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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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 Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Fabry Disease
Intervention Biological: Fabrazyme (agalsidase beta)
Enrollment 21
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Fabrazyme
Hide 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
Arm/Group Title Fabrazyme
Hide 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
Hide 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
21
1.Primary Outcome
Title Globotriaosylceramide (GL-3) Clearance in Kidney Interstitial Capillary Endothelium
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
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
Hide 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   --/--   --/--   --/-- 
Show Serious Adverse Events Hide 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
Show Other (Not Including Serious) Adverse Events Hide 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
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
Name/Title: Genzyme MedInfo
Organization: Genzyme Corporation
Phone: 800-745-4447
Responsible Party: Medical Monitor, Genzyme Corporation
ClinicalTrials.gov Identifier: NCT00196716     History of Changes
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