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

• ClinicalTrials.gov Identifier: NCT03018730
• Recruitment Status: Completed
• First Posted: January 12, 2017
• Results First Posted: June 29, 2022
• Last Update Posted: August 26, 2022
• Sponsor: Protalix
• Information provided by (Responsible Party): Protalix

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Fabry Disease	Biological: PRX-102 (pegunigalsidase alfa)	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Study of the Safety and Efficacy of PRX-102 in Patients With Fabry Disease Currently Treated With REPLAGAL® (Agalsidase Alfa)
• Actual Study Start Date: May 17, 2017
• Actual Primary Completion Date: December 17, 2019
• Actual Study Completion Date: January 9, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Other Outcome Measures:

1. eGFR [ Time Frame: Baseline and Month 12 (week 52) ]
   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.
2. Mean Annualised Change in eGFR (Slope) [ Time Frame: Pre-switch, Post-switch ]

   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.

3. Plasma Lyso-Gb3 [ Time Frame: Baseline and month 12 (week 52) ]
   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.
4. Number of Participants According to Protein/Creatinine Ratio (UPCR) [ Time Frame: 12 months ]
   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
5. Left Ventricular Mass Index (g/m^2) by MRI [ Time Frame: 12 months ]
   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.
6. Quality of Life EQ VAS [ Time Frame: 12 months ]
   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").

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Australia, Victoria

Royal Melbourne Hospital

Parkville, Victoria, Australia, 3050

Canada, Nova Scotia

Capital Health

Halifax, Nova Scotia, Canada, B3H 1V8

Czechia

Vseobecna fakultni nemocnice v Praze

Prague, Czechia

Netherlands

Academisch Medisch Centrum

Amsterdam, Netherlands

Norway

Helse Bergen HF Haukeland Universitetssykehus

Bergen, Norway

Slovenia

General Hospital Slovenj Gradec

Slovenj Gradec, Slovenia, SI-2380

United Kingdom

Queen Elizabeth Hospital, Department of Neurology,

Edgbaston, Birmingham, United Kingdom, B15 2TH

The Royal Free Hospital

London, United Kingdom, NW3 2QG

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)

Documents provided by Protalix:

Study Protocol  [PDF] June 6, 2017

Statistical Analysis Plan  [PDF] April 28, 2020

More Information

• Responsible Party: Protalix
• ClinicalTrials.gov Identifier: NCT03018730
• Other Study ID Numbers: PB-102-F30
• First Posted: January 12, 2017
• Results First Posted: June 29, 2022
• Last Update Posted: August 26, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Protalix:

Fabry disease; Enzyme-Replacement Therapy; pegunigalsidase alfa; PRX-102; alpha galactosidase-A

Additional relevant MeSH terms:

Fabry Disease; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Lipid Metabolism Disorders