lymphatic system disorders ANAEMIA	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Blood and lymphatic system disorders EOSINOPHILIA	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Blood and lymphatic system disorders LEUKOPENIA	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	13.3% 2/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Blood and lymphatic system disorders LYMPHADENOPATHY	12.5% 2/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	0.00% 0/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Blood and lymphatic system disorders MONOCYTOPENIA	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Cardiac disorders ARRHYTHMIA	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Cardiac disorders TACHYCARDIA	12.5% 2/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Ear and labyrinth disorders CONDUCTIVE DEAFNESS	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	13.3% 2/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Ear and labyrinth disorders DEAFNESS	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	0.00% 0/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Ear and labyrinth disorders DEAFNESS BILATERAL	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	0.00% 0/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Ear and labyrinth disorders DEAFNESS NEUROSENSORY	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	0.00% 0/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Ear and labyrinth disorders DEAFNESS UNILATERAL	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	13.3% 2/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Ear and labyrinth disorders MIDDLE EAR EFFUSION	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Ear and labyrinth disorders OTORRHOEA	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Ear and labyrinth disorders TINNITUS	18.8% 3/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	26.7% 4/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Ear and labyrinth disorders TYMPANIC MEMBRANE HYPERAEMIA	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	0.00% 0/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Endocrine disorders HYPERPARATHYROIDISM SECONDARY	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Eye disorders CONJUNCTIVAL HYPERAEMIA	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	13.3% 2/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Eye disorders CORNEAL DEPOSITS	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	0.00% 0/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Eye disorders DRY EYE	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	0.00% 0/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Eye disorders LACRIMATION INCREASED	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Eye disorders OCULAR VASCULAR DISORDER	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Eye disorders PHOTOPHOBIA	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	0.00% 0/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Eye disorders VISION BLURRED	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Eye disorders VISUAL ACUITY REDUCED	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	0.00% 0/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Gastrointestinal disorders ABDOMINAL PAIN	56.2% 9/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	40.0% 6/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Gastrointestinal disorders ABDOMINAL PAIN LOWER	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	0.00% 0/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Gastrointestinal disorders ABDOMINAL PAIN UPPER	25.0% 4/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	26.7% 4/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Gastrointestinal disorders CONSTIPATION	12.5% 2/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	0.00% 0/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Gastrointestinal disorders DENTAL CARIES	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Gastrointestinal disorders DIARRHOEA	62.5% 10/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	53.3% 8/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Gastrointestinal disorders EPIGASTRIC DISCOMFORT	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Gastrointestinal disorders FOOD POISONING	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	0.00% 0/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Gastrointestinal disorders FREQUENT BOWEL MOVEMENTS	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Gastrointestinal disorders GASTROINTESTINAL DISORDER	12.5% 2/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Gastrointestinal disorders NAUSEA	56.2% 9/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	46.7% 7/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Gastrointestinal disorders ORAL MUCOSAL ERYTHEMA	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Gastrointestinal disorders SALIVARY HYPERSECRETION	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Gastrointestinal disorders STOMATITIS	6.2% 1/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	0.00% 0/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.
Gastrointestinal disorders TOOTHACHE	0.00% 0/16 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.	6.7% 1/15 • 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. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the time from the first infusion of the study drug up to 28 days after the last infusion of study drug). Safety population included all randomized participants who received at least one infusion of Fabrazyme.