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

NCT ID: NCT02795676

Last Updated: 2023-09-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2022-07-31

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.

Detailed Description

This was a randomized, double-blind, active control study examining the safety and efficacy of pegunigalsidase alfa (PRX-102) in Fabry disease patients with impaired renal function. Participants had to have been taking the licensed ERT drug agalsidase beta (Fabrazyme®) for at least 1 year prior to study entry, and to have been on a stable dose of that product for at least the last 6 months. Since the disease expresses itself differently in males and females, gender could have an impact on the therapeutic effect; thus, there was additionally a requirement that no more than 50% of the patients could be female.

Following screening, eligible patients were randomized in a 2:1 ratio to either switch to PRX-102 or continue treatment with agalsidase beta, with randomization stratified according to whether the urine protein-to-creatinine ratio (UPCR), a measure of kidney function, was above or below a specified threshold. Both products were administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg, for up to 24 months. Both patients and study staff were blinded as to which treatment was being given.

Patients who completed the study were invited to continue in a long-term open-label extension study, PB-102-F60, in which all participants would receive PRX-102 1 mg/kg every 2 weeks.

Conditions

Fabry Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

PRX-102 (pegunigalsidase alfa)

PRX-102 infusion every 2 weeks

Group Type: EXPERIMENTAL

PRX-102 (pegunigalsidase alfa)

Intervention Type: BIOLOGICAL

PRX-102 1 mg/kg every 2 weeks

agalsidase beta

agalsidase beta infusion every 2 weeks

Group Type: ACTIVE_COMPARATOR

agalsidase beta

Intervention Type: BIOLOGICAL

agalsidase beta 1 mg/kg every 2 weeks

Interventions

PRX-102 (pegunigalsidase alfa)

PRX-102 1 mg/kg every 2 weeks

Intervention Type: BIOLOGICAL

agalsidase beta

agalsidase beta 1 mg/kg every 2 weeks

Intervention Type: BIOLOGICAL

Other Intervention Names

pegunigalsidase alfa; Recombinant human alpha galactosidase-A; Fabrazyme

Eligibility Criteria

Inclusion Criteria

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

1. 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chiesi Farmaceutici S.p.A.

INDUSTRY

Sponsor Role: collaborator

Protalix

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UAB Medicine

Birmingham, Alabama, United States

Phoenix Children's Hospital

Phoenix, Arizona, United States

University of California Irvine Center

Orange, California, United States

University of California San Diego

San Diego, California, United States

Emory University School of Medicine

Atlanta, Georgia, United States

University of Iowa Hosptials and Clinics

Iowa City, Iowa, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Infusion Associates

Grand Rapids, Michigan, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Institute of Metabolic Disease, Baylor Healthcare

Dallas, Texas, United States

Renal Disease Research Institute, LLC - Dallas

Dallas, Texas, United States

Eccles Primary Children's Outpatient Services Building

Salt Lake City, Utah, United States

O+O Alpan LLC

Fairfax, Virginia, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Vseobecna fakultni nemocnice v Praze

Prague, Czech Republic, Czechia

Turku University Central Hospital

Turku, , Finland

Hôpital Raymond Poincaré

Paris, , France

Semmelweis Egyetem

Budapest, , Hungary

Azienda Ospedaliera Universitaria "Federico II"

Napoli, , Italy

Academisch Medisch Centrum

Amsterdam, , Netherlands

Haukeland University Hospital Klinisk Forskningspost

Bergen, , Norway

General Hospital Slovenj Gradec

Slovenj Gradec, , Slovenia

Hospital de Dia Quiron Zaragoza

Zaragoza, , Spain

Klinik und Poliklinik für Innere Medizin UniversitätsSpital Zürich

Zurich, , Switzerland

Institute of Metabolism and Systems Research

Edgbaston, Birmingham, United Kingdom

Addenbrooke's Hospital

Cambridge, , United Kingdom

The Royal Free Hospital

London, , United Kingdom

Salford Royal NHS Foundation Trust

Salford, , United Kingdom

Countries

United States; Czechia; Finland; France; Hungary; Italy; Netherlands; Norway; Slovenia; Spain; Switzerland; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 39847314 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37940383 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

PB-102-F20

Identifier Type: -

Identifier Source: org_study_id