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

Fabry Disease Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03018730
• Other study ID #: PB-102-F30
• Status: Completed
• Phase: Phase 3
• Start date: May 17, 2017
• Est. completion date: January 9, 2020

Study information

• Verified date: September 2023
• Source: Protalix
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: January 9, 2020
• Est. primary completion date: December 17, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Fabry Disease

Intervention

Biological:
• PRX-102 (pegunigalsidase alfa)
PRX-102 1 mg/kg every 2 weeks

Locations

Country	Name	City	State
Australia	Royal Melbourne Hospital	Parkville	Victoria
Canada	Capital Health	Halifax	Nova Scotia
Czechia	Vseobecna fakultni nemocnice v Praze	Prague
Netherlands	Academisch Medisch Centrum	Amsterdam
Norway	Helse Bergen HF Haukeland Universitetssykehus	Bergen
Slovenia	General Hospital Slovenj Gradec	Slovenj Gradec
United Kingdom	Queen Elizabeth Hospital, Department of Neurology,	Edgbaston	Birmingham
United Kingdom	The Royal Free Hospital	London
United Kingdom	Salford Royal NHS Foundation Trust	Salford

Sponsors (2)

Lead Sponsor	Collaborator
Protalix	Chiesi Farmaceutici S.p.A.

Countries where clinical trial is conducted

Australia,  Canada,  Czechia,  Netherlands,  Norway,  Slovenia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Other	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
Other	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)
Other	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
Other	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
Other	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
Primary	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