Safety and Efficacy of PRX-102 in Patients With Fabry Disease Currently Treated With REPLAGAL® (Agalsidase Alfa)

An Open Label Study of the Safety and Efficacy of PRX-102 in Patients With Fabry Disease Currently Treated With REPLAGAL® (Agalsidase Alfa)

This is an open label switch over study to assess the safety and efficacy of PRX-102 (pegunigalsidase alfa). Patients treated with agalsidase alfa for at least 2 years and on a stable dose (>80% labelled dose/kg) for at least 6 months. Patients will be screened and evaluated over 3 months while continuing on agalsidase alfa. Following the screening period, the patient will be enrolled and switched from their agalsidase alfa treatment to receive intravenous (IV) infusions of PRX-102 1 mg/kg every two weeks for 12 months. No more than 25% of treated patients will be female.

Study Overview

• Status: Completed
• Conditions: Fabry Disease
• Intervention / Treatment: Biological: PRX-102 (pegunigalsidase alfa)

Detailed Description

Dosage and administration details:

pegunigalsidase alfa individual dose for each patient was prepared according to the patient's weight. Pegunigalsidase alfa administrated at 1 mg/kg, intravenously over 3 hours, every 2 weeks. After the first 2 months of treatment with pegunigalsidase alfa, infusion time may be reduced gradually to 1.5 hours pending patient tolerability.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V8
      • Capital Health
• Czechia
  • Prague, Czechia
    • Vseobecna fakultni nemocnice v Praze
• Netherlands
  • Amsterdam, Netherlands
    • Academisch Medisch Centrum
• Norway
  • Bergen, Norway
    • Helse Bergen HF Haukeland Universitetssykehus
• Slovenia
  • Slovenj Gradec, Slovenia, SI-2380
    • General Hospital Slovenj Gradec
• United Kingdom
  • London, United Kingdom, NW3 2QG
    • The Royal Free Hospital
  • Salford, United Kingdom, M6 8HD
    • Salford Royal NHS Foundation Trust
  • Birmingham
    • Edgbaston, Birmingham, United Kingdom, B15 2TH
      • Queen Elizabeth Hospital, Department of Neurology,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age: 18-60 years
2. A documented diagnosis of Fabry disease
3. Males: plasma and/or leucocyte alpha galactosidase activity (by activity assay) less than lower limit of normal according to laboratory range and one or more of the characteristic features of Fabry disease i. Neuropathic pain ii. Cornea verticillata iii. Clustered angiokeratoma
4. Females: historical genetic test results consistent with Fabry mutations, or in the case of novel mutations a first degree male relative with Fabry disease, and one or more of the characteristic features of Fabry disease i. Neuropathic pain ii. Cornea verticillata iii. Clustered angiokeratoma
5. Treatment with agalsidase alfa for at least 2 years and on a stable dose (>80% labelled dose/kg) for at least 6 months
6. eGFR ≥ 40 ml/min/1.73 m2 by CKD-EPI equation
7. Availability of at least 2 historical serum creatinine evaluations since starting agalsidase alfa treatment and not more than 2 years
8. Female patients and male patients whose co-partners are of child-bearing potential agree to use a medically acceptable method of contraception, not including the rhythm method

Exclusion Criteria:

1. History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase alfa
2. History of renal dialysis or transplantation
3. 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)
4. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated or dose changed in the 4 weeks prior to screening
5. Urine protein to creatinine ratio (UPCR) > 0.5 g/g and not treated with an ACE inhibitor or ARB
6. Known history of hypersensitivity to Gadolinium contrast agent that was not managed by the use of premedication;
7. Females who are pregnant, planning to become pregnant during the study, or are breast feeding
8. Cardiovascular event (myocardial infarction, unstable angina) in the 6 month period before screening
9. Congestive heart failure NYHA Class IV
10. Cerebrovascular event (stroke, transient ischemic attack) in the 6 month period before screening
11. Presence of any medical, emotional, behavioral or psychological condition that, in the judgment of the Investigator and/or Medical Monitor would interfere with the patient's compliance with the requirements of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRX-102; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03	Results represent the number of treatment-emergent adverse events (TEAE) that were considered possibly, probably, or definitely related to treatment	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
eGFR	eGFR was calculated based on the serum creatinine values that were assessed at weeks 4, 8, 12, 16, 20, 26, 30, 34, 38, 42, 46, 52 according to the CKD-EPI formula, baseline and Month 12 (week 52) reported. The absolute change in eGFR from baseline measurement at visit 1 prior to first PRX-102 infusion to last measurement at Month 12 was summarized using descriptive statistics.	Baseline and Month 12 (week 52)
Mean Annualised Change in eGFR (Slope)	The annualized change in eGFR (slope) per patient was calculated with all available eGFR values using a linear regression. The mean pre-switch slope is the eGFR slope during screening period and pre-infusion visit 1 (while on Replagal®). The mean post-switch slope is the eGFR slope during PRX-102 treatment, calculated based on eGFR vales at weeks 4, 8, 12, 16, 20, 26, 30, 34, 38, 42, 46, 52 after visit 1. The mean change in eGFR slope from pre- to post-switch is the mean difference between the two slopes. eGFR was calculated based on the serum creatinine values according to the CKD-EPI formula.	Pre-switch, Post-switch
Plasma Lyso-Gb3	Plasma Lyso-Gb3 is Fabry disease specific biomarker that can assess treatment outcome which was measured at Baseline and weeks 12, 26, 38, 52. Baseline and Month 12 (week 52) reported.	Baseline and month 12 (week 52)
Number of Participants According to Protein/Creatinine Ratio (UPCR)	Urine Protein to Creatinine Ratio (UPCR), assessed by spot urine test, at Month 12 (Week 52).Number of Participants According to Protein/Creatinine Ratio (UPCR) level	12 months
Left Ventricular Mass Index (g/m^2) by MRI	Left ventricular mass was determined based on cardiac MRI data and the LVMI was indexed to patient's body surface area (g/m^2). In male patients the normal range for LVMI was 57-91 g/m^2, in female patients 47-77 g/m^2.	12 months
Quality of Life EQ VAS	The EQ VAS, of the EQ 5D 5L questionnaire, records the subject's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' (score "100") and 'Worst imaginable health state' (score "0").	12 months

Collaborators and Investigators

• Sponsor: Protalix
• Collaborators: Chiesi Farmaceutici S.p.A.

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2017
• Primary Completion (Actual): December 17, 2019
• Study Completion (Actual): January 9, 2020

Study Registration Dates

• First Submitted: January 9, 2017
• First Submitted That Met QC Criteria: January 10, 2017
• First Posted (Estimated): January 12, 2017

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Fabry disease; PRX-102; pegunigalsidase alfa; Enzyme-Replacement Therapy; alpha galactosidase-A
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Fabry Disease
• Other Study ID Numbers: PB-102-F30

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No