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A Randomized, Double blind, Active Control Study of the Safety and Efficacy of PRX-102 compared to Agalsidase Beta on Renal Function in Patients with Fabry Disease Previously Treated With Agalsidase Beta

Phase 3
Completed
Conditions
Fabry disease
lysosomal storage disease
10027424
Registration Number
NL-OMON45301
Lead Sponsor
Protalix Ltd
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Completed
Sex
Not specified
Target Recruitment
5
Inclusion Criteria

1. Symptomatic adult Fabry disease patients, age 18-60 years
a. Plasma and/or leucocyte alpha galactosidase activity (by activity assay) less than 30% mean normal levels
b. One or more of the described characteristic features of Fabry disease:
i. neuropathic pain,
ii. cornea verticillata,
iii. clustered angiokeratoma
2. Screening eGFR by CKD-EPI equation 40 to 90 mL/min/1.73 m2
3. Linear negative slope of eGFR of * 2 mL/min/1.73 m2 based on at least 3 serum creatinine values over approximately 1 year (range of 9 to 18 months, including the value obtained at the screening visit)
4. Treatment with a dose of 1 mg/kg agalsidase beta per infusion every 2 weeks for at least one year and at least 80% of 13 (10.4) mg/kg total dose over the last 6 months
5. Female patients and male patients whose co-partners are of child-bearing potential agree to use a medically accepted method of contraception, not including the rhythm method.

Exclusion Criteria

1. History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase beta
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. Cardiovascular event (myocardial infarction, unstable angina) in the 6 month period before randomization
7. Congestive heart failure NYHA Class IV
8. Cerebrovascular event (stroke, transient ischemic attack) in the 6 month period before randomization
9. Known history of hypersensitivity to Gadolinium contrast agent
10. Female subjects who are pregnant, planning to become pregnant during the study, or are breastfeeding
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
NameTimeMethod
<p>The primary efficacy parameter is the comparison of the mean annualized change<br /><br>(slope) in estimated glomerular filtration rate (eGFRCKD-EPI) between treatment<br /><br>groups.</p><br>
Secondary Outcome Measures
NameTimeMethod
<p>* Left Ventricular Mass Index (g/ m2) by MRI<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>
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