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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02795676




Registration number
NCT02795676
Ethics application status
Date submitted
2/06/2016
Date registered
10/06/2016
Date last updated
28/03/2019

Titles & IDs
Public title
Study of the Safety and Efficacy of PRX-102 Compared to Agalsidase Beta on Renal Function
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
Secondary ID [1] 0 0
PB-102-F20
Universal Trial Number (UTN)
Trial acronym
BALANCE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fabry Disease 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - PRX-102 (pegunigalsidase alfa)
Other interventions - agalsidase beta

Experimental: PRX-102 (pegunigalsidase alfa) - PRX-102 infusion every 2 weeks

Active Comparator: agalsidase beta - agalsidase beta infusion every 2 weeks


Other interventions: PRX-102 (pegunigalsidase alfa)
PRX-102 1 mg/kg every 2 weeks

Other interventions: agalsidase beta
agalsidase beta 1 mg/kg every 2 weeks

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
eGFR Slope - eGFR Slope
Timepoint [1] 0 0
Every month for 2 years
Secondary outcome [1] 0 0
Left Ventricular Mass Index (g/m2) by MRI
Timepoint [1] 0 0
Every 12 months for 2 years
Secondary outcome [2] 0 0
Plasma Lyso-Gb3
Timepoint [2] 0 0
Every 3 months for 2 years
Secondary outcome [3] 0 0
Plasma Gb3
Timepoint [3] 0 0
Every 3 months for 2 years
Secondary outcome [4] 0 0
Urine Lyso-GB3
Timepoint [4] 0 0
Every 6 weeks for 2 years
Secondary outcome [5] 0 0
Protein/creatinine ratio
Timepoint [5] 0 0
Every 4 months for 24 months
Secondary outcome [6] 0 0
Frequency of pain medication use
Timepoint [6] 0 0
Every 2 weeks for 2 years
Secondary outcome [7] 0 0
Exercise tolerance (Stress Test)
Timepoint [7] 0 0
Every year for 2 years
Secondary outcome [8] 0 0
Short Form Brief Pain Inventory (BPI)
Timepoint [8] 0 0
Every 6 months for 2 years
Secondary outcome [9] 0 0
Mainz Severity Score Index (MSSI)
Timepoint [9] 0 0
Every 6 months for 2 years
Secondary outcome [10] 0 0
Quality of life EQ-5D-5L
Timepoint [10] 0 0
Every 6 months for 2 years

Eligibility
Key inclusion criteria
- Symptomatic adult Fabry disease patients, age 18-60 years

1. 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

2. Females:

a. historical genetic test results consistent with Fabry pathogenic mutation and
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

- Screening eGFR by CKD-EPI equation 40 to 120 mL/min/1.73 m²

- Linear negative slope of eGFR 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) of = 2 mL/min/1.73 m²/year

- 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.

- 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.
Minimum age
18 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase beta

- Known non-pathogenic Fabry mutations

- 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

- 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)

- Urine protein to creatinine ratio (UPCR) > 0.5 g/g and not treated with an ACE
inhibitor or ARB

- Cardiovascular event (myocardial infarction, unstable angina) in the 6 month period
before randomization

- Congestive heart failure NYHA Class IV

- Cerebrovascular event (stroke, transient ischemic attack) in the 6 month period before
randomization

- Known history of hypersensitivity to Gadolinium contrast agent that is not managed by
the use of pre-medication

- Female subjects who are pregnant, planning to become pregnant during the study, or are
breastfeeding

- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Iowa
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Oregon
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
Tennessee
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Utah
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
United States of America
State/province [21] 0 0
West Virginia
Country [22] 0 0
United States of America
State/province [22] 0 0
Wisconsin
Country [23] 0 0
Argentina
State/province [23] 0 0
Buenos Aires
Country [24] 0 0
Belgium
State/province [24] 0 0
Edegem
Country [25] 0 0
Brazil
State/province [25] 0 0
Rio Grande Do Sul
Country [26] 0 0
Canada
State/province [26] 0 0
Nova Scotia
Country [27] 0 0
Czechia
State/province [27] 0 0
Czech Republic
Country [28] 0 0
Germany
State/province [28] 0 0
Bayern
Country [29] 0 0
Hungary
State/province [29] 0 0
Budapest
Country [30] 0 0
Italy
State/province [30] 0 0
Firenze
Country [31] 0 0
Italy
State/province [31] 0 0
Napoli
Country [32] 0 0
Italy
State/province [32] 0 0
Roma
Country [33] 0 0
Netherlands
State/province [33] 0 0
Amsterdam
Country [34] 0 0
Norway
State/province [34] 0 0
Bergen
Country [35] 0 0
Paraguay
State/province [35] 0 0
Asuncion
Country [36] 0 0
Slovenia
State/province [36] 0 0
Slovenj Gradec
Country [37] 0 0
Spain
State/province [37] 0 0
Zaragoza
Country [38] 0 0
Switzerland
State/province [38] 0 0
Zürich
Country [39] 0 0
Turkey
State/province [39] 0 0
Ankara
Country [40] 0 0
Turkey
State/province [40] 0 0
Izmir
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Birmingham
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Cambridge
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Cardiff
Country [44] 0 0
United Kingdom
State/province [44] 0 0
London
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Salford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Protalix
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a randomized, double blind, active control study of PRX-102 (pegunigalsidase alfa) in
Fabry disease patients with impaired renal function. Patients treated for approximately 1
year with agalsidase beta and on a stable dose for at least 6 months will be screened and
then randomized to continue treatment with 1mg/kg agalsidase beta or to treatment with 1
mg/kg of PRX-102. The identity of the enzyme will be blinded to the patient and the
investigator. Patients will receive intravenous infusions every two weeks. Patients will be
randomized in a 2:1 ratio of PRX-102 to agalsidase beta. Randomization will be stratified by
urinary protein to creatinine ratio (UPCR) of < or = 1 g/g by spot urine sample. No more than
50% of the patients will be female.
Trial website
https://clinicaltrials.gov/show/NCT02795676
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Raul Chertkoff, MD
Address 0 0
Protalix Ltd
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Raul Chertkoff, MD
Address 0 0
Country 0 0
Phone 0 0
+972-4-9028100
Fax 0 0
Email 0 0
raul@protalix.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02795676