Purpose

This is a randomized, double blind, active control study of PRX-102 (pegunigalsidase alfa) 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 1mg/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. Patients will be randomized in a 2:1 ratio of PRX-102 to agalsidase beta. Randomization will be stratified by urinary protein to creatinine ratio (UPCR) of < or ≥ 1 g/g by spot urine sample. No more than 50% of the patients will be female.

Condition

Eligibility

Eligible Ages
Between 18 Years and 60 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Symptomatic adult Fabry disease patients, age 18-60 years
  • 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

2. 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

- Screening eGFR by CKD-EPI equation 40 to 120 mL/min/1.73 m²

- Linear negative slope of eGFR 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) of ≥ 2 mL/min/1.73 m²/year

- 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.

- 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

  • History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase beta
  • Known non-pathogenic Fabry mutations
  • History of renal dialysis or transplantation
  • 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)
  • Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated or dose changed in the 4 weeks prior to screening
  • Patient with a screening eGFR value between 91-120 mL/min/1.73 m², having an historical eGFR value higher than 120 mL/min/1.73 m² (during 9 to 18 months before screening)
  • Urine protein to creatinine ratio (UPCR) > 0.5 g/g and not treated with an ACE inhibitor or ARB
  • Cardiovascular event (myocardial infarction, unstable angina) in the 6 month period before randomization
  • Congestive heart failure NYHA Class IV
  • Cerebrovascular event (stroke, transient ischemic attack) in the 6 month period before randomization
  • Known history of hypersensitivity to Gadolinium contrast agent that is not managed by the use of pre-medication
  • Female subjects who are pregnant, planning to become pregnant during the study, or are breastfeeding
  • 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

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
PRX-102 (pegunigalsidase alfa)
PRX-102 infusion every 2 weeks
  • Biological: PRX-102 (pegunigalsidase alfa)
    PRX-102 1 mg/kg every 2 weeks
    Other names:
    • pegunigalsidase alfa
    • Recombinant human alpha galactosidase-A
Active Comparator
agalsidase beta
agalsidase beta infusion every 2 weeks
  • Biological: agalsidase beta
    agalsidase beta 1 mg/kg every 2 weeks
    Other names:
    • Fabrazyme

Recruiting Locations

UAB Medicine
Birmingham, Alabama 35233
Contact:
Eric L Wallace, MD
205-975-9676
ericlwallace@uab.edu

Arkansas Children's hospital
Little Rock, Arkansas 30020-8341
Contact:
Thomas Burrow, MD
501-364-2966
taburrow@uams.edu

University of California Los Angeles
Los Angeles, California 90024
Contact:
Anjay Rastogi, MD
310-954-2692
ARastogi@mednet.ucla.edu

University of California Irvine Center
Orange, California 92868
Contact:
Virginia Kimonis
714-456-5791
vkimonis@uci.edu

University of California San Diego
San Diego, California 92093
Contact:
Bruce Barshop
619-543-5237
bbarshop@ucsd.edu

Emory University School of Medicine
Atlanta, Georgia 30322
Contact:
William Wilcox, MD
404-727-5624
william.wilcox@emory.edu

Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois 60611
Contact:
Joel Charrow, MD
773-880-4462
jcharrow@northwestern.edu

University of Iowa Hosptials and Clinics
Iowa City, Iowa 52242
Contact:
Myrl Holida, PA
319-356-2007
myrl-holida@uiowa.edu

Massachusetts General Hospital
Boston, Massachusetts 02114
Contact:
Amel Karaa
617-726-1561
akaraa@mgh.harvard.edu

Infusion Associates
Grand Rapids, Michigan 49525
Contact:
Kahn Nedd, MD
616-954-0600
khannedd@yahoo.com

Regents of the University of Minnesota
Minneapolis, Minnesota 55455
Contact:
Chester Whitley
612-625-7422
whitley@umn.edu

New York University Medical Center
New York, New York 10016
Contact:
Heather Lau, MD
212-263-8344

Duke University Medical Center
Durham, North Carolina 27705
Contact:
Marie McDonald
919-681-1982
marie.mcdonald@duke.edu

Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio 45229
Contact:
Robert Hopkin, MD
513-636-4760
rob.hopkin@cchmc.org

Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania 15224
Contact:
Gerard Vockley, MD, PhD
412-692-7746
gerard.vockley@chp.edu

Institute of Metabolic Disease, Baylor Healthcare
Dallas, Texas 75226
Contact:
Raphael Schiffmann, MD, MHSc
214-820-4533
raphael.schiffmann@baylorhealth.edu

Eccles Primary Children's Outpatient Services Building
Salt Lake City, Utah 84132
Contact:
Nicola Longo, MD, PhD
801-587-3605
nicola.longo@hsc.utah.edu

O+O Alpan LLC
Fairfax, Virginia 22030
Contact:
Ozlem Goker-Alpan, MD
571-308-1900
ogokeralpan@oandoalpan.com

West Virginia University
Morgantown, West Virginia 26506
Contact:
Tarachandra Narumanchi, MD
304-293-7332
tnarumanchi@hsc.wvu.edu

Medical College of Wisconsin
Milwaukee, Wisconsin 53226-3596
Contact:
William Rhead
414-266-3345
wrhead@mcw.edu

More Details

NCT ID
NCT02795676
Status
Recruiting
Sponsor
Protalix

Study Contact

Raul Chertkoff, MD
+972-4-9028100
raul@protalix.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.