Trial record 1 of 1 for: NCT00196716

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A Study of the Safety and Efficacy of Fabrazyme in Patients With Fabry Disease

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ClinicalTrials.gov Identifier: NCT00196716

Recruitment Status : Completed

First Posted : September 20, 2005

Results First Posted : April 2, 2009

Last Update Posted : April 3, 2015

Sponsor:

Information provided by:

Sanofi

Study Type	Interventional
Study Design	Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Fabry Disease
Intervention	Biological: Fabrazyme (agalsidase beta)
Enrollment	21

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Fabrazyme
Arm/Group Description	Open-label study. Patients received...
Arm/Group Description	Open-label study. Patients received 1.0 mg/kg Fabrazyme every two weeks for approximately six months followed by 0.3 mg/kg Fabrazyme every two weeks for approximately 18 months.
Period Title: 1.0 mg/kg Period
Started	21
Completed	21
Not Completed	0
Period Title: 0.3 mg/kg Period
Started	21
Completed	21
Not Completed	0

Baseline Characteristics

Arm/Group Title		Fabrazyme
Arm/Group Description		Open-label study. Patients received...
Arm/Group Description		Open-label study. Patients received 1.0 mg/kg Fabrazyme every two weeks for approximately six months followed by 0.3 mg/kg Fabrazyme every two weeks for approximately 18 months.
Overall Number of Baseline Participants		21
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	21 participants
		34.0 (10.0)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	21 participants
	Female	0 0.0%
	Male	21 100.0%
Race/Ethnicity, Customized Measure Type: Number Unit of measure: Participants
Caucasian	Number Analyzed	21 participants
Caucasian		21

Outcome Measures

1.Primary Outcome


Title	Globotriaosylceramide (GL-3) Clearance in Kidney Interstitial Capillary Endothelium
Description	Kidney biopsies were taken at Baseline, Week 24, and Week 96 and analy...
Description	Kidney biopsies were taken at Baseline, Week 24, and Week 96 and analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Each biopsy was evaluated by pathologists for the total number of vessels with GL-3 accumulation on an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe).
Time Frame	Throughout study; 96 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population. One patient switched back to 1.0 mg/kg Fabrazyme treatment at Week 76 and therefore assessments at Week 76 and thereafter for this patient were excluded from the analysis.


Arm/Group Title	Fabrazyme
Arm/Group Description:	Open-label study. Patients received...
Arm/Group Description:	Open-label study. Patients received 1.0 mg/kg Fabrazyme every two weeks for approximately six months followed by 0.3 mg/kg Fabrazyme every two weeks for approximately 18 months.
Overall Number of Participants Analyzed	21
Measure Type: Number Unit of Measure: Participants
Zero (0) Kidney GL-3 Score at Baseline	3
Zero (0) Kidney GL-3 Score at Week 24	21
Zero (0) Kidney GL-3 Score at Week 96	18
Mild (1) Kidney GL-3 Score at Baseline	17
Mild (1) Kidney GL-3 Score at Week 24	0
Mild (1) Kidney GL-3 Score at Week 96	2
Moderate (2) Kidney GL-3 Score at Baseline	1
Moderate (2) Kidney GL-3 Score at Week 24	0
Moderate (2) Kidney GL-3 Score at Week 96	0
Severe (3) Kidney GL-3 Score at Baseline	0
Severe (3) Kidney GL-3 Score at Week 24	0
Severe (3) Kidney GL-3 Score at Week 96	0

2.Secondary Outcome


Title	Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium
Description	Skin biopsies were taken at Baseline, Week 24, Week 48, Week 72, and W...
Description	Skin biopsies were taken at Baseline, Week 24, Week 48, Week 72, and Week 96 and analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Each biopsy was evaluated by pathologists for the total number of vessels with GL-3 accumulation on an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe).
Time Frame	Throughout study ; 96 weeks

Outcome Measure Data

Analysis Population Description

ITT Population. One patient switched back to 1.0 mg/kg Fabrazyme treatment at Week 76 and therefore assessments at Week 76 and thereafter for this patient were excluded from the analysis.


Arm/Group Title	Fabrazyme
Arm/Group Description:	Open-label study. Patients received...
Arm/Group Description:	Open-label study. Patients received 1.0 mg/kg Fabrazyme every two weeks for approximately six months followed by 0.3 mg/kg Fabrazyme every two weeks for approximately 18 months.
Overall Number of Participants Analyzed	21
Measure Type: Number Unit of Measure: Participants
Zero (0) Skin GL-3 Score at Baseline	5
Zero (0) Skin GL-3 Score at Week 24	20
Zero (0) Skin GL-3 Score at Week 48	15
Zero (0) Skin GL-3 Score at Week 72	17
Zero (0) Skin GL-3 Score at Week 96	16
Mild (1) Skin GL-3 Score at Baseline	1
Mild (1) Skin GL-3 Score at Week 24	1
Mild (1) Skin GL-3 Score at Week 48	4
Mild (1) Skin GL-3 Score at Week 72	3
Mild (1) Skin GL-3 Score at Week 96	2
Moderate (2) Skin GL-3 Score at Baseline	11
Moderate (2) Skin GL-3 Score at Week 24	0
Moderate (2) Skin GL-3 Score at Week 48	2
Moderate (2) Skin GL-3 Score at Week 72	1
Moderate (2) Skin GL-3 Score at Week 96	2
Severe (3) Skin GL-3 Score at Baseline	4
Severe (3) Skin GL-3 Score at Week 24	0
Severe (3) Skin GL-3 Score at Week 48	0
Severe (3) Skin GL-3 Score at Week 72	0
Severe (3) Skin GL-3 Score at Week 96	0

3.Secondary Outcome


Title	Estimated Glomerular Filtration Rate (eGFR)
Description	Evaluated at Baseline, Week 24 and Week 96. eGFR is an estimation of t...
Description	Evaluated at Baseline, Week 24 and Week 96. eGFR is an estimation of the glomerular filtration rate of the kidneys (how much blood the kidneys are filtering). For this study, normal eGFR was defined as greater than 90 mL/min/1.73 m2
Time Frame	Throughout study; 96 weeks

Outcome Measure Data

Analysis Population Description

ITT Population. One patient switched back to 1.0 mg/kg Fabrazyme treatment at Week 76 and therefore assessments at Week 76 and thereafter for this patient were excluded from the analysis.


Arm/Group Title	Fabrazyme
Arm/Group Description:	Open-label study. Patients received...
Arm/Group Description:	Open-label study. Patients received 1.0 mg/kg Fabrazyme every two weeks for approximately six months followed by 0.3 mg/kg Fabrazyme every two weeks for approximately 18 months.
Overall Number of Participants Analyzed	21
Mean (Standard Deviation) Unit of Measure: ml/min/1.73 m2
eGFR at Baseline	92.5 (21.12)
eGFR at Week 24	93.1 (24.10)
eGFR at Week 96	92.8 (27.42)

4.Secondary Outcome


Title	Plasma Globotriaosylceramide (GL-3)
Description	Evaluated at Baseline, Week 24, Week 48, Week 72 and Week 96. Plasma G...
Description	Evaluated at Baseline, Week 24, Week 48, Week 72 and Week 96. Plasma GL-3 is often elevated in the plasma of patients diagnosed with Fabry disease. This outcome measure evaluated the mean plasma GL-3 values for all patients to see if it decreased while on Fabrazyme. Normal plasma GL-3 level was <= 7.03 µg/mL.
Time Frame	Throughout study; 96 weeks

Outcome Measure Data

Analysis Population Description

ITT population. One patient switched back to 1.0 mg/kg Fabrazyme treatment at Week 76 and therefore assessments at Week 76 and thereafter for this patient were excluded from the analysis.


Arm/Group Title	Fabrazyme
Arm/Group Description:	Open-label study. Patients received...
Arm/Group Description:	Open-label study. Patients received 1.0 mg/kg Fabrazyme every two weeks for approximately six months followed by 0.3 mg/kg Fabrazyme every two weeks for approximately 18 months.
Overall Number of Participants Analyzed	21
Mean (Standard Deviation) Unit of Measure: μg/mL
Plasma GL-3 values at Baseline	12.24 (3.369)
Plasma GL-3 values at Week 24	5.18 (1.276)
Plasma GL-3 values at Week 48	5.50 (1.480)
Plasma GL-3 values at Week 72	5.64 (1.635)
Plasma GL-3 values at Week 96	6.53 (1.497)

5.Secondary Outcome


Title	Urine Globotriaosylceramide (GL-3)
Description	Evaluated at Baseline, Week 24 and Week 96. Urine GL-3 is often elevat...
Description	Evaluated at Baseline, Week 24 and Week 96. Urine GL-3 is often elevated in the urine of patients diagnosed with Fabry disease. This outcome measure evaluated the mean urine GL-3 in first morning void urine for all patients to see if it decreased while on Fabrazyme. Normal Urine GL-3 threshold was < 8.8 μg/mg.
Time Frame	Throughout study, 96 weeks

Outcome Measure Data

Analysis Population Description

ITT population. One patient switched back to 1.0 mg/kg Fabrazyme treatment at Week 76 and therefore assessments at Week 76 and thereafter for this patient were excluded from the analysis.


Arm/Group Title	Fabrazyme
Arm/Group Description:	Open-label study. Patients received...
Arm/Group Description:	Open-label study. Patients received 1.0 mg/kg Fabrazyme every two weeks for approximately six months followed by 0.3 mg/kg Fabrazyme every two weeks for approximately 18 months.
Overall Number of Participants Analyzed	21
Mean (Standard Deviation) Unit of Measure: μg/mg
Urine GL-3 values at Baseline	221.3 (152.0)
Urine GL-3 values at Week 24	109.2 (120.00)
Urine GL-3 values at Week 96	122.5 (181.06)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables.

Arm/Group Title	1.0 mg/kg Fabrazyme	0.3 mg/kg Fabrazyme	Total
Arm/Group Description	1.0 mg/kg Fabrazyme, Week 0 to Week...	0.3 mg/kg Fabrazyme, Week 24 to Wee...	Total of all reporting groups
Arm/Group Description	1.0 mg/kg Fabrazyme, Week 0 to Week 24.	0.3 mg/kg Fabrazyme, Week 24 to Week 96.	Total of all reporting groups
All-Cause Mortality
	1.0 mg/kg Fabrazyme	0.3 mg/kg Fabrazyme	Total
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events Serious Adverse Events
	1.0 mg/kg Fabrazyme	0.3 mg/kg Fabrazyme	Total
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/21 (0.00%)	4/21 (19.05%)	5/21 (23.81%)
Cardiac disorders
Atrioventricular block complete ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
General disorders
Asthenia ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Fatigue ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Metabolism and nutrition disorders
Dehydration ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Nervous system disorders
Cerebral ischaemia ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Dizziness ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Polyneuropathy ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Syncope ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Renal and urinary disorders
Renal failure ^† 1	0/21 (0.00%)	0/21 (0.00%)	1/21 (4.76%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 8.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	1.0 mg/kg Fabrazyme	0.3 mg/kg Fabrazyme	Total
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	9/21 (42.86%)	12/21 (57.14%)	14/21 (66.67%)
Blood and lymphatic system disorders
Eosinophilia ^† 1	0/21 (0.00%)	2/21 (9.52%)	2/21 (9.52%)
Cardiac disorders
Tachycardia ^† 1	2/21 (9.52%)	0/21 (0.00%)	2/21 (9.52%)
Ventricular hypertrophy ^† 1	0/21 (0.00%)	2/21 (9.52%)	2/21 (9.52%)
Ear and labyrinth disorders
Vertigo ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Eye disorders
Diplopia ^† 1	1/21 (4.76%)	0/21 (0.00%)	1/21 (4.76%)
Visual acuity reduced ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Gastrointestinal disorders
Aphthous stomatitis ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Diarrhoea ^† 1	0/21 (0.00%)	4/21 (19.05%)	4/21 (19.05%)
Food poisoning ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Nausea ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
General disorders
Asthenia ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Chills ^† 1	3/21 (14.29%)	1/21 (4.76%)	3/21 (14.29%)
Fatigue ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Feeling abnormal ^† 1	1/21 (4.76%)	0/21 (0.00%)	1/21 (4.76%)
Feeling cold ^† 1	1/21 (4.76%)	0/21 (0.00%)	1/21 (4.76%)
Feeling hot ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Oedema peripheral ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Pyrexia ^† 1	2/21 (9.52%)	1/21 (4.76%)	3/21 (14.29%)
Infections and infestations
Bronchitis acute ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Gastroenteritis ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Nasopharyngitis ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Obstructive chronic bronchitis with acute exacerbation ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Tracheobronchitis ^† 1	1/21 (4.76%)	0/21 (0.00%)	1/21 (4.76%)
Viral infection ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Injury, poisoning and procedural complications
Post procedural haematoma ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Investigations
Alanine aminotransferase increased ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Aspartate aminotransferase increased ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Blood bicarbonate decreased ^† 1	1/21 (4.76%)	0/21 (0.00%)	1/21 (4.76%)
Blood bilirubin increased ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Blood creatinine increased ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Creatinine urine decreased ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Protein total decreased ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Musculoskeletal and connective tissue disorders
Muscle spasms ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Pain in extremity ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Nervous system disorders
Dizziness ^† 1	1/21 (4.76%)	1/21 (4.76%)	2/21 (9.52%)
Epilepsy ^† 1	1/21 (4.76%)	1/21 (4.76%)	2/21 (9.52%)
Headache ^† 1	0/21 (0.00%)	2/21 (9.52%)	2/21 (9.52%)
Paraesthesia ^† 1	0/21 (0.00%)	3/21 (14.29%)	3/21 (14.29%)
Partial seizures ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Syncope ^† 1	1/21 (4.76%)	1/21 (4.76%)	1/21 (4.76%)
Psychiatric disorders
Depression ^† 1	0/21 (0.00%)	0/21 (0.00%)	1/21 (4.76%)
Sleep disorder ^† 1	1/21 (4.76%)	0/21 (0.00%)	1/21 (4.76%)
Renal and urinary disorders
Proteinuria ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Renal failure ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	0/21 (0.00%)	3/21 (14.29%)	3/21 (14.29%)
Dyspnoea ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Skin and subcutaneous tissue disorders
Acne ^† 1	0/21 (0.00%)	2/21 (9.52%)	2/21 (9.52%)
Angiokeratoma ^† 1	0/21 (0.00%)	3/21 (14.29%)	3/21 (14.29%)
Periorbital oedema ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Rash ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Urticaria ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Urticaria generalised ^† 1	1/21 (4.76%)	0/21 (0.00%)	1/21 (4.76%)
Vascular disorders
Diastolic hypertension ^† 1	1/21 (4.76%)	0/21 (0.00%)	1/21 (4.76%)
Flushing ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
Hypertension ^† 1	0/21 (0.00%)	0/21 (0.00%)	1/21 (4.76%)
Thrombophlebitis superficial ^† 1	0/21 (0.00%)	1/21 (4.76%)	1/21 (4.76%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 8.1

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

In multi-site studies, PI can publish after Genzyme publishes or 18 months after study completion. PI gives Genzyme a draft 60 days before publication. Genzyme can ask that confidential information be removed, and can defer publication another 60 days upon notifying PI that it will file a patent application on inventions contained in the draft.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Genzyme MedInfo
Organization:	Genzyme Corporation
Phone:	800-745-4447
EMail:	medinfo@genzyme.com

Layout table for additonal information

Responsible Party:	Medical Monitor, Genzyme Corporation
ClinicalTrials.gov Identifier:	NCT00196716
Other Study ID Numbers:	AGAL-017-01
First Submitted:	September 12, 2005
First Posted:	September 20, 2005
Results First Submitted:	December 5, 2008
Results First Posted:	April 2, 2009
Last Update Posted:	April 3, 2015

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