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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
78
PRX-102 1 mg/kg every 2 weeks
agalsidase beta 1 mg/kg every 2 weeks
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.
Time frame: 24 months
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.
Time frame: Baseline and Month 24
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.
Time frame: Baseline and Month 24
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.
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UAB Medicine
Birmingham, Alabama, United States
Phoenix Children's Hospital
Phoenix, Arizona, United States
University of California Irvine Center
Orange, California, United States
University of California San Diego
San Diego, California, United States
Emory University School of Medicine
Atlanta, Georgia, United States
University of Iowa Hosptials and Clinics
Iowa City, Iowa, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Infusion Associates
Grand Rapids, Michigan, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States
...and 19 more locations
Time frame: Baseline and Month 24
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.
Time frame: Baseline and Month 24
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.
Time frame: Baseline and Month 24
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.
Time frame: Baseline and Month 24
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.
Time frame: Baseline and Month 24