Balance

Principal Investigator: Nicola Longo
Keywords: Fabry , Enzyme Replacement Department: Pediatric Genetics
IRB Number: 00093689 Co Investigator:  
Specialty: Pediatric Genetics
Sub Specialties: Medical Genetics
Recruitment Status: Recruiting

Contact Information

Carrie Bailey
carrie.bailey@hsc.utah.edu
8015873605

Brief Summary

Study Purpose:

This is a randomized, double blind, active control study of PRX-102 in Fabry disease patients with impaired renal function. Patients treated for approximately 1 year with agalsidase beta and on a stable dose for at least 6 months will be screened and then randomized to continue treatment with 1 mg/kg agalsidase beta or to treatment with 1 mg/kg of PRX-102. The identity of the enzyme will be blinded to the patient and the investigator. Patients will receive intravenous infusions every two weeks.

Objectives:

The objective of this study is to evaluate the safety and efficacy of PRX-102 compared to agalsidase beta in adult Fabry disease patients with impaired renal function.

Inclusion Criteria

Study participants:
1. Symptomatic adult Fabry disease patients, age 18-60 years
2. Males: Plasma and/or leucocyte alpha galactosidase activity (by activity assay) less than 30% mean normal levels and one or more of the characteristic features of Fabry disease: 
i. neuropathic pain,
ii. cornea verticillata,
iii. clustered angiokeratoma
3. Females: 
a. historical genetic test results consistent with Fabry pathogenic mutation and one or more of the described characteristic features of Fabry disease: 
i. neuropathic pain,
ii. cornea verticillata,
iii. clustered angiokeratoma 
b. or in the case of novel mutations a first degree male family member with Fabry disease with the same mutation and one or more of the characteristic features of Fabry disease: 
i. neuropathic pain,
ii. cornea verticillata,
iii. clustered angiokeratoma 
4. Screening eGFR by CKD-EPI equation 40 to 120 mL/min/1.73 m2
5. 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)
6. 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
7. 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.
 
A subject that fails screening based on Inclusion Criteria #2 and/or #3 (eGFR range and/or slope) may be re-tested for serum creatinine with cystatin C within a period of 2 months pending the approval of the Protalix Medical Director.  In those occasions, the patient will maintain same screening number with no need to perform additional evaluations.
 
Pregnant Partners and Infants
no formal inclusion criteria in protocol.  Consent will be collected to gather medical records from pregnant partners and infants. 

Exclusion Criteria

Study Participants 
1. History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase beta
2. Known non-pathogenic Fabry mutations 
3. History of renal dialysis or transplantation
4. 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)
5. Patient with screening eGFR value between 91-120 mL/min/1.73 m2 having a historical eGFR value higher than 120 mL/min/1.73 m2 (during 9 to 18 months before screening) 
6. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated or dose changed in the 4 weeks prior to screening
7. Urine protein to creatinine ratio (UPCR) > 0.5 g/g and not treated with an ACE inhibitor or ARB
8. Cardiovascular event (myocardial infarction, unstable angina) in the 6 month period before randomization
9. Congestive heart failure NYHA Class IV
10. Cerebrovascular event (stroke, transient ischemic attack) in the 6 month period before randomization
11. Known history of hypersensitivity to Gadolinium contrast agent that is not managed by the use of premedication 
12. Female subjects who are pregnant, planning to become pregnant during the 
study, or are breastfeeding
13. 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
 
Pregnant Partners and Infants
no formal exclusion criteria in protocol.  Consent will be collected to gather medical records from pregnant partners and infants.