Fabry disease lysosomal storage disease
Conditions
Interventions
During the first 3 months, Study Part A, patients will be on agalsidase alfa
every other week infusion according to their previous dose and rate of
infusion. At Study Part B patients will be switche
Efficacy
Safety
Sponsors
Protalix Ltd
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Age: 18-60 years;2. A documented diagnosis of Fabry disease.;3. Males: plasma and/or leucocyte alpha galactosidase activity (by activity assay) less than lower limit of normal according to laboratory range and one or more of the characteristic features of Fabry disease;i. Neuropathic pain;ii. Cornea verticillata;iii. Clustered angiokeratoma;4. Females: historical genetic test results consistent with Fabry mutations, or in the case of novel mutations a first degree male relative with Fabry disease, and one or more of the characteristic features of Fabry disease;i. Neuropathic pain;ii. Cornea verticillata;iii. Clustered angiokeratoma;5. Treatment with agalsidase alfa for at least 2 years and on a stable dose (>80% labelled dose/kg) for at least 6 months;6. eGFR * 40 ml/min/1.73 m2 by CKD-EPI equation;7. Availability of at least 2 historical serum creatinine evaluations since starting agalsidase alfa treatment and not more than 2 years;8. Female patients and male patients whose co-partners are of child-bearing potential agree to use a medically acceptable method of contraception, not including the rhythm method
Exclusion criteria
Exclusion criteria: 1. History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase alfa;2. History of renal dialysis or transplantation;3. History of acute kidney injury in the 12 months prior to screening, including specific kidney diseases (e.g., acute interstitial nephritis, acute glomerular and vasculitic renal diseases); non-specific conditions (e.g, ischemia, toxic injury); as well as extrarenal pathology (e.g., prerenal azotemia, and acute postrenal obstructive nephropathy);4. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated or dose changed in the 4 weeks prior to screening;5. Urine protein to creatinine ratio (UPCR) > 0.5 g/g and not treated with an ACE inhibitor or ARB;6. Known history of hypersensitivity to Gadolinium contrast agent that is not managed by the use of premedication;7. Females who are pregnant, planning to become pregnant during the study, or are breast feeding;8. Cardiovascular event (myocardial infarction, unstable angina) in the 6 month period before screening;9. Congestive heart failure NYHA Class IV;10. Cerebrovascular event (stroke, transient ischemic attack) in the 6 month period before screening;11. Presence of any medical, emotional, behavioral or psychological condition that, in the judgment of the Investigator and/or Medical Director, would interfere with the patient*s compliance with the requirements of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| SAFETY ENDPOINTS: Change from baseline in: * Clinical laboratory tests * Physical examination * Assessment of the injection site * Electrocardiogram * Treatment-emergent adverse events * Ability to taper off infusion premedication throughout the first 2 months of the study * Requirement for use of premedication overall to manage infusion reactions * Treatment-emergent anti-PRX-102 antibodies | — |
Secondary
| Measure | Time frame |
|---|---|
| EFFICACY ENDPOINTS: * Mean annualised change in estimated glomerular filtration rate (eGFRCKD-EPI) * Left Ventricular Mass Index (g/m2) preferably by MRI (echocardiogram can be used as an alternative) * Plasma Lyso-Gb3 * Plasma Gb3 * Urine Lyso-Gb3 * Protein/Creatinine ratio spot urine test * Frequency of pain medication use * Exercise tolerance (Stress Test) * Short Form Brief Pain Inventory (BPI) * Mainz Severity Score Index (MSSI) * Quality of life EQ-5D-5L | — |
Countries
Algeria
Outcome results
None listed