Fabry disease (a-galactosidase A deficiency) MedDRA version: 20.0 Level: PT Classification code 10016016 Term: Fabry's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Pegunigalsidase alfa
Product Code: PRX-102
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Pegunigalsidase
Sponsors
Protalix Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Eligible subjects must fulfill the following inclusion criteria: 1. Symptomatic adult Fabry disease patients, age 18-60 years 2. Males: Plasma and/or leucocyte alpha galactosidase activity (by activity assay) less than 30% mean normal levels and one or more of the described characteristic features of Fabry disease: i. neuropathic pain, ii. cornea verticillata, iii. clustered angiokeratoma 3. Females: a.historical genetic test results consistent with Fabry pathogenic mutation 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 4. Screening eGFR by CKD-EPI equation 40 to 120 mL/min/1.73 m2 5. Linear negative slope of eGFR of = 2 mL/min/1.73 m2 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) 6. 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 7. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 78 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: The presence of any of the following excludes a subject from study enrollment: 1. History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase beta 2. Known non-pathogenic Fabry mutations 3. History of renal dialysis or transplantation 4. 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) 5. Patient with a screening eGFR value between 91-120 mL/min/1.73m2, havingan historical eGFR value higher than 120ml/min/1.73m2 (during 9 to18 months before screening) 6. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated or dose changed in the 4 weeks prior to screening 7. Urine protein to creatinine ratio (UPCR) > 0.5 g/g (0.5 mg/mg or 500 mg/g) and not treated with an ACE inhibitor or ARB 8. Cardiovascular event (myocardial infarction, unstable angina) in the 6 month period before randomization 9. Congestive heart failure NYHA Class IV 10. Cerebrovascular event (stroke, transient ischemic attack) in the 6 month period before randomization 11. Known history of hypersensitivity to Gadolinium contrast agent that is not managed by the use of premedication 12. Female subjects who are pregnant, planning to become pregnant during the study, or are breastfeeding 13. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and efficacy of PRX-102 compared to agalsidase beta in Fabry disease patients with impaired renal function.;Secondary Objective: N/A; Primary end point(s): The primary efficacy parameter is the comparison of the mean annualized change (slope) in estimated glomerular filtration rate (eGFRCKD-EPI) between treatment groups. Safety endpoints: Changes from baseline in: ? Clinical laboratory tests ? Physical examination ? Assessment of the injection site ? ECG ? Treatment-emergent adverse events ? Ability to taper off infusion pre-medication throughout the first 3 months of the study ? Requirement for use of pre-medication overall to manage infusion reactions ? Treatment-emergent anti-PRX-102 antibodies ? Treatment-emergent anti-agalsidase beta antibodies ; Timepoint(s) of evaluation of this end point: Efficacy will be determined by the slope of eGFR over the course of the study. Two analyses of efficacy will be performed – at 12 and 24 months of treatment The eGFR endpoint is calculated based on serum creatinine and the serum creatinine will be collected in the following visits - screening - V1 baseline - All odd numbered visits | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints: ? Left Ventricular Mass Index (g/m2) by MRI ? Plasma Lyso-Gb3 ? Plasma Gb3 ? Urine Lyso-Gb3 ? Protein/Creatinine ratio spot urine test ? Frequency of pain medication use ? Exercise tolerance (Stress Test) ? Short Form Brief Pain Inventory (BPI) ? Mainz Severity Score Index (MSSI) ? Quality of life EQ-5D-5L ;Timepoint(s) of evaluation of this end point: In addition to the primary efficacy comparison described above, a series of secondary efficacy analyses will be performed to compare groups on the secondary outcomes of interest. | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Czech Republic, Finland, France, Germany, Hungary, Italy, Netherlands, Norway, Paraguay, Slovenia, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactRaul Chertkoff
Protalix Ltd.
Outcome results
None listed