|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Medical condition in easily understood language
|Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|10010331 - Congenital, familial and genetic disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To assess reduction of plasma lyso-GL3 level after switch to agalsidase beta from agalsidase alfa
|Secondary objectives of the trial
|To assess reduction of kidney podocyte GL3 content after switch to agalsidase beta from agalsidase alfa
To assess reduction of GL3 content in endothelial skin cells after switch to agalsidase beta from agalsidase alfa
To assess change in renal function after switch to agalsidase beta from agalsidase alfa
To assess disease severity and clinical changes after switch to agalsidase beta from agalsidase alfa
To assess improvement in symptoms of Fabry disease after switch to agalsidase beta from agalsidase alfa
|Trial contains a sub-study
|Principal 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 or absence of characteristic Fabry disease symptoms including neuropathic pain, clustered angiokeratoma and/or cornea verticillata, leucocyte α-GAL A enzyme activity (3% or less compared to control), and genotype (optional).
Participants who are currently receiving agalsidase alfa for a minimum of 6 months at an average dose of 0.2 mg/kg every other week (ie, every 2 weeks) at baseline.
Participants who are naïve to agalsidase beta.
Participants with estimated glomerular filtration rate (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 averaged urine protein-creatinine ratio of <0.5 (ie, <500 mg protein per 1 g creatinine) between the 2 samples. For participants on angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), the criterion is to be met both prior and after a temporary interruption of ACEIs/ARBs for 4 weeks.
Participants with plasma lyso-GL3 levels >20 ng/mL on 2 consecutive samples taken at least 4 weeks apart.
Participant’s medical records (including eGFR values) available and accessible during the study period.
Participant and/or participant’s legal representative has given signed informed consent as described in the protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. For potential participants age 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.
|Principal exclusion criteria
|Participants with severe renal impairment (end-stage renal disease, dialysis, or renal transplantation) and/or nephropathies (including diabetic).
Participants with rapid renal decline: Loss of >6mL/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 with diagnosed diabetes.
Participants with history of anaphylaxis to Enzyme Replacement Therapy (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 5 years with agalsidase alfa at an average dose of 0.2 mg/kg every other week (ie, every 2 weeks) prior to randomization.
Exposure to migalastat or any investigational study intervention, except agalsidase alfa, for Fabry disease in the last 5 years prior to study participation. Patients who previously participated in any agalsidase alfa clinical study will be eligible if they meet other criteria.
Exposure to any investigational drugs in the last 4 weeks or 5 halflives, whichever is longer, prior to screening visit or concomitant enrollment in any other clinical study involving an investigational study treatment.
Individuals accommodated in an institution because of regulatory or legal order; prisoners or subjects 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 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
|E.5 End points
|Primary end point(s)
|Change in Plasma globotriaosylsphingosine (lyso-GL3) level
|Timepoint(s) of evaluation of this end point
|Baseline, 12 months (week 52)
|Secondary end point(s)
|1) Change in GL3 content in podocytes
2) Change in GL3 content in endothelial skin cells
3) Change in measured glomerular filtration rate (mGFR)
4) Change in estimated glomerular filtration rate (eGFR) calculated
5) Change in Mainz Severity Score Index (MSSI) total score
6) Change in Fabry Disease Patient Reported Outcomes (FD-PRO) total symptom score
|Timepoint(s) of evaluation of this end point
|Timepoint for all secondary end points: Baseline, 12 months (week 52)
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days