An Open Label Study of the Safety and Efficacy of PRX 102 in Patients with Fabry Disease Currently Treated With REPLAGAL® (Agalsidase alfa)

Phase 3

Completed

• Conditions: Fabry disease; lysosomal storage disease; 10027424

• Registration Number: NL-OMON47873
• Lead Sponsor: Protalix Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 28 February 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 5

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

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>SAFETY ENDPOINTS:<br /><br>Change from baseline in:<br /><br>* Clinical laboratory tests<br /><br>* Physical examination<br /><br>* Assessment of the injection site<br /><br>* Electrocardiogram<br /><br>* Treatment-emergent adverse events<br /><br>* Ability to taper off infusion premedication throughout the first 2 months of<br /><br>the study<br /><br>* Requirement for use of premedication overall to manage infusion reactions<br /><br>* Treatment-emergent anti-PRX-102 antibodies</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>EFFICACY ENDPOINTS:<br /><br>* Mean annualised change in estimated glomerular filtration rate (eGFRCKD-EPI)<br /><br>* Left Ventricular Mass Index (g/m2) preferably by MRI (echocardiogram can be<br /><br>used as an alternative)<br /><br>* Plasma Lyso-Gb3<br /><br>* Plasma Gb3<br /><br>* Urine Lyso-Gb3<br /><br>* Protein/Creatinine ratio spot urine test<br /><br>* Frequency of pain medication use<br /><br>* Exercise tolerance (Stress Test)<br /><br>* Short Form Brief Pain Inventory (BPI)<br /><br>* Mainz Severity Score Index (MSSI)<br /><br>* Quality of life EQ-5D-5L</p><br>