An Open Label Study of the Safety and Efficacy of PRX-102 in Patients With Fabry Disease Currently Treated With REPLAGAL® (Agalsidase Alfa)
Phase: PHASE3
Conditions: Fabry Disease
Sponsor: Protalix

Protocol Number PB-102-F30 
Protalix Ltd. 
Version 3.0 
EudraCT 2016-01318-11 
NCT number: NCT03018730 
06 Jun 2017 
 
 
 
CLINICAL STUDY PROTOCOL 
 
Protocol Title: An Open Label Study of the Safety and Efficacy of PRX-102 
in Patients with Fabry Disease Currently Treated With REPLAGAL® 
(Agalsidase alfa) 
Protocol Number PB-102-F30 
Study Product: 
Pegunigalsidase alfa (PRX-102) a recombinant human alpha 
galactosidase-A 
Indication: 
PRX-102 is indicated for long-term enzyme replacement 
therapy in patients with a confirmed diagnosis of Fabry 
disease (alpha galactosidase deficiency) 
Phase: 
3 
Protocol Version 
Version 1.0, 11 August 2016 
Version 2.0, 4 December 2016 
Version 3.0, 06 June 2017 
Name and Affiliation of 
Principal Investigator: 
A list of the Principal Investigators is maintained in the trial 
master file 
Name and Address of Sponsor: 
Protalix Ltd. 
2 Snunit Street 
Science Park 
Carmiel 20100, Israel 
GCP Statement: 
This study will be performed in compliance with GCP, 
including the archiving of essential documents. 
 
 
The information in this document is confidential and is proprietary to Protalix Ltd.. It is 
understood that information in this document shall not be disclosed to any third party, in any 
form, without prior written consent of Protalix. 

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1. 
SYNOPSIS 
 
TITLE:  An Open Label Study to Assess the Safety and Efficacy of PRX-102 in Patients with 
Fabry Disease Currently Treated with REPLAGAL® (Agalsidase alfa) 
INVESTIGATIONAL PRODUCT:  Pegunigalsidase alfa (PRX-102), a chemically modified 
human alpha galactosidase-A 
INDICATION: PRX-102 is indicated for long-term enzyme replacement therapy in patients 
with a confirmed diagnosis of Fabry disease (alpha galactosidase deficiency) 
PHASE OF DEVELOPMENT:  3 
INVESTIGATIONAL SITES/LOCATIONS:  Multicenter 
OBJECTIVES: To evaluate the safety and efficacy of PRX-102 in patients with Fabry 
disease currently treated with agalsidase alfa 
STUDY DESIGN: This is an open label switch over study to assess the safety and efficacy of 
PRX-102. 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. 
At the time of enrolment, premedication, if used for the agalsidase alfa infusions before 
enrolment, will be continued through the first infusion with PRX-102 and then will be 
gradually tapered at the investigator’s discretion during the first 2 months.  The first infusions 
of PRX-102 will be administered under controlled conditions at the investigation site.  The 
patient can receive their PRX-102 infusions at a home care setup once the investigator and 
Sponsor Medical Director agree that it is safe to do so. 
NUMBER OF SUBJECTS (PLANNED):  22 
DIAGNOSIS AND MAIN CRITERIA FOR INCLUSION: 
Inclusion criteria: 
Eligible patients must fulfill the following inclusion criteria: 
1. Age: 18-60 years 
2. A documented diagnosis of Fabry disease. 

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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 is 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 

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judgment of the Investigator and/or Medical Director, would interfere with the patient’s 
compliance with the requirements of the study 
TEST PRODUCT(S), DOSE AND MODE OF ADMINISTRATION:  During the first 3 
months (Screening period), patients will be on agalsidase alfa according to their previous 
regimen (dose, frequency and rate of infusion). Upon confirmation of eligibility, patients will 
be switched to PRX-102 1 mg/kg, intravenously to be administered over 3 hours, every 2 
weeks.  After the first 2 months of treatment with PRX-102, infusion time may be reduced 
gradually to 1.5 hours pending patient tolerability, investigator evaluation, and Sponsor 
Medical Monitor/Director approval. 
STUDY DURATION: Total 15 months, with 3 months Screening while on agalsidase alfa 
and 12 months Treatment on PRX-102, with the option to be enrolled in an extension study 
upon completion of this study. 
DISCONTINUATION FROM TREATMENT: 
Reasons for permanent discontinuation include the following: 
• The subject experiences two or more Grade 3 toxicities or one or more Grade 4 toxicity 
considered by the investigator associated with PRX-102 treatment (CTCAE v. 4.03, 2010) 
• The subject experiences progressive hypersensitivity or severe hypersensitivity that is not 
allayed with pre-treatment 
• The subject requests to discontinue treatment 
• The Investigator feels that it is not in the best interest of the subject to continue treatment 
and/or if the investigator believes that the subject can no longer be compliant with the 
requirements of the study 
SAFETY ENDPOINTS: 
Change from baseline in: 
• Clinical laboratory tests 
• Physical examination 
• Assessment of the injection site 
• Electrocardiogram 
• Treatment-emergent adverse events 
• Ability to taper off infusion premedication throughout the first 2 months of the study 
• Requirement for use of premedication overall to manage infusion reactions 
• Treatment-emergent anti-PRX-102 antibodies 
EFFICACY ENDPOINTS: 
• Mean annualised change in estimated glomerular filtration rate (eGFRCKD-EPI) 

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• Left Ventricular Mass Index (g/m2) preferably by MRI (echocardiogram can be used as 
an alternative) 
• 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 
 
STATISTICAL ANALYSIS: 
The sample size of 22 patients is adequate to evaluate the safety of switching from agalsidase 
alfa to PRX-102 in this orphan disease in which patient recruitment in clinical trials is difficult. 
The study endpoints will be evaluated by various summary analyses by study visit and by 
change from baseline data for each efficacy endpoint.  Safety and efficacy endpoints will be 
compared to baseline using summary statistics.  Data will not be analysed by inferential 
statistics. 
 
An interim analysis may be conducted for administrative purposes. 

 
 
Protocol Number PB-102-FJO 
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EudraCT  2016-01318-1 I 
Protalix Ltd. 
 
06 Jun 2017 
 
 
DOCUMENT APPROVAL 
This study will be conducted in compliance with the protocol, Good Clinical Practice (GCP) and 
applicable regulatory requirements. 
 
 
SPONSOR  REPRESENTATIVE 
 
 
 
 
 
-
 
June 6, 2017_ 
 
Signature 
Date 
 
 
 
 
PRINCIPAL  INVESTIGATOR 
 
 
 
 
 
 
 
 
Signature 
Date 
 
Print Name:  ------------- 
 
 
 
 
 
 
 
 
 
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TABLE OF CONTENTS 
1. SYNOPSIS ..............................................................................................................................2 
2. LIST OF ABBREVIATIONS ...............................................................................................10 
3. ETHICAL CONDUCT OF THE STUDY AND REGULATORY REQUIREMENTS ........11 
3.1 Institutional Review Board (IRB) ......................................................................................11 
3.2 Ethical Conduct of the Study .............................................................................................11 
3.3 Subject Information and Consent .......................................................................................11 
4. INTRODUCTION ................................................................................................................12 
5. STUDY OBJECTIVES .........................................................................................................15 
5.1 Primary Objective ..............................................................................................................15 
5.2 Secondary Objectives .........................................................................................................16 
6. INVESTIGATIONAL PLAN ...............................................................................................16 
6.1 Overall Study Design and Plan – Description ....................................................................16 
6.2 
Discussion of Study Design and Choice of Control Group(s) ...........................................16 
6.3 Selection of Study Population ............................................................................................16 
6.3.1 
Inclusion Criteria ........................................................................................................16 
6.3.2 
Exclusion Criteria .......................................................................................................17 
6.3.3 
Removal of Subjects from Therapy or Assessment ....................................................18 
6.3.4 
Replacement Policy ....................................................................................................18 
7. STUDY PRODUCT ..............................................................................................................18 
7.1 Study Medication Supply ...................................................................................................18 
7.2 Description of Study Product .............................................................................................18 
7.3 Study drug dosage and preparation ....................................................................................19 
7.4 Study Drug Administration ................................................................................................19 
7.5 Packaging and Labeling .....................................................................................................19 
7.6 Conditions for Storage and Use .........................................................................................20 
7.7 Dispensing, Compliance and Accountability .....................................................................20 
7.8 Prior and Concomitant Therapy .........................................................................................20 
8. EFFICACY AND SAFETY ASSESSMENTS .....................................................................21 
8.1 Safety Variable(s) ...............................................................................................................21 
8.1.1 
Clinical Laboratory .....................................................................................................21 
8.2 Efficacy Variables ..............................................................................................................21 
8.3 Adverse Events ..................................................................................................................22 
8.3.1 
Adverse Events (AE) and Serious Adverse Events (SAE) .........................................22 
8.3.2 
Procedures for Assessing, Recording, and Reporting Adverse Events and Serious 
Adverse Events ...........................................................................................................23 
8.3.3 
Acute Kidney Injury ...................................................................................................24 
9. STUDY PROCEDURES AND FLOW CHART ..................................................................25 
9.1 Study Visits ........................................................................................................................27 
9.1.1 
Screening Visit S1 (3 Months ±7days   before Visit 1) ..............................................27 
9.1.2 
Visits A and B (2 and 1 Month ±7 days before Visit 1) .............................................27 

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9.1.3 
Visit 1(±7Days  ) .........................................................................................................28 
9.1.4 
Visits 2, 4, 6, 8, 10, 12, 13, 15, 17, 19, 21, 23, 25, 26 (±3 Days) ...............................29 
9.1.5 
Visits 3, 5, 9, 11 (±3 Days) .........................................................................................29 
9.1.6 
Visits 7, 20 (±7 days) ..................................................................................................29 
9.1.7 
Visit 14 (±7 days) .......................................................................................................30 
9.1.8 
Visits 16, 18, 22, 24 (±3 Days) ...................................................................................31 
9.1.9 
Visit 27 (±7 days) or Premature Withdrawal ..............................................................31 
10. STATISTICAL METHODS PLANNED AND SAMPLE SIZE ..........................................33 
10.1 Determination of Sample Size..........................................................................................33 
10.2 Subject Populations ..........................................................................................................33 
10.3 Subject Disposition ..........................................................................................................33 
10.4 Safety Analysis .................................................................................................................33 
10.4.1 Adverse Events ...........................................................................................................33 
10.4.2 Clinical Laboratory .....................................................................................................33 
10.5 Efficacy Analysis .............................................................................................................34 
10.6 Interim Analysis ...............................................................................................................34 
11. QUALITY CONTROL AND QUALITY ASSURANCE ....................................................35 
11.1 Source Data and Records .................................................................................................35 
11.2 Reporting of Results .........................................................................................................35 
11.3 Confidentiality of Subject Data ........................................................................................36 
12. REPORTING AND PUBLICATION ...................................................................................37 
12.1 Confidentiality of Study Data ...........................................................................................37 
13. REFERENCES .....................................................................................................................38 
14. APPENDICES ......................................................................................................................42 
14.1 Appendix 1. Vial Label ........................................................................................................ 42 
14.2 Appendix 2.  Infusion Rate Algorithm .............................................................................43 
14.3 Appendix 3.  PRX-102 Evaluation and Treatment Algorithm .........................................46 
14.4 Appendix 4.  Cardiac MRI ...............................................................................................49 
14.4.1 Patients and sites .........................................................................................................49 
14.4.2 Magnetic Resonance Imaging (MRI) data ..................................................................50 
14.4.3 MRI evaluation parameters .........................................................................................50 
14.4.4 Sites and image data management ..............................................................................50 
14.4.5 Image processing and centralized analysis .................................................................51 
14.4.6 Data and report transfers to Sponsor ...........................................................................52 
14.4.7 Direct access to Study data .........................................................................................52 
14.4.8 Unevaluable MRI ........................................................................................................52 
14.5 Appendix 5.  The Mainz Severity Score Index (MSSI) ...................................................53 
14.6 Appendix 6.  National Kidney Foundation Guidelines for Chronic Kidney Disease .........56 
14.6.1 Estimation of GFR ......................................................................................................56 
14.6.2 CKD-EPI Equation: ....................................................................................................56 
14.7 Appendix 7.  Brief Pain Inventory- BPI (Short Form) .....................................................57 
14.8 Appendix 8. Premedication Discontinuation Guide .........................................................60 
14.9 Appendix 9. EQ-5D-5L ....................................................................................................61 

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2. LIST OF ABBREVIATIONS 
 
ACE 
Angiotensin converting enzyme 
AE 
Adverse event 
Alpha-GAL-A 
Alpha galactosidase-A 
ARB 
Angiotensin receptor blocker 
BPI 
Brief pain inventory 
CKD 
Chronic kidney disease 
Cmax 
Maximum concentration observed 
CRF 
Case report form 
EC 
Ethics Committee 
ECG 
Electrocardiography 
eGFR 
Estimated glomerular filtration rate 
ERT 
Enzyme replacement therapy 
Gb3 
Globotriaosylceramide 
GCP 
Good Clinical Practice 
HBsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C virus 
HIV 
Human immunodeficiency virus 
IC 
Informed consent 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
IV 
Intravenous 
LLN 
Lower limit of normal 
LVH 
Lt. ventricular hypertrophy 
LVM 
Lt. ventricular mass 
Lyso-Gb3 
Globotriaosylsphingosine 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
Magnetic resonance imaging 
PP 
Per Protocol 
PT 
Prothrombin time 
PTT 
Partial Thromboplastin time 
SAE 
Serious adverse event 
TIA 
Transient ischaemic attack 

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3. 
ETHICAL CONDUCT OF THE STUDY AND REGULATORY 
REQUIREMENTS 
3.1 
Institutional Review Board (IRB) 
The study protocol and any amendments will be reviewed by an Institutional Review Board 
(IRB). The IRB will review the informed consent form, their updates (if any), and any written 
materials given to the subjects. A list of all IRBs and contact information will be included in the 
study report. 
 
3.2 
Ethical Conduct of the Study 
This study will be conducted in accordance with the ethical principles that have their origins in 
the Declaration of Helsinki, in compliance with the approved protocol, GCP and applicable 
regulatory requirements. 
 
3.3 
Subject Information and Consent 
The investigator will obtain a freely given written consent from each subject after an appropriate 
explanation of the aims, methods, anticipated benefits, potential hazards, and any other aspects 
of the study that are relevant to the subject's decision to participate. The consent form must be 
signed and dated by the subject before he/she is exposed to any protocol-specific procedure. 
 
The investigator will explain that the subjects are completely free to refuse to enter the study or 
to withdraw from it at any time, without any consequences for their further care and without the 
need to justify. 
 
The patient will receive a copy of the patient information and the signed informed consent. 
 
The patient will be informed if information becomes available that may be relevant to his/her 
willingness to continue participation in the study. 
 
Each subject will be informed that a monitor or a health authority inspector, in accordance with 
applicable regulatory requirements, may review the portions of their source records and source 
data related to the study. Data protection and confidentiality will be handled in compliance with 
local laws. 

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4. 
INTRODUCTION 
Fabry disease is a progressive lysosomal storage disease that is seriously debilitating and 
ultimately life-threatening. It is caused by X-linked deficiency of the enzyme alpha 
galactosidase-A (alpha-GAL-A), and affects both males and females. The disease is 
characterized by subnormal or absent activity of alpha-GAL-A. Clinical onset of the disease 
typically occurs during childhood or adolescence (Schaefer et al. 2009) and will progress to end- 
stage renal disease, cardiac complications and cerebrovascular problems in the fourth or fifth 
decade of life (Wilcox et al. 2008). Although Fabry disease is a X-linked disorder, females are 
also affected and develop manifestations of the disease due to lack of cross-correction between 
cells with normal alpha-GAL-A activity (mutated X chromosome is inactivated) and cells with 
enzyme deficiency (non-mutated X chromosome is inactivated). The clinical abnormalities in 
females are more variable, and of later onset compared to males (Schiffmann 2009a). 
 
Fabry disease is regarded as a rare disease and it is estimated that 1 in 40,000 males has the 
disease, whereas the estimated prevalence in the general population is 1 in 117,000 (Meikle et al. 
1999). 
 
Alpha-GAL-A is a lysosomal enzyme which primarily catalyses the hydrolysis of the glycolipid 
globotriaosylceramide (Gb3) to galactose and lactosylceramide. Fabry disease is characterized 
by massive storage of Gb3, predominantly in cells of the vascular system, cardiomyocytes, 
neuronal cells and kidney podocytes. Progressive accumulation of Gb3, and related lipids, leads 
to impaired tissue and organ function. The ultimate consequence of glycolipid deposition in the 
vasculature and other tissues is end-organ failure, particularly the kidney, but also heart and 
cerebrovascular system (Schiffmann 2009a). In addition, involvement of the central, peripheral 
and autonomic nervous systems result in episodes of pain and impaired peripheral sensation. 
Vascular changes in the skin also result in angiokeratomas (Hoffmann et al. 2009). The 
mechanism by which alpha-GAL-A deficiency and glycolipid accumulation cause such a wide 
variety of complications is not well understood. Based on the pathology of Fabry disease, the 
ongoing accumulation of alpha-D-galactosyl moieties, particularly of Gb3, appears to be a 
chronic toxicity state (Schiffmann 2009a). A recent study by Aerts et al. reported that 
globotriaosylsphingosine (lysoGb3), a Gb3 metabolite, is dramatically increased in the plasma of 
male Fabry patients, and plasma and tissues of Fabry mice, and may have an important role in 
the pathogenesis of Fabry disease (Aerts et al. 2008). Increased levels of lysoGb3 occur also in 
symptomatic Fabry females (Van Breemen et al. 2011). 
 
As Fabry disease is an X-linked disorder, the prevalence of the mutation is predicted to be two 
times higher in women than in men. There is considerable variation in phenotype in 
heterozygous females. However, despite the X-linked nature of the disease, heterozygous and 
therefore tissue-mosaic females can be as severely affected by Fabry disease as hemizygous 
males, experiencing progressive, multi-organ involvement, reduced quality of life and reduced 
life expectancy. Case-finding studies have reported mutations that are known to be associated 
with Fabry disease in 0.3–2.4% of women who had unexplained stroke, hypertrophic 
cardiomyopathy, or renal failure requiring haemodialysis. A recent study by Hughes et al, that 
compared men and women with Fabry disease, using data from FOS—the Fabry Outcome 
Survey, showed no significant differences between men and women for most clinical features 

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evaluated. Overall, both sexes responded to enzyme replacement treatment in a similar way 
(Hughes et al. 2011). 
 
Most men and some women with Fabry disease exhibit deterioration of renal function 
(Schiffmann et al., 2009b; Wanner et al., 2010; Ortiz et al., 2008), and many eventually develop 
end-stage renal disease (ESRD) (Ortiz et al., 2010; Mignani et al., 2010). Although progression 
to ESRD is much less common in women, the median age at which patients reached ESRD (38 
years) was the same in both genders (Ortiz et al., 2010; Mignani et al., 2010). Studies of 
untreated patients with Fabry disease have identified proteinuria as a major risk factor for renal 
disease progression (Schiffmann et al., 2009b; Wanner et al., 2010). 
 
Enzyme replacement therapy (ERT), by exogenous administration of purified recombinant 
enzyme, is nowadays among the most successfully employed drug treatments for lysosomal 
storage disorders. The first disorder for which this treatment modality has proven to be effective 
is type 1 Gaucher disease (Barton et al. 1991; Hollak et al. 1995). This success has paved the 
way for the development of ERT for other lysosomal storage disorders, including Fabry disease. 
 
Recombinant human alpha-GAL-A has the ability to restore enzyme function in patients, and 
currently two ERTs using this enzyme are commercially available; agalsidase alpha (Replagal), 
that was approved in Europe, and agalsidase beta (Fabrazyme), that was approved both in Europe 
and in the United States. Both recombinant enzymes are comparable in their properties and differ 
only slightly in glycan composition (Blom et al. 2003). They are produced using different protein 
expression systems and are administered at different doses. Fabrazyme is produced in Chinese 
Hamster Ovary (CHO) cells and is administered by IV infusion every 2 weeks at a dose of 1 
mg/kg. Replagal is produced in a human cell line (stably expressed in human foreskin fibroblast) 
(Schiffmann et al. 2000), and is administrated by IV infusion every 2 weeks at a dose of 0.2 
mg/kg. Both products have shown their efficacy in clinical studies with regard to clearance of 
Gb3 from plasma, kidney cells (such as capillary endothelial cells, glomerular endothelial cells, 
noncapillary endothelial cells and noncapillary smooth muscle cells), and capillary endothelial 
cells of the cardiac and skin (Eng & Guffon et al. 2001; Germain et al. 2007; Schaefer et al. 
2009). In addition, ERT with both products leads to improvement in quality of life, reduction or 
stabilization of cardiac mass, preservation of renal function, and slowing down the decline of 
glomerular function (Wilcox et al. 2004; Schiffmann et al. 2006; Germain et al. 2007; 
Schiffmann 2009b). Although these findings are encouraging, the clinical effects of the current 
treatment of Fabry patients are not as robust as anticipated and show only limited clinical 
improvement (Schaefer et al. 2009; Lidove et al. 2010; El Dib et al. 2011). 
 
In clinical studies, agalsidase beta provided long-term stabilization of renal function in patients 
with mild renal involvement (serum creatinine <2.2 mg/dL) (Germain et al., 2007) and delayed 
time to renal, cardiovascular and cerebrovascular events in patients with more advanced Fabry 
disease (Banikazemi et al., 2007). Agalsidase beta treatment did not stabilize renal function in 
patients with severe renal involvement (i.e., proteinuria > 1 g/24 h or estimated glomerular 
filtration rate (eGFR) <60 mL/min/1.73m2) at the time treatment was started (Germain et al., 
2007: Banikazemi et al., 2007). Schiffmann (2007) showed that increasing the frequency of 
dosing with agalsidase alfa from every other week to weekly in a subgroup of patients with 
Fabry disease whose eGFR continued to decline at rapid rate while being treated every other 
week significantly slowed the rate of decline in eGFR. Nine (82%) of 11 patients demonstrated 

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either a positive eGFR slope (n = 3, 27%) or a slowing in their rate of decline (i.e., less negative 
eGFR slope; n = 6, 55%) after switching to weekly administration of agalsidase alfa. 
 
One of the major factors responsible for the limited efficacy of current treatment is the presence 
of irreversible organ damage. Another factor that may contribute to this is the characteristics of 
the current ERTs (such as short circulatory half-life and dose regimens) which seem to be 
insufficient in preventing the chronic toxic effect of Gb3. One way to improve enzyme 
bioavailability maybe to extend circulation residence and tissue half-life. A third factor, which 
may influence the treatment outcome, is the induction of antibodies towards the recombinant 
proteins (Hollak et al. 2009). Emergence of antibodies with in vivo neutralizing capacities is 
frequently encountered in treated Fabry disease patients, resulting in inhibition of enzyme 
activity and adversely affecting Gb3 clearance (Hollak et al. 2009). In early clinical studies, 25 to 
88% (Schiffmann et al. 2006; Eng & Banikazemi et al. 2001; Eng & Guffon et al. 2001) of male 
patients developed these IgG antibodies within the first 6 months of treatment. Regarding 
treatment outcome, it was shown that antibodies against alpha-GAL-A interfere with the 
clearance of Gb3 from plasma, urine (Linthorst et al. 2004; Vedder et al. 2008), and from the 
tissue (Benichou et al. 2009). The cross-reactivity of alpha-GAL-A antibodies suggests that it is 
unlikely that switching from one recombinant protein to the other may prevent the immune 
response and related effects (Linthorst et al. 2004; Hollak et al. 2009). Currently, administration 
of a higher dose of the recombinant enzyme is an effective way to overcome the negative effect 
of the neutralizing antibodies by providing excess enzyme (Vedder et al. 2008; Hollak et al. 
2009). However, this approach is not considered a long-term solution. 
 
Protalix has developed PRX-102, a chemically modified recombinant human alpha-GAL-A 
expressed in plant cell culture. As a result of this modification, PRX-102 exhibits more stabilized 
homo dimer with active enzyme over longer period, extended circulation residence time and 
enhanced bioavailability of the enzyme relative to the commercial drug. Therefore, PRX-102 
provides continuous presence of enzyme over the 2 week dosing interval. 
 
Studies have shown that human alpha-GAL-A is a non-covalently bound homodimeric 
glycoprotein (Garman et al. 2004) and that the dimerization is important for the enzymatic 
activity and stability of the enzyme (Bishop et al. 1988). The chemical modification of PRX-102 
utilises the reagent bis-NHS-PEG and renders PEGylated protein subunits the majority of which 
are crosslinked into homodimers thus, reinforce the homodimeric structure, which is crucial for 
the enzymatic activity of this enzyme. In addition, the PEGylation modification may have an 
additive value through increasing drug retention time in blood and bioavailability (Veronese et 
al. 2005; Veronese et al. 2008). Preliminary non-clinical data shows that this modification 
improves PRX-102 stability in vitro under lysosomal and plasma conditions, and extends 
circulation residence and bioavailability in vivo, probably due to stabilization of its quaternary 
structure. Therefore, the modifications in PRX-102 have the potential to improve the efficacy of 
ERT. 
 
PRX-102 has been studied in Fabry disease patients in a Phase 1/2 study PB-102-F01 for 12 
weeks and continued in extension studies for long-term treatment. The extension studies are 
ongoing. The results of the study are summarized in the Investigator’s Brochure. At the time of 
database freeze on 31Jul2015, six (6) patients in the 0.2 mg/kg treatment group completed 12 

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months of treatment, six (6) in the 1.0 mg/kg treatment group completed 6 months of treatment 
and four (4) in the 2.0 mg/kg completed 3 months of treatment. 
 
The interim efficacy analysis results demonstrated that all patients exhibited stable cardiac and 
renal function with favorable trends after receiving six months of PRX-102. Gb3 inclusions in 
kidney peritubular capillaries were substantially reduced after 6 months of treatment with both 
0.2 and 1.0 mg/kg doses. A mean reduction was observed in the total score of the Mainz 
Severity Score Index (MSSI) for the severity of Fabry disease in general, neurological, 
cardiovascular and renal systems; a stable or favorable trend was observed in the severity and 
frequency of abdominal pain, and frequency of diarrhea in Gastrointestinal Symptoms 
Assessment (GSA); and the reduction in pain severity score and pain interference score with the 
Brief Pain Inventory (BPI) scale indicates an improvement in general activity, walking, working, 
sleeping, enjoyment of life and other people. 
 
PRX-102 has enhanced pharmacokinetic properties including a half-life (T½) of approximately 
70 hours, and AUC of approximately 400,000 ng/mL*hour for the 1.0 mg/kg dose after one day 
of treatment (Day 1), which are believed to be the result of the covalent cross-linking to make 
PRX-102 enzyme a more stable homo-dimer. This extended exposure of the target organs to 
enzyme may be important for improving efficacy similar to what Schiffmann et al., (2007) 
showed with weekly compared to every other week agalsidase alfa. 
 
The most commonly experienced AEs in PRX-102 were fatigue in 6 patients, and nausea and 
vomiting each in 5 patients. The most commonly experienced AEs that  were  considered 
possibly related to the treatment were nausea in 3 patients, chest discomfort and fatigue each in 2 
patients. 
 
Two patients each experienced an SAE. One patient experienced a Grade 3 hypersensitivity 
related serious adverse event of bronchospasm. The second patient experienced renal hematoma 
following kidney biopsy and was not considered related to the treatment. 
 
Currently, the safety results of the one completed and two ongoing studies showed that PRX-102 
is well tolerated with a favorable safety profile, the majority of adverse events being mild and 
moderate in severity and a low rate of treatment induced antibody formation. 
 
In view of the data it is concluded that dosing of PRX-102 at 1.0 mg/kg every 2 weeks offers an 
appropriate treatment regimen for attenuating disease progression. 
 
5. 
STUDY OBJECTIVES 
5.1 
Primary Objective 
The primary objective of this trial is to evaluate the safety of PRX-102 in patients with Fabry 
disease currently treated with agalsidase alfa. 

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5.2 
Secondary Objectives 
The secondary objective of this trial is to evaluate the efficacy of PRX-102 in patients with Fabry 
disease currently treated with agalsidase alfa. 
 
6. 
INVESTIGATIONAL PLAN 
6.1 
Overall Study Design and Plan – Description 
This is an open label switch over study to assess the safety and efficacy of PRX-102. 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 enter the study for 3 month Screening period for baseline data 
generation. Eligible patients will be 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. 
 
At the time of enrolment, premedication, if used for the agalsidase alfa infusions before study 
entry, will be continued during the Screening period and to the first infusion with PRX-102 
treatment and then gradually tapered at the investigator’s discretion during the first 2 months. 
The first infusions of PRX-102 will be administered under controlled conditions at the 
investigation site. The patient can receive their PRX-102 infusions at a home care setup once the 
investigator and Sponsor Medical Director agree that it is safe to do so. 
 
6.2 
Discussion of Study Design and Choice of Control Group(s) 
This is a Phase 3, open-label, switchover study to assess the safety and efficacy of PRX-102 
(pegunigalsidase alfa) in patients with Fabry disease who have been treated with agalsidase alfa 
(Replagal®) ERT. The dose of pegunigalsidase alfa is 1 mg/kg and switching from agalsidase 
alfa is an appropriate study design in this rare disease population. 
 
PRX-102 and agalsidase alfa are different products and immunogenicity and hypersensitivity 
may be different between the products. Premedication to prevent adverse reactions during 
infusion is administered in some patients receiving agalsidase alfa. Because the requirements for 
premedication may be different between the two products, premedication will be tapered off, as 
tolerated, over the initial 2 months of infusions under careful observation after switching to 
PRX-102. Premedication to prevent infusion reactions can be maintained or re-introduced as 
required. 
 
6.3 
Selection of Study Population 
6.3.1 
Inclusion Criteria 
The subjects must meet the following inclusion criteria: 
1. Age: 18-60 years 
2. A documented diagnosis of Fabry disease 

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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 
6.3.2 
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 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 is 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 

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11. 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 
6.3.3 
Removal of Subjects from Therapy or Assessment 
Reasons for permanent discontinuation include the following: 
• The subject experiences two or more Grade 3 toxicities or one or more Grade 4 toxicity 
considered by the investigator associated with PRX-102 (CTCAE v. 4.03, 2010) 
• The subject experiences progressive hypersensitivity or severe hypersensitivity that is not 
allayed with pre-treatment 
• The subject requests to discontinue treatment 
• The Investigator feels that it is not in the best interest of the subject to continue treatment 
and/or if the investigator believes that the subject can no longer be compliant with the 
requirements of the study 
 
For any discontinuation, the Investigator will obtain all the required details and document the 
date and the main reason for the premature termination. If the reason for discontinuation is an 
adverse event, the specific event or the main laboratory abnormality will be recorded in the 
eCRF. The Investigator will make thorough efforts to document the outcome. The Investigator 
will attempt to continue to follow the subject for the full duration of the study or at least for 90 
days following discontinuation. If circumstances prevent the subject from completing all visits, 
every attempt will be made to complete all procedures listed in Section 9 for Visit 27. 
6.3.4 
Replacement Policy 
Withdrawn patients will not be replaced. 
 
7. 
STUDY PRODUCT 
7.1 
Study Medication Supply 
Protalix will provide PRX-102 to the sites as needed. 
 
7.2 
Description of Study Product 
PRX-102  is  a  purified  recombinant,  plant  cell-expressed  chemically modified  human  alpha 
galactosidase, which is described in detail in the Investigator’s Brochure. 
Each vial contains 10.2 ml of the following contents in liquid form: 
20 mg PRX-102 (2mg/ml) 
0.7% NaCl 
25-30 mM Sodium Citrate (pH 5.7 - 6.3). 

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7.3 
Study drug dosage and preparation 
PRX-102  1  mg/kg;  the  individual  dose  for  each  patient  will  be  prepared  according to  the 
patient’s weight. 
 
Dose of PRX-102 will be adjusted at visit 14 (6 months on pegunigalsidase alfa treatment) if the 
weight changes by 25% from first infusion. 
 
Each dose will be prepared by a pharmacist or nurse at each site. 
 
The required amount of PRX-102 will be adjusted with normal saline (0.9% NaCl) to a final 
volume of : 
 
150 mL/infusion, for patients weighting up to 70 Kg 
 
250 mL/infusion, for patients weighting between 70 Kg-100Kg 
500 ml/infusion for patients weighting above 100 Kg 
The infusion Volume will be recalculated , only if the dosage adjustment was performed. 
7.4 
Study Drug Administration 
PRX-102 will be administered by intravenous infusion over 3 hours (0.83 mL/min). After 3 
months of infusions, if the patient is tolerating the infusions well, the infusion time may be 
reduced gradually to 1.5 hours based on investigator evaluation and Protalix Medical Director 
approval. The patient will be clinically observed for 2 hours post dosing when under PRX-102. 
Observation period may be shorten to 1 hour pending patient tolerability per investigator 
discretion and after Medical Monitor approval. 
 
At any time the infusion  rate may be adjusted  according to  individual subject’s signs  and 
symptoms (see Appendix 2). 
 
7.5 
Packaging and Labeling 
PRX-102 is packed in vials containing 20 mg (2mg/ml), 0.7% NaCl and 25-30 mM Sodium 
Citrate (pH 5.7 - 6.3). 
 
It is presented as a liquid stored in 15 ml clear injection glass vials (Müller + Müller-Joh. GmbH 
+  Co,  Germany).  Grey rubber  stoppers  (formulation  4432/50/Grey)  used  for  closure  (West 
Pharmaceutical Services Duetschland GmbH & Co KG). 
 
Sample Vial labels are provided in Appendix 1. 

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7.6 
Conditions for Storage and Use 
PRX-102 is stored at 2-8°C (36-46°F). 
 
7.7 
Dispensing, Compliance and Accountability 
Protalix will provide drug accountability forms to assist the pharmacist in maintaining current 
and accurate inventory records covering receipt, dispensing, and the return of investigational 
drug supplies. When a shipment is received, the pharmacist will verify the quantities received 
and return the acknowledgment to the Protalix’s CTM (Clinical Trial Material) coordinator. The 
drug will not be used without Protalix’s approval in writing. The pharmacist investigational drug 
accountability record includes the identification of the person to whom the drug is dispensed, the 
quantity and the date of dispensing and any returned or unused drug, as well as full record of 
CTM storage temperature. This record is in addition to any drug accountability information 
recorded on the Case Report Form (CRF). These records will be readily available for inspection 
by a monitor and/or Protalix audits and are open to regulatory authority inspection at any time. 
 
The investigator is responsible for maintaining accountability for the receipt, dispensing, and 
return of all study medication. 
 
7.8 
Prior and Concomitant Therapy 
Medications having the potential to interfere with the evaluation of efficacy are excluded 
throughout the trial. 
 
The following medications are strictly prohibited during the study treatment period: 
• Fabrazyme® (agalsidase-beta) 
• Replagal ® (agalsidase alfa) 
• Any other investigational or approved drug for treating Fabry disease 
The use of premedication to prevent infusion reactions associated with agalsidase alfa initiated 
before entry to the study and recorded in the eCRF will be continued, but subjects will be titrated 
down over the course of the two months after switching to PRX-102 The rate of down 
titration/removal of the premedication will be at the investigator’s discretion and recurrence of 
infusion reactions. Re-institution of premedication to manage infusion reactions will be allowed 
(see also Appendix 3 and 8). 
 
Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) 
at a stable dose for 4 weeks prior to entry into the study are allowed, but once a subject is 
randomized in the study, initiation of ACEI or ARB therapy is prohibited unless the subject 
develops proteinuria and the Protalix Medical Director approves. ACEI or ARB therapy may not 
be initiated for the treatment of hypertension in the absence of proteinuria. 

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8. 
EFFICACY AND SAFETY ASSESSMENTS 
8.1 
Safety Variable(s) 
• Safety will be assessed by the frequency, severity, and duration of treatment-emergent AEs 
(see Section 8.3, Adverse Events), including clinically significant laboratory abnormalities, 
ECG changes from baseline, physical examination findings and assessment of the injection 
site after administration of the study drug 
• Anti-Drug (i.e., PRX-102) IgG antibodies will be assessed before dosing with PRX-102 at 
baseline (Visit 1). Anti-PRX IgG antibodies will be assessed every month for the first 6 
months and every 3 month until the end of study through the last infusion. If a patient 
continues treatment in an extension study, the anti-drug antibodies will be assessed as part of 
that study. For patients who end treatment with PRX-102, anti-PRX-102 antibodies will be 
assessed 1 and 3 months after last infusion 
• Anti-Drug IgE antibodies will be assessed in events of hypersensitivity reaction following 
Sponsor request 
• Ability to taper off infusion premedication at the start of the study 
• Requirement for use of premedication overall to manage infusion reactions 
8.1.1 
Clinical Laboratory 
• Hematology: total white blood cell count, hemoglobin, and platelets. 
• Coagulation profile: prothrombin time (PT) and partial thromboplastin time (PTT) 
• Biochemistry: sodium, potassium, glucose, blood urea nitrogen, creatinine, Cystatin c, 
calcium, phosphate (inorganic), uric acid, total protein, albumin, bilirubin (total), alkaline 
phosphatase, aspartate transaminase, alanine transaminase, gamma-glutamyl transferase, 
lactate dehydrogenase, and creatine phosphokinase 
• Vitamin D 
• Urinalysis: dipstick for presence of blood, glucose, ketones, and protein 
8.2 
Efficacy Variables 
• Mean  annualised  change  in  estimated  glomerular  filtration  rate  (eGFRCKD-EPI)  (See 
Appendix 6) 
• Left Ventricular Mass Index (g/m2) preferably by MRI (echocardiogram can be used as 
an alternative) (See Appendix 4) 
• 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) (See Appendix 7) 
• Mainz Severity Score Index (MSSI) (See Appendix 5) 

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• Quality of life EQ-5D-5L (See Appendix 9) 
8.3 
Adverse Events 
8.3.1 
Adverse Events (AE) and Serious Adverse Events (SAE) 
An adverse event (AE) is any untoward medical occurrence in a subject participating in a clinical 
trial. An adverse event can be any unfavorable and unintended sign, symptom or disease 
temporally associated with the use of the study medication, whether or not considered related to 
the study medication. AEs will be collected from the start of treatment until 30 days following 
the final visit dose. Any events occurring prior to treatment will be recorded on the medical 
history page with the event name and onset date and end date if not continuing. Pre-existing, 
known clinically significant conditions observed at screening should be recorded as medical 
history. 
 
This definition also includes accidental injuries, reasons for any change in medication (drug 
and/or dose) other than planned titration, reasons for admission to a hospital, or reasons for 
surgical procedures (unless for minor elective surgery for a pre-existing condition). It also 
includes adverse events commonly observed and adverse events anticipated based on the 
pharmacological effect of the study medication. Any laboratory abnormality assessed as 
clinically significant by the Investigator must be recorded as an adverse event. 
 
A treatment emergent adverse event is any adverse event occurring after start of study 
medication and within the time of residual drug effect, or a pre-treatment adverse event or pre- 
existing medical condition that worsens in intensity after start of study medication and within the 
time of residual drug effect. 
 
Adverse events should be recorded as diagnoses, if available. If not, separate sign(s) and 
symptom(s) are recorded. One diagnosis/symptom should be entered per record. 
 
Note that death is not an event, but the cause of death is. An exception is the event of sudden 
death of unknown cause. Note that hospitalization is not an event; however, the reason for 
hospitalization is. Procedures are not events; the reasons for conducting the procedures are. In 
general, only the reason for conducting the procedure will be captured as an adverse event. 
However, if deemed necessary by the Investigator, a procedure can be captured along with the 
reason for conducting the procedure. 
 
An overdose or medication error is not an adverse event unless it is temporally associated with 
an unfavourable or unintended sign or symptom. 
 
Each AE is to be classified by the investigator as serious or non-serious. A serious adverse event 
(SAE) is any untoward medical occurrence or effect that occurs at any dose: 
 
• Results in death 
 
• Is life-threatening (i.e., an immediate risk of death) 

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• Requires in-patient hospitalization or prolongation of existing hospitalization 
 
• Results in persistent or significant disability/incapacity 
 
• Is associated with a congenital anomaly/birth defect 
 
• Is an important medical event 
 
An adverse event caused by an overdose or medication error is considered serious if a criterion 
listed in the definition above is fulfilled. 
 
Important adverse events that may not result in death, may not be life-threatening, or do not 
require hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the subject’s safety or may require medical or surgical 
intervention to prevent one of the outcomes listed above. 
 
Serious adverse events also include any other event that the investigator or sponsor judges to be 
serious or which is defined as serious by the regulatory agency. 
 
The investigator is to report all directly observed adverse events and all adverse events 
spontaneously reported by the trial subject using concise medical terminology. In addition, each 
trial subject will be questioned about adverse events. The question asked will be “Since you 
began taking the study medication, have you had any health problems?” 
 
8.3.2 
Procedures for Assessing, Recording, and Reporting Adverse Events and 
Serious Adverse Events 
Throughout the duration of the study, the Investigator will closely monitor each subject for 
evidence of drug intolerance and for the development of clinical or laboratory evidence of 
adverse events. All adverse events (expected or unexpected) which occur during the course of 
the study, whether observed by the Investigator or by the subject, and whether or not thought to 
be drug-related, will be reported and followed until resolution or until they become stable. 
 
The description of the adverse event will include description of event, start date, stop date, 
intensity, if it was serious, relationship to test drug, change in test drug dosage, if the subject 
died, and if treatment was required. 
 
Events will be coded to one of the following intensity categories below: 
 
Severity 
Definition 
Mild 
Awareness of signs or symptoms, but no disruption of usual activity 
Moderate 
Event sufficient to affect usual activity (disturbing) 
Severe 
Event causes inability to work or perform usual activities 
(unacceptable) 

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Events will be coded into one of the following causality categories as defined below: 
 
Category 
Definition 
Unrelated 
Clearly and incontrovertibly due only to extraneous causes, and does 
not meet criteria listed under possible or probable. 
Unlikely 
Does not follow a reasonable temporal sequence from administration. 
May have been produced by the subject’s clinical state or by 
environmental factors or other therapies administered. 
Possible 
Follows a reasonable temporal sequence from administration, but 
may have been also produced by the subject’s clinical state, 
environmental factors or other therapies administered. 
Probable 
Clear-cut temporal association with administration with improvement 
on cessation of investigational medicinal product or reduction in 
dose. Reappears upon rechallenge. Follows a known pattern of 
response to the investigational medicinal product. 
Adverse events with the causality assessed as unrelated or unlikely are categorized as not related 
to study medication. 
 
Adverse events with the causality assessed as possible or probable are categorized as related to 
study medication and are called adverse drug reactions. 
 
All SAEs must be reported immediately (no more than 24 hours after becoming aware of 
the event) by entering the information about the event in the eCRF forms. The Sponsor’s 
Medical Director and Safety Monitor will be notified of the event by the eCRF system. In the 
case that the eCRF system is not available, the Investigator must contact Medical Director (972- 
54-2228472) or Safety Monitor (1-212-681-2100) to notify the Sponsor of the event. 
 
8.3.3 
Acute Kidney Injury 
Episodes of Acute Kidney Injury (AKI) will be considered adverse events. AKI will be defined 
by a 1.5 fold or greater increase in serum creatinine from the immediately previous laboratory 
value and assessment by the investigator. The Protalix Medical Director will work with the 
investigator to ensure that such changes in renal function are thoroughly evaluated. 

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9. 
STUDY PROCEDURES AND FLOW CHART 
 
 
 
Screening Period 
Visits Treatment Period PRX-102 (Pegunigalsidase alfa) 
Activity 
Screening 
Visit A 
Visit 1 
Visits 2, 
Visits 3, 5, 9, 
Visits 7, 
Visit 14 
Visits 
Visit 27 
Visit (-3 
(-2 Month) 
4, 6, 8, 
11 
20 
(Month 
16, 18, 
(Month 
Month) 
and B 
10, 12, 
(Months 
6) 
22, 24 
12) 
(-1 Month) 
13, 15, 
3 and 9) 
17, 19, 
21, 23, 
25, 26 
Sign IC 
x 
Assign screening number 
x 
Medical history 
x 
Demographics 
x 
Alpha-galactosidase activity in 
plasma and leucocytes 
x 
Historical serum creatinine 
x 
Vital signs (blood pressure, 
pulse, temperature and 
respiration) 
x 
x 
x 
x 
x 
x 
x 
x 
Body weight 
x 
x 
x 
x 
x 
Body height 
x 
Physical examination 
x 
x 
x 
x 
x 
Concomitant medications 
(including pain and 
premedications) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Hematology 
x 
x 
x 
x 
x 
Biochemistry 
x 
x 
x 
x 
x 
Serum Creatinine and Cystatin 
C 
x 
x 
x 
x 
x 
x 
x 
x 
Urinalysis - dipstick 
x 
x 
x 
x 
x 
Protein/Creatinine ratio spot 
urine test 
x 
x 
x 
x 
x 
x 
HbsAg, HCV & HIV 
x 
Serum pregnancy test (beta 
HCG) 
x 
x 

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Screen ing Period 
Visits Treatment Period PRX-102 (P egunigalsidase alfa) 
Activity 
Screening 
Visit (-3 
Month) 
Visit A 
(-2 Month) 
and B 
(-1 Month) 
Visit 1 
Visits 2, 
4, 6, 8, 
10, 12, 
13, 15, 
17, 19, 
21, 23, 
25, 26 
Visits 3, 5, 9, 
11 
Visits 7, 
20 
(Months 
3 and 9) 
Visit 14 
(Month 
6) 
Visits 
16, 18, 
22, 24 
Visit 27 
(Month 
12) 
Urine Lyso Gb3 concentration 
x 
x 
x 
x 
x 
Plasma Lyso Gb3 
x 
x 
x 
x 
x 
Plasma Gb3 
x 
x 
x 
x 
x 
Anti PRX-102 Antibodies 
(IgG) 
x 
x 
x 
x 
x 
Electrocardiography (ECG) 
x 
x 
x 
x 
x 
Chest X-ray 
x 
Cardiac function assessment 
(echocardiography and stress 
test) 
x 
x 
x 
x 
Cardiac MRI 
x 
x 
Inclusion/exclusion criteria 
x 
Request for subject approval 
x 
Enrolment approval 
x1 
Mutation analysis 
x 
PT, PTT 
x 
C3, C4 
x 
Vit D 
x 
Short Form Brief Pain 
Inventory (BPI) 
x 
x 
x 
x 
Brain MRI 
x 
x 
Mainz Severity Score Index 
(MSSI) 
x 
x 
x 
EQ-ED-5L 
x 
x 
x 
PRX-102 infusion+clinical 
observation 
x 
x 
x 
x 
x 
x 
x 
Adverse event assessments 
x 
x 
x 
x 
x 
x 
x 
x 
1 After Visit B 

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9.1 
Study Visits 
9.1.1 
Screening Visit S1 (3 Months ±7days   before Visit 1) 
The following procedures will be performed: 
• Administration of informed consent 
• Assign Screening number 
• Medical history, including Fabry disease history 
• Demographics 
• Alpha-galactosidase activity in plasma and leucocytes 
• Historical serum creatinine values 
• Vital signs (blood pressure, pulse, temperature and respiration rate) 
• Body weight and height 
• Physical examination 
• Concomitant medications , including review of pain medication and premedication 
• Clinical laboratory 
o Hematology 
o Biochemistry 
o Serum Creatinine and Cystatin C 
o Urinalysis by dipstick 
o Spot urine test for proteinuria 
o HbsAg, HCV, HIV 
o Serum pregnancy test (beta HCG) 
o Vit D 
o PT, PTT 
o C3, C4 
o Urine Lyso Gb3 concentration 
o Plasma Lyso Gb3 
o Plasma Gb3 
• Electrocardiogram 
• Chest X-ray – an X-ray from the previous three months is acceptable 
• Cardiac function assessment with echocardiography and stress test 
• Review of inclusion and exclusion criteria 
• Request subject approval 
Schedule the patient for the next visit. 
 
9.1.2 
Visits A and B (2 and 1 Month ±7 days before Visit 1) 
The following procedures will be performed: 

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• Clinical laboratory 
o Serum Creatinine and Cystatin C 
o Spot urine test for proteinuria 
• Concomitant medications including review of pain medication and premedication 
• Adverse event assessment 
Final enrolment approval will be determined after Visit B. 
Schedule the patient for the next visit. 
9.1.3 
Visit 1(±7Days ) 
The initial PRX-102 infusion will occur at this visit and will take place at the clinic and will 
continue every two weeks.  Vital signs will be measured at every infusion. 
 
The following procedures will be performed: 
• Vital signs (blood pressure, pulse, temperature and respiration rate) 
• Body weight 
• Physical examination 
• Concomitant medications, including review of pain medication and premedication 
• Clinical laboratory 
o Hematology 
o Biochemistry 
o Serum Creatinine and Cystatin C 
o Urinalysis by dipstick 
o Protein/Creatinine ratio spot urine test 
o Serum pregnancy test (beta HCG) 
o Antidrug antibodies(pre-infusion) (PRX-102) 
o Mutation  analysis 
o Urine Lyso Gb3 concentration 
o Plasma Lyso Gb3 
o Plasma Gb3 
• Electrocardiogram 
• Cardiac function assessment with echocardiography and stress test 
• Cardiac MRI 
• Mainz Severity Score Index 
• Quality of Life EQ-5D-5L 
• Short Form Brief Pain Inventory 
• Adverse event assessment 
• PRX-102 infusion 
• Brain MRI 
 
The following procedures will be performed after all infusions: 

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1. 
Patients will be observed clinically for a minimum of 2 hours after dosing. 
2. 
Vital signs will be evaluated every 30 minutes for the first hour, then  every hour and at 
the end of clinical observation  , if the patient tolerates the infusion. 
3. 
The injection site will be evaluated. 
 
A follow up telephone call with the patient will be held the day after the first infusion. 
Schedule the patient for the next visit. 
9.1.4 
Visits 2, 4, 6, 8, 10, 12, 13, 15, 17, 19, 21, 23, 25, 26 (±3 Days) 
Taper of premedication will  start at Visit 2 and occur over the next two months at the 
investigator’s discretion. 
 
The following procedures will be performed: 
• Vital signs (blood pressure, pulse, temperature and respiration rate) 
• Concomitant medications, including review of pain mediciation and premedication 
• Adverse event assessment 
• PRX-102 infusion 
• Post dosing clinical observation 
 
Schedule the patient for the next visit. 
9.1.5 
Visits 3, 5, 9, 11 (±3 Days) 
Premedication tapering will complete by visit 5 (Appendix 8).  The following procedures will 
be performed: 
• Vital signs (blood pressure, pulse, temperature and respiration rate) 
• Concomitant medications, including review of pain medication and premedication 
• Serum Creatinine and Cystatin C 
• Antidrug antibodies (pre-infusion) (PRX-102) 
• Adverse event assessment 
• PRX-102 infusion 
• Post dosing clinical observation 
 
Schedule the patient for the next visit. 
9.1.6 
Visits 7, 20 (±7 days) 
PRX-102 infusions continue every 2 weeks.   At Visit 7 if infusions are tolerated, infusion 
duration can be decreased to 1.5 hours as described in Appendix 2 

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The post dosing clinical observation length can be shortened to 1 hour pending patient 
tolerability per investigator discreation and after Medical Monitor approval when the patient 
has reached a stable infusion duration. Vital signs will be measured every 30 minutes when 
post dosing observation is reduced to 1 hour. 
 
The following procedures will be performed: 
• Vital signs (blood pressure, pulse, temperature and respiration rate) 
• Physical examination 
• Body weight 
• Concomitant medications, including review of pain medication and premedication 
• Clinical laboratory 
o Hematology 
o Biochemistry 
o Serum Creatinine and Cystatin C 
o Urinalysis by dipstick 
o Protein/Creatinine ratio spot urine test 
o Urine Lyso Gb3 concentration 
o Plasma Lyso Gb3 
o Plasma Gb3 
o Antidrug antibodies (pre dose) (PRX-102) 
• Electrocardiogram 
• Short Form Brief Pain Inventory 
• Adverse event assessment 
• PRX-102 infusion 
• Post dosing clinical observation 
 
 
Schedule the patient for the next visit. 
9.1.7 
Visit 14 (±7 days) 
The following procedures will be performed: 
• Vital signs (blood pressure, pulse, temperature and respiration rate) 
• Body weight 
• Physical examination 
• Concomitant medications, including review of pain medication and premedication 
• Clinical laboratory 
o Hematology 
o Biochemistry 
o Serum Creatinine and Cystatin C 
o Urinalysis by dipstick 
o Protein/Creatinine ratio spot urine test 
o Urine Lyso Gb3 concentration 

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o Plasma Lyso Gb3 
o Plasma Gb3 
o Antidrug antibodies (pre dose) (PRX-102) 
• Electrocardiogram 
• Cardiac function assessment with echocardiography and stress test 
• Short Form Brief Pain Inventory 
• Mainz Severity Score Index 
• Quality of Life EQ-5D-5L 
• PRX-102 infusion 
• Adverse event assessment 
• Post dosing clinical observation 
Schedule the patient for the next visit 
9.1.8 
Visits 16, 18, 22, 24 (±3 Days) 
The following procedures will be performed: 
• Vital signs (blood pressure, pulse, temperature and respiration rate) 
• Concomitant medications, including review of pain medication and premedication 
• Adverse event assessment 
• Serum Creatinine and Cystatin C 
• PRX-102 infusion 
• Post dosing clinical observation 
Schedule the patient for the next visit. 
9.1.9 
Visit 27 (±7 days) or Premature Withdrawal 
The following procedures will be performed: 
• Vital signs (blood pressure, pulse, temperature and respiration rate) 
• Body weight 
• Physical examination 
• Concomitant medications, including review of pain medication and premedication 
• Clinical laboratory 
o Hematology 
o Biochemistry 
o Serum Creatinine and Cystatin C 
o Urinalysis by dipstick 
o Protein/Creatinine ratio spot urine test 
o Urine Lyso Gb3 concentration 
o Plasma Lyso Gb3 

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o Plasma Gb3 
o Antidrug antibodies( pre dose) (PRX-102) 
• Electrocardiogram 
• Cardiac function assessment with echocardiography and stress test 
• Cardiac MRI 
• Brain MRI 
• Short Form Brief Pain Inventory 
• Mainz Severity Score Index 
• Quality of Life EQ-5D-5L 
• PRX-102 infusion 
• Adverse event assessment 
• Post dosing clinical observation 

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10. STATISTICAL METHODS PLANNED AND SAMPLE SIZE 
10.1 Determination of Sample Size 
The sample size of 22 patients is adequate to evaluate the safety of switching from agalsidase 
alfa to PRX-102 in this orphan disease in which patient recruitment in clinical trials is difficult. 
 
10.2 Subject Populations 
The safety population will be all subjects receiving at least one partial dose of PRX-102. The 
efficacy population will be all subjects with at least one endpoint evaluation after the first PRX- 
102 infusion. 
 
10.3 Subject Disposition 
The number and percentage of subjects who were enrolled, treated, completed, and withdrawn, 
as well as the reason(s) for withdrawal will be summarized. 
10.4 Safety Analysis 
Safety will be assessed by evaluation of adverse events and clinical laboratory results. 
 
10.4.1 
Adverse Events 
Adverse events will be coded to system organ class and preferred term using MedDRA version 
15.0 or higher. All adverse events occurring after the initiation of the study treatment (treatment 
emergent adverse events) will be reported, including events present at baseline that worsened 
during the study. 
 
Adverse events will be summarized with respect to incidence of adverse events (the number of 
subjects reporting at least one episode of a specific adverse event), incidence of adverse events 
by severity within body system, incidence of adverse events by attribution within body system, 
and incidence of adverse events causing withdrawal and incidence of serious adverse events. 
Regarding severity and attribution summaries, the most extreme outcome (highest severity and 
closest to study drug related) will be used for those subjects who experience the same adverse 
event on more than one occasion. 
 
Written narratives will be provided for all serious, unexpected or other significant adverse events 
that are judged to be of special interest because of their clinical importance. 
 
10.4.2 
Clinical Laboratory 
Summary statistics of all central and local laboratory test results (biochemistry, hematology, and 
urinalysis) will be presented for each visit. The change from baseline (Visit 1) to each post- 
treatment visit will also be presented. 

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If the test results were classified (e.g., low, normal, high), the frequency count and percentage 
will be presented for each visit, and shift table from baseline will be provided as well. 
 
10.5 Efficacy Analysis 
Descriptive statistics of measurements by visit, change and percent change from baseline will be 
presented for Left Ventricular Mass Index, plasma lyso-Gb3, plasma Gb3, urine Lyso-Gb3, and 
protein/creatinine ratio spot urine test. Descriptive statistics will be presented for the mean 
annualised eGFRCKD-EPI. eGFR is calculated from the serum creatinine according to the CKD- 
EPI formula: 
 
eGFR (ml/min/1.73 m2) = 141 × min(Scr/κ,1)α × max(Scr/κ, 1)-1.209 × 0.993Age × 
1.018 [if female] * 1.159 [if black] 
 
Scr = serum creatinine; κ = 0.7 for females and 0.9 for males; α = -0.329 for females and 
-0.411 for males, min indicates the minimum of Scr/κ or 1, and max  indicates the 
maximum of Scr/κ or 1. 
 
Descriptive statistics for the Brief Pain Inventory regarding pain severity, and pain interference 
will be summarized at baseline, 3-month, 6-month and 12-month treatments. The change of the 
assessments will be examined using a shift table from baseline for individual qualitative items, 
and by change from baseline for individual scores and composite scores. This will be done 
according to the Brief Pain Inventory User Guide. 
 
Descriptive statistics of the qualitative assessments regarding the sign/symptom in general, 
neurological, cardiovascular, renal dysfunction and the total change in each score will be 
summarized. 
 
10.6 Interim Analysis 
An interim analysis may be conducted for administrative purposes. 

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11. QUALITY CONTROL AND QUALITY ASSURANCE 
11.1 Source Data and Records 
Source data are all the information in original records and certified copies of original records of 
clinical findings, observations, laboratory reports, data sheets provided by the sponsor or other 
activities in the study, which are necessary for the reconstruction and evaluation of the study. 
The investigator will permit study-related monitoring, audit(s), IRB review(s) and regulatory 
inspection(s), with direct access to all the required source records. 
 
All study records will be retained for a period of time as defined by the regulatory authority for 
the country in which the investigation is conducted. Generally, this means at least 2 years 
following the date on which the drug is approved by the regulatory authority for marketing for 
the purposes that were the subject of the investigation. In other situations (e.g., where the 
investigation is not in support of or as part of an application for a research or marketing permit), 
a period of 2 years following the date on which the entire clinical program is completed, 
terminated or discontinued or the investigational application under which the investigation is 
being conducted is terminated or withdrawn by the regulatory authorities. 
 
In the event the Investigator retires, relocates or for any other reason withdraws from the 
responsibility for maintaining records for the period of time required, custody of the records may 
be transferred to any other person who will accept responsibility for the records. Notice of such 
a transfer must be given in writing to the Sponsor. The Investigator must contact the Sponsor 
prior to disposal of any records related to this study. 
 
11.2 Reporting of Results 
The Case Report Form (CRF) is an integral part of the study and subsequent reports. The CRF 
must be used to capture all study data recorded in the patient’s medical record. The CRF must 
be kept current to reflect patient status during the course of the study. Only a patient screening 
and randomization number and patient initials will be used to identify the patient. 
 
The monitor is responsible for performing on-site monitoring at regular intervals throughout the 
study to verify adherence to the protocol; verify adherence to local regulations on the conduct of 
clinical research; and ensure completeness, accuracy, and consistency of the data entered in the 
CRF. 
 
SPONSOR or CRO will monitor completed Case Report Forms (CRFs). A case report form will 
be provided for each screened patient. 
 
All protocol-required information collected during the study must be entered by the Investigator, 
or designated representative, in the Target e*CRF, an Internet-based electronic data collection 
system.  All details of the CRF completion and correction will be explained to the investigator. 

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The management module of Target e*CRF includes edit check and query systems that 
seamlessly integrate with the data entry system. All modifications to the data in the eCRF are 
tracked by an electronic audit trail (date and identity of the person making the change are 
instantaneously recorded).  Target e*CRF is 21CFR Part 11 compliant. 
 
If the Investigator authorizes other persons to make entries in the CRF, the names, positions, and 
signatures of these persons must be supplied to the sponsor. 
 
The Investigator, or designated representative, should complete the eCRF as soon as possible 
after information is collected, preferably on the same day that a study patient is seen for an 
examination, treatment, or any other study procedure. Any outstanding entries must be 
completed immediately after the final examination. By design, an explanation must be provided 
for all missing data, altered data, and/or out of range data. 
 
The completed case report form must be reviewed and signed by the Investigator named in the 
study protocol or by a designated sub investigator. 
 
Final monitored and audited eCRFs will be provided by the Sponsor to the sites at the end of the 
study in the format of a PDF file. 
 
11.3 Confidentiality of Subject Data 
The investigator will ensure that the confidentiality of the subjects' data will be preserved. In the 
CRF or any other documents submitted to the sponsor, the subjects will not be identified by their 
names, but by an identification system, which consists of their initials and number in the study. 
The investigator will maintain documents not meant for submission to the sponsor, e.g., the 
confidential subject identification code and the signed informed consent forms, in strict 
confidence. 

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12. REPORTING AND PUBLICATION 
12.1 Confidentiality of Study Data 
Any information relating to the study product or the study, including any data and results from 
the study, will be the exclusive property of the sponsor. The investigator and any other persons 
involved in the study will protect the confidentiality of this proprietary information belonging to 
Protalix Ltd. 

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13. REFERENCES 
Aerts, JM, Groener, JE, Kuiper, S, Donker-Koopman, WE, Strijland, A, Ottenhoff, R, van 
Roomen, C, Mirzaian, M, Wijburg, FA, Linthorst, GE, Vedder, AC, Rombach, SM, Cox- 
Brinkman, J, Somerharju, P, Boot, RG, Hollak, CE, Brady, RO, Poorthuis, BJ (2008). Elevated 
globotriaosylsphingosine is a hallmark of Fabry disease. Proc Natl Acad Sci U S A Feb 
26;105(8):2812-7. 
 
Banikazemi M, Bultas J, Waldek S et al. Agalsidase-beta therapy for advanced Fabry disease: a 
randomized trial. Ann Intern Med 2007;146: 77–86 
 
Barton, NW, Brady, RO, Dambrosia, JM, Di Bisceglie, AM, Doppelt, SH, Hill, SC, Mankin, HJ, 
Murray, GJ, Parker, RI, Argoff, CE (1991). Replacement therapy for inherited enzyme 
deficiency--macrophage-targeted glucocerebrosidase for Gaucher's disease. N. Engl. J. Med., 
324, 21:1464-70. 
 
Benichou, B, Goyal, S, Sung, C, Norfleet, AM, O'Brien, F (2009). A retrospective analysis of the 
potential impact of IgG antibodies to agalsidase beta on efficacy during enzyme replacement 
therapy for Fabry disease. Mol. Genet. Metab., 96, 1:4-12. 
 
Bishop, D. F. and R. J. Desnick (1988). Affinity purification of alpha-galactosidase A from 
human spleen, placenta, and plasma with elimination of pyrogen contamination. Properties of the 
purified splenic enzyme compared to other forms. J Biol Chem 256(3): 1307-16 
 
Blom, D, Speijer, D, Linthorst, GE, Donker-Koopman, WG, Strijland, A, Aerts, JM (2003). 
Recombinant enzyme therapy for Fabry disease: absence of editing of human alphagalactosidase 
A mRNA. Am. J. Hum. Genet., 72, 1:23-31. 
 
BPI- 
Brief 
Pain 
Inventory, 
Short 
Form. 
(www.mdanderson.org/education-and- 
research/symptom-assessment-tools/BPI User Guide pdf) 
 
El Dib, RP, Pastores, GM (2010). Enzyme replacement therapy for Anderson-Fabry disease. 
Cochrane Database Syst Rev May 12;(5):CD006663. 
 
Eng, CM, Guffon, N, Wilcox, WR, Germain, DP, Lee, P, Waldek, S, Caplan, L, Linthorst, GE, 
Desnick, RJ (2001). Safety and efficacy of recombinant human alpha-galactosidase A-- 
replacement therapy in Fabry's disease. N. Engl. J. Med., 345, 1:9-16. 
 
Eng CM, Banikazemi M, Gordon RE, Goldman M, Phelps R, Kim L, Gass A, Winston J, 
Dikman S, Fallon JT, Brodie S, Stacy CB, Mehta D, Parsons R, Norton K, Michael O’Callaghan 
M,8 Desnick RJ. A Phase 1/2 clinical trial of enzyme replacement in Fabry disease: 
Pharmacokinetic, substrate clearance, and safety studies. Am J Hum Genet 2001;68:711-22. 
 
Garman, SC, Garboczi, DN (2004). The molecular defect leading to Fabry disease: structure of 
human alpha-galactosidase. J Mol Biol 337(2): 319-35. 

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Germain, DP, Waldek, S, Banikazemi, M, Bushinsky, DA, Charrow, J, Desnick, RJ, Lee, P, 
Loew, T, Vedder, AC, Abichandani, R, Wilcox, WR, Guffon, N (2007). Sustained, long-term 
renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease. J. 
Am. Soc. Nephrol., 18, 5:1547-57. 
 
Hoffmann, B, Mayatepek, E (2009). Fabry disease-often seen, rarely diagnosed. Dtsch Arztebl 
Int, 106, 26:440-7. 
 
Hollak, CE, Aerts, JM, Goudsmit, R, Phoa, SS, Ek, M, van Weely, S, von dem Borne, AE, van 
Oers, MH (1995). Individualised low-dose alglucerase therapy for type 1 Gaucher's disease. 
Lancet 345(8963): 1474-8. 
 
Hollak, CE, Linthorst, GE (2009). Immune response to enzyme replacement therapy in Fabry 
disease: impact on clinical outcome?. Mol. Genet. Metab., 96, 1:1-3. 
 
Hughes, DA, Barba Romero, MA, Hollak, CE, Giugliani, R, Deegan, PB (2011). Response of 
women with Fabry disease to enzyme replacement therapy: comparison with men, using data 
from FOS--the Fabry Outcome Survey. Mol. Genet. Metab., 103, 3:207-14. 
 
Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. 
Ann Intern Med. 2009;150:604-612. 
 
Lidove, O, West, ML, Pintos-Morell, G, Reisin, R, Nicholls, K, Figuera, LE, Parini, R, Carvalho, 
LR, Kampmann, C, Pastores, GM, Mehta, A (2010). Effects of enzyme replacement therapy in 
Fabry disease--a comprehensive review of the medical literature. Genet Med Nov;12(11):668- 
79. 
 
Linthorst, GE, Hollak, CE, Donker-Koopman, WE, Strijland, A, Aerts, JM (2004). Enzyme 
therapy for Fabry disease: neutralizing antibodies toward agalsidase alpha and beta. Kidney Int., 
66, 4:1589-95. 
 
Meikle PJ, Hopwood JJ, Clague AE, Carey WF (1999). Prevalence of lysosomal storage 
disorders.  JAMA Jan 20;281(3):249-54. 
 
Mignani R, Feriozzi S, Schaefer RM et al. Dialysis and transplantation in Fabry disease: 
indications for enzyme replacement therapy. Clin J Am Soc Nephrol 2010; 5: 379–385 
 
Ortiz A, Oliveira JP, Waldek S et al. Nephropathy in males and females with Fabry disease: 
cross-sectional description of patients before treatment with enzyme replacement therapy. 
Nephrol Dial Transplant 2008; 23: 1600–1607. 
 
Ortiz A, Cianciaruso B, Cizmarik M et al. End-stage renal disease in patients with Fabry disease: 
natural history data from the Fabry Registry. Nephrol Dial Transplant 2010; 25: 769–775. 

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National Kidney Foundation (2002). KDOQI Clinical Practice Guidelines for Chronic Kidney 
Disease:       Evaluation,       Classification,       and       Stratification. 
Available 
at 
http://www.kidney.org/professionals/kdoqi/guidelines_ckd/toc.htm. 
 
Schaefer, RM, Tylki-Szymanska, A, Hilz, MJ (2009). Enzyme replacement therapy for Fabry 
disease: a systematic review of available evidence. Drugs, 69, 16:2179-205. 
 
Schiffmann, R, Murray, GJ, Treco, D, Daniel, P, Sellos-Moura, M, Myers, M, Quirk, JM, 
Zirzow, GC, Borowski, M, Loveday, K, Anderson, T, Gillespie, F, Oliver, KL, Jeffries, NO, 
Doo, E, Liang, T, Kreps, C, Gunter, K, Frei, K, Crutchfield K, Selden, R F, Brady, RO (2000). 
Infusion of a-galactosidase A reduces tissue globotriaosylceramide storage in patients with Fabry 
disease. PNAS,  97, 1:365–70. 
 
Schiffmann, R, Ries, M, Timmons, M, Flaherty, JT, Brady, RO (2006). Long-term therapy with 
agalsidase alfa for Fabry disease: safety and effects on renal function in a home infusion setting. 
Nephrol. Dial. Transplant., 21, 2:345-54. 
 
Schiffmann R, Askari H, Timmons M, Robinson C, Benko W, Brady RO, Ries M. (2007) 
Weekly enzyme replacement therapy may slow decline of renal function in patients with Fabry 
disease who are on long-term biweekly dosing. Am Soc Nephrol 18:576-83. 
 
Schiffmann, R (2009a). Fabry disease. Pharmacol. Ther., 122, 1:65-77. 
 
Schiffmann R, Warnock DG, Banikazemi M et al. (2009b) Fabry disease: progression of 
nephropathy, and prevalence of cardiac and cerebrovascular events before enzyme replacement 
therapy. Nephrol Dial Transplant 24: 2102–2111 
 
U.S.DEPARTMENT OF HEALTH AND HUMAN SERVICES. National Institutes of 
Health.National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) 
Version 4.0 Published: May 28, 2009 (v4.03: June 14, 2010) 
 
van Breemen, MJ, Rombach, SM, Dekker, N, Poorthuis, BJ, Linthorst, GE, Zwinderman, AH, 
Breunig, F, Wanner, C, Aerts, JM, Hollak, CE. (2011). Reduction of elevated plasma 
globotriaosylsphingosine in patients with classic Fabry disease following enzyme replacement 
therapy. Biochimica et Biophysica Acta 1812: 70–76 
 
Vedder, AC, Breunig, F, Donker-Koopman, WE, Mills, K, Young, E, Winchester, B, Ten Berge, 
IJ, Groener, JE, Aerts, JM, Wanner, C, Hollak, CE (2008). Treatment of Fabry disease with 
different dosing regimens of agalsidase: effects on antibody formation and GL-3. Mol. Genet. 
Metab., 94, 3:319-25. 
 
Veronese, FM, Pasut, G (2005). Pegylation, successful approach to drug delivery. Drug Discov. 
Today, 10, 21:1451-8. 
 
Veronese, FM, Mero, A (2008). The impact of Pegylation on biological therapies. Biodrugs, 22, 
5:315-29. 

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Wanner C, Oliveira JP, Ortiz A et al. Prognostic indicators of renal disease progression in adults 
with Fabry disease: natural history data from the Fabry Registry. Clin J Am Soc Nephrol 2010; 
5:2220–2228. 
 
Weidemann, F, Niemann, M, Breunig, F, Herrmann, S, Beer, M, Stork, S, Voelker, W, Ertl, G, 
Wanner, C, Strotmann, J (2009). Long-term effects of enzyme replacement therapy on fabry 
cardiomyopathy: evidence for a better outcome with early treatment. Circulation, 119,4:524-9. 
 
Wilcox, WR, Banikazemi, M, Guffon, N, Waldek, S, Lee, P, Linthorst, GE, Desnick, RJ, 
Germain, DP (2004). Long-term safety and efficacy of enzyme replacement therapy for Fabry 
disease. Am. J. Hum. Genet., 75, 1:65-74. 
 
Wilcox, WR, Oliveira, JP, Hopkin RJ, Ortiz A, Banikazemi, M, Feldt-Rasmussen, U, Sims, K, 
Waldek, S, Pastores, GM, Lee, P, Eng, CM, Marodi, L, Stanford KE, Frank Breunig, F, 
Wanner, C, Warnock, DG, Lemay, RM, Germain, DP (2008). Females with Fabry disease 
frequently have major organ involvement: lessons from the Fabry Registry. Mol Genet Metab 
93(2): 112-28. 

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14. APPENDICES 
14.1 Appendix 1. Vial Label 
Sample labels for the study drug are illustrated below in Figures 1 and 2. Labels will be adapted 
in accordance with local regulatory and language requirements. 
 
 
Figure 1. 
Outer Package Label (example) 
 
 
 
 
Figure 2. 
Individual Vials Label (example) 
 
 
Study drug name: Pegunigalsidase alfa (PRX-102) 
20 mg/vial for intravenous injection only as directed 
10mL in each vial 
Batch number: 
Expiry:  MM-YYYY 
Protocol #: PB-102-F30 
Caution: New Drug-Limited by Federal (or United States) 
law to investigational use. 
Subject/patient number: 
 
Visit 
number: 
Sponsor: Protalix 
Ltd, 2 Snunit St., Carmiel, Israel, Tel: +972-4-
9889488 
Protocol #: PB-102-F30 
Study drug name: Pegunigalsidase alfa (PRX-102) 
20 mg/vial; 10mL in each vial 
Qty: N vials  
 
For intravenous injections only as directed 
Batch number: 
Expiry: MM-YYYY 
IND No. 110,161 
Directions for use: 
Store at: 2-8°C (36-46°F) 
Caution: New Drug-Limited by Federal (or United States) law to investigational use. 
Sponsor: Protalix Ltd, 2 Snunit St., Carmiel, Israel, Tel: +972-4-9889488 

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14.2 Appendix 2. Infusion Rate Algorithm 
The infusion rate (IR) may be adjusted according to individual subject symptoms and signs. The 
infusion rate will be adjusted according to Section 7.4 Study Drug Administration under the 
direction of the Investigator and Protalix Medical director. Premedications if given when under 
agalsidase alfa will be tapered gradually during the first 2 months when under PRX-102 under 
the direction of the Investigator and Protalix Medical Director (See Appendix 8). The 
assumptions with respect to adverse experiences to the infusion are: 
1. Most of the subjects will tolerate the infusion without any special symptom or event. 
2. Subjects presenting symptoms and signs of severe hypersensitivity will be evaluated 
according to the CTCAE Drug Toxicity criteria and there may be a discontinuation of 
treatment according to the protocol. 
3. Subjects may present signs and symptoms that will respond to reducing the infusion rate 
and may not appear at the next infusion. 
4. Tolerability and the subject specific infusion rate will be assessed and decided by the 
Investigator according to vital signs and clinical status of the subject. 
Definitions to be applied regarding tolerability of infusions are as follows: 
 
Good tolerability 
Partial tolerability 
Poor tolerability 
Infusion was performed 
without signs and symptoms 
(such as burning, pruritus, 
flushing, discomfort, or 
change in vital signs). 
Signs and symptoms appeared 
during the infusion and 
resolved after slowing 
infusion rate or at the end of 
the infusion. 
Signs and symptoms meeting 
the definitions of CTCAE 
Grade 1 or 2 toxicity 
responding to reduction of 
infusion rate or responding to 
treatment (example, 
antihistamine for urticaria). 
 
 
 
The specific algorithm for other infusion rate changes to be followed: 

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Evaluate tolerability of the 
infusion 
 
 
 
 
 
 
 
 
 
 
Good 
Tolerability 
Signs and symptoms 
during the infusion 
Severe or progressive 
Hypersensitivity 
Adjust IR 
according to 
protocol 
Reduce IR (by ~25%): 
Tolerability 
achieved 
Persistant signs and symptoms 
during the infusion 
Continue same IR 
Consult with Medical 
Director about subsequent 
infusions 
Further reduce IR 
(by ~25%): 
Persistant signs and 
symptoms during the infusion 
or severe Hypersensitivity 
Tolerability 
achieved 
Consider discontinuation 
according to protocol 
following consulting with 
Medical Director 
Severe 
Hypersensitivity 

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Changes in infusion rates according to the protocol: 
The tolerability of the infusions in these patients will be determined by signs and symptoms 
during the infusion, and observation in the hospital, and by telephone contact the day after the 
infusion. 
 
For patients with good tolerability after the first 2 months of treatment and the finalization of the 
attempt of premedication discontinuation (in patients who were previously on premedication) the 
time of infusion can be decreased by 30 minutes every third infusion, up to a minimum infusion 
time of 1.5 hours under the agreement between the Investigator and the Medical Director. 
 
Infusion rate should be adjusted according to patient tolerability as described above; continuation 
of the rate of infusion should be agreed between the PI and the Medical Director. 

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14.3 Appendix 3. PRX-102 Evaluation and Treatment Algorithm 
During and after infusion of PRX-102, the following algorithm will be followed to monitor and 
manage the occurrence of hypersensitivity, anaphylaxis, or anaphylactoid reactions. 
Clinical signs 
Early 
 Sensation of warmth and itching 
 Feelings of anxiety 
Moderate 
 Pruritus 
 Flushing 
 Urticaria 
 Chest discomfort 
 Mild Hypotension 
Progressive 
 Erythematous or massive urticarial rash 
 Edema of face, neck, soft tissues 
Severe 
 Hypotension 
 Bronchospasm (wheezing) 
 Laryngeal edema (dyspnea, stridor, aphonia, drooling) 
 Arrhythmias 
Treatment algorithm: 
With the onset of any of the above clinical signs, immediately discontinue study medication 
administration and initiate the following monitoring. 
 Continuous electrocardiographic monitoring 
 Continuous pulse oximetry 
 Measure blood pressure every 5 minutes 
 Perform chest auscultation every 5 minutes 
 Collect blood samples for Tryptase (29-33), antibodies and C3, C4. Tryptase samples need 
to be withdrawn at: 
o 1st sample taken 0.25-3 hours after onset of symptoms 
o 2nd sample taken between 3-6 hours 
o 3rd sample taken 24-48 hours to verify the return to baseline. 
In the case of progressive or severe hypersensitivity, treat appropriately. 

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Treat as follows: 
 
Urticaria or edema of the face, neck, or soft tissues 
 Epinephrine 1:1000 solution, 0.5 mL subcutaneously, repeat as needed every 5-10 minutes 
 Antihistamines 
 Corticosteroids 
Hypotension (systolic blood pressure (SBP) ≤ 90 mmHg) 
 Isotonic sodium chloride solution, 1 L every 30 minutes as needed to maintain SBP > 90 
mmHg 
 Epinephrine 1:10,000 solution given IV at 1 μg/minute initially, then 2-10 μg/minute to 
maintain SBP > 90 mmHg 
 Norepinephrine 4 mg in 1 L 5% dextrose in water given IV at 2-12 μg/min to maintain 
SBP > 90 mmHg 
 Glucagon 1 mg in 1 L 5% dextrose in water give IV at 5-15 μg/minute for refractory 
hypotension 
Bronchospasm 
 Oxygen by face mask at 6-8 L/minute to maintain oxygen saturation at > 90% 
 Epinephrine 1:1000 solution, 0.5 mL subcutaneously 
 Albuterol 0.5 mL of 0.5% solution in 2.5 mL of sterile saline every 15 minutes up to three 
doses or other inhaled beta agonists 
 Corticosteroids 
Laryngeal edema 
 Epinephrine 1:1000 solution, 0.5 mL subcutaneously, repeat as needed every 5 to 10 
minutes 
 Corticosteroids 
If symptoms resolve within a single study visit and the investigator determines the symptoms 
were not an occurrence of progressive or severe hypersensitivity, anaphylaxis, or anaphylactoid 
reactions then administration of the drug may continue according to the algorithm provided 
above, and at the discretion of the Investigator and Medical Director. 
 
Premedication 
 
Premedication for subsequent PRX-102 infusions may be considered at the discretion of the 
investigator and Medical Director for subjects experiencing early clinical signs of 
hypersensitivity or rash/urticaria that responds promptly to oral antihistamine administration (see 
also Appendix 2 for adjustment of infusion rate). The premedication will be administered 
according to the following steps as needed to prevent progressive hypersensitivity: 

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1. Antihistamine 
(H1 blocker: 
diphenhydramine, 
hydroxyzine, 
cetrizine, 
loratadine, 
desloratidine) at a standard dose 12 hours and 2 hours before the start of the infusion. 
 
2. H1 blocker plus H2 blocker (ranitidine, cimetidine, famotidine) at standard doses 12 hours 
and 2 hours before the start of the infusion. 
 
3. H1 blocker plus H2 blocker plus prednisone up to 50 mg administered 12 hours and 2 hours 
before the start of the infusion. 

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14.4 Appendix 4. Cardiac MRI 
14.4.1 
Patients and sites 
Twenty-two patients will be enrolled in this trial in several sites worldwide. 
 
For each cardiac MRI to be conducted throughout the study, the test will be performed only after 
the Investigator reviews the patient’s kidney function. 
 
For patients who may present one of the following conditions the performance of the Cardiac 
MRI will be discussed with Protalix Medical Director: 
 
• GFR < 30 mL/min/1.73m2 based on the last Serum Creatinine value 
 
or 
 
• Suspected Acute Kidney Injury 
Gadolinium warnings from USPI: 
 
 

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14.4.2 
Magnetic Resonance Imaging (MRI) data 
Each patient enrolled in this trial will have a cardiac MRI at baseline (Visit 1) as a reference for 
further MRI evaluations in the study. A set of ECG gated cine and delayed contrast enhanced 
MRI sequences (SSFP resp. Inversion recovery Gradient echo) will be acquired. A Gadolinium 
based contrast agent will be used during image acquisition of the delayed contrast enhanced 
scan. 
 
The sequences will be defined based on the equipment and ability to provide sufficient image 
quality and contrast for myocardium and fibrosis detection and quantification in Fabry’s disease 
patients. 
 
14.4.3 
MRI evaluation parameters 
The following MRI parameters will be evaluated during this trial: 
• Number and location of left ventricular segments with fibrosis 
• Percentage and mass of cardiac fibrosis (in grams) 
• Left ventricular myocardial mass (in grams) 
 
14.4.4 
Sites and image data management 
All image management activities will be centralized and conducted by an independent imaging 
Contract Research Organization (imaging CRO) with operational capabilities in Europe and the 
United States in compliance with all regulatory requirements. An overview of the main activities 
performed by the imaging CRO is provided in the next sections. 
 
14.4.4.1 Standardization of image acquisition, initial site qualification 
The image acquisition procedure will be standardized by the imaging CRO among all 
participating sites. The same image acquisition and management procedure will be used by all 
sites. This procedure will be defined by the imaging CRO and approved by the Sponsor. The 
sites will be trained and qualified by the imaging CRO prior to start of patient enrolment. Each 
site will provide test MRI scan(s) during the initial site qualification phase. The source of the test 
scan(s) will be (in order of preference) a patient volunteer, a healthy volunteer, or the screening 
image from the first patient tested at the site. No contrast agent will be used for the test scans 
except when the first image from the first patient is used. All images will be anonymized by the 
sites (in order to remove any patient-related nominative information) and provided in digital 
format (DICOM). Only digital images will be centrally processed by the imaging CRO. 
 
14.4.4.2 Subject Sedation 
Subjects may require sedation in order to obtain the high quality images required. Sites may use 
standard sedation protocols approved by the institution. 

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14.4.4.3 Quality control of image data and site Quality Assurance 
The image data will be collected and quality controlled by the imaging CRO for checking the 
technical adequacy, the compliance of data acquisition with the study imaging protocol, the 
anonymization of the images and the diagnostic quality of the images (their appropriateness for 
centralized evaluations). If any quality-related issue is detected by the imaging CRO, specific 
queries will be sent to the sites to implement appropriate corrective (including potential repeat 
scans if needed) and preventive actions. 
 
14.4.5 
Image processing and centralized analysis 
14.4.5.1 Cardiac MRI assessment 
Analysis of the cine short-axis and delayed contrast enhanced images of the left ventricle will be 
performed with dedicated MRI quantification software. 
 
Myocardial contours will be detected semi-automatically and manually edited and quality 
controlled by an expert technician at the imaging CRO. 
 
The left ventricular contours will be submitted for final approval to an independent and blinded 
reader. 
 
Based on approved contours, the left ventricular mass and % and mass of the fibrotic area are 
calculated automatically by the software algorithm. 
 
14.4.5.2 Centralized and Blinded Image Review by Independent Readers 
The MRI data will be centrally evaluated in a fully blinded manner by an independent reader. 
The reading sessions will be organized at the imaging CRO site. The same image evaluation 
procedure will be used for all patients’ MRI scans in this trial. 
Expertise of independent readers, training sessions 
The reader will be a Cardiologist with a significant experience in cardiac MRI. The reader will 
be trained prior to start of centralized image review sessions. 
 
He/she will be provided with a Read Rules document and will be given a training on the use of 
the software. Test cases representing non-study Fabry patients (as described in Section 14.4.4.1) 
will be used for the training. Main consensus issues (contour detection in apical and basal LV 
slices, trabeculae and papillary muscles, threshold for delayed enhanced areas, etc.) will be 
discussed with the reader and documented. 

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Conduct of centralized image review sessions 
The reader will be fully blinded with regard to Treatment Groups, patient’s ID and site number. 
The images will have been pre-analyzed by experienced image analysis technologists from the 
imaging CRO. 
 
The image review sessions by the cardiologist will include: 
Efficacy Image Review: 
MRI analysis results at baseline as a reference for further MRI evaluations in the study will be 
evaluated by the reader. 
 
14.4.6 
Data and report transfers to Sponsor 
• Efficacy image Review sessions will be exported to the Sponsor using a predefined, 
standardized and secure data transfer procedure. 
• The final Study database will be submitted to the Sponsor in digital format. 
 
14.4.7 
Direct access to Study data 
• A Direct access to Study data will be made possible by the imaging CRO for audit 
purposes. 
• Such Study data include: 
o Information related to interactions between the imaging CRO and the sites 
(Queries, Data Clarification Forms, test data submitted by the sites, etc.) 
o Native MRI data 
o Data processed and generated by the imaging CRO 
o Data generated by the blinded reader 
o Audit trails 
 
14.4.8 
Unevaluable MRI: 
Unevaluable MRI data can result from poor quality image, due to patient motion, improper left 
ventricular coverage, technical problems with the image transmission to the imaging CRO, etc. 
The imaging CRO procedures for ensuring quality images are meant to reduce or eliminate such 
poor quality images (Section 14.4.4.3 above). 
 
If an adequate patient image cannot be obtained for a given time point in the study, the problem 
with the image will be documented at the imaging CRO. In addition, the imaging CRO will 
document all attempted corrective actions with the investigative site imaging centre. 

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14.5 Appendix 5. The Mainz Severity Score Index (MSSI) 
The MSSI score has been proven representative in patients with ‘classic’ Fabry disease and is 
useful for monitoring clinical improvement in patients receiving enzyme replacement therapy 
(Weidemann et al, 2009). 
 
The MSSI scoring system is composed of four sections that cover the general, neurological, 
cardiovascular and renal signs and symptoms of Fabry disease. Each section includes a group of 
signs and symptoms that are associated with Fabry disease. 
 
The MSSI will be performed only at Visit 1 and then every 6 months (Visits 1, 14 and 27). 
The Mainz Severity Score Index (MSSI): 
 
General Score 
Neurological Score 
Sign/symptom 
Rating 
MSSI 
score 
Sign/symptom 
Rating 
MSSI 
score 
Characteristic 
facial appearance 
No 
0 
Tinnitus 
No 
0 
Yes 
1 
Mild 
1 
Angiokeratoma 
None 
0 
Severe 
2 
Some 
1 
Vertigo 
No 
0 
Extensive 
2 
Mild 
1 
Oedema 
No 
0 
Severe 
2 
Yes 
1 
Acroparaesthesia 
No 
0 
Musculoskeletal 
No 
0 
Occasional 
3 
Yes 
1 
Chronic 
6 
Cornea verticillata 
No 
0 
Fever pain crisis 
No 
0 
Yes 
1 
Yes 
2 
Diaphoresis 
Normal 
0 
Cerebrovascular 
No 
0 
Hypo/Hyper 
1 
Ischemic lesions 
(in MRI/CT) 
1 
Anhidrosis 
2 
TIA/migraine 
etc. 
3 
Abdominal pain 
No 
0 
Stroke 
5 
Yes 
2 
Psychiatric/ 
psychosocial 
Diarrhoea/ 
constipation 
No 
0 
Depression 
No 
0 
Yes 
1 
Yes 
1 
Haemorrhoids 
No 
0 
Fatigue 
No 
0 
Yes 
1 
Yes 
1 
Pulmonary 
No 
0 
Reduced activity 
No 
0 

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level 
Yes 
2 
Yes 
1 
New York Heart 
Association 
(NYHA) 
classification* 
No 
0 
Class I 
1 
Class II 
2 
Class III 
3 
Class IV 
4 
Maximum Score 
18 
Maximum Score 
20 
Cardiovascular Score 
Renal Score 
Sign/symptom 
Rating 
MSSI 
score 
Sign/symptom 
Rating 
MSSI 
score 
Changes in cardiac 
muscle thickness 
No 
0 
Evidence of renal 
dysfunction 
No proteinuria 
0 
Thickening of 
wall/septum 
1 
Proteinuria 
4 
LVH seen on 
ECG 
6 
Tubular 
dysfunction/low 
GFR or 
creatinine 
clearance 
8 
Cardiomyopathy 
(<15) 
8 
End-stage renal 
failure (serum 
creatinine levels 
>3.5 mg/dl) 
12 
Severe 
cardiomyopathy 
(>15) 
12 
Dialysis 
18 
Valve 
insufficiency 
No 
0 
Yes 
1 
ECG abnormalities 
No 
0 
Yes 
2 
Pacemaker 
No 
0 
Yes 
4 
Hypertension 
No 
0 
Yes 
1 
Maximum Score 
20 
Maximum Score 
18 

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* Limitation on physical activity according to NYHA classification is as follows. Class I: none; 
Ordinary physical activity does not cause undue fatigue, palpitation, dyspnoea or anginal pain, 
but echocardiography reveals heart involvement. Class II: slight; comfortable at rest, but 
ordinary physical activity results in fatigue, etc. Class III: marked; comfortable at rest, but less 
than ordinary physical activity causes fatigue, etc. Class IV: unable to carry out any physical 
activity without discomfort; symptoms of cardiac insufficiency or of anginal syndrome may be 
present even at rest and physical activity increases discomfort. 
 
Abbreviations: 
 
CT, computed tomography; ECG, electrocardiogram; GFR, glomerular filtration rate; LVH, left 
ventricular hypertrophy; MRI, magnetic resonance imaging; TIA, transient ischaemic attack. 

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14.6 Appendix 6. National Kidney Foundation Guidelines for Chronic 
Kidney Disease 
Stages of Chronic kidney disease (National Kidney Foundation 2002): 
• Stage 1- Kidney damage with normal or elevated GFR (≥ 90) 
• Stage 2- Kidney damage with mild reduction in GFR (60-89) 
• Stage 3- Kidney damage with moderate reduction in GFR (30-59) 
• Stage 4- Kidney damage with severe reduction in GFR (15-29) 
• Stage 5- Kidney failure (<15 or dialysis) 
 
14.6.1 
Estimation of GFR: 
Estimates of GFR are the best overall indices of the level of kidney function. The level of GFR 
should be estimated from prediction equations that take into account the serum creatinine 
concentration and some or all of the following variables: age, gender, race, and body size. 
Among adults, the CKD-EPI equation provides a clinically useful estimate of GFR (Levey et al., 
2009). This equation provides estimate of GFR standardized for body surface area. 
 
14.6.2 
CKD-EPI Equation: 
The CKD-EPI equation performed better than the MDRD (Modification of Diet in Renal Disease 
Study) equation, especially at higher GFR, with less bias and greater accuracy. When looking at 
NHANES (National Health and Nutrition Examination Survey) data, the median estimated GFR 
was 94.5 mL/min per 1.73 m2 vs. 85.0 mL/min per 1.73 m2, and the prevalence of chronic kidney 
disease was 11.5% versus 13.1%. The CKD-EPI equation, expressed as a single equation, is: 
GFR = 141 * min(Scr/κ,1)α * max(Scr/κ,1)-1.209 * 0.993Age * 1.018 [if female] * 1.159 [if 
black/African american] 
Where Scr is serum creatinine (mg/dL), κ is 0.7 for females and 0.9 for males, α is –0.329 for 
females and –0.411 for males, min indicates the minimum of Scr/κ or 1, and max indicates the 
maximum of Scr/κ or 1. 

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14.7 Appendix 7. Brief Pain Inventory- BPI (Short Form) 
(www.mdanderson.org/education-and-research/symptom-assessment-tools/BPI User Guide pdf) 

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14.8 Appendix 8. Premedication Discontinuation Guide 
Patients on agalsidase alfa can be included in the study when under premedication to diminish 
the side effects to the drug. 
 
During the first 2 months of PRX-102 treatment (5 infusions), the Investigator will manage a 
stepwise discontinuation of the premedication based on the appropriate tolerability of the patient 
to the changes. Premedication will resume in the case that the patient will present signs and 
symptoms of non-tolerability of the infusion. 
 
All cases of non-tolerabilty and need of premedication will be discussed between the Investigator 
and the Medical Director before reaching infusion 7 and evaluating the reduction of infusion 
rate, see also Appendix 2. 

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14.9 Appendix 9. EQ-5D-5L 
 
 

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