Safety, Efficacy, & PK of PRX-102 in Patients With Fabry Disease Administered Intravenously Every 4 Weeks

NCT03180840 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: PB-102-F50
• Study Type: interventional
• Target: 30
• Locations: 7 countries
• Sites: 14

Brief Summary

This open-label switchover study will assess the safety, efficacy, and pharmacokinetics of pegunigalsidase alfa (PRX-102) 2 mg/kg administered every 4 weeks for 52 weeks in Fabry patients previously treated with ERT: agalsidase alfa or agalsidase beta for at least 3 years. Safety and efficacy exploratory endpoints will be evaluated throughout the study period and pharmacokinetics will be obtained on Day 1 and Week 52.

Conditions

Fabry Disease

Keywords

Enzyme-Replacement Therapy; pegunigalsidase alfa; Fabry Disease

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-related Adverse Events (TEAE) 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.

  Month 12

Other Outcomes (6)

• Estimated Glomerular Filtration Rate (eGFR)

  Baseline and Month 12 (week 52)

• Plasma Lyso-Gb3

  Baseline and month 12 (Week 52)

• Quality of Life by EQ-VAS

  Baseline and 12 months (week 52)

Study Arms (1)

Pegunigalsidase alfa

EXPERIMENTAL

Pegunigalsidase alfa 2 mg/kg intravenous infusion every 4 weeks

Biological: Pegunigalsidase alfa

Interventions

Pegunigalsidase alfa BIOLOGICAL

Pegunigalsidase alfa 2 mg/kg every 4 weeks

Also known as: PRX-102, Recombinant human alpha galactosidase-A

Pegunigalsidase alfa

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 the laboratory reference ranges and one or more of the characteristic features of Fabry disease
• Neuropathic pain
• Cornea verticillata
• 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
• Neuropathic pain
• Cornea verticillata
• Clustered angiokeratoma
• Treatment with agalsidase alfa or agalsidase beta for at least 3 years and on a stable dose (\>80% labelled dose/kg) for at least last 6 months
• eGFR ≥ 30 mL/min/1.73m\^2 by CKD-EPI equation at screening visit
• Availability of at least 3 historical serum creatinine evaluations since starting agalsidase alfa or agalsidase beta treatment and not more than 2 years old
• Female patients and male patients whose co-partners are of child-bearing potential agree to use a medically accepted, highly effective method of contraception. These include combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, or sexual abstinence
• Patients whose clinical condition, in the opinion of the Investigator, is suitable for treatment with ERT every 4 weeks.

You may not qualify if:

• The presence of any of the following excludes a subject from study enrollment:
• History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase alfa or agalsidase beta
• History of renal dialysis or transplantation
• Linear negative slope of eGFR of ≥ 2 mL/min/1.73m\^2/year based on at least 4 serum creatinine values over approximately 2 years (including the value obtained at the screening visit)
• 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 post renal 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) at screening \> 0.5 g/g or mg/mg or 500 mg/g and not treated with an ACE inhibitor or ARB
• 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
• 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 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 (14)

UAB Medicine

Birmingham, Alabama, 35294, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Infusion Associates

Grand Rapids, Michigan, 49525, United States

Location

Institute of Metabolic Disease

Dallas, Texas, 75226, United States

Location

University of Utah Hospital & Clinics

Salt Lake City, Utah, 84132, United States

Location

O & O Alpan

Fairfax, Virginia, 22030, United States

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

Fakultní poliklinika Všeobecné fakultní nemocnice v Praze

Prague, 120 00, Czechia

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Azienda Ospedaliera Universitaria "Federico II"

Napoli, Italy

Location

Helse Bergen HF Haukeland Universitetssykehus

Bergen, 5021, Norway

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

The Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Related Publications (1)

• 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

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

Limitations and Caveats

Small number of subjects.

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

Model Details: Switch over study in patients previously receiving either agalsidase alfa or agalsidase beta and switched to pegunigalsidase alfa (PRX-102) for the treatment of Fabry disease.

Study Record Dates

• First Submitted: May 29, 2017
• First Posted: June 8, 2017
• Study Start: July 10, 2017
• Primary Completion: August 1, 2020
• Study Completion: August 1, 2020
• Last Updated: September 13, 2023
• Results First Posted: January 5, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1); NO (1); US (7); IT (1); GB (2); DK (1); BE (1)