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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
Information provided by (Responsible Party):
Protalix

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.

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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

Resource links provided by the National Library of Medicine


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




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").



Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03018730


Locations
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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
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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

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Responsible Party: Protalix
ClinicalTrials.gov Identifier: NCT03018730    
Other Study ID Numbers: PB-102-F30
First Posted: January 12, 2017    Key Record Dates
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

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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:
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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