A Study of Patients With Fabry Disease (US Specific)

This is a prospective, multicenter, observational, effectiveness, safety, and outcomes study enrolling at least 450 patients with Fabry disease globally (at least 250 patients in the migalastat-treated group, approximately 100 patients in the ERT-treated group, and approximately 100 patients in the untreated group \[patients who have never been on treatment for Fabry disease\]). Enrollment will continue for a period of 5 years and all patients will be followed for up to 5 years after their enrollment.

Disclaimer: This is a global study, the country level requirements may vary from site to site. The requirements noted in this posting are specific to the US.

• migalastat HCl (Drug): Non-interventional study of participants receiving migalastat HCl 150 mg
• ERT (Drug): Non-interventional study of participants receiving enzyme replacement therapy

Primary outcomes

• Annualized rate of change in Estimated Glomerular Filtration Rate (eGFR) [Baseline and prospective up to 5 years]: Annualized rate of change in eGFR(CKD-EPI) over time from study enrollment for the comparison between migalastat-treated and untreated patients who have risk factors for eGFR decline

Secondary outcomes

• Time to the first Fabry-associated clinical event (FACE) [Baseline and prospective up to 5 years]: Time to first FACE, which are cardiac, cerebrovascular, and renal events, and death due to FACEs, from enrollment in the study to compare between migalastat-treated and untreated patients.
• Time to the first Fabry-associated clinical event (FACE) [Retrospective and prospective up to 5 years]: Time to first FACE, which are cardiac, cerebrovascular, and renal events, and death due to FACEs, from start of treatment to compare between migalastat-treated and ERT-treated patients.
• Annualized rate of change in Estimated Glomerular Filtration Rate (eGFR) [Retrospective and prospective up to 5 years]: Annualized rate of change in eGFR(CKD-EPI) from start of treatment over time for the comparison between migalastat-treated and ERT-treated patients
• Incidence and occurrence of FACE [Retrospective and prospective up to 5 years]: Incidence and occurrence of FACE will be evaluated overall, and separately by cardiac, cerebrovascular, and renal clinical events (including death in these categories)
• Changes in plasma lyso Gb3 [Retrospective and prospective up to 5 years]: Biomarker of disease
• Changes in WBC α-Gal A enzyme activity in males [Retrospective and prospective up to 5 years]: Biomarker of disease
• Brief Pain Inventory (BPI)-Short Form [Baseline and prospective up to 5 years]: A 12-question form using a 10-point scale to allow patients to rate the severity of their pain and the degree to which their pain interferes with common dimensions of feeling and function, along with a question about percentage of pain relief by analgesics
• FABPRO-GI Short Form-v2-stomach pain domain [Baseline and prospective up to 5 years]: Three questions regarding GI signs and symptoms over a 7-day recall period and a Bristol Stool Scale (BSS), providing a pictorial chart and descriptive text for 7 types of stools. Using a 10-point scale, patients will rate the severity of their worst occurrence of stomach pain and diarrhea from 0 (none) to 10 (worst possible). Frequency and consistency of diarrhea will be assessed, as patients will provide the number of stools they have each day of BSS Type 1 through BSS Type 7.
• FABPRO-GI Short Form-v2-diarrhea domain [Baseline and prospective up to 5 years]: Three questions regarding GI signs and symptoms over a 7-day recall period and a Bristol Stool Scale (BSS), providing a pictorial chart and descriptive text for 7 types of stools. Using a 10-point scale, patients will rate the severity of their worst occurrence of stomach pain and diarrhea from 0 (none) to 10 (worst possible). Frequency and consistency of diarrhea will be assessed, as patients will provide the number of stools they have each day of BSS Type 1 through BSS Type 7.
• Weekly number of stools of BSS Types 6 and 7 (frequency) [Baseline and prospective up to 5 years]
• Number of days per week with at least 1 stool of BSS Type 6 or 7 (consistency) [Baseline and prospective up to 5 years]
• HRQOL by using PROs and health preference measures utility (SF-12) [Baseline and prospective up to 5 years]: Patient-reported health-related quality of life (HRQOL) will be assessed using Short Form-12 (SF-12): An abridged practical version of the 36-item Short Form Health Survey (SF-36), which contains 8 subscales: physical functioning (2 items), role limitations due to physical problems (2 items), bodily pain (1 item), general health perceptions (1 item), vitality (1 item), social functioning (1 item), role limitations due to emotional problems (2 items), and mental health (2 items)
• HRQOL by using PROs and health preference measures utility (EQ-5D) [Baseline and prospective up to 5 years]: Patient-reported health-related quality of life (HRQOL) will be assessed using EuroQol-5D (EQ-5D), a preference-based HRQOL measure with 1 question for each of the 5 dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The EQ-5D questionnaire also includes a Visual Analog Scale, by which respondents can report their perceived health status with a grade ranging from 0 (the worst possible health status) to 100 (the best possible health status)
• HRQOL by using PROs and health preference measures utility (TSQM-9) [Baseline and prospective up to 5 years]: Patient-reported health-related quality of life (HRQOL) will be assessed using Treatment Satisfaction Questionnaire for Medications-9 (TSQM-9, migalastat-treated patients only): A generic measure of treatment satisfaction for medication which assesses patient perception of effectiveness, side effects, convenience, and global satisfaction
• Occurrence of SAEs [Baseline and prospective up to 5 years]
• Overall survival among all patients enrolled [Baseline and prospective up to 5 years]: Assessed by recorded patient deaths from any cause
• Number of participants with male infertility [Baseline and prospective up to 5 years]

Sex: All, ages: 18 Years to any

I. Migalastat-treated patients (Commercial only participants)

1. Patients with Fabry disease 18 years or older with amenable GLA variants who have commenced commercial migalastat treatment within 24 months preceding enrollment, who have an eGFR greater than or equal to 30 mL/min/1.73 m2 at the time of enrollment and are still taking migalastat at the time of enrollment, or who are starting migalastat at the time of enrollment, excluding those who participated in a prior migalastat clinical trial
2. Patients who show a decline in their Fabry disease symptomatology based on any of the following:

   1. a decrease in annualized rate of decline eGFRCKD-EPI of ≥ 2 mL/min/1.73 m2 during the 2 years prior to enrollment
   2. microalbuminuria/macroalbuminuria (≥ 30 mg/24 h or ≥ 20 mg on first morning urine) or urine ACR of ≥ 30 mg/g (via spot urine collection) at any time prior to or at enrollment
   3. proteinuria (> 0.5 g/g UPCR) any time prior to or at enrollment
   4. males with classic Fabry disease phenotype

II. Migalastat-treated patients who are not considered to be in renal decline (Commercial migalastat users only)

1\. Patients with Fabry disease with amenable GLA variants who have been on commercial migalastat regardless of the duration of treatment

III. Migalastat-treated patients (Prior clinical trial participants)

1. Patients with Fabry disease 18 years or older who had commenced treatment with migalastat while in a clinical trial and were exposed to treatment for at least 24 months preceding enrollment, who have an eGFR greater than or equal to 30 mL/min/1.73 m2 at the time of enrollment, and who are still taking migalastat at the time of enrollment, having switched to commercial product

IV. Untreated patients

1. Patients with Fabry disease 18 years or older with amenable GLA variants, who have never been on treatment for Fabry disease, who have an eGFR greater than or equal to 30 mL/min/1.73 m2 at the time of enrollment, and who meet local treatment guidelines for Fabry disease
2. Patients who show a decline in their Fabry disease symptomatology based on any of the following:

   1. a decrease in annualized rate of decline eGFRCKD-EPI of ≥ 2 mL/min/1.73 m2 during the 2 years prior to enrollment
   2. microalbuminuria/macroalbuminuria (≥ 30 mg/24 h or ≥ 20 mg on first morning urine) or urine ACR of ≥ 30 mg/g (via spot urine collection) at any time prior to or at enrollment
   3. proteinuria (> 0.5 g/g UPCR) any time prior to or at enrollment
   4. males with classic Fabry disease phenotype

V. ERT-treated patients

1. Patients with Fabry disease 18 years or older who have commenced ERT within 24 months preceding enrollment, who have an eGFR greater than or equal to 30 mL/min/1.73 m2 at the time of enrollment and are still being treated with ERT at the time of enrollment, and who have amenable GLA variants
2. Patients who show a decline in their Fabry disease symptomatology based on any of the following:

   1. a decrease in eGFRCKD-EPI annualized rate of decline of ≥ 2 mL/min/1.73 m2 during the 2 years prior to enrollment
   2. microalbuminuria/macroalbuminuria (≥ 30 mg/24 h or ≥ 20 mg on first morning urine) or urine ACR of ≥ 30 mg/g (via spot urine collection) at any time prior to or at enrollment
   3. proteinuria (> 0.5 g/g UPCR) any time prior to or at enrollment
   4. males with classic Fabry disease phenotype

All patients 1. All treated and untreated patients with Fabry disease who are enrolled in the study must be able to understand and provide written informed consent or assent.

Exclusion Criteria

1\. Patients who currently are participating in a clinical trial of any investigational medicinal product or device at the time of enrollment

• Clinical Research, Study director, Amicus Therapeutics