Study of the Safety and Efficacy of PRX-102 Compared to Agalsidase Beta on Renal Function

NCT02795676 | Completed Phase 3 Results

• 1 other identifier: PB-102-F20
• Study Type: interventional
• Target: 78
• Locations: 12 countries
• Sites: 29

Brief Summary

This was a randomized, double-blind, active control study of the enzyme replacement therapy (ERT) drug PRX-102 (pegunigalsidase alfa) in Fabry disease patients with impaired renal function. Patients who had been treated for approximately 1 year with agalsidase beta and who had been on a stable dose of that product for at least 6 months were randomized in a 2:1 ratio to either switch to PRX-102 or to continue treatment with agalsidase beta. Both treatments were delivered by intravenous infusions every two weeks, at a dosage of 1 mg/kg.

Conditions

Fabry Disease

Keywords

Glomerular filtration rate; Proteinuria; PRX-102; pegunigalsidase alfa; Fabry Disease

Outcome Measures

Primary Outcomes (1)

• Annualized Change (Slope) in Estimated Glomerular Filtration Rate (eGFR)

  The individual annualized mean change (slope) in eGFR (mL/min/1.73 m\^2/year) is an estimate of the individual patient's annualized change in eGFR, which is derived from the eGFR assessments over time, for up to 24 months. The individual annualized mean change (slope) in eGFR is estimated for each patient with at least 4 eGFR observations. For patients with fewer than 4 eGFR observations, the slope will be missing.

  24 months

Secondary Outcomes (7)

• Estimated Glomerular Filtration Rate (eGFR)

  Baseline and Month 24

• Plasma Lyso-Gb3

  Baseline and Month 24

• Short Form Brief Pain Inventory (BPI)

  Baseline and Month 24

• Mainz Severity Score Index (MSSI)

  Baseline and Month 24

• Urine Protein/Creatinine Ratio (UPCR)

  Baseline and Month 24

Study Arms (2)

PRX-102 (pegunigalsidase alfa)

EXPERIMENTAL

PRX-102 infusion every 2 weeks

Biological: PRX-102 (pegunigalsidase alfa)

agalsidase beta

ACTIVE COMPARATOR

agalsidase beta infusion every 2 weeks

Biological: agalsidase beta

Interventions

PRX-102 (pegunigalsidase alfa) BIOLOGICAL

PRX-102 1 mg/kg every 2 weeks

Also known as: pegunigalsidase alfa, Recombinant human alpha galactosidase-A

PRX-102 (pegunigalsidase alfa)

agalsidase beta BIOLOGICAL

agalsidase beta 1 mg/kg every 2 weeks

Also known as: Fabrazyme

agalsidase beta

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Protalix: lead
• Chiesi Farmaceutici S.p.A.: collaborator

Study Sites (29)

UAB Medicine

Birmingham, Alabama, 35233, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

University of California Irvine Center

Orange, California, 92868, United States

Location

University of California San Diego

San Diego, California, 92093, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

University of Iowa Hosptials and Clinics

Iowa City, Iowa, 52242, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Infusion Associates

Grand Rapids, Michigan, 49525, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Institute of Metabolic Disease, Baylor Healthcare

Dallas, Texas, 75226, United States

Location

Renal Disease Research Institute, LLC - Dallas

Dallas, Texas, 75235, United States

Location

Eccles Primary Children's Outpatient Services Building

Salt Lake City, Utah, 84132, United States

Location

O+O Alpan LLC

Fairfax, Virginia, 22030, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226-3596, United States

Location

Vseobecna fakultni nemocnice v Praze

Prague, Czech Republic, 12808, Czechia

Location

Turku University Central Hospital

Turku, 20520, Finland

Location

Hôpital Raymond Poincaré

Paris, 92380, France

Location

Semmelweis Egyetem

Budapest, 1083, Hungary

Location

Azienda Ospedaliera Universitaria "Federico II"

Napoli, Italy

Location

Academisch Medisch Centrum

Amsterdam, 1105 AZ, Netherlands

Location

Haukeland University Hospital Klinisk Forskningspost

Bergen, 5021, Norway

Location

General Hospital Slovenj Gradec

Slovenj Gradec, 2380, Slovenia

Location

Hospital de Dia Quiron Zaragoza

Zaragoza, 50012, Spain

Location

Klinik und Poliklinik für Innere Medizin UniversitätsSpital Zürich

Zurich, Switzerland

Location

Institute of Metabolism and Systems Research

Edgbaston, Birmingham, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

The Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Salford Royal NHS Foundation Trust

Salford, M6 8HD, United Kingdom

Location

Related Publications (2)

• Azimpour K, Dorling P, Koulinska I, Kunduri S, Lan Z, Poritz J, Tremblay G, Raad-Faherty A. Health State Utility Values in Fabry Disease: Insights from the Pegunigalsidase Alfa Clinical Trials. Adv Ther. 2025 Mar;42(3):1421-1434. doi: 10.1007/s12325-024-03095-2. Epub 2025 Jan 23.

  PMID: 39847314 DERIVED

• Wallace EL, Goker-Alpan O, Wilcox WR, Holida M, Bernat J, Longo N, Linhart A, Hughes DA, Hopkin RJ, Tondel C, Langeveld M, Giraldo P, Pisani A, Germain DP, Mehta A, Deegan PB, Molnar MJ, Ortiz D, Jovanovic A, Muriello M, Barshop BA, Kimonis V, Vujkovac B, Nowak A, Geberhiwot T, Kantola I, Knoll J, Waldek S, Nedd K, Karaa A, Brill-Almon E, Alon S, Chertkoff R, Rocco R, Sakov A, Warnock DG. Head-to-head trial of pegunigalsidase alfa versus agalsidase beta in patients with Fabry disease and deteriorating renal function: results from the 2-year randomised phase III BALANCE study. J Med Genet. 2024 May 21;61(6):520-530. doi: 10.1136/jmg-2023-109445.

  PMID: 37940383 DERIVED

MeSH Terms

Conditions

Fabry Disease; Proteinuria

Interventions

agalsidase beta

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

* Small sample size * Randomization of 2:1

Results Point of Contact

• Title: Sari Alon, MSc
• Organization: Protalix Ltd.

sari@protalix.com

+972-4-9028100

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2016
• First Posted: June 10, 2016
• Study Start: June 1, 2016
• Primary Completion: October 1, 2021
• Study Completion: July 1, 2022
• Last Updated: September 13, 2023
• Results First Posted: August 2, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1); HU (1); FR (1); IT (1); NO (1); SL (1); ES (1); CH (1); NL (1); US (15); GB (4); CZ (1)