Real World Evidence Study of Danish Fabry Patients

NCT06303466 | Active Not Recruiting DMC

• 1 other identifier: R-23053109
• Study Type: observational
• Target: 115
• Locations: 1 country
• Sites: 1

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.

Conditions

Fabry Disease

Keywords

Cardiovascular Diseases; Renal Disease; Cerebrovascular disease

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (24)

• Time to first individual FACE since confirmed diagnosis (cardiac)

  10 years post baseline

• Time to first individual FACE after initiation of Migalastat treatment (cardiac)

  5 years post baseline

• Time to first individual FACE since confirmed diagnosis (renal)

  10 years post baseline

• Time to first individual FACE after initiation of Migalastat treatment (renal)

  5 years post baseline

• Time to first individual FACE after initiation of Migalastat treatment (cerebrovascular)

  5 years post baseline

Other Outcomes (1)

• Organ-specific decline

  20 years post baseline

Study Arms (1)

Danish Fabry Patients

Patients with a genetically-verified diagnosis of Fabry Disease.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients having been assessed for Fabry Disease in Denmark

You may qualify if:

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

Sponsors & Collaborators

• Caroline Michaela Kistorp: lead
• Amicus Therapeutics: collaborator
• Rigshospitalet, Denmark: collaborator

Study Sites (1)

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Biospecimen

Retention: SAMPLES WITH DNA

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.

MeSH Terms

Conditions

Fabry Disease; Cardiovascular Diseases; Kidney Diseases; Cerebrovascular Disorders

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Vascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Caroline M Kistorp, MD, Ph.D

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 14, 2024
• First Posted: March 12, 2024
• Study Start: August 1, 2023
• Primary Completion: August 1, 2024
• Study Completion: December 31, 2024
• Last Updated: March 12, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)