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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: October 2021

Interventions

  • Biological: PRX-102 (pegunigalsidase alfa)
    • PRX-102 1 mg/kg every 2 weeks
  • Biological: agalsidase beta
    • agalsidase beta 1 mg/kg every 2 weeks

Arms, Groups and Cohorts

  • Experimental: PRX-102 (pegunigalsidase alfa)
    • PRX-102 infusion every 2 weeks
  • Active Comparator: agalsidase beta
    • agalsidase beta infusion every 2 weeks

Clinical Trial Outcome Measures

Primary Measures

  • eGFR Slope
    • Time Frame: Every month for 2 years
    • eGFR Slope

Secondary Measures

  • Left Ventricular Mass Index (g/m2) by MRI
    • Time Frame: Every 12 months for 2 years
  • Plasma Lyso-Gb3
    • Time Frame: Every 3 months for 2 years
  • Plasma Gb3
    • Time Frame: Every 3 months for 2 years
  • Urine Lyso-GB3
    • Time Frame: Every 6 weeks for 2 years
  • Protein/creatinine ratio
    • Time Frame: Every 4 months for 24 months
  • Frequency of pain medication use
    • Time Frame: Every 2 weeks for 2 years
  • Exercise tolerance (Stress Test)
    • Time Frame: Every year for 2 years
  • Short Form Brief Pain Inventory (BPI)
    • Time Frame: Every 6 months for 2 years
  • Mainz Severity Score Index (MSSI)
    • Time Frame: Every 6 months for 2 years
  • Quality of life EQ-5D-5L
    • Time Frame: Every 6 months for 2 years

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 60 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Protalix
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Raul Chertkoff, MD, Study Director, Protalix Ltd.

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