Safety and Efficacy of PRX 102 in Patients With Fabry Disease Currently Treated With REPLAGAL® (Agalsidase Alfa)

Study Description

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Brief Summary:

This is an open label switch over study to assess the safety and efficacy of PRX-102 (pegunigalsidase alfa). Patients treated with agalsidase alfa for at least 2 years and on a stable dose (>80% labelled dose/kg) for at least 6 months. Patients will be screened and evaluated over 3 months while continuing on agalsidase alfa. Following the screening period, the patient will be enrolled and switched from their agalsidase alfa treatment to receive intravenous (IV) infusions of PRX-102 1 mg/kg every two weeks for 12 months. No more than 25% of treated patients will be female.

Condition or disease	Intervention/treatment	Phase
Fabry Disease	Biological: PRX-102 (pegunigalsidase alfa)	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	22 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	An Open Label Study of the Safety and Efficacy of PRX 102 in Patients With Fabry Disease Currently Treated With REPLAGAL® (Agalsidase Alfa)
Actual Study Start Date :	February 23, 2017
Estimated Primary Completion Date :	June 2019
Estimated Study Completion Date :	September 2019

Arms and Interventions

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Arm	Intervention/treatment
Experimental: PRX-102; 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

Outcome Measures

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Primary Outcome Measures :

1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: Throughout the 12 months study ]

Secondary Outcome Measures :

1. Mean annualised change in eGFR [ Time Frame: Every 4 weeks for 12 months ]
   Mean annualised change in eGFR
2. Left Ventricular Mass Index (g/m2) preferably by MRI [ Time Frame: Every 6 months for 12 months ]
   Left Ventricular Mass Index (g/m2) preferably by MRI (ECG can be used as an alternative)
3. Plasma Lyso-Gb3 [ Time Frame: Every 3 months for 12 months ]
4. Plasma Gb3 [ Time Frame: Every 3 months for 12 months ]
5. Urine Lyso-Gb3 [ Time Frame: Every 3 months for 12 months ]
6. Protein/Creatinine ratio [ Time Frame: Every 3 months for 12 months ]
   Protein/Creatinine ratio spot urine test
7. Frequency of pain medication use [ Time Frame: Every 2 weeks for 12 months ]
8. Exercise tolerance (Stress Test) [ Time Frame: Every 6 months for 12 months ]
9. Short Form Brief Pain Inventory (BPI) [ Time Frame: Every 3 months for 12 months ]
10. Mainz Severity Score Index (MSSI) [ Time Frame: Every 6 months for 12 months ]
11. Quality of life EQ-5D-5L [ Time Frame: Every 6 months for 12 months ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 60 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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:

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
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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Raul Chertkoff, MD	+972-54-2228472	raul@protalix.com

Locations

Australia, Victoria
Royal Melbourne Hospital	Recruiting
Parkville, Victoria, Australia, 3050
Contact: Kathleen Nicholls, MD 61393427000 kathy.nicholls@mh.org.au
Contact: Donna North +61 393424219 donna.north@mh.org.au
Principal Investigator: Kathleen Nicholls, MD
Canada, Nova Scotia
Capital Health	Recruiting
Halifax, Nova Scotia, Canada, B3H 1V8
Contact: Michael West, MD +1 902 473 4023 mlwest@dal.ca
Contact: Dawn Menon +1 9024731156 Dawn.Menon@nshealth.ca
Principal Investigator: Michael West, MD
Czechia
Vseobecna fakultni nemocnice v Praze	Recruiting
Prague, Czechia
Contact: Ales Linhart, MD 420224962605 alinh@lf1.cuni.cz
Contact: Zuzana Kristofova 420 224 962 605 zuzana.kristofova@vfn.cz
Principal Investigator: Ales Linhart, MD
Germany
Universitaetsklinikum Wuerzburg	Not yet recruiting
Wurzburg, Germany
Contact: Christoph Wanner, MD 49 931 20139030 wanner_c@klinik.uni-wuerzburg.de
Principal Investigator: Christoph Wanner, MD
Netherlands
Academisch Medisch Centrum	Recruiting
Amsterdam, Netherlands
Contact: Mirjam Langeveld, MD 31205666071 m.langeveld@amc.nl
Contact: Shirley Klein 31205665972 shirley.klein@amc.uva.nl
Principal Investigator: Mirjam Langeveld, MD
Norway
Helse Bergen HF Haukeland Universitetssykehus	Recruiting
Bergen, Norway
Contact: Camilla Tøndel, MD +47 55975962 camilla.tondel@helse-bergen.no
Contact: Jorunn Syltoy +47 55971490 jorunn.johanne.jacobsen.syltoy@helse-bergen.no
Principal Investigator: Camilla Tøndel, MD
Slovenia
General Hospital Slovenj Gradec	Recruiting
Slovenj Gradec, Slovenia, SI-2380
Contact: Bojan Vujkovac, MD 00386 2 8823 708 bojan.vujkovac@guest.arnes.si
Principal Investigator: Bojan Vujkovac, MD
Spain
Hospital de Dia Quiron Zaragoza	Recruiting
Zaragoza, Spain, 50012
Contact: Pilar Giraldo, MD 34670285339 giraldocastellano@gmail.com
Contact: Beatriz Escuder 34676605758 bea.escuderazuara@gmail.com
Principal Investigator: Pilar Giraldo, MD
United Kingdom
Institute of Metabolism and Systems Research	Not yet recruiting
Edgbaston, Birmingham, United Kingdom, B15 2UR
Contact: Tarekegn G Hiwot, MD +44 (0)121 371 6982 t.g.hiwot@bham.ac.uk
Contact: Tarekegn G Hiwot, MD +44 (0)121 371 6982 tarekegn.hiwot@uhb.nhs.uk
Principal Investigator: Tarekegn G Hiwot, MD
Addenbrooke's Hospital	Recruiting
Cambridge, United Kingdom, CB2 0QQ
Contact: Patrick Deegan, MD 441223245151 patrick.deegan@addenbrookes.nhs.uk
Contact: Lisa Morris-Bacon 441223 274634 ext 4634 lisa.morris-bacon@addenbrookes.nhs.uk
Principal Investigator: Patrick Deegan, MD
The Royal Free Hospital	Recruiting
London, United Kingdom, NW3 2QG
Contact: Derralynn Hughes, MD 4402077940500 ext 22496 rmgvdah@ucl.ac.uk
Contact: Allison Warwick 44 0207 7940500 ext 22488 allison.warwick@nhs.net
Principal Investigator: Derralynn Hughes, MD
Salford Royal NHS Foundation Trust	Recruiting
Salford, United Kingdom, M6 8HD
Contact: Ana Jovanovic, MD +441612064365 ana.jovanovic@srft.nhs.uk
Contact: Marie Meehan +441612064192 Marie.Meehan@srft.nhs.uk
Principal Investigator: Ana Jovanovic, MD

Sponsors and Collaborators

Protalix

Investigators

Study Director:	Raul Chertkoff, MD	Protalix Ltd

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Protalix
ClinicalTrials.gov Identifier:	NCT03018730 History of Changes
Other Study ID Numbers:	PB-102-F30
First Posted:	January 12, 2017
Last Update Posted:	January 17, 2018
Last Verified:	January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Protalix:

Fabry disease; Enzyme-Replacement Therapy; pegunigalsidase alfa; PRX-102; alpha galactosidase-A

Additional relevant MeSH terms:

Fabry Disease; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders	Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Lipid Metabolism Disorders