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

NCT03018730 | Completed Phase 3 Results FDA Drug

• 1 other identifier: PB-102-F30
• Study Type: interventional
• Target: 22
• Locations: 7 countries
• Sites: 9

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.

Conditions

Fabry Disease

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03

  Results represent the number of treatment-emergent adverse events (TEAE) that were considered possibly, probably, or definitely related to treatment

  12 months

Other Outcomes (6)

• eGFR

  Baseline and Month 12 (week 52)

• Mean Annualised Change in eGFR (Slope)

  Pre-switch, Post-switch

• Plasma Lyso-Gb3

  Baseline and month 12 (week 52)

Study Arms (1)

PRX-102

EXPERIMENTAL

PRX-102 infusion every 2 weeks

Biological: PRX-102 (pegunigalsidase alfa)

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

Eligibility Criteria

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

You may qualify if:

• Age: 18-60 years
• A documented diagnosis of Fabry disease
• 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
• 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
• Treatment with agalsidase alfa for at least 2 years and on a stable dose (\>80% labelled dose/kg) for at least 6 months
• eGFR ≥ 40 ml/min/1.73 m2 by CKD-EPI equation
• Availability of at least 2 historical serum creatinine evaluations since starting agalsidase alfa treatment and not more than 2 years
• 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

You may not qualify if:

• History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase alfa
• 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
• Urine protein to creatinine ratio (UPCR) \> 0.5 g/g and not treated with an ACE inhibitor or ARB
• Known history of hypersensitivity to Gadolinium contrast agent that was not managed by the use of premedication;
• Females who are pregnant, planning to become pregnant during the study, or are breast feeding
• Cardiovascular event (myocardial infarction, unstable angina) in the 6 month period before screening
• Congestive heart failure NYHA Class IV
• Cerebrovascular event (stroke, transient ischemic attack) in the 6 month period before screening
• Presence of any medical, emotional, behavioral or psychological condition that, in the judgment of the Investigator and/or Medical Monitor 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 (9)

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Capital Health

Halifax, Nova Scotia, B3H 1V8, Canada

Location

Vseobecna fakultni nemocnice v Praze

Prague, Czechia

Location

Academisch Medisch Centrum

Amsterdam, Netherlands

Location

Helse Bergen HF Haukeland Universitetssykehus

Bergen, Norway

Location

General Hospital Slovenj Gradec

Slovenj Gradec, SI-2380, Slovenia

Location

Queen Elizabeth Hospital, Department of Neurology,

Edgbaston, Birmingham, B15 2TH, 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

• Linhart A, Dostalova G, Nicholls K, West ML, Tondel C, Jovanovic A, Giraldo P, Vujkovac B, Geberhiwot T, Brill-Almon E, Alon S, Chertkoff R, Rocco R, Hughes D. Safety and efficacy of pegunigalsidase alfa in patients with Fabry disease who were previously treated with agalsidase alfa: results from BRIDGE, a phase 3 open-label study. Orphanet J Rare Dis. 2023 Oct 21;18(1):332. doi: 10.1186/s13023-023-02937-6.

  PMID: 37865771 DERIVED

MeSH Terms

Conditions

Fabry Disease

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

Results Point of Contact

• Title: Sari Alon
• Organization: Protalix Ltd.

sari@protalix.com

+972-4-9028100

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2017
• First Posted: January 12, 2017
• Study Start: May 17, 2017
• Primary Completion: December 17, 2019
• Study Completion: January 9, 2020
• Last Updated: September 13, 2023
• Results First Posted: June 29, 2022

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1); GB (3); SL (1); CZ (1); NL (1); AU (1); CA (1)