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| Name | Class |
|---|---|
| Amicus Therapeutics | INDUSTRY |
| Rigshospitalet, Denmark | OTHER |
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Fabry is a rare X-linked metabolic lysosomal disorder caused by deficiency in the enzyme α-galactosidase A (alpha-Gal A) by mutations in the GLA gene, encoding the alpha-Gal A enzyme, which catalyses glycosphingolipids, namely globotriaosylceramide (Gb3). Reduced or absent alpha-Gal A activity leads to accumulation of Gb3 in various organs as well as cellular dysfunction and inflammation causing phsyical symptoms and eventual organ failure. Treatment has been available since 2001 for Fabry patients - first enzyme replacement therapy and since 2016, an oral chaperone therapy, Migalastat. Although the initial trials of Migalastat had some both short and extended outcome treatment comparisons, the overall evidence of clinical efficacy is based on too small numbers considering the heterogeneity of the Fabry patient population as well as the very slow progression of the disease. Though the body of real-world evidence is growing, there is a need for more publications of real-world long-term data on clinical outcomes with a focus on treatment with Migalastat.
Research Question:
Is the incidence and prevalence of Fabry associated clinical events (FACEs) (cardiac, renal, and cerebrovascular) associated with sex, genotype, phenotype at time of diagnosis, biomarkers, and Fabry specific therapy?
Objectives:
Primary outcomes - Time to first FACE (cardiac, renal, and cerebrovascular) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy.
Secondary outcomes
Exploratory outcomes
- To describe disease progression with focus on organ involvement.
The study design is a retrospective clinical and paraclinical follow-up of the Danish National Fabry cohort in the period 01.01.2001-31.12.2022. Patient followed a structured yearly monitoring program as part of routine clincal care.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Danish Fabry Patients | Patients with a genetically-verified diagnosis of Fabry Disease. |
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| Measure | Description | Time Frame |
|---|---|---|
| Time to first individual FACE since confirmed diagnosis (Composite endpoint) | Time to first FACE (cardiac, renal, and cerebrovascular) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy. | 10 years post baseline |
| Time to first FACE after initiation of Migalastat treatment (Composite endpoint) | Time to first FACE (cardiac, renal, and cerebrovascular) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy. | 5 years post baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Time to first individual FACE since confirmed diagnosis (cardiac) | Time to first individual FACE (cardiac) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy. | 10 years post baseline |
| Time to first individual FACE after initiation of Migalastat treatment (cardiac) |
| Measure | Description | Time Frame |
|---|---|---|
| Organ-specific decline | Reflecting the montoring program of the annual clinical examinations and questionnaires of the Danish Fabry patients, the study will evaluate the organ-specific change prior to and after initiation of Fabry-specific treatment. | 20 years post baseline |
Inclusion Criteria:
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All patients having been assessed for Fabry Disease in Denmark
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| Name | Affiliation | Role |
|---|---|---|
| Caroline M Kistorp, MD, Ph.D | Rigshospitalet, Denmark | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rigshospitalet | Copenhagen | 2100 | Denmark |
Due to national legistlative restrictions, unrestricted access to individual participant data is not possible. However, data exchange will be possible upon reasonable request under the assurance of data-management in accordance with Danish law.
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 30, 2023 | Feb 21, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 13, 2023 | Jan 12, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000795 | Fabry Disease |
| D002318 | Cardiovascular Diseases |
| D007674 | Kidney Diseases |
| D002561 | Cerebrovascular Disorders |
| ID | Term |
|---|---|
| D013106 | Sphingolipidoses |
| D020140 | Lysosomal Storage Diseases, Nervous System |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
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Blood and urine samples collected over the last 20+ years as part of routine monitoring of patients with Fabry Disease by the Danish National Fabry Center at Rigshospitalet, Copenhagen University Hospital, Denmark.
Time to first individual FACE (cardiac) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy. |
| 5 years post baseline |
| Time to first individual FACE since confirmed diagnosis (renal) | Time to first individual FACE (renal) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy. | 10 years post baseline |
| Time to first individual FACE after initiation of Migalastat treatment (renal) | Time to first individual FACE (renal) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy. | 5 years post baseline |
| Time to first individual FACE after initiation of Migalastat treatment (cerebrovascular) | Time to first individual FACE (cerebrovascular) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy. | 5 years post baseline |
| Time to first individual FACE since confirmed diagnosis (cerebrovascular) | Time to first individual FACE (cerebrovascular) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy. | 10 years post baseline |
| Prevalence of FACE since confirmed diagnosis | The prevalence of FACEs since confirmed diagnosis | 20 years post baseline |
| Prevalence of FACE after initiation of Fabry-specific treatment | The prevalence of FACEs after initiation of Fabry-specific treatment | 5 years post baseline |
| Incidence of FACE since confirmed diagnosis | The incidence of FACEs since confirmed diagnosis | 20 years post baseline |
| Incidence of FACE after initiation of Fabry-specific treatment | The incidence of FACEs after initiation of Fabry-specific treatment | 5 years post baseline |
| Incidence of cardiac events since confirmed diagnosis | Incidence of cardiac, cerebrovascular, and renal clinical events separately by each specific category | 20 years post baseline |
| Incidence of renal events since confirmed diagnosis | Incidence of cardiac, cerebrovascular, and renal clinical events separately by each specific category | 20 years post baseline |
| Incidence of cerebrovascular events since confirmed diagnosis | Incidence of cardiac, cerebrovascular, and renal clinical events separately by each specific category | 20 years post baseline |
| Incidence of cardiac events after initiation of Fabry-specific treatment | Incidence of cardiac, cerebrovascular, and renal clinical events separately by each specific category | 5 years post baseline |
| Incidence of renal events after initiation of Fabry-specific treatment | Incidence of cardiac, cerebrovascular, and renal clinical events separately by each specific category | 5 years post baseline |
| Incidence of cerebrovascular events after initiation of Fabry-specific treatment | Incidence of cardiac, cerebrovascular, and renal clinical events separately by each specific category | 5 years post baseline |
| Annualized rate of change in eGFR by CKDEPI-formula since initiation of treatment | Annualized rate of change in eGFR based on the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI) over time to compare between Migalastat-treated, ERT, and untreated patients | 20 years post baseline |
| Annualized rate of change in eGFR by CKDEPI-formula after initiation of Fabry-specific treatment | Annualized rate of change in eGFR based on the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI) over time to compare between Migalastat-treated, ERT, and untreated patients | 5 years post baseline |
| Rapid renal progression of disease since confirmed diagnosis | Prevalence of clinically significant change in mGFR or eGFR defined as rapid progression (Using the KDIGO guidelines ie. sustained decline in GFR by 5 mL/min/1.73 m2/yr) since confirmed diagnosis. | 20 years post baseline |
| Rapid renal progression of disease after initiation of Fabry-specific treatment | Prevalence of clinically significant change in mGFR or eGFR defined as rapid progression (Using the KDIGO guidelines ie. sustained decline in GFR by 5 mL/min/1.73 m2/yr) after initiation for Fabry-specific treatment. | 5 years post baseline |
| Incidence of albuminuria since confirmed diagnosis | The incidence of albuminuria; defined as micro (> 30 mg/g creatinine) or macroalbuminuria (>300) by urinary albumin/creatinine ratio (ACR) or urinary 24 h protein excretion. | 20 years post baseline |
| Incidence of albuminuria after initiation of Fabry-specific treatment | The incidence of albuminuria; defined as micro (> 30 mg/g creatinine) or macroalbuminuria (>300) by urinary albumin/creatinine ratio (ACR) or urinary 24 h protein excretion. | 5 years post baseline |
| Prevalence of albuminuria since confirmed diagnosis | The prevalence of albuminuria; defined as micro (> 30 mg/g creatinine) or macroalbuminuria (>300) by urinary albumin/creatinine ratio (ACR) or urinary 24 h protein excretion. | 20 years post baseline |
| Prevalence of albuminuria after initiation of Fabry-specific treatment | The prevalence of albuminuria; defined as micro (> 30 mg/g creatinine) or macroalbuminuria (>300) by urinary albumin/creatinine ratio (ACR) or urinary 24 h protein excretion. | 5 years post baseline |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D059345 | Cerebral Small Vessel Diseases |
| D014652 | Vascular 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 |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |