Fabry Disease
Conditions
Brief summary
The objective of the study is to document long term data on treatment with Migalastat under real world conditions. The selection of patients is based on the SmPC/Fachinformation. The study duration/patient will be 2 years.
Detailed description
Phase 3 data should be confirmed in this study with long-term data. * LVMI is expected to remain stable or to be ameliorated over an average of 24 months treatment duration. The LVMI reduction observed in patients followed up to 24 months is expected to be significantly reduced with a mean change of -6.6 g/m2 (-11.0, -2.1, 95% CI). * eGFR \[CKD-EPI\] is expected to remain stable over an average of 24 months treatment duration. The long-term effect of Migalastat on eGFR is expected to be comparable to the decline over time in healthy adults. The annualized rate of change over this period is expected to be ≤1 mL/min/1.73 m2 in females and ≤3 mL/min/1.73 m2 in males. * Significant reduction is expected in plasma lyso-Gb3 concentration at month 6, month 12 and month 24 following treatment with Migalastat. * ERT-naïve patients treated with Migalastat are expected to show an improvement of GI symptoms (diarrhea) over 24 months. * No progression of White Matter Lesions (WML) during treatment duration is expected. * No higher frequency of stroke/transient cerebral ischemia during treatment duration is expected. * Severity of neuropathic pain is expected to remain stable or to improve during treatment duration. * Dosing/amount of symptomatic medications of neuropathic symptoms is expected to decrease during treatment duration.
Interventions
None listed
Sponsors
Amicus Therapeutics
University Hospital Muenster
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
16 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Males and females, 16 to 74 years, diagnosed with Fabry disease. * Amenable GLA mutation. * Treatment with Migalastat (initiation of therapy according to recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease: the European Fabry Working Group consensus document. Biegstraaten et al, Orphanet J Rare Dis. 2015;10:36. AWMF-Leitlinien Morbus Fabry, Diagnose und Therapie, Registernummer 030-134). The following Inclusion criteria refer to the time of Migalastat initiation (T0): * ERT naïve (patients with signs of organ involvement (kidney, heart and/or CNS signs) to be considered for ERT following the European Consensus Guidelines on ERT (Biegstraaten et al 2015) or patients with neuropathic pain not controlled with pain medication or patients with GI symptoms not relieved with standard medication or ERT switch patients (under ERT for ≥12 months). * Estimated GFR (eGFR, CKD-EPI formula) at screening ≥30 ml/min/1.73 m2 * Subjects taking no ACE inhibitors, ARBs, or renin inhibitors or are on a stable dose for at least 4 weeks before screening. * Subjects taking no analgesics/antidepressants or are on a stable dose for at least 4 weeks before screening.
Exclusion criteria
* Patient has a non-amenable GLA mutation or the mutation A143T or D313Y (for verification of amenable mutations please refer to: www.GalafoldAmenablityTable.com or to the Fachinformation). * Patient is unwilling to give informed consent. * Patient is unable to comply with the clinical protocol. * Patients on co-medication: Galafold plus Enzyme Replacement Therapy (ERT) * Pregnant or breast feeding women. The following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| LVMI | two years | Primary endpoint of the observational study is the change in left ventricular mass index (LVMI) over two years. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neuropathic Pain (NPSI) | 24 months | Change in severity of neuropathic pain measured by Neuropathic Pain Symptom Inventory (NPSI) Score (items are quantified on a (0-10) numerical scale). |
| Neuropathic Pain (GCPS) | 24 months | Change in severity of neuropathic pain measured by Graded Chronic Pain Scale (GCPS) |
| GFR | 24 months | Change in GFR over 24 months |
| Cerebral ischemia or stroke. | 24 months | Incidence of transient/manifest cerebral ischemia or stroke over 24 months. |
| Fabry Disease Severity (DS3) | 24 months | Change in disease severity measured by the Disease Severity Scoring System (DS3) |
| Fabry Disease Severity (MSSI) | 24 months | Change in disease severity measured by Mainz Severity Score Index (MSSI) |
| White Matter Lesion load | 24 months | Change of White Matter Lesion load (quantified by WML volumetry \[ml\]). |
| Cerebral microbleeds/hemorrhagic lesions. | 24 months | Stabilization of cerebral microbleeds/hemorrhagic lesions. |
| Gastrointestinal symptoms | 24 months | Change in gastrointestinal symptoms (gastrointestinal symptoms rating scale, GSRS). |
| Quality of life (SF-36) | 24 months | Change in quality of life (Short Form (SF-36) Health Survey: 36-item, patient-reported survey of patient health). |
| Lyso-Gb3 | 24 months | Change in Lyso-Gb3 |
Countries
Germany
Outcome results
None listed