Back to resultsSafety and Efficacy of PRX-102 in Patients With Fabry Disease Currently Treated With REPLAGAL® (Agalsidase Alfa)
Primary Purpose
Fabry Disease
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
PRX-102 (pegunigalsidase alfa)
Sponsored by
About this trial
This is an interventional treatment trial for Fabry Disease focused on measuring Fabry disease, Enzyme-Replacement Therapy, pegunigalsidase alfa, PRX-102, alpha galactosidase-A
Eligibility Criteria
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
Sites / Locations
- Royal Melbourne Hospital
- Capital Health
- Vseobecna fakultni nemocnice v Praze
- Academisch Medisch Centrum
- Helse Bergen HF Haukeland Universitetssykehus
- General Hospital Slovenj Gradec
- Queen Elizabeth Hospital, Department of Neurology,
- The Royal Free Hospital
- Salford Royal NHS Foundation Trust
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PRX-102
Arm Description
PRX-102 infusion every 2 weeks
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Full Information
NCT ID
NCT03018730
First Posted
January 9, 2017
Last Updated
September 11, 2023
Sponsor
Protalix
Collaborators
Chiesi Farmaceutici S.p.A.
1. Study Identification
Unique Protocol Identification Number
NCT03018730
Brief Title
Safety and Efficacy of PRX-102 in Patients With Fabry Disease Currently Treated With REPLAGAL® (Agalsidase Alfa)
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)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
May 17, 2017 (Actual)
Primary Completion Date
December 17, 2019 (Actual)
Study Completion Date
January 9, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Protalix
Collaborators
Chiesi Farmaceutici S.p.A.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fabry Disease
Keywords
Fabry disease, Enzyme-Replacement Therapy, pegunigalsidase alfa, PRX-102, alpha galactosidase-A
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PRX-102
Arm Type
Experimental
Arm Description
PRX-102 infusion every 2 weeks
Intervention Type
Biological
Intervention Name(s)
PRX-102 (pegunigalsidase alfa)
Other Intervention Name(s)
pegunigalsidase alfa, Recombinant human alpha galactosidase-A
Intervention Description
PRX-102 1 mg/kg every 2 weeks
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03
Description
Results represent the number of treatment-emergent adverse events (TEAE) that were considered possibly, probably, or definitely related to treatment
Time Frame
12 months
Other Pre-specified Outcome Measures:
Title
eGFR
Description
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.
Time Frame
Baseline and Month 12 (week 52)
Title
Mean Annualised Change in eGFR (Slope)
Description
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.
Time Frame
Pre-switch, Post-switch
Title
Plasma Lyso-Gb3
Description
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.
Time Frame
Baseline and month 12 (week 52)
Title
Number of Participants According to Protein/Creatinine Ratio (UPCR)
Description
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
Time Frame
12 months
Title
Left Ventricular Mass Index (g/m^2) by MRI
Description
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.
Time Frame
12 months
Title
Quality of Life EQ VAS
Description
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").
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Royal Melbourne Hospital
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
Capital Health
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 1V8
Country
Canada
Facility Name
Vseobecna fakultni nemocnice v Praze
City
Prague
Country
Czechia
Facility Name
Academisch Medisch Centrum
City
Amsterdam
Country
Netherlands
Facility Name
Helse Bergen HF Haukeland Universitetssykehus
City
Bergen
Country
Norway
Facility Name
General Hospital Slovenj Gradec
City
Slovenj Gradec
ZIP/Postal Code
SI-2380
Country
Slovenia
Facility Name
Queen Elizabeth Hospital, Department of Neurology,
City
Edgbaston
State/Province
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Facility Name
The Royal Free Hospital
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
Facility Name
Salford Royal NHS Foundation Trust
City
Salford
ZIP/Postal Code
M6 8HD
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Safety and Efficacy of PRX-102 in Patients With Fabry Disease Currently Treated With REPLAGAL® (Agalsidase Alfa)
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