Clinical trial NCT06303466: Real World Evidence Study of Danish Fabry Patients
Official title: Real World Evidence Study of Danish Fabry Patients: a >20- Year Longitudinal Retrospective Analysis of Prospectively Collected Data.
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Fabry Disease
Keywords: Cardiovascular Diseases
Renal Disease
Cerebrovascular disease
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Amicus Therapeutics
name: Rigshospitalet, Denmark
First posted: 2024-03-12
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients having been assessed for Fabry Disease in Denmark

Brief 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.


Eligibility criteria: Inclusion Criteria:

* Genetically-verified Fabry disease
* Age above or equal to 18

Primary outcomes:
measure: Time to first individual FACE since confirmed diagnosis (Composite endpoint)
timeFrame: 10 years post baseline
measure: Time to first FACE after initiation of Migalastat treatment (Composite endpoint)
timeFrame: 5 years post baseline
Secondary outcomes:
measure: Time to first individual FACE since confirmed diagnosis (cardiac)
timeFrame: 10 years post baseline
measure: Time to first individual FACE after initiation of Migalastat treatment (cardiac)
timeFrame: 5 years post baseline
measure: Time to first individual FACE since confirmed diagnosis (renal)
timeFrame: 10 years post baseline
measure: Time to first individual FACE after initiation of Migalastat treatment (renal)
timeFrame: 5 years post baseline
measure: Time to first individual FACE after initiation of Migalastat treatment (cerebrovascular)
timeFrame: 5 years post baseline
measure: Time to first individual FACE since confirmed diagnosis (cerebrovascular)
timeFrame: 10 years post baseline
measure: Prevalence of FACE since confirmed diagnosis
timeFrame: 20 years post baseline
measure: Prevalence of FACE after initiation of Fabry-specific treatment
timeFrame: 5 years post baseline
measure: Incidence of FACE since confirmed diagnosis
timeFrame: 20 years post baseline
measure: Incidence of FACE after initiation of Fabry-specific treatment
timeFrame: 5 years post baseline
measure: Incidence of cardiac events since confirmed diagnosis
timeFrame: 20 years post baseline
measure: Incidence of renal events since confirmed diagnosis
timeFrame: 20 years post baseline
measure: Incidence of cerebrovascular events since confirmed diagnosis
timeFrame: 20 years post baseline
measure: Incidence of cardiac events after initiation of Fabry-specific treatment
timeFrame: 5 years post baseline
measure: Incidence of renal events after initiation of Fabry-specific treatment
timeFrame: 5 years post baseline
measure: Incidence of cerebrovascular events after initiation of Fabry-specific treatment
timeFrame: 5 years post baseline
measure: Annualized rate of change in eGFR by CKDEPI-formula since initiation of treatment
timeFrame: 20 years post baseline
measure: Annualized rate of change in eGFR by CKDEPI-formula after initiation of Fabry-specific treatment
timeFrame: 5 years post baseline
measure: Rapid renal progression of disease since confirmed diagnosis
timeFrame: 20 years post baseline
measure: Rapid renal progression of disease after initiation of Fabry-specific treatment
timeFrame: 5 years post baseline
measure: Incidence of albuminuria since confirmed diagnosis
timeFrame: 20 years post baseline
measure: Incidence of albuminuria after initiation of Fabry-specific treatment
timeFrame: 5 years post baseline
measure: Prevalence of albuminuria since confirmed diagnosis
timeFrame: 20 years post baseline
measure: Prevalence of albuminuria after initiation of Fabry-specific treatment
timeFrame: 5 years post baseline
Other outcomes:
measure: Organ-specific decline
timeFrame: 20 years post baseline
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
Study officials:
affiliation: Rigshospitalet, Denmark
name: Caroline M Kistorp, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: