Safety and effectiveness study comparing PRX-102 and Agalsidase Beta on Kidney function for patients with Fabry Disease who have previously been treated with Agalsidase Beta

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2016-000378-38-BE
• Date of registration: 30/09/2016
• Prospective Registration: Yes
• Primary sponsor: Protalix Ltd.
• Public title: Safety and effectiveness study comparing PRX-102 and Agalsidase Beta on Kidney function for patients with Fabry Disease who have previously been treated with Agalsidase Beta
• Scientific title: A Randomized, Double blind, Active Control Study of the Safety and Efficacy of PRX-102 compared to Agalsidase Beta on Renal Function in Patients with Fabry Disease Previously Treated With Agalsidase Beta
• Date of first enrolment: 05/12/2016
• Target sample size: 78
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000378-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Canada, Czech Republic, Finland, France, Germany, Hungary, Italy, Netherlands, Norway, Paraguay, Slovenia, Spain, Turkey, United Kingdom, United States

Contacts

• Name: Raul Chertkoff
• Affiliation: Protalix Ltd.

• Name: Raul Chertkoff
• Affiliation: Protalix Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
Eligible subjects must fulfill the following inclusion criteria:
1. Symptomatic adult Fabry disease patients, age 18-60 years
2. Males:
plasma and/or leucocyte alpha galactosidase activity (by activity assay) less than 30% mean normal levels and one or more of the characteristic features of Fabry disease
i. neuropathic pain
ii. cornea verticillata
iii. clustered angiokeratoma
3. Females:
a. historical genetic test results consistent with Fabry pathogenic mutation One or more of the described characteristic features of Fabry disease:
I. neuropathic pain,
ii. cornea verticillata,
iii. clustered angiokeratoma
b. or in the case of novel mutations a first degree male family member with Fabry disease with the same mutation, and one or more of the characteristic features of Fabry disease
i. neuropathic pain,
ii. cornea verticillata,
iii. clustered angiokeratoma
4. Screening eGFR by CKD-EPI equation 40 to 120 mL/min/1.73 m2
5. Linear negative slope of eGFR of = 2 mL/min/1.73 m2 based on at least 3 serum creatinine values over approximately 1 year (range of 9 to 18 months, including the value obtained at the screening visit)
6. Treatment with a dose of 1 mg/kg agalsidase beta per infusion every 2 weeks for at least one year and at least 80% of 13 (10.4) mg/kg total dose over the last 6 months
7. Female patients and male patients whose co-partners are of child-bearing potential agree to use a medically accepted method of contraception, not including the rhythm method.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 78
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
The presence of any of the following excludes a subject from study enrollment:
1. History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase beta
2. Known non-pathogenic Fabry mutations
3. History of renal dialysis or transplantation
4. 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)
5. Patient with a screening eGFR value between 91-120 mL/min/1.73 m2, having an historical eGFR value higher than 120 mL/min/1.73 m2 (during 9 to 18 months before screening)
6. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated or dose changed in the 4 weeks prior to screening
7. Urine protein to creatinine ratio (UPCR) > 0.5 g/g (0.5 mg/mg or 500 mg/g) and not treated with an ACE inhibitor or ARB
8. Cardiovascular event (myocardial infarction, unstable angina) in the 6 month period before randomization
9. Congestive heart failure NYHA Class IV
10. Cerebrovascular event (stroke, transient ischemic attack) in the 6 month period before randomization
11. Known history of hypersensitivity to Gadolinium contrast agent that is not managed by the use of premedication
12. Female subjects who are pregnant, planning to become pregnant during the study, or are breastfeeding
13. Presence of any medical, emotional, behavioral or psychological condition that, in the judgment of the Investigator and/or Medical Director, would interfere with the patient’s compliance with the requirements of the study


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Fabry disease (a-galactosidase A deficiency)
MedDRA version: 20.0 Level: PT Classification code 10016016 Term: Fabry's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Body processes [G] - Genetic Phenomena [G05]

Intervention(s)

Product Name: Pegunigalsidase alfa
Product Code: PRX-102
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Pegunigalsidase alpha
CAS Number: 1333358-30-7
Current Sponsor code: PRX-102
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Trade Name: Fabrazyme
Product Name: Fabrazyme
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: AGALSIDASE BETA
CAS Number: 104138-64-9
Current Sponsor code: N/A
Other descriptive name: N/A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 35 -

Trade Name: Fabrazyme
Product Name: Fabrazyme
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: AGALSIDASE BETA
CAS Number: 104138-64-9
Current Sponsor code: N/A
Other descriptive name: N/A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5 -

Primary Outcome(s)

Primary end point(s): The primary efficacy parameter is the comparison of the mean annualized change (slope) in estimated glomerular filtration rate (eGFRCKD-EPI) between treatment groups.

Safety endpoints:
Changes from baseline in:
? Clinical laboratory tests
? Physical examination
? Assessment of the injection site
? ECG
? Treatment-emergent adverse events
? Ability to taper off infusion pre-medication throughout the first 3 months of the study
? Requirement for use of pre-medication overall to manage infusion reactions
? Treatment-emergent anti-PRX-102 antibodies
? Treatment-emergent anti-agalsidase beta antibodies

Timepoint(s) of evaluation of this end point: Efficacy will be determined by the slope of eGFR over the course of the study. Two analyses of efficacy will be performed – at 12 and 24 months of treatment

The eGFR endpoint is calculated based on serum creatinine and the serum creatinine will be collected in the following visits - screening
- V1 baseline
- All odd numbered visits

Main Objective: To evaluate the safety and efficacy of PRX-102 compared to agalsidase beta in Fabry disease patients with impaired renal function.

Secondary Objective: N/A

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: In addition to the primary efficacy comparison described above, a series of secondary efficacy analyses will be performed to compare groups on the secondary outcomes of interest.

Secondary end point(s): Secondary efficacy endpoints:
? Left Ventricular Mass Index (g/m2) by MRI
? Plasma Lyso-Gb3
? Plasma Gb3
? Urine Lyso-Gb3
? Protein/Creatinine ratio spot urine test
? Frequency of pain medication use
? Exercise tolerance (Stress Test)
? Short Form Brief Pain Inventory (BPI)
? Mainz Severity Score Index (MSSI)
? Quality of life EQ-5D-5L

Secondary ID(s)

2016-000378-38-GB

PB-102-F20

Source(s) of Monetary Support

Protalix Ltd.

Ethics review

Status: Approved
Approval date:
Contact: