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People with Fabry disease have an alteration in their genetic material (DNA) which causes a deficiency of the alpha-galactosidase A enzyme. This enzyme helps to break down and remove certain types of fatty substances called "glycolipids." These glycolipids are normally present within the body in most cells. In people with Fabry disease, glycolipids build up in various tissues such as the liver, kidney, skin, and blood vessels because alpha-galactosidase A is not present, or is present in small quantities. The build up of glycolipid levels (also referred to as "globotriaosylceramide" or "GL-3") in these tissues is thought to cause the clinical symptoms that are common to Fabry disease. Symptoms commonly appear during childhood with pain in the hands and feet. This trial is designed to evaluate the efficacy of a lower dose of Fabrazyme in patients who initially received 1.0 mg/kg every 2 weeks of Fabrazyme by investigating if the achieved clearance of glycosphingolipid deposits in the vascular endothelium of the kidney can be maintained at a lower dose.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fabrazyme | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fabrazyme (agalsidase beta) | Biological | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Globotriaosylceramide (GL-3) Clearance in Kidney Interstitial Capillary Endothelium | 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). | Throughout study; 96 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium | 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Genzyme, a Sanofi Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| II. interní klinika 1. LF UK | Prague | 128 02 | Czechia | |||
| Tartu University Clinics, Department of Internal Medicine |
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| ID | Title | Description |
|---|---|---|
| FG000 | Fabrazyme | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1.0 mg/kg Period |
| |||||||||||||
| 0.3 mg/kg Period |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Fabrazyme | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Globotriaosylceramide (GL-3) Clearance in Kidney Interstitial Capillary Endothelium | 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). | 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. | Posted | Number | Participants | Throughout study; 96 weeks |
|
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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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 1.0 mg/kg Fabrazyme | 1.0 mg/kg Fabrazyme, Week 0 to Week 24. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrioventricular block complete | Cardiac disorders | MedDRA 8.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Eosinophilia | Blood and lymphatic system disorders | MedDRA 8.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Genzyme MedInfo | Genzyme Corporation | 800-745-4447 | medinfo@genzyme.com |
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| ID | Term |
|---|---|
| D000795 | Fabry Disease |
| ID | Term |
|---|---|
| D013106 | Sphingolipidoses |
| D020140 | Lysosomal Storage Diseases, Nervous System |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
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| ID | Term |
|---|---|
| C459420 | agalsidase beta |
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|
| Throughout study ; 96 weeks |
| Estimated Glomerular Filtration Rate (eGFR) | 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 | Throughout study; 96 weeks |
| Plasma Globotriaosylceramide (GL-3) | 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. | Throughout study; 96 weeks |
| Urine Globotriaosylceramide (GL-3) | 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. | Throughout study, 96 weeks |
| Tartu |
| 51014 |
| Estonia |
| Klinika Chorob Metabolicznych, Instytut "Pomnik-Centrum Zdrowia Dziecka" | Warsaw | 04-736 | Poland |
| Detská fakultná nemocnica Kramáre I. Interná klinika | Bratislava | 833 40 | Slovakia |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | Participants |
|
|
|
| Secondary | Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium | 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). | 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. | Posted | Number | Participants | Throughout study ; 96 weeks |
|
|
|
| Secondary | Estimated Glomerular Filtration Rate (eGFR) | 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 | 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. | Posted | Mean | Standard Deviation | ml/min/1.73 m2 | Throughout study; 96 weeks |
|
|
|
| Secondary | Plasma Globotriaosylceramide (GL-3) | 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. | 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. | Posted | Mean | Standard Deviation | μg/mL | Throughout study; 96 weeks |
|
|
|
| Secondary | Urine Globotriaosylceramide (GL-3) | 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. | 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. | Posted | Mean | Standard Deviation | μg/mg | Throughout study, 96 weeks |
|
|
|
| 0 |
| 21 |
| 9 |
| 21 |
| EG001 | 0.3 mg/kg Fabrazyme | 0.3 mg/kg Fabrazyme, Week 24 to Week 96. | 4 | 21 | 12 | 21 |
| EG002 | Total | 5 | 21 | 14 | 21 |
| Asthenia | General disorders | MedDRA 8.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 8.1 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 8.1 | Systematic Assessment |
|
| Cerebral ischaemia | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Polyneuropathy | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA 8.1 | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA 8.1 | Systematic Assessment |
|
| Ventricular hypertrophy | Cardiac disorders | MedDRA 8.1 | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA 8.1 | Systematic Assessment |
|
| Diplopia | Eye disorders | MedDRA 8.1 | Systematic Assessment |
|
| Visual acuity reduced | Eye disorders | MedDRA 8.1 | Systematic Assessment |
|
| Aphthous stomatitis | Gastrointestinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Food poisoning | Gastrointestinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 8.1 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 8.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 8.1 | Systematic Assessment |
|
| Feeling abnormal | General disorders | MedDRA 8.1 | Systematic Assessment |
|
| Feeling cold | General disorders | MedDRA 8.1 | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA 8.1 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 8.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 8.1 | Systematic Assessment |
|
| Bronchitis acute | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Obstructive chronic bronchitis with acute exacerbation | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Tracheobronchitis | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Post procedural haematoma | Injury, poisoning and procedural complications | MedDRA 8.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 8.1 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 8.1 | Systematic Assessment |
|
| Blood bicarbonate decreased | Investigations | MedDRA 8.1 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 8.1 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 8.1 | Systematic Assessment |
|
| Creatinine urine decreased | Investigations | MedDRA 8.1 | Systematic Assessment |
|
| Protein total decreased | Investigations | MedDRA 8.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 8.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 8.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Epilepsy | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Partial seizures | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 8.1 | Systematic Assessment |
|
| Sleep disorder | Psychiatric disorders | MedDRA 8.1 | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA 8.1 | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA 8.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA 8.1 | Systematic Assessment |
|
| Angiokeratoma | Skin and subcutaneous tissue disorders | MedDRA 8.1 | Systematic Assessment |
|
| Periorbital oedema | Skin and subcutaneous tissue disorders | MedDRA 8.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 8.1 | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 8.1 | Systematic Assessment |
|
| Urticaria generalised | Skin and subcutaneous tissue disorders | MedDRA 8.1 | Systematic Assessment |
|
| Diastolic hypertension | Vascular disorders | MedDRA 8.1 | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA 8.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 8.1 | Systematic Assessment |
|
| Thrombophlebitis superficial | Vascular disorders | MedDRA 8.1 | Systematic Assessment |
|
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.
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D059345 | Cerebral Small Vessel Diseases |
| D002561 | Cerebrovascular Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008661 | Metabolism, Inborn Errors |
| D008064 | Lipidoses |
| D008052 | Lipid Metabolism, Inborn Errors |
| D016464 | Lysosomal Storage Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D052439 | Lipid Metabolism Disorders |
| Title | Measurements |
|---|---|
|
| Zero (0) Skin GL-3 Score at Week 72 |
|
| Zero (0) Skin GL-3 Score at Week 96 |
|
| Mild (1) Skin GL-3 Score at Baseline |
|
| Mild (1) Skin GL-3 Score at Week 24 |
|
| Mild (1) Skin GL-3 Score at Week 48 |
|
| Mild (1) Skin GL-3 Score at Week 72 |
|
| Mild (1) Skin GL-3 Score at Week 96 |
|
| Moderate (2) Skin GL-3 Score at Baseline |
|
| Moderate (2) Skin GL-3 Score at Week 24 |
|
| Moderate (2) Skin GL-3 Score at Week 48 |
|
| Moderate (2) Skin GL-3 Score at Week 72 |
|
| Moderate (2) Skin GL-3 Score at Week 96 |
|
| Severe (3) Skin GL-3 Score at Baseline |
|
| Severe (3) Skin GL-3 Score at Week 24 |
|
| Severe (3) Skin GL-3 Score at Week 48 |
|
| Severe (3) Skin GL-3 Score at Week 72 |
|
| Severe (3) Skin GL-3 Score at Week 96 |
|
| Title | Measurements |
|---|---|
|
|
| Plasma GL-3 values at Week 72 |
|
| Plasma GL-3 values at Week 96 |
|
|