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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 : October 7, 2019
Sponsor:
Collaborator:
Amicus Therapeutics
Information provided by (Responsible Party):
University Hospital Muenster

Tracking Information
First Submitted Date April 20, 2017
First Posted Date May 1, 2017
Last Update Posted Date October 7, 2019
Actual Study Start Date June 8, 2017
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: April 25, 2017)
LVMI [ Time Frame: two years ]
Primary endpoint of the observational study is the change in left ventricular mass index (LVMI) over two years.
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT03135197 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: August 28, 2018)
  • GFR [ Time Frame: 24 months ]
    Change in GFR over 24 months
  • Cerebral ischemia or stroke. [ Time Frame: 24 months ]
    Incidence of transient/manifest cerebral ischemia or stroke over 24 months.
  • Neuropathic Pain (GCPS) [ Time Frame: 24 months ]
    Change in severity of neuropathic pain measured by Graded Chronic Pain Scale (GCPS)
  • 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).
  • Fabry Disease Severity (MSSI) [ Time Frame: 24 months ]
    Change in disease severity measured by Mainz Severity Score Index (MSSI)
  • Fabry Disease Severity (DS3) [ Time Frame: 24 months ]
    Change in disease severity measured by the Disease Severity Scoring System (DS3)
  • Lyso-Gb3 [ Time Frame: 24 months ]
    Change in Lyso-Gb3
  • White Matter Lesion load [ Time Frame: 24 months ]
    Change of White Matter Lesion load (quantified by WML volumetry [ml]).
  • Cerebral microbleeds/hemorrhagic lesions. [ Time Frame: 24 months ]
    Stabilization of cerebral microbleeds/hemorrhagic lesions.
  • Gastrointestinal symptoms [ Time Frame: 24 months ]
    Change in gastrointestinal symptoms (gastrointestinal symptoms rating scale, GSRS).
  • 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).
Original Secondary Outcome Measures
 (submitted: April 25, 2017)
  • GFR [ Time Frame: 24 months ]
    Change in GFR over 24 months
  • Cerebral ischemia or stroke. [ Time Frame: 24 months ]
    Incidence of transient/manifest cerebral ischemia or stroke over 24 months.
  • Neuropathic Pain (GCPS) [ Time Frame: 24 months ]
    Change in severity of neuropathic pain measured by Graded Chronic Pain Scale (GCPS)
  • 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).
  • Fabry Disease Severity (MSSI) [ Time Frame: 24 months ]
    Change in disease severity measured by Mainz Severity Score Index (MSSI)
  • Fabry Disease Severity (DS3) [ Time Frame: 24 months ]
    Change in disease severity measured by the Disease Severity Scoring System (DS3)
  • Lyso-Gb3 [ Time Frame: 24 months ]
    Change in Lyso-Gb3
  • White Matter Lesion load [ Time Frame: 24 months ]
    Change of White Matter Lesion load (quantified by WML volumetry [ml]).
  • Cerebral microbleeds/hemorrhagic lesions. [ Time Frame: 24 months ]
    Stabilization of cerebral microbleeds/hemorrhagic lesions.
  • Gastrointestinal symptoms [ Time Frame: 24 months ]
    Change in gastrointestinal symptoms (gastrointestinal symptoms rating scale, GSRS).
  • Quality of life [ Time Frame: 24 months ]
    Change in quality of life (Short Form (SF-36) Health Survey: 36-item, patient-reported survey of patient health).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title German Observational Multicenter Study of Patients With Fabry Disease Under Chaperone Therapy With Migalastat-HCl.
Official Title German Observational Multicenter Study of Patients With Fabry Disease Under Chaperone Therapy With Migalastat-HCl.
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.
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
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
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).
Condition Fabry Disease
Intervention Not Provided
Study Groups/Cohorts Migalastat
Migalastat administered according to SmPC
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Active, not recruiting
Estimated Enrollment
 (submitted: April 25, 2017)
60
Original Estimated Enrollment Same as current
Estimated Study Completion Date July 2020
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Eligibility 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.
Sex/Gender
Sexes Eligible for Study: All
Ages 16 Years to 74 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Germany
Removed Location Countries  
 
Administrative Information
NCT Number NCT03135197
Other Study ID Numbers Fabry_Migalastat
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party University Hospital Muenster
Study Sponsor University Hospital Muenster
Collaborators Amicus Therapeutics
Investigators
Principal Investigator: Eva Brand, Prof. University Hospital Muenster
PRS Account University Hospital Muenster
Verification Date September 2019