- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03018730
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)
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Victoria
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Parkville, Victoria, Australia, 3050
- Royal Melbourne Hospital
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Nova Scotia
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Halifax, Nova Scotia, Canada, B3H 1V8
- Capital Health
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Prague, Czechia
- Vseobecna fakultni nemocnice v Praze
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Amsterdam, Netherlands
- Academisch Medisch Centrum
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Bergen, Norway
- Helse Bergen HF Haukeland Universitetssykehus
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Slovenj Gradec, Slovenia, SI-2380
- General Hospital Slovenj Gradec
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London, United Kingdom, NW3 2QG
- The Royal Free Hospital
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Salford, United Kingdom, M6 8HD
- Salford Royal NHS Foundation Trust
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Birmingham
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Edgbaston, Birmingham, United Kingdom, B15 2TH
- Queen Elizabeth Hospital, Department of Neurology,
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age: 18-60 years
- A documented diagnosis of Fabry disease
- 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
- 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
- Treatment with agalsidase alfa for at least 2 years and on a stable dose (>80% labelled dose/kg) for at least 6 months
- eGFR ≥ 40 ml/min/1.73 m2 by CKD-EPI equation
- Availability of at least 2 historical serum creatinine evaluations since starting agalsidase alfa treatment and not more than 2 years
- 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:
- History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase alfa
- History of renal dialysis or transplantation
- 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)
- Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated or dose changed in the 4 weeks prior to screening
- Urine protein to creatinine ratio (UPCR) > 0.5 g/g and not treated with an ACE inhibitor or ARB
- Known history of hypersensitivity to Gadolinium contrast agent that was not managed by the use of premedication;
- Females who are pregnant, planning to become pregnant during the study, or are breast feeding
- Cardiovascular event (myocardial infarction, unstable angina) in the 6 month period before screening
- Congestive heart failure NYHA Class IV
- Cerebrovascular event (stroke, transient ischemic attack) in the 6 month period before screening
- 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)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: PRX-102
PRX-102 infusion every 2 weeks
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PRX-102 1 mg/kg every 2 weeks
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03
Time Frame: 12 months
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Results represent the number of treatment-emergent adverse events (TEAE) that were considered possibly, probably, or definitely related to treatment
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12 months
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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eGFR
Time Frame: Baseline and Month 12 (week 52)
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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.
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Baseline and Month 12 (week 52)
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Mean Annualised Change in eGFR (Slope)
Time Frame: Pre-switch, Post-switch
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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
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Plasma Lyso-Gb3
Time Frame: Baseline and month 12 (week 52)
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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.
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Baseline and month 12 (week 52)
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Number of Participants According to Protein/Creatinine Ratio (UPCR)
Time Frame: 12 months
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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
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12 months
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Left Ventricular Mass Index (g/m^2) by MRI
Time Frame: 12 months
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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.
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12 months
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Quality of Life EQ VAS
Time Frame: 12 months
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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").
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12 months
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Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
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)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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ProtalixChiesi Farmaceutici S.p.A.CompletedFabry DiseaseUnited States, Spain, United Kingdom, Paraguay
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ProtalixChiesi Farmaceutici S.p.A.CompletedFabry DiseaseUnited States, Netherlands, Hungary, United Kingdom, Czechia, Norway, Slovenia, Spain, Finland, France, Italy, Switzerland
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ProtalixChiesi Farmaceutici S.p.A.CompletedFabry DiseaseUnited States, Denmark, Belgium, United Kingdom, Norway, Italy, Czechia
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ProtalixWithdrawn
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Chiesi Farmaceutici S.p.A.ICON plcNot yet recruiting
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Chiesi Farmaceutici S.p.A.ICON plcRecruiting
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Westfälische Wilhelms-Universität MünsterChiesi GmbHRecruiting
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Chiesi Farmaceutici S.p.A.Chiesi USA, Inc.AvailableFabry DiseaseUnited States