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

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ClinicalTrials.gov Identifier: NCT03135197
Recruitment Status : Active, not recruiting
First Posted : May 1, 2017
Last Update Posted : August 31, 2018
Sponsor:
Collaborator:
Amicus Therapeutics
Information provided by (Responsible Party):
University Hospital Muenster

Brief Summary:
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.

Condition or disease
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.

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Study Type : Observational
Estimated Enrollment : 60 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: German Observational Multicenter Study of Patients With Fabry Disease Under Chaperone Therapy With Migalastat-HCl.
Actual Study Start Date : June 8, 2017
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine


Group/Cohort
Migalastat
Migalastat administered according to SmPC



Primary Outcome Measures :
  1. LVMI [ Time Frame: two years ]
    Primary endpoint of the observational study is the change in left ventricular mass index (LVMI) over two years.


Secondary Outcome Measures :
  1. GFR [ Time Frame: 24 months ]
    Change in GFR over 24 months

  2. Cerebral ischemia or stroke. [ Time Frame: 24 months ]
    Incidence of transient/manifest cerebral ischemia or stroke over 24 months.

  3. Neuropathic Pain (GCPS) [ Time Frame: 24 months ]
    Change in severity of neuropathic pain measured by Graded Chronic Pain Scale (GCPS)

  4. Neuropathic Pain (NPSI) [ Time Frame: 24 months ]
    Change in severity of neuropathic pain measured by Neuropathic Pain Symptom Inventory (NPSI) Score (items are quantified on a (0-10) numerical scale).

  5. Fabry Disease Severity (MSSI) [ Time Frame: 24 months ]
    Change in disease severity measured by Mainz Severity Score Index (MSSI)

  6. Fabry Disease Severity (DS3) [ Time Frame: 24 months ]
    Change in disease severity measured by the Disease Severity Scoring System (DS3)

  7. Lyso-Gb3 [ Time Frame: 24 months ]
    Change in Lyso-Gb3

  8. White Matter Lesion load [ Time Frame: 24 months ]
    Change of White Matter Lesion load (quantified by WML volumetry [ml]).

  9. Cerebral microbleeds/hemorrhagic lesions. [ Time Frame: 24 months ]
    Stabilization of cerebral microbleeds/hemorrhagic lesions.

  10. Gastrointestinal symptoms [ Time Frame: 24 months ]
    Change in gastrointestinal symptoms (gastrointestinal symptoms rating scale, GSRS).

  11. Quality of life (SF-36) [ Time Frame: 24 months ]
    Change in quality of life (Short Form (SF-36) Health Survey: 36-item, patient-reported survey of patient health).



Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years to 74 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03135197


Locations
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Germany
Universtiy Hospital Münster
Münster, Germany, 48149
Sponsors and Collaborators
University Hospital Muenster
Amicus Therapeutics
Investigators
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Principal Investigator: Eva Brand, Prof. University Hospital Muenster

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Responsible Party: University Hospital Muenster
ClinicalTrials.gov Identifier: NCT03135197     History of Changes
Other Study ID Numbers: Fabry_Migalastat
First Posted: May 1, 2017    Key Record Dates
Last Update Posted: August 31, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Fabry Disease
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
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Metabolism, Inborn Errors
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders