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

Study Overview
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Brief Summary
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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. Fabrazyme (agalsidase beta) is a drug that helps to break down and removes certain types of fatty substances called glycolipids. These glycolipids are normally present within the body in most cells. In Fabry disease, glycolipids build up in various tissues such as the liver, kidney, skin, and blood vessels because a-galactosidase A is not present, or is present in small quantities. The build up of glycolipid (globatriaosylceramide or GL-3) levels in these tissues in particular is thought to cause the clinical symptoms that are common to Fabry disease. This study analyzed the safety and efficacy of Fabrazyme in the treatment of patients with Fabry disease that previously participated in the AGAL-008-00 (NCT0074984) study.

Official Title
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Multi-Center, Open-Label Study of the Safety and Efficacy of Fabrazyme in Patients With Fabry Disease That Previously Participated in the AGAL-008-00 Study

Conditions
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Fabry Disease

Intervention / Treatment
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* Biological: agalsidase beta


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have successfully completed the previous double-blind study AGAL-008-00 (NCT00074984) Patients must provide written informed consent prior to study participation Female patients of childbearing potential must have a negative pregnancy test prior to each dosing and all female patients must use a medically accepted form of contraception throughout the study Exclusion Criteria: The patient was unable to complete AGAL-008-00 (NCT00074984) The patient has undergone kidney transplantation or is currently on dialysis The patient has diabetes mellitus or presence of confounding renal disease The patient has a clinically significant organic disease or an unstable condition that precludes participation The patient is unwilling to comply with the protocol requirements

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fabrazyme 1.0 mg/kg every 2 weeks<br>This is an open-label extension study to AGAL-008-00 (NCT00074984) and all patients received Fabrazyme treatment. | Biological: agalsidase beta<br>* 1.0 mg/kg every 2 weeks<br>* Other names: r-hαGAL;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in Inverse Serum Creatinine Within Patients' Slopes Between the Placebo AGAL-008-00 (NCT00074984) and Fabrazyme AGAL02503 (NCT00081497) Periods | The primary efficacy analysis was the summary of change in slope of inverse serum creatinine for Placebo/Fabrazyme patients in the Intent to Treat (ITT) Population. It compared the placebo period slope with the Fabrazyme period slope. | Placebo period AGAL-008-00 (up to 35 months) through Fabrazyme period AGAL02503 (18 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Creatinine at Pre-Fabrazyme and 6, 12, and 18 Months | Pre-Fabrazyme=baseline visit of AGAL-008-00 (NCT00074984) for Fabrazyme patients; assessment prior to open-label for placebo patients who transitioned to Fabrazyme in AGAL-008-00 (NCT00074984); assessment prior to first Fabrazyme infusion in AGAL02503 (NCT00081497) for placebo patients who did not transition to Fabrazyme in AGAL-008-00 (NCT00074984). | Pre-Fabrazyme, 6, 12, and 18 months | 
| Estimated Glomerular Filtration Rate (eGFR) at Pre-Fabrazyme and 6, 12, and 18 Months | Pre-Fabrazyme=baseline visit of AGAL-00-800 (NCT00074984) for Fabrazyme patients; assessment prior to open-label for placebo patients who transitioned to Fabrazyme in AGAL-008-00 (NCT00074984); assessment prior to first Fabrazyme infusion in AGAL02503 (NCT00081497) for placebo patients who did not transition to Fabrazyme in AGAL-008-00 (NCT00074984). | Pre-Fabrazyme, 6, 12, and 18 months | 
| Plasma Globotriaosylceramide (GL-3) (Normal Plasma GL-3 Level is ≤ 7.03 µg/mL) at Pre-Fabrazyme and 6, 12, and 18 Months | Pre-Fabrazyme=baseline visit of AGAL00800 for Fabrazyme patients; assessment prior to open-label for placebo patients who transitioned to Fabrazyme in AGAL00800; assessment prior to first Fabrazyme infusion in AGAL02503 for placebo patients who did not transition to Fabrazyme in AGAL00800. | Pre-Fabrazyme and 6, 12, and 18 months | 
| Proteinuria at Pre-Fabrazyme and 6, 12, and 18 Months | Pre-Fabrazyme=baseline visit of AGAL-008-00 (NCT00074984) for Fabrazyme patients; assessment prior to open-label for placebo patients who transitioned to Fabrazyme in AGAL-008-00 (NCT00074984); assessment prior to first Fabrazyme infusion in AGAL02503 (NCT00081497) for placebo patients who did not transition to Fabrazyme in AGAL-008-00 (NCT00074984). | Pre-Fabrazyme and 6, 12, and 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alpha-galactosidase A, a-GAL, r-haGAL, Fabry, GL-3, Fabrazyme