Real World Evidence Study of Danish Fabry Patients

Fabry Disease Clinical Trial

— RWE-FABRY  

Official title:

Real World Evidence Study of Danish Fabry Patients: a >20- Year Longitudinal Retrospective Analysis of Prospectively Collected Data.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06303466
• Other study ID #: R-23053109
• Status: Active, not recruiting
• Start date: August 1, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: March 2024
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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:

• To investigate time to first Fabry associated clinical events (FACE) (cardiac, renal, and cerebrovascular) with particular focus on Migalastat clinical outcomes and treatment outcomes preceding Migalastat therapy.

• To investigate the incidence and prevalence of FACEs with respect to Fabry specific treatment, Migalastat, ERT or no treatment.

• To describe FACEs in accordance with different geno- and phenotypic groups.

• To investigate the incidence and time to a first fatal or non-fatal cardiac, renal, and cerebrovascular clinical event, separated by each category.

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

• To investigate the incidence and prevalence of FACEs with respect to Fabry specific treatment, Migalastat, ERT or no treatment.

• To describe FACEs in accordance with different geno- and phenotypic groups To investigate the incidence and time to a first fatal or non-fatal cardiac, renal and cerebrovascular clinical event, separated by each category.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 115
• Est. completion date: December 31, 2024
• Est. primary completion date: August 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Genetically-verified Fabry disease

• Age above or equal to 18

Related Conditions & MeSH terms

• Fabry Disease

Locations

Country	Name	City	State
Denmark	Rigshospitalet	Copenhagen

Sponsors (3)

Lead Sponsor	Collaborator
Caroline Michaela Kistorp	Amicus Therapeutics, Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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
Primary	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
Secondary	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
Secondary	Time to first individual FACE after initiation of Migalastat treatment (cardiac)	Time to first individual FACE (cardiac) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy.	5 years post baseline
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Prevalence of FACE since confirmed diagnosis	The prevalence of FACEs since confirmed diagnosis	20 years post baseline
Secondary	Prevalence of FACE after initiation of Fabry-specific treatment	The prevalence of FACEs after initiation of Fabry-specific treatment	5 years post baseline
Secondary	Incidence of FACE since confirmed diagnosis	The incidence of FACEs since confirmed diagnosis	20 years post baseline
Secondary	Incidence of FACE after initiation of Fabry-specific treatment	The incidence of FACEs after initiation of Fabry-specific treatment	5 years post baseline
Secondary	Incidence of cardiac events since confirmed diagnosis	Incidence of cardiac, cerebrovascular, and renal clinical events separately by each specific category	20 years post baseline
Secondary	Incidence of renal events since confirmed diagnosis	Incidence of cardiac, cerebrovascular, and renal clinical events separately by each specific category	20 years post baseline
Secondary	Incidence of cerebrovascular events since confirmed diagnosis	Incidence of cardiac, cerebrovascular, and renal clinical events separately by each specific category	20 years post baseline
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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