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

• ClinicalTrials.gov Identifier: NCT03018730
• Recruitment Status: Active, not recruiting
• First Posted: January 12, 2017
• Last Update Posted: October 1, 2019
• Sponsor: Protalix
• Information provided by (Responsible Party): Protalix

Study Description

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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Allocation: N/A
• 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: January 2020
• Estimated Study Completion Date: July 2020

Arms and Interventions

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

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

• 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

Locations

Australia, Victoria

Royal Melbourne Hospital

Parkville, Victoria, Australia, 3050

Canada, Nova Scotia

Capital Health

Halifax, Nova Scotia, Canada, B3H 1V8

Czechia

Vseobecna fakultni nemocnice v Praze

Prague, Czechia

Germany

Universitaetsklinikum Wuerzburg

Wurzburg, Germany

Netherlands

Academisch Medisch Centrum

Amsterdam, Netherlands

Norway

Helse Bergen HF Haukeland Universitetssykehus

Bergen, Norway

Slovenia

General Hospital Slovenj Gradec

Slovenj Gradec, Slovenia, SI-2380

Spain

Hospital de Dia Quiron Zaragoza

Zaragoza, Spain, 50012

United Kingdom

Institute of Metabolism and Systems Research

Edgbaston, Birmingham, United Kingdom, B15 2UR

Addenbrooke's Hospital

Cambridge, United Kingdom, CB2 0QQ

The Royal Free Hospital

London, United Kingdom, NW3 2QG

Salford Royal NHS Foundation Trust

Salford, United Kingdom, M6 8HD

Sponsors and Collaborators

Protalix

Investigators

• Study Director: Raul Chertkoff, MD; Protalix Ltd

More Information

• Responsible Party: Protalix
• ClinicalTrials.gov Identifier: NCT03018730
• Other Study ID Numbers: PB-102-F30
• First Posted: January 12, 2017
• Last Update Posted: October 1, 2019
• Last Verified: September 2019

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