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

Sponsor
Protalix (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02795676
Collaborator
(none)
78
Enrollment
29
Locations
2
Arms
71
Anticipated Duration (Months)
2.7
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized, double blind, active control study of PRX-102 (pegunigalsidase alfa) in Fabry disease patients with impaired renal function. Patients treated for approximately 1 year with agalsidase beta and on a stable dose for at least 6 months will be screened and then randomized to continue treatment with 1mg/kg agalsidase beta or to treatment with 1 mg/kg of PRX-102. The identity of the enzyme will be blinded to the patient and the investigator. Patients will receive intravenous infusions every two weeks. Patients will be randomized in a 2:1 ratio of PRX-102 to agalsidase beta. Randomization will be stratified by urinary protein to creatinine ratio (UPCR) of < or ≥ 1 g/g by spot urine sample. No more than 50% of the patients will be female.

Condition or Disease Intervention/Treatment Phase
  • Biological: PRX-102 (pegunigalsidase alfa)
  • Biological: agalsidase beta
 Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
78 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jun 1, 2016
Actual Primary Completion Date :
Oct 1, 2021
Anticipated Study Completion Date :
May 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: PRX-102 (pegunigalsidase alfa)

PRX-102 infusion every 2 weeks

Biological: PRX-102 (pegunigalsidase alfa)
PRX-102 1 mg/kg every 2 weeks
Other Names:
  • pegunigalsidase alfa
  • Recombinant human alpha galactosidase-A

    		•
    Active Comparator: agalsidase beta

    agalsidase beta infusion every 2 weeks

    Biological: agalsidase beta
    agalsidase beta 1 mg/kg every 2 weeks
    Other Names:
  • Fabrazyme

    		•

    Outcome Measures

    Primary Outcome Measures

    1. eGFR Slope [Every month for 2 years]

      eGFR Slope

    Secondary Outcome Measures

    1. Left Ventricular Mass Index (g/m2) by MRI [Every 12 months for 2 years]

    2. Plasma Lyso-Gb3 [1.5 month, every 3 months for 1 year and then every 6 months up to 24 months]

    3. Plasma Gb3 [1.5 month, every 3 months for 1 year and then every 6 months up to 24 months]

    4. Urine Lyso-GB3 [1.5 month, every 3 months for 1 year and then every 6 months up to 24 months]

    5. Protein/creatinine ratio [Every 3 months for 2 years]

    6. Frequency of pain medication use [Every 2 weeks for 2 years]

    7. Exercise tolerance (Stress Test) [Every year for 2 years]

    8. Short Form Brief Pain Inventory (BPI) [Every 6 months for 2 years]

    9. Mainz Severity Score Index (MSSI) [Every 6 months for 2 years]

    10. Quality of life EQ-5D-5L [Every 6 months for 2 years]

    Other Outcome Measures

    1. PRX-102 pharmacokinetics [Day 1, 6 months, 12 months and 24 months]

      PRX-102 pharmacokinetics parameters

    2. Anti-drug IgG antibodies [Every 2 weeks for 1 month, then every month for the first 6 months and every 3 month up to 24 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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
    1. neuropathic pain

    1. cornea verticillata

    2. clustered angiokeratoma

    1. Females:

    1. historical genetic test results consistent with Fabry pathogenic mutation and one or more of the described characteristic features of Fabry disease:

    2. neuropathic pain

    1. cornea verticillata

    2. clustered angiokeratoma

    1. 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

    2. neuropathic pain

    1. cornea verticillata

    2. 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UAB Medicine Birmingham Alabama United States 35233
    2 Phoenix Children's Hospital Phoenix Arizona United States 85016
    3 University of California Irvine Center Orange California United States 92868
    4 University of California San Diego San Diego California United States 92093
    5 Emory University School of Medicine Atlanta Georgia United States 30322
    6 University of Iowa Hosptials and Clinics Iowa City Iowa United States 52242
    7 Massachusetts General Hospital Boston Massachusetts United States 02114
    8 Infusion Associates Grand Rapids Michigan United States 49525
    9 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
    10 Children's Hospital of Pittsburgh Pittsburgh Pennsylvania United States 15224
    11 Institute of Metabolic Disease, Baylor Healthcare Dallas Texas United States 75226
    12 Renal Disease Research Institute, LLC - Dallas Dallas Texas United States 75235
    13 Eccles Primary Children's Outpatient Services Building Salt Lake City Utah United States 84132
    14 O+O Alpan LLC Fairfax Virginia United States 22030
    15 Medical College of Wisconsin Milwaukee Wisconsin United States 53226-3596
    16 Vseobecna fakultni nemocnice v Praze Prague Czech Republic Czechia 12808
    17 Turku University Central Hospital Turku Finland 20520
    18 Hôpital Raymond Poincaré Paris France 92380
    19 Semmelweis Egyetem Budapest Hungary 1083
    20 Azienda Ospedaliera Universitaria "Federico II" Napoli Italy
    21 Academisch Medisch Centrum Amsterdam Netherlands 1105 AZ
    22 Haukeland University Hospital Klinisk Forskningspost Bergen Norway 5021
    23 General Hospital Slovenj Gradec Slovenj Gradec Slovenia 2380
    24 Hospital de Dia Quiron Zaragoza Zaragoza Spain 50012
    25 Klinik und Poliklinik für Innere Medizin UniversitätsSpital Zürich Zürich Switzerland
    26 Institute of Metabolism and Systems Research Edgbaston Birmingham United Kingdom
    27 Addenbrooke's Hospital Cambridge United Kingdom CB2 0QQ
    28 The Royal Free Hospital London United Kingdom NW3 2QG
    29 Salford Royal NHS Foundation Trust Salford United Kingdom M6 8HD

    Sponsors and Collaborators

    • Protalix

    Investigators

    • Study Director: Raul Chertkoff, MD, Protalix Ltd.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Protalix
    ClinicalTrials.gov Identifier:
    NCT02795676
    Other Study ID Numbers:
    • PB-102-F20
    First Posted:
    Jun 10, 2016
    Last Update Posted:
    Apr 7, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Keywords provided by Protalix
    Glomerular filtration rate
    Proteinuria
    PRX-102
    pegunigalsidase alfa
    Fabry Disease
    Additional relevant MeSH terms:
    Fabry Disease

    Study Results

    No Results Posted as of Apr 7, 2022