Fabry disease MedDRA version: 20.0 Level: PT Classification code 10016016 Term: Fabry's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Sanofi Aventis Groupe (SAG)
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Male participant must be 16 to 45 years of age inclusive, at the time of signing the informed consent. Participants who are diagnosed with classic Fabry disease based on phenotype, presence of characteristic Fabry disease symptoms including neuropathic pain, clustered angiokeratoma and/or cornea verticillata, leucocyte a-GAL A enzyme activity (3% or less compared to control), and genotype (optional). Participants who are currently receiving migalastat for a minimum of 6 months up to a maximum of 12 months at baseline. Participants are naive to agalsidase beta. Participants with eGFR =60 mL/min/1.73 m^2 at screening and baseline. Proteinuria level as measured by 2 separate, morning, clean-catch urine samples taken a few days apart demonstrating an average urine protein-creatinine ratio of 20 ng/mL on 2 consecutive samples taken at least 4 weeks apart during screening period. Participant’s medical records (including eGFR values) available and accessible during the study period. Male, only male participants will be included in the study. Participants and/or participant’s legal representative capable of giving signed informed consent as described in Appendix 1 (Section 10.1.3) which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. For potential participants aged 16 to 18 years, a parent or legal representative is required to sign the ICF, and the potential participant is also required to sign an informed assent form. Are the trial subjects under 18? yes Number of subjects for this age range: 4 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 31 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Participants with a history of renal transplantation, or who are currently receiving hemo- or peritoneal dialysis; participants with comorbid nonFabry nephropathies (e.g., diabetic nephropathy, glomerulonephritis, etc.). Participants with rapid renal decline: Loss of >6 mL/min/1.73 m^2 at screening compared to the most recent eGFR value approximately 12 months prior to screening. Participants with advanced cardiac failure (Stage D). Participants with bleeding disorder, prior history of unexplained bleeding episodes or receiving mandatory anticoagulants or antiplatelets for any indication not allowing interruption of therapy for renal biopsy. Participants diagnosed with diabetes. Participants with history of anaphylaxis to ERT. Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study. Participants treated for more than 3 years with agalsidase alfa prior to initiating migalastat therapy. Exposure to any investigational study intervention other than migalastat in the last 4 weeks or 5 half-lives, whichever is longer, prior to screening visit or concomitant enrollment in any other clinical study involving an investigational study intervention (patients participating in any migalastat clinical study may be considered upon discontinuation and meeting eligibility criteria). Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized. Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures. Participants who are dependent on the Sponsor or Investigator or deemed vulnerable for any reason (in conjunction with Section 1.61 of the International Council for Harmonisation Good Clinical Practice [ICH GCP] Ordinance E6). Participants who are employees of the clinical study center or other individuals directly involved in the conduct of the study, or immediate family members of such individuals. Any specific situation during study implementation/course that may raise ethics consideration.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess reduction of plasma lyso-GL3 level after switch to agalsidase beta from migalastat ;Secondary Objective: To assess reduction of kidney podocyte GL3 content after switch to agalsidase beta from migalastat To assess reduction of GL3 content in endothelial skin cells after switch to agalsidase beta from migalastat To assess change in renal function after switch to agalsidase beta from migalastat To assess disease severity and clinical changes after switch to agalsidase beta from migalastat To assess improvement in symptoms of Fabry disease after switch to agalsidase beta from migalastat ;Primary end point(s): Change from baseline for Plasma globotriaosylsphingosine (lyso-GL3) level;Timepoint(s) of evaluation of this end point: Baseline, 12 months (week 52) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Change from baseline for GL3 content in podocytes : Change from baseline to 12 months (week 52) for GL3 content in podocytes 2) Change from baseline for GL3 content in endothelial skin cells : Change from baseline to 12 months (Week 52) for GL3 content in endothelial skin cells 3) Change from baseline for measured glomerular filtration rate (mGFR) : Change from baseline to 12 months (Week 52) for measured glomerular filtration rate (mGFR) (measured by iohexol clearance) 4) Change from baseline for estimated glomerular filtration rate (eGFR) calculated : Change from baseline to 12 months (Week 52) for estimated glomerular filtration rate (eGFR) calculated using age appropriate formula [Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)/ Bedside-Schwartz 5) Change from baseline for Mainz Severity Score Index (MSSI) total score : Change from baseline to 12 months (Week 52) for Mainz Severity Score Index (MSSI), based on MSSI total score 6) Change from baseline in Fabry Disease Patient Reported Outcomes (FD-PRO) total symptom score : Change from baseline to 12 months (Week 52) in Fabry Disease Patient Reported Outcomes (FD-PRO) score, based on FD-PRO total symptom score;Timepoint(s) of evaluation of this end point: Timepoint for all secondary endpoints: Baseline, 12 months (week 52) | — |
Countries
Canada, France, Norway, United States
Contacts
Public ContactClinical Study Unit
Sanofi Norge AS
Outcome results
None listed