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Fabry DiseasePhase 3BALANCENCT02795676

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

A Phase 3 study testing PRX-102 (pegunigalsidase alfa) and agalsidase beta in people with Fabry Disease, run by Protalix at 29 sites in 12 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Fabry Disease
What is being tested?
PRX-102 (pegunigalsidase alfa) and agalsidase beta
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
29 sitesin 12 countries
Study dates
Jun 2016to Jul 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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
  • neuropathic pain
  • cornea verticillata
  • clustered angiokeratoma
  • Females:
Show all 18Show fewer
  • historical genetic test results consistent with Fabry pathogenic mutation and one or more of the described characteristic features of Fabry disease:
  • neuropathic pain
  • cornea verticillata
  • clustered angiokeratoma
  • 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
  • neuropathic pain
  • cornea verticillata
  • 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.

Who cannot join

  • 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)
Show all 13Show fewer
  • 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

Trial locations and contacts

29 sites in 12 countries.

29 sites in 12 countries

United States15 sites
  • Emory University School of Medicine

    Atlanta, Georgia, 30322

  • UAB Medicine

    Birmingham, Alabama, 35233

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Institute of Metabolic Disease, Baylor Healthcare

    Dallas, Texas, 75226

  • Renal Disease Research Institute, LLC - Dallas

    Dallas, Texas, 75235

  • O+O Alpan LLC

    Fairfax, Virginia, 22030

  • Infusion Associates

    Grand Rapids, Michigan, 49525

  • University of Iowa Hosptials and Clinics

    Iowa City, Iowa, 52242

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226-3596

  • University of California Irvine Center

    Orange, California, 92868

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016

  • Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15224

  • Eccles Primary Children's Outpatient Services Building

    Salt Lake City, Utah, 84132

  • University of California San Diego

    San Diego, California, 92093

Other trials in United States

United Kingdom4 sites
  • Addenbrooke's Hospital

    Cambridge, CB2 0QQ

  • Institute of Metabolism and Systems Research

    Edgbaston, Birmingham

  • The Royal Free Hospital

    London, NW3 2QG

  • Salford Royal NHS Foundation Trust

    Salford, M6 8HD

Other trials in United Kingdom

Czechia1 site
  • Vseobecna fakultni nemocnice v Praze

    Prague, Czech Republic, 12808

Other trials in Czechia

Finland1 site
  • Turku University Central Hospital

    Turku, 20520

Other trials in Finland

France1 site
  • Hôpital Raymond Poincaré

    Paris, 92380

Other trials in France

Hungary1 site
  • Semmelweis Egyetem

    Budapest, 1083

Other trials in Hungary

Italy1 site
  • Azienda Ospedaliera Universitaria "Federico II"

    Naples

Other trials in Italy

Netherlands1 site
  • Academisch Medisch Centrum

    Amsterdam, 1105 AZ

Other trials in Netherlands

Norway1 site
  • Haukeland University Hospital Klinisk Forskningspost

    Bergen, 5021

Other trials in Norway

Slovenia1 site
  • General Hospital Slovenj Gradec

    Slovenj Gradec, 2380

Other trials in Slovenia

Spain1 site
  • Hospital de Dia Quiron Zaragoza

    Zaragoza, 50012

Other trials in Spain

Switzerland1 site
  • Klinik und Poliklinik für Innere Medizin UniversitätsSpital Zürich

    Zurich

Other trials in Switzerland

About this study

Official title: A Randomized, Double Blind, Active Control Study of the Safety and Efficacy of PRX-102 Compared to Agalsidase Beta on Renal Function in Patients With Fabry Disease Previously Treated With Agalsidase Beta

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.

Read the 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
Being tested
PRX-102 (pegunigalsidase alfa), agalsidase beta
Keywords
Glomerular filtration rate, Proteinuria, PRX-102, pegunigalsidase alfa, Fabry Disease
Medical subject headings
Fabry Disease, Proteinuria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PRX-102 (pegunigalsidase alfa)Biological

    Also called pegunigalsidase alfa, Recombinant human alpha galactosidase-A

    PRX-102 1 mg/kg every 2 weeks

  • agalsidase betaBiological

    Also called Fabrazyme

    agalsidase beta 1 mg/kg every 2 weeks

Study groups in NCT02795676
Study groupRoleWhat they receive
PRX-102 (pegunigalsidase alfa)ExperimentalPRX-102 infusion every 2 weeks
Receives: Biological: PRX-102 (pegunigalsidase alfa)
agalsidase betaActive comparatoragalsidase beta infusion every 2 weeks
Receives: Biological: agalsidase beta

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 24 months

Secondary outcomes (7)
  1. Estimated Glomerular Filtration Rate (eGFR)

    eGFR was calculated based on measured serum creatinine levels according to the CKD-EPI formula. The median values obtained at baseline and at Month 24 are reported.

    The change in eGFR from baseline measurement prior to first infusion to last measurement at Month 24 was summarized using descriptive statistics.

    The change was calculated for each subject and the reported value is the median (full range) of these changes.

    Measured: Baseline and Month 24

  2. Plasma Lyso-Gb3

    Globotriaosylsphingosine (lyso-Gb3) is a Fabry disease-specific biomarker measured in the plasma. The median concentrations obtained at baseline and at Month 24, and the change from baseline to Month 24 in median concentration, are reported.

    The change in Lyso-Gb3 from baseline measurement prior to first infusion to last measurement at Month 24 was summarized using descriptive statistics.

    The change was calculated for each subject and the reported value is the median (full range) of these changes.

    Measured: Baseline and Month 24

  3. Short Form Brief Pain Inventory (BPI)

    The Short Form Brief Pain Inventory ( BPI) questioner is self-completed by patients regarding pain severity and interference.

    Descriptive statistics summarize the findings for the change from baseline at Week 104 for "Pain at Its Worst in Last 24 Hours".

    The severity of various aspects of pain scored on a scale of 0 to 10 ( no pain / pain as bad as you can imagine).

    The change in BPI from baseline measurement prior to first infusion to the last measurement at Month 24 was summarized using descriptive statistics.

    The change was calculated for each subject and the reported value is the mean (Standard Error) of these changes.

    Measured: Baseline and Month 24

  4. Mainz Severity Score Index (MSSI)

    The Mainz Severity Score Index (MSSI) is an instrument that is specifically designed to measure the severity of Fabry disease signs/symptoms and to monitor the clinical course of the disease. The MSSI is administered by the investigator, and yields scores for general, neurological, cardiovascular, renal, and overall assessments. The overall score range from 0 to 76. An overall score of less than 20 points is considered mild signs and symptoms of Fabry disease, 20 to 40 is considered moderate, and greater than 40 is considered severe.

    The change in overall MSSI score from baseline measurement prior to first infusion to the last measurement at Month 24 was summarized using descriptive statistics.

    The change was calculated for each subject and the reported value is the mean (Standard Error) of these changes.

    Measured: Baseline and Month 24

  5. Urine Protein/Creatinine Ratio (UPCR)

    The UPCR provides an estimate of protein excretion in urine, and is used as an indicator of the extent of chronic kidney disease. It was classified into three categories: 1) UPCR ≤ 0.5 gr/gr, 2) 0.5 gr/gr < UPCR < 1 gr/gr, 3) 1 gr/gr ≤ UPCR. The results are presented as the percentage of patients (%) in each category at baseline and Month 24.

    There are no statistical analyses for this endpoint.

    Measured: Baseline and Month 24

  6. Left Ventricular Mass Index With Hypertrophy at Baseline

    Left Ventricular Mass Index (LVMI) based on cardiac MRI for patients with hypertrophy at baseline (for males, hypertrophy is above 91 g/m^2 and for females, above 77 g/m^2).

    The change in LVMI from baseline measurement prior to first infusion to the last measurement at Month 24 was summarized using descriptive statistics.

    The change was calculated for each subject and the reported value is the median (full range) of these changes.

    Measured: Baseline and Month 24

  7. Left Ventricular Mass Index Without Hypertrophy at Baseline

    Left Ventricular Mass Index (LVMI) based on cardiac MRI for patients without hypertrophy at baseline (for males, hypertrophy is above 91 g/m^2 and for females, above 77 g/m^2).

    The change in LVMI from baseline measurement prior to first infusion to the last measurement at Month 24 was summarized using descriptive statistics.

    The change was calculated for each subject and the reported value is the median (full range) of these changes.

    Measured: Baseline and Month 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jun 2016 (estimated)
  2. Study startJun 2016
  3. Primary completionOct 2021
  4. Study completionJul 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02795676
Sponsor's protocol ID
PB-102-F20
Acronym
BALANCE
Status last verified
Sep 2023
First submitted
2 Jun 2016
Last updated
13 Sep 2023
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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.

    PubMed 39847314
  • 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.

    PubMed 37940383

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing PRX-102 (pegunigalsidase alfa) and agalsidase beta in people with Fabry Disease, run by Protalix at 29 sites in 12 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in United States, United Kingdom, Czechia, Finland, France and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Annualized Change (Slope) in Estimated Glomerular Filtration Rate (eGFR) (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02795676, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2023.

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