German Observational Multicenter Study of Patients With Fabry Disease Under Chaperone Therapy With Migalastat-HCl.

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.

Study Overview

• Status: Completed
• Conditions: Fabry Disease

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.

• Study Type: Observational
• Enrollment (Actual): 75

Contacts and Locations

Study Locations

• Germany
  • Münster, Germany, 48149
    • Universtiy Hospital Münster

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 74 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

At therapy initiation adult male and female patients with FD will be identified, whose GLA mutations are amenable for a stimulation with Migalastat-HCl, and will be treated with Migalastat-HCl at the recommended dose continuously for 24 months according to the manufacturers' instructions (SmPC).

Description

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 Exclusion criteria refer to the time of Migalastat initiation (T0):

• Patients on dialysis
• Patient has a clinically significant organ disease (e.g. cancer in the past 5 years) that in the opinion of the investigator would preclude participation in the trial.
• Patients with a history of organ transplantation.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Migalastat; Migalastat administered according to SmPC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LVMI	Primary endpoint of the observational study is the change in left ventricular mass index (LVMI) over two years.	two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GFR	Change in GFR over 24 months	24 months
Cerebral ischemia or stroke.	Incidence of transient/manifest cerebral ischemia or stroke over 24 months.	24 months
Neuropathic Pain (GCPS)	Change in severity of neuropathic pain measured by Graded Chronic Pain Scale (GCPS)	24 months
Neuropathic Pain (NPSI)	Change in severity of neuropathic pain measured by Neuropathic Pain Symptom Inventory (NPSI) Score (items are quantified on a (0-10) numerical scale).	24 months
Fabry Disease Severity (MSSI)	Change in disease severity measured by Mainz Severity Score Index (MSSI)	24 months
Fabry Disease Severity (DS3)	Change in disease severity measured by the Disease Severity Scoring System (DS3)	24 months
Lyso-Gb3	Change in Lyso-Gb3	24 months
White Matter Lesion load	Change of White Matter Lesion load (quantified by WML volumetry [ml]).	24 months
Cerebral microbleeds/hemorrhagic lesions.	Stabilization of cerebral microbleeds/hemorrhagic lesions.	24 months
Gastrointestinal symptoms	Change in gastrointestinal symptoms (gastrointestinal symptoms rating scale, GSRS).	24 months
Quality of life (SF-36)	Change in quality of life (Short Form (SF-36) Health Survey: 36-item, patient-reported survey of patient health).	24 months

Collaborators and Investigators

• Sponsor: University Hospital Muenster
• Collaborators: Amicus Therapeutics
• Investigators: Principal Investigator: Eva Brand, Prof., University Hospital Muenster

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 8, 2017
• Primary Completion (ACTUAL): June 30, 2020
• Study Completion (ACTUAL): June 30, 2020

Study Registration Dates

• First Submitted: April 20, 2017
• First Submitted That Met QC Criteria: April 25, 2017
• First Posted (ACTUAL): May 1, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 5, 2021
• Last Update Submitted That Met QC Criteria: January 4, 2021
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Fabry Disease
• Other Study ID Numbers: Fabry_Migalastat

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No