A Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Birtamimab Plus Standard of Care vs. Placebo Plus Standard of Care in Mayo Stage IV Subjects With Light Chain (AL) Amyloidosis
Phase: PHASE3
Conditions: Light Chain (AL) Amyloidosis
Sponsor: Prothena Biosciences Ltd.

CLINICAL RESEARCH PROTOCOL 
Study Title: 
A Phase 3, Randomized, Multicenter, Double-Blind, Placebo-
Controlled, Efficacy and Safety Study of Birtamimab Plus 
Standard of Care vs. Placebo Plus Standard of Care in Mayo 
Stage IV Subjects with Light Chain (AL) Amyloidosis  
Protocol Number: 
NEOD001-301 
Version Number: 
5.0 
Investigational Product: 
Birtamimab  
US IND Number: 
146070 
EudraCT Number: 
2021-000037-14 
EU CT Number: 
2024-511066-36-00 
Indication: 
Light Chain (AL) Amyloidosis 
Sponsor: 
Prothena Biosciences Limited 
77 Sir John Rogerson’s Quay, Block C 
Grand Canal Docklands, Dublin 2 
D02 T804, Ireland 
Sponsor Representative: 
Prothena Biosciences Inc 
1800 Sierra Point Parkway 
Brisbane, CA 94005 USA 
Sponsor’s Responsible Signatory: 
, MD, PhD 
Coordinating Investigator: 
, MD 
Development Phase: 
Phase 3 
Date of Original Protocol: 
26 January 2021 
Date of Protocol Version 2.0: 
10 January 2022 
Date of Protocol Version 3.0: 
30 November 2022 
Date of Protocol Version 4.0: 
18 October 2023 
Date of Protocol Version 5.0: 
27 March 2024 
Confidential
The information contained in this document and all information provided to you related to birtamimab is the confidential and 
proprietary information of Prothena Therapeutics Limited (Prothena). It is intended solely for the recipient clinical investigator(s) 
and must not be disclosed to any other party. This material may be used only for evaluating or conducting clinical investigations; 
any other proposed use requires written consent from Prothena.

Prothena 
 
Study Drug: Birtamimab 
Study Protocol: NEOD001-301 Version 5.0 
 
 
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PROTOCOL APPROVAL PAGE  
 
 
Protocol Title: A Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled, 
Efficacy and Safety Study of Birtamimab Plus Standard of Care vs. Placebo Plus Standard of 
Care in Mayo Stage IV Subjects with Light Chain (AL) Amyloidosis 
Protocol Number: 
 
 
NEOD001-301 
Version Number: 
 
 
5.0 
Date of Original Protocol:  
26 January 2021 
Date of Protocol Version 2.0: 
10 January 2022 
Date of Protocol Version 3.0:  
30 November 2022 
Date of Protocol Version 4.0: 
18 October 2023 
Date of Protocol Version 5.0: 
27 March 2024 
 
Declaration of Sponsor 
This clinical study protocol was subjected to critical review. The information it contains is 
consistent with current knowledge of the risks and benefits of the study drug, as well as with the 
moral, ethical, and scientific principles governing clinical research as set out in the Declaration 
of Helsinki and the guidelines on Good Clinical Practices applicable to this clinical study. 
 
 
 
 
 
 
This protocol has been approved by Prothena. The following person is authorized on behalf of 
Prothena to approve this protocol and the signature below documents this approval. 
 
 
 
 
Chief Medical Officer 
 
Date 
 
 
 
 

Prothena 
 
Study Drug: Birtamimab 
Study Protocol: NEOD001-301 Version 5.0 
 
 
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INVESTIGATOR SIGNATURE PAGE  
 
Protocol Title: A Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled, 
Efficacy and Safety Study of Birtamimab Plus Standard of Care vs. Placebo Plus Standard of 
Care in Mayo Stage IV Subjects with Light Chain (AL) Amyloidosis 
Protocol Number: 
 
 
NEOD001-301 
Version Number: 
 
 
5.0 
Date of Original Protocol:  
26 January 2021 
Date of Protocol Version 2.0: 
10 January 2022 
Date of Protocol Version 3.0:  
30 November 2022 
Date of Protocol Version 4.0:  
18 October 2023 
Date of Protocol Version 5.0:  
27 March 2024 
 
 
 
 
 
 
I have read the foregoing protocol and agree to conduct this study in accordance with the current 
protocol. 
 
 
 
Investigator Signature 
 
Date 
 
 
Investigator Name (Print) 
 
 
 
Please sign, date, and return this form to Prothena or its designee. Contact details will be 
provided to the Investigator. Please retain a copy for your study files. 

Prothena 
 
Study Drug: Birtamimab 
Study Protocol: NEOD001-301 Version 5.0 
 
 
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Page 4 of 124 
TABLE OF CONTENTS 
CLINICAL RESEARCH PROTOCOL ...........................................................................................1 
PROTOCOL APPROVAL PAGE ...................................................................................................2 
INVESTIGATOR SIGNATURE PAGE .........................................................................................3 
PROTOCOL SYNOPSIS ................................................................................................................9 
GLOSSARY OF TERMS ..............................................................................................................29 
1. 
INTRODUCTION ......................................................................................................32 
1.1. 
Light Chain (AL) Amyloidosis ...................................................................................32 
1.2. 
Rationale for the Clinical Study .................................................................................33 
1.3. 
Background on Birtamimab ........................................................................................33 
1.3.1. 
Nonclinical Safety ......................................................................................................34 
1.3.2. 
Clinical Experience .....................................................................................................34 
1.4. 
Rationale for Study Design and Dose Selection .........................................................37 
1.5. 
Benefit-Risk Assessment ............................................................................................38 
2. 
OBJECTIVES .............................................................................................................39 
2.1. 
Primary Objective .......................................................................................................39 
2.2. 
Secondary Objectives .................................................................................................39 
2.3. 
Exploratory Objectives ...............................................................................................39 
3. 
STUDY PLAN............................................................................................................40 
3.1. 
Study Design ...............................................................................................................40 
3.2. 
Number of Sites and Subjects .....................................................................................40 
3.3. 
Endpoints ....................................................................................................................41 
3.3.1. 
Efficacy Endpoints ......................................................................................................41 
3.3.1.1. 
Primary Efficacy Endpoint .........................................................................................41 
3.3.1.2. 
Secondary Efficacy Endpoints ....................................................................................41 
3.3.1.3. 
Exploratory Efficacy Endpoints .................................................................................41 
3.3.2. 
Safety Endpoints .........................................................................................................41 
3.4. 
Estimated Study Duration ...........................................................................................41 
3.5. 
Definition of Primary Endpoint and End of Study .....................................................42 
3.6. 
Termination of the Clinical Study ..............................................................................42 
4. 
SUBJECT SELECTION .............................................................................................43 
4.1. 
Inclusion Criteria ........................................................................................................43 

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4.2. 
Exclusion Criteria .......................................................................................................45 
5. 
SUBJECT SCREENING AND RANDOMIZATION ...............................................48 
6. 
INVESTIGATIONAL MEDICINAL PRODUCT AND TREATMENT ..................49 
6.1. 
Formulation, Packaging, and Labeling of Birtamimab ..............................................49 
6.2. 
Shipping, Storage, and Handling of Birtamimab ........................................................49 
6.3. 
Placebo ........................................................................................................................49 
6.4. 
Accountability and Return of Study Drug Supplies ...................................................49 
6.5. 
Dosage, Administration, and Schedule .......................................................................50 
6.5.1. 
Study Drug ..................................................................................................................50 
6.5.2. 
Study Drug Premedication ..........................................................................................51 
6.5.3. 
Standard of Care Chemotherapy .................................................................................51 
6.6. 
Dosage Adjustments ...................................................................................................52 
6.6.1. 
Withholding of Study Drug ........................................................................................52 
6.6.2. 
Management of Suspected Infusion-Related/Hypersensitivity Adverse 
Events .........................................................................................................................52 
6.6.3. 
Dose Reductions .........................................................................................................53 
6.7. 
Treatment Compliance ................................................................................................53 
6.8. 
Concomitant Therapy .................................................................................................54 
6.8.1. 
Allowed Concomitant Therapy ...................................................................................54 
6.8.2. 
Prohibited Concomitant Therapy ................................................................................54 
6.8.3. 
 ..................................................................................55 
7. 
STUDY PROCEDURES ............................................................................................56 
7.1. 
Study Visits and Assessments ....................................................................................56 
7.1.1. 
Double-blind Phase .....................................................................................................56 
7.1.1.1. 
First Screening Visit: Day -28 to Day -1 ....................................................................56 
7.1.1.2. 
Second Screening Visit: Day -3 to Day -1..................................................................57 
7.1.1.3. 
Treatment Visits ..........................................................................................................58 
7.1.1.4. 
Concomitant Chemotherapy Visits .............................................................................71 
7.1.1.5. 
Double-blind Phase End of Treatment (EOT)/Early Treatment 
Discontinuation (ETD) (28 to 35 Days Post Final Dose) ...........................................72 
7.1.2. 
Open-label Extension Phase .......................................................................................73 
7.1.2.1. 
Treatment Visits ..........................................................................................................73 

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7.1.2.2. 
Open-Label End of Treatment/Early Treatment Discontinuation (28 to 
35 Days Post-Final Dose) ...........................................................................................81 
7.1.3. 
Vital Status Assessment Every 
 ...................................................................82 
7.1.4. 
Unscheduled Visit .......................................................................................................82 
7.2. 
Order of Assessments .................................................................................................83 
7.3. 
Laboratory and Additional Evaluations ......................................................................83 
7.4. 
6-Minute Walk Test ....................................................................................................84 
7.5. 
Monitoring Anti-Birtamimab Antibodies During the Study ......................................84 
8. 
EMERGENCY UNBLINDING OF STUDY DRUG, EARLY 
DISCONTINUATION, OR TERMINATION FROM STUDY ................................85 
8.1. 
Emergency Unblinding ...............................................................................................85 
8.2. 
Early Treatment Discontinuation ................................................................................85 
8.3. 
Early Termination from the Study ..............................................................................86 
8.4. 
Replacement of Subjects .............................................................................................86 
9. 
ADVERSE EVENTS/SERIOUS ADVERSE EVENTS AND REPORTING ...........87 
9.1. 
Definitions ..................................................................................................................87 
9.2. 
Adverse Events – Detecting, Recording, and Reporting ............................................88 
9.2.1. 
Reporting Period for Adverse Events .........................................................................88 
9.2.2. 
Reporting of Adverse Events ......................................................................................89 
9.3. 
Severity Assessment ...................................................................................................89 
9.4. 
Relationship to Study Drug ........................................................................................90 
9.5. 
Adverse Event Outcome Assessment .........................................................................91 
9.6. 
Reporting of Serious Adverse Events .........................................................................91 
9.6.1. 
SAE Reporting to Prothena via Paper Safety Reporting Form...................................92 
9.6.2. 
Regulatory Reporting Requirements for SAEs ...........................................................92 
9.7. 
Follow-up of Adverse Events .....................................................................................93 
9.8. 
Pregnancy ...................................................................................................................93 
9.9. 
Urgent Safety Measures ..............................................................................................94 
10. 
STATISTICAL CONSIDERATIONS .......................................................................95 
10.1. 
Analysis Populations ..................................................................................................95 
10.2. 
General Considerations ...............................................................................................95 
10.3. 
Efficacy Analyses .......................................................................................................95 
10.3.1. 
Primary Analysis ........................................................................................................95 

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10.3.2. 
Secondary Efficacy Analyses .....................................................................................96 
10.3.3. 
Handling of Missing Data ...........................................................................................96 
10.4. 
Safety Analyses ..........................................................................................................96 
10.4.1. 
Adverse Events ...........................................................................................................96 
10.4.2. 
Clinical Laboratory Evaluations .................................................................................97 
10.4.3. 
Vital Signs and Electrocardiograms ...........................................................................97 
10.5. 
Immunogenicity ..........................................................................................................97 
10.6. 
Interim Analysis ..........................................................................................................97 
10.7. 
Determination of Sample Size ....................................................................................97 
10.8. 
Data Monitoring Committee .......................................................................................98 
11. 
DATA RECORDING, RETENTION, AND MONITORING ...................................99 
11.1. 
Case Report Forms .....................................................................................................99 
11.2. 
Availability and Retention of Records .......................................................................99 
11.3. 
Quality Control and Quality Assurance ....................................................................100 
11.4. 
Subject Confidentiality .............................................................................................100 
12. 
ETHICAL AND LEGAL ISSUES ...........................................................................101 
12.1. 
Ethical Conduct of the Study ....................................................................................101 
12.2. 
Regulatory Approval ................................................................................................101 
12.3. 
Independent Review Board / Ethics Committee (EC) Approval ..............................101 
12.4. 
Subject Informed Consent ........................................................................................101 
12.5. 
Privacy of Personal Data ..........................................................................................102 
12.6. 
Subject Compensation for Adverse Effects on Health .............................................102 
12.7. 
Protocol Amendments and Study Termination.........................................................102 
12.8. 
Finance, Insurance, and Indemnity ...........................................................................103 
12.9. 
Serious Breaches of the Protocol or ICH GCP .........................................................103 
13. 
PUBLICATION ........................................................................................................104 
14. 
REFERENCES .........................................................................................................105 
15. 
APPENDICES ..........................................................................................................107 
 
LIST OF TABLES  
Table 1: 
Schedule of Events for Double-blind Phase ...............................................................22 
Table 2: 
Schedule of Events for Open-label Extension Phase ..................................................26 

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Table 3: 
Overview of Birtamimab Clinical Studies ..................................................................35 
Table 4: 
Adverse Event Severity Grading Scale .......................................................................90 

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PROTOCOL SYNOPSIS  
Title 
A Phase 3, Randomized, Multicenter, Double-Blind, Placebo-
Controlled, Efficacy and Safety Study of Birtamimab Plus Standard 
of Care vs. Placebo Plus Standard of Care in Mayo Stage IV 
Subjects with Light Chain (AL) Amyloidosis 
Study Phase 
Phase 3 
Indication 
Birtamimab is indicated for the treatment of Mayo Stage IV patients 
with AL amyloidosis to reduce the risk of mortality.  
Primary Objective 
Double-blind Phase 
To evaluate the efficacy of birtamimab plus standard of care 
compared to placebo plus standard of care when administered 
intravenously in Mayo Stage IV subjects with AL amyloidosis by 
assessing time to all-cause mortality. 
Open-label Extension Phase 
To evaluate the long-term safety of birtamimab plus standard of care 
in Mayo Stage IV subjects with AL amyloidosis 
Secondary Objectives 
Double-blind Phase 
To evaluate birtamimab plus standard of care compared to placebo 
plus standard of care on the following: 
• 
Change from baseline to Month 9 in the 6-Minute Walk 
Test (6MWT) distance 
• 
Change from baseline to Month 9 in health-related 
quality of life using the Short Form-36 questionnaire 
Version 2 (SF-36v2) 
Open-label Extension Phase 
 
Exploratory Objectives 
Double-blind Phase 
 
Open-label Extension Phase 
To explore the long-term efficacy of birtamimab plus standard of 
care  
Study Design 
This study comprises a multicenter, global, randomized, double-
blind, placebo-controlled, efficacy and safety evaluation in Mayo 
Stage IV subjects with AL amyloidosis (i.e., Double-blind Phase), 
followed by a long-term, open-label extension (i.e., Open-label 
Extension [OLE] Phase).  
In the Double-blind Phase, newly diagnosed Mayo Stage IV subjects 
with AL amyloidosis will be randomized in a 2:1 ratio to 
birtamimab or placebo. The initial first-line chemotherapy regimen 
must include bortezomib. 

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holiday), then it is acceptable for the homecare visit to take place on 
the previous Friday. 
The number of cycles of first-line chemotherapy that is administered 
is at the discretion of the Investigator, and subsequent chemotherapy 
regimens may be prescribed as per standard of care at the 
Investigator’s discretion.  
In the event that bortezomib doses are missed, the chemotherapy 
cycles may become misaligned with the monthly study drug dosing. 
In this case, the weekly visits during Months through  should 
continue as described above in order to closely monitor subjects’ 
health during the initial months of concomitant chemotherapy. 
Throughout the study, monthly doses of study drug should not be 
delayed or skipped due to adjustments that are made to 
chemotherapy dosing. 
Safety and efficacy assessments will be performed at each visit as 
outlined in the Double-blind Phase Schedule of Events (Table 1). 
 is not allowed during the 
Double-blind Phase. 
Open-label Extension Phase 
After the Double-blind Phase portion of the study, eligible subjects 
may enter the optional OLE Phase, in which all subjects will receive 
open-label birtamimab treatment, regardless of Double-blind Phase 
randomized treatment assignment. The first visit (Month 1-Day 1) of 
the OLE Phase should be the same day as the Double-blind Phase 
EOT Visit but no later than 2 months after the last dose of 
randomized treatment, if feasible. If the first visit of the OLE Phase 
occurs on the same day as the Double-blind Phase EOT Visit or 
within 14 days of that visit, results of procedures performed at that 
visit may be used for the pre-infusion procedures for the first visit of 
the OLE Phase.  
All doses of study drug will be administered at the study site, 
starting at the first visit of the OLE Phase and then every 28 days 
 until the OLE Phase EOT/ETD Visit.  
During the OLE Phase, chemotherapy regimens (including 
daratumumab) should be prescribed per standard of care at the 
Investigator’s discretion, 
. Safety and efficacy 
assessments will be performed as outlined in the OLE Phase 
Schedule of Events (Table 2). 
Number of Sites and Subjects 
This is a multicenter, global study in approximately 120 centers. 
Approximately 220 subjects may be enrolled in the study, with 
approximately 147 and 73 subjects per arm (birtamimab and 
placebo, respectively).  
Estimated Study Duration 
The Double-blind Phase of the study is event-driven and will 
continue until approximately 
primary endpoint events of all-
cause mortality have occurred. All subjects who discontinue 
treatment during the Double-blind Phase will be followed until the 
last primary endpoint event has occurred. The estimated overall 
Double-blind Phase duration is approximately 42 months, including 

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the screening, enrollment, treatment period, and postdose follow-up 
for subjects not entering the optional OLE Phase. 
For subjects who enter the OLE Phase, treatment will continue for 
an additional 24 months or until birtamimab is commercially 
available in the subject’s country of residence, whichever occurs 
first (in accordance with country-specific regulations). For subjects 
not transitioning to commercially available birtamimab treatment, a 
postdose follow-up will occur 28 to 35 days after the last study drug 
administration. 
The estimated overall study duration is approximately 69 months, 
including the screening, enrollment, double-blind and open-label 
treatment periods, and postdose follow-up.  
Summary of Subject 
Eligibility Criteria 
Inclusion Criteria (subjects must meet all of the following criteria 
to be eligible for participation in the Double-blind Phase of the 
study): 
1. Aged ≥18 years and legal age of consent according to local 
regulations 
2. Newly diagnosed and AL amyloidosis treatment naive 
3. 
 
4. Confirmed diagnosis of AL amyloidosis by the following: 
• 
 
 
AND 
• 
 
 
5. If the subject meets any of the following: 
• 
 
• 
  
• 
  
AND 
  
THEN  
 
  
AND  

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GLOSSARY OF TERMS  
Abbreviation/Acronym 
Definition 
AA 
amyloid A 
AE 
adverse event 
AL 
amyloid light chain 
 
 
 
 
 
 
 
 
 
 
BP 
blood pressure 
 
 
 
 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
 
 
dFLC 
difference between involved and uninvolved free light chain 
DMC 
Data Monitoring Committee 
EC 
Ethics Committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
 
 
EMA 
European Medicines Agency 
EOI 
end of infusion 
EOT 
End of Treatment 
ETD 
Early Treatment Discontinuation 
EU 
European Union 
FDA 
Food and Drug Administration 

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Abbreviation/Acronym 
Definition 
GCP 
Good Clinical Practice 
 
 
 
 
 
 
HR 
heart rate 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
 
 
IMWG 
International Myeloma Working Group 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
 
 
IXRS 
Interactive Voice and Web Response System 
 
 
NCI-CTCAE 
National Cancer Institute-Common Terminology Criteria for 
Adverse Events  
NT-proBNP 
N-terminal pro-brain natriuretic peptide  
 
 
OLE 
Open-label Extension (Phase) 
PCD 
plasma cell dyscrasia 
PCS 
Physical Component Summary 
PE 
physical examination 
PK 
pharmacokinetic(s) 
 
 
 
 
 
 
SAE 
serious adverse event 
SAP 
statistical analysis plan 

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Abbreviation/Acronym 
Definition 
sFLC 
serum-free light chain 
SF-36v2 
Short Form-36 questionnaire Version 2 
SUSAR 
suspected unexpected serious adverse reaction 
6MWT 
6-Minute Walk Test 
TEAE 
treatment-emergent adverse event 
TRIAD 
Transgenic Rapidly Inducible Amyloid Disease 
 
 
ULN 
upper limit of normal 
US 
United States 
USP 
United States Pharmacopeial Convention 
 
 
WOCBP 
women of childbearing potential 

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1. 
INTRODUCTION  
1.1. 
Light Chain (AL) Amyloidosis  
Systemic amyloidoses are a complex group of diseases caused by tissue deposition of misfolded 
proteins. The most common type, AL amyloidosis, is caused by amyloid deposits composed of 
insoluble light chain aggregates that infiltrate multiple organs and progressively affect organ 
structure and function. Soluble light chain aggregates have been shown in vitro to cause cellular 
toxicity and may be involved in the pathogenesis of AL amyloidosis. Approximately 75% of 
patients with AL amyloidosis present with 1 or 2 major organ systems involved (e.g., cardiac, 
renal, gastrointestinal tract, hepatic, autonomic nervous system, peripheral nervous system, soft 
tissues) while 25% of patients present with more than 2 systems involved (Palladini 2005; 
Gertz 2010). AL amyloidosis is most commonly associated with cardiac and/or renal 
dysfunction, with overt restrictive cardiomyopathy observed in approximately 50% to 70% of all 
cases, and subclinical cardiac involvement detected in almost every case on endomyocardial 
biopsy or at autopsy (Falk 2010; Siddiqi 2018; Shams 2022). In a study examining morbidity and 
mortality in patients with AL amyloidosis compared with matched disease-free controls within 
the Medicare population, common individual comorbidities for patients with AL amyloidosis 
were congestive heart failure (36.1% in patients with AL amyloidosis compared to 11.2% in 
controls), cerebrovascular disease (27.7% versus 16.1%, respectively), chronic pulmonary 
disease (37.8% versus 22.5%, respectively), moderate or severe liver disease (29.7% versus 
10.2%, respectively), renal disease (35.7% versus 13.8%, respectively), diabetes without chronic 
complications (42.6% versus 29.2%, respectively), and malignancy/lymphoma/leukemia (35.7% 
versus 15.1%, respectively). Furthermore, hypothyroidism (cases: 32.1% versus controls: 22.2%) 
and hyperlipidemia (77.5% versus 65.6%, respectively) were common among Medicare 
beneficiaries with newly diagnosed AL amyloidosis (Quock 2018). 
AL amyloidosis is a rare disease with an estimated incidence between 3 to 14 cases per million 
persons per year, which translates to approximately 30,000 to 45,000 patients in the United 
States (US) and European Union (EU). Overall, there are approximately 12,000 patients living 
with AL amyloidosis in the US (Hemminki 2012; Quock 2018). Patients with AL amyloidosis 
have a poor prognosis and median survival is estimated to range from 6 months to 3 years 
depending on the specific patient population and data assessed (Kyle 1992; Goodman 2006; 
Palladini 2016; Weiss 2016). The outcome of patients with AL amyloidosis is highly dependent 
on the spectrum and severity of organ involvement, especially cardiac involvement, which is the 
main determinant of survival (Milani 2018). Global longitudinal strain (GLS), measured by 
echocardiogram, was shown to be an independent predictor of overall survival in patients with 
AL amyloidosis (Buss 2012; Chuy 2020; Salinaro 2017). Patients who are categorized as Mayo 
Stage IV, defined as N-terminal pro-brain natriuretic peptide (NT-proBNP) ≥1800 pg/mL, 
Troponin-T >0.025 ng/mL and difference between involved and uninvolved free light chain 
(dFLC) ≥18 mg/dL, are at high risk for early death, with an overall median survival of 
5.8 months and a 5-year survival rate of 14% (Kumar 2012).  
AL amyloidosis has 2 important disease components. The first component is the plasma cell 
dyscrasia (PCD), which results in the overproduction of immunoglobulin light chain, and the 
second component is the impact of the soluble and insoluble amyloid on organ structure and 
function, leading to the clinical manifestations of the disease. There are currently no approved 

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treatments for AL amyloidosis that have been shown to reduce the risk of mortality in Mayo 
Stage IV patients with AL amyloidosis. The current standard of care for patients is aimed at 
reducing or eliminating the bone marrow disorder, i.e., the PCD. The most aggressive treatment 
options include autologous stem cell transplant (ASCT) and high-dose chemotherapy for those 
patients who can tolerate it. Other treatment regimens include combinations of drugs often used 
to treat hematological malignancies including melphalan, prednisone, dexamethasone, 
immunomodulatory drugs (e.g., thalidomide, lenalidomide), and proteasome inhibitors (e.g., 
bortezomib) in an attempt to reduce light chain production. Daratumumab, in combination with 
bortezomib, cyclophosphamide, and dexamethasone, has recently been approved by the US Food 
and Drug Administration (FDA) and other regulatory authorities, including European Medicines 
Agency (EMA), and Pharmaceuticals and Medical Devices Agency (PMDA) for the treatment of 
AL amyloidosis. However, there are no currently approved treatments for AL amyloidosis that 
directly target potentially toxic forms of the soluble and insoluble amyloidogenic light chain 
aggregate. 
1.2. 
Rationale for the Clinical Study  
Unlike other hematologic disorders such as multiple myeloma, the morbidity and mortality of 
AL amyloidosis is almost entirely related to organ dysfunction and not hematologic parameters. 
One of the major determinants of prognostic outcome in patients with AL amyloidosis is the 
extent of cardiac involvement; 75% of the deaths are due to cardiac amyloidosis (Merlini 2011). 
The process of amyloid formation results in cellular injury, tissue damage, and organ dysfunction 
through mechanisms that are not completely understood. Because the currently available 
treatment options are limited to treatment for the PCD component of the disease, the rate of 
organ function improvement or stabilization (“organ response”) after achieving hematologic 
response from chemotherapy regimens is highly variable, ranging from 25% to 78% based on 
published information (Cohen 2007; Michael 2010; Cibeira 2011). Furthermore, the incidence of 
treatment-related mortality following high dose melphalan and ASCT was 13% within the first 
100 days in patients with AL amyloidosis (Skinner 2004) and with the greatest mortality in 
patients with cardiac involvement. Though the ASCT approach is effective and results in rapid 
hematologic response, the average treatment-related mortality in 4 single-center studies ranged 
from 21% to 39% (Falk 2010). Given the high burden of morbidity and mortality in AL 
amyloidosis, as well as the significant impact on healthcare costs and health-related quality of 
life (Quock 2018), there is a substantial unmet need for effective treatments targeting patients 
with AL amyloidosis. This need is particularly acute for Mayo Stage IV patients, who represent 
the equivalent of an ultra-rare patient population of <2800 in the US with a median survival of 
only 5.8 months (Kumar 2012). Treatments that reduce or eliminate PCD in conjunction with 
treatments that target toxic soluble aggregates and insoluble amyloid such as birtamimab may be 
of great clinical benefit in the treatment of AL amyloidosis. 
1.3. 
Background on Birtamimab  
Birtamimab is an immunoglobulin G1 kappa monoclonal antibody that specifically binds to both 
insoluble and soluble light chain aggregates. The proposed mechanism of action of birtamimab is 
to neutralize soluble toxic aggregates and induce clearance of insoluble deposited fibrils 
(amyloid) through phagocytosis (Renz 2016). In vitro studies have shown that the murine 
precursor of birtamimab binds light chain aggregates deposited in multiple organs of patients 

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allow for continued access to birtamimab for subjects who completed treatment in the Double-
blind Phase.  
The highest dose of birtamimab tested in clinical studies was 24.0 mg/kg, which was deemed to 
be safe and well tolerated and is the same dose used in Study NEOD001-CL002 and the current 
Study NEOD001-301.  
1.5. 
Benefit-Risk Assessment  
Birtamimab is being developed for the treatment of patients with systemic AL amyloidosis. The 
ongoing Phase 3 study, NEOD001-301 AFFIRM-AL Study, is being conducted to confirm the 
observations from post hoc analyses for the previous Phase 3 NEOD001-CL002 VITAL study. 
In the VITAL study, post hoc analyses of time to all-cause mortality revealed a potential survival 
benefit favoring birtamimab (74%) compared to control (49%) for the subjects categorized as 
Mayo Stage IV, with a hazard ratio of 0.413 (91% CI: 0.191, 0.895; p=0.0251). 
In the five previous studies completed or terminated by the Sponsor, a total of 302 subjects 
received birtamimab (
subjects at the recommended dose of 24 mg/kg dose level; not to 
exceed 
 total). Overall, there was no significant imbalance in events when compared to 
placebo and/or when considering the study population and background therapy. Furthermore, in 
the VITAL study, the safety profile of birtamimab in Mayo Stage IV subjects was consistent 
with the safety profile of the overall study population. 
A favorable benefit/risk profile for birtamimab was shown in the post hoc analyses in Mayo 
Stage IV patients in the VITAL study together with the safety profile in the clinical studies 
conducted to date. Birtamimab offers the potential benefit for Mayo Stage IV patients of 
reducing mortality risk with relatively minimal safety risk based on the demonstrated safety 
profile to date, supporting the continued development of birtamimab in the Phase 3 
NEOD001-301 AFFIRM-AL Study. 
 

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3.5. 
Definition of Primary Endpoint and End of Study  
The Double-blind Phase of the study will end when approximately 
primary endpoint events 
have occurred and End of Treatment (EOT) Visits have been completed for all subjects who 
remain in the Double-blind Phase at that time. Events are defined as deaths due to any cause.  
An interim analysis will be conducted when approximately 50% of the events (
 have 
occurred. The O’Brien-Fleming group sequential methodology will be used to divide the overall 
study significance level between the interim (p=
) and the final analysis (p=
). If 
overwhelming efficacy (p<
) is achieved at the interim analysis, the Double-blind Phase 
may be stopped early. 
The end of the study is defined as the date when the last subject last visit occurs in the OLE 
Phase. 
3.6. 
Termination of the Clinical Study  
If the Investigator, the Sponsor, or the Medical Monitor becomes aware of conditions or events 
that suggest a possible hazard to subjects if the clinical study continues, then the clinical study 
may be terminated. The clinical study may also be terminated at the Sponsor’s discretion in the 
absence of such a finding, at any time and for any reason. 
Conditions that may warrant termination of the clinical study include, but are not limited to: 
• The discovery of an unexpected, relevant, or unacceptable risk to the subjects 
enrolled in the clinical study 
• 
 
• A decision by the Sponsor to suspend the study, or to suspend or discontinue 
development of the study drug, for any reason 

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2. Symptomatic orthostatic hypotension that in the medical judgment of the Investigator 
would interfere with subject’s ability to safely receive treatment or complete study 
assessments 
3. History of Grade ≥3 infusion-related AEs during the Double-blind Phase or 
hypersensitivity to birtamimab  
4. Unable or unwilling to adhere to the study-specified procedures and restrictions 
5. Planning to use any other investigational treatment during the study 

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At any point in the study, if a subject who has received a dose of study drug is unwilling to 
return to the study site for further visits but is willing to discuss his/her health status by phone, 
conduct vital status assessments for the subject, per Section 7.1.2.  
8.3. 
Early Termination from the Study  
Subject participation in the Double-blind Phase of this study will continue until the end of the 
Double-blind Phase (i.e., until approximately 
 primary endpoint events of all-cause mortality 
have occurred). Early termination from the Double-blind Phase occurs if the subject fails to 
complete the entire Double-blind Phase and is no longer participating in study visits. Subject 
participation in the optional OLE Phase of this study will continue for 24 months or until 
birtamimab is commercially available in a subject’s country of residence, whichever occurs first 
(in accordance with country-specific regulations). Early termination from the OLE Phase occurs 
if the subject fails to complete the entire OLE Phase and is no longer participating in study visits. 
Subjects may withdraw their consent to participate in this study at any time without prejudice. 
The Investigator must withdraw from the study any subject who requests to be withdrawn. A 
subject’s participation in the study may be discontinued at any time at the discretion of the 
Investigator in accordance with his/her clinical judgment. The Sponsor should be notified in a 
timely manner of all subject discontinuations. 
Early termination from the study may occur if: 
• Subject needs to receive any of the prohibited concomitant therapies listed in 
Section 6.8.2 
• In the opinion of the Investigator, the subject cannot safely participate in the 
procedures required by the protocol 
• Subject withdraws consent 
• Subject is unwilling or unable to comply with the study requirements 
• Subject is lost to follow-up 
• Prothena reserves the right to discontinue the study at any time for any reason, 
including but not limited to, clinical or administrative reasons, or to discontinue 
participation of an individual Investigator or site for any reason, including but not 
limited to, poor enrollment or noncompliance. 
Vital status will be collected within legal and ethical boundaries for all subjects receiving at least 
1 dose of study drug and will be searched in public sources. During the Double-blind Phase 
close-out period and the final study close-out period, survival status will be collected within legal 
and ethical boundaries for all subjects who withdrew participation from the study. If vital status 
is determined, the subject will not be considered lost to follow-up. 
8.4. 
Replacement of Subjects  
Subjects who drop out of the study for any reason will not be replaced. 

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9. 
ADVERSE EVENTS/SERIOUS ADVERSE EVENTS AND 
REPORTING  
9.1. 
Definitions  
Consistent with the current regulatory guidance provided by the US Code of Federal Regulations 
(CFR) and the International Council for Harmonisation (ICH) Guideline for Good Clinical 
Practice (GCP), AEs and serious adverse events (SAEs) are defined below. 
AE Definition: AE means any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. An AE can be any unfavorable and unintended 
sign (including an abnormal laboratory finding), symptom, syndrome, or disease temporally 
associated with the use of a medicinal product, whether or not considered related to the 
medicinal product.  
This includes: 
• The emergence of any signs and symptoms that were not present at baseline (an event 
present at baseline that has not changed is not considered an AE) 
• Pre-existing conditions that are marked by a worsening from the subject’s 
baseline/entry status (i.e., an increase in severity or frequency of the pre-existing 
abnormality or disorder) 
• Reactions to study drug, sensitivity, or toxicity to study drug 
• Apparently unrelated illnesses 
• Injuries or accidents 
• Extensions or exacerbations or symptomatology, subjective events reported by the 
subject, or new clinically significant abnormalities in clinical laboratory tests, 
physiological tests or PE 
SAE Definition: An SAE is an AE that results in any of the following:  
• Death 
• Life threatening AE 
• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• Inpatient hospitalization or prolongation of existing hospitalization 
• A congenital anomaly or birth defect (in a child or fetus of a subject exposed to the 
study drug prior to conception or during pregnancy) 
• An important medical event that, based on appropriate medical judgment, may 
jeopardize the subject and may require medical or surgical intervention to prevent one 
of the outcomes listed above (e.g., anaphylaxis) 
An SAE may also include other event(s) that the Investigator or Sponsor deems to be serious 
based on medical judgment.  

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Death: Death, in and of itself, is not an AE; it is only an outcome. The cause of death is the AE. 
Therefore, the Investigator should make every effort to obtain and document the cause of death 
for all subjects who die during the study. If, despite all efforts, the cause of death remains 
unknown, the SAE should be documented as an “unspecified fatal event.” 
Life-threatening AE: Any AE that places the subject, in the view of the Investigator, at 
immediate risk of death from the event as it occurred. This does not include an event that, had it 
occurred in a more severe form, might have caused death. 
Hospitalization: Hospitalization is defined by the Sponsor as a full admission to the hospital for 
diagnosis and treatment. This includes prolongation of an existing inpatient hospitalization. 
Examples of visits to a hospital facility that do not meet the serious criteria for hospitalization 
include: 
• Emergency room visits that do not result in a full hospital admission or that last for a 
period of less than 24 hours 
• Outpatient surgery 
• Preplanned or elective procedures 
• Protocol procedures 
A pre-scheduled elective procedure or a routinely scheduled treatment is not to be considered an 
SAE, even if the subject is hospitalized, provided the site stipulates that: 
• The condition requiring the pre-scheduled elective procedure or routinely scheduled 
treatment was present before and did not worsen or progress between the subject’s 
consent to participate in the clinical trial and the time of the procedure or treatment 
• The pre-scheduled elective procedure or routinely scheduled treatment is the sole 
reason for admission and intervention 
An untoward medical event occurring during the pre-scheduled elective procedure or routinely 
scheduled treatment should be recorded as an AE or an SAE, as appropriate.  
Disability: A persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions. 
9.2. 
Adverse Events – Detecting, Recording, and Reporting  
9.2.1. 
Reporting Period for Adverse Events  
The reporting period for AEs for both the Double-Blind and OLE Phases is as follows: 
• All non-serious AEs and SAEs are reported from when the first administration of study drug 
is initiated through 28 days after the last dose of study drug or until the EOT/ETD Visit, 
whichever is later. 
• After the ICF is signed but prior to the first administration of study drug: only SAEs related 
to any protocol-imposed intervention are reported. Other SAEs and AEs that occur between 
the signing of the ICF and first study drug administration should be captured as concurrent 
Medical History.  

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• New SAEs occurring beyond the EOT/ETD Visit or >28 days after the last administration of 
study drug, whichever is later, will be reported to the Sponsor or its designee only if, in the 
judgment of the Investigator, the SAE is related to any protocol intervention (related to study 
procedure or previous study drug exposure).  
9.2.2. 
Reporting of Adverse Events  
All AEs (which includes SAEs), whether or not related to the study drug, must be fully and 
completely documented on the eCRF and in the subject’s medical notes. Pre-existing conditions 
(noted before Screening) should not be reported as AEs unless they worsen (i.e., become more 
severe or more frequent) after the first administration of study drug is initiated. At each visit, the 
Investigator will ask the subject if any AEs were experienced since the last visit. The Investigator 
must follow all AEs until the events have resolved or until the condition has stabilized and no 
further medical follow-up is warranted. The Investigator may be asked to provide additional 
follow-up information to the Sponsor upon request. At the discretion of the Investigator, 
unscheduled visits and assessments may be performed during the study based on medical 
judgment and documented in the eCRFs. 
If a subject is withdrawn from study drug treatment and/or the study because of an AE, it must 
be recorded on the AE and Disposition eCRFs. The subject should be followed and treated by the 
Investigator until the AE has resolved, stabilized, or a new chronic baseline has been established. 
Whenever feasible, AEs should be documented as medical diagnoses and a unifying diagnosis 
should be provided. For example, symptoms including fever, productive cough, opacity in the 
left lower lobe of the lung on x-ray would be reported as a single AE of pneumonia. Otherwise, 
if reported AEs do not appear clearly inter-related as part of a diagnosis, individual signs or 
symptoms may be reported as separate AEs. Information recorded on the appropriate page of the 
eCRF will include the description of the AE, the date and time of onset and resolution (if 
applicable), severity, seriousness, relationship to the study drug, action taken, and the outcome.  
When an AE resulting from disease progression meets the requirements to be considered serious 
the SAE verbatim term should be reported as the sign/symptom that best describes the event 
rather than as disease progression. For example, if a subject presents with worsening shortness of 
breath due to a pleural effusion from disease progression, the event term should be reported as 
“pleural effusion” instead of as disease progression.  
9.3. 
Severity Assessment  
Severity (e.g., NCI-CTCAE Grade 1, 2, 3, etc.) is not equivalent to seriousness, which is based 
on subject/event outcome or action criteria usually associated with events that pose a threat to a 
subject’s life or functioning. 
The Investigator will determine the severity of each AE/SAE using the NCI-CTCAE 
Version 5.0. AEs that do not have a corresponding CTCAE term will be assessed according to 
the general guidelines for grading used in the CTCAE as stated in Table 4. 

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Table 4: 
Adverse Event Severity Grading Scale  
CTCAE 
Grade 
Description 
1 
Mild: asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 
2 
Moderate: minimal, local or noninvasive intervention indicated; limiting age-appropriate 
instrumental ADLa 
3 
Severe or medically significant but not immediately life-threatening: hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care ADLb 
4 
Life-threatening consequences; urgent intervention indicated 
5 
Death related to AE 
ADL = activities of daily living; AE = adverse event; CTCAE = Common Terminology Criteria for Adverse Events; 
SAE = serious adverse event 
a. 
Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing 
money, etc.   
b. 
Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and 
not bedridden. 
Source: CTCAE. 
 
The severity of the AE should be recorded in the appropriate section of the AE eCRF. 
9.4. 
Relationship to Study Drug  
The causality of each AE should be assessed and classified by the Investigator as “related” or 
“not related.” An event is considered related if there is “a reasonable possibility” that the event 
may have been caused by the product under investigation (i.e., there are facts, evidence, or 
arguments to suggest possible causation). 
Guidelines for “Related” Events 
• There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. 
• There is evidence to suggest a causal relationship, and the influence of other factors is 
unlikely. 
• There is some evidence to suggest a causal relationship (e.g., the event occurred 
within a reasonable time after administration of the study drug). However, the 
influence of other factors may have contributed to the event (e.g., the subject’s 
clinical condition, other concomitant events). 
Guidelines for “Not related” Events 
• There is little evidence to suggest there is a causal relationship. There is another 
reasonable explanation for the event. 
• An AE will be considered “not related” to the use of the product if any of the 
following tests are met: 

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− An unreasonable temporal relationship between administration of the product and 
the onset on the AE (e.g., the event occurred either before, or too long after 
administration of the product for it to be considered product-related) 
− A causal relationship between the product and the AE is biologically implausible 
(e.g., death as a passenger in an automobile accident) 
− A clearly more likely alternative explanation for the AE is present (e.g., typical 
adverse reaction to a concomitant drug and/or typical disease-related event) 
Consider the Following When Assessing Causality 
• Temporal associations between the agent and the event 
• Effect of dechallenge and/or rechallenge 
• Compatibility with known class effect 
− The likelihood the AE can be attributed to the use of concomitant drugs, in 
particular chemotherapeutic agents used in treating the subject’s underlying PCD 
(see the current prescribing information for chemotherapeutic products used as 
standard of care; refer to Appendix 6) 
• Pre-existing risk factors 
• A plausible mechanism 
• Concurrent illnesses 
9.5. 
Adverse Event Outcome Assessment  
• Recovered/Resolved: The subject has recuperated or the event has improved. 
• Recovered/Resolved with Sequelae: The subject recuperated but retained pathological 
conditions resulting from the prior disease or injury. 
• Recovering/Resolving: Event is improving. 
• Not Recovered/Not Resolved: Event has not improved or recuperated.  
• Fatal: The termination of life as a result of an AE. 
• Unknown: Not known, not observed, not recorded, or refused. 
(Source: Clinical Data Interchange Standards Consortium [CDISC] in collaboration with the 
National Cancer Institute’s Enterprise Vocabulary Services.) 
9.6. 
Reporting of Serious Adverse Events  
During both phases of the study, it is the responsibility of the Principal Investigator to report 
SAEs to the Sponsor or its designee.  
• Any SAE that occurs at any time from the first study drug administration to 28 days 
after the last dose of study drug or until the EOT/ETD Visit, whichever is later, 
whether or not related to study drug, must be reported within 24 hours of discovery to 
the Sponsor or its designee.  

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• During the Screening period (e.g., after the ICF is signed but prior to the first 
administration of study drug, only) SAEs related to any protocol-imposed 
intervention are reported. Other SAEs and AEs that occur between the signing of the 
ICF and first study drug administration should be captured as concurrent Medical 
History. 
• New SAEs occurring beyond the EOT/ETD Visit or >28 days after the last 
administration of study drug, whichever is later, will be reported to the Sponsor or its 
designee only if, in the judgment of the Investigator, the SAE is related to any 
protocol intervention (i.e., related to study procedure or previous study drug 
exposure).  
Do not delay in the reporting of an SAE in order to obtain additional information. Any additional 
information, if collected, can be reported to the Sponsor as a follow-up to the initial report. The 
SAE report should include the subject identification number or other appropriate terminology 
and the narrative should be comprehensive, including a chronology and assessment of the event. 
The SAE report should also include the Investigator’s assessment of the relationship of the event 
to the use of study drug. This assessment can be changed as more information becomes 
available. 
The Investigator is encouraged to discuss with the Medical Monitor any AEs for which the 
assessment of seriousness is unclear or questionable. Contact information for the Medical 
Monitor is found in the Study Manual. 
9.6.1. 
SAE Reporting to Prothena via Paper Safety Reporting Form  
All SAEs will be recorded and reported to the Sponsor or designee within 24 hours. The 
Investigator will submit any updated or follow-up SAE data to the Sponsor within 24 hours of 
the receipt of information. Either facsimile (fax) transmission or a scan and email of the 
Investigator-signed hard-copy SAE paper form is the preferred method to transmit this 
information of SAE information to Prothena Drug Safety at ProthenaDrugSafety@Prothena.com.  
In rare circumstances if fax or email transmission is not available, notification by telephone to 
the Medical Monitor is acceptable. Initial notification via telephone does not replace the need for 
the Investigator to complete and sign the SAE hard-copy pages within the designated reporting 
time frames. 
Contacts for SAE reporting can be found in the Safety Reporting Completion Guideline. 
9.6.2. 
Regulatory Reporting Requirements for SAEs  
Prompt notification by the Investigator to the Sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
intervention under clinical investigation are met.  
During the study, the Sponsor or its designee will inform health authorities, central Institutional 
Review Boards (IRBs)/Ethics Committees (ECs), and the participating investigators of any 
suspected unexpected serious adverse reactions (SUSARs) occurring in other study centers or 
other studies of the active study drug, as appropriate, per local reporting requirements. In 
addition, the Sponsor or its designee will comply with any additional local safety reporting 
requirements.  

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Event expectedness for study drug is assessed by the Sponsor against the Reference Safety 
Information section of the Investigator’s Brochure that is effective for expedited safety reporting. 
An Investigator who receives an Investigator safety report describing an SAE/SUSAR or other 
specific safety information (e.g., summary or listing of SAEs) from the Sponsor will review and 
then file with the study records as appropriate and notify the IRB/EC, if appropriate, according to 
local requirements.  
At the completion of the study, the Sponsor will report all safety observations made during the 
conduct of the trial in the Clinical Study Report to health authorities and IRBs/ECs as required. 
9.7. 
Follow-up of Adverse Events  
All AEs experienced by a subject, regardless of the suspected causality, will be followed until 
the event has resolved, until the Investigator and/or the Medical Monitor deems the event to be 
chronic or stable, until there is a satisfactory explanation for the changes observed, or until the 
subject is lost to follow-up. 
9.8. 
Pregnancy  
WOCBP are those who have experienced menarche and who are not permanently sterile or 
postmenopausal (12 consecutive months with no menses without an alternative medical cause). 
The inclusion of female subjects of childbearing potential requires use of a highly effective 
contraceptive measures, which when used consistently and correctly, result in low failure rates. 
Highly effective methods of birth control must be used in WOCBP from Screening through 
90 days after the last dose of study drug administration and include: hormonal contraceptives 
(e.g., combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine 
device or intrauterine system; vasectomy and tubal ligation.  
WOCBP must have 2 negative pregnancy tests during Screening (serum and urine with the 
second (i.e., urine) within 24 hours prior to the first administration of study drug). Serum or urine 
pregnancy testing for WOCBP is collected locally on dosing visits and the local laboratory result 
must be reviewed prior to dosing.  
If a urine pregnancy test result is positive, a local serum pregnancy test must be done to confirm 
the pregnancy status. Subjects with a confirmed positive pregnancy test result will be 
discontinued (see Section 8.2).  
For male subjects who are not surgically sterile with female partners of childbearing potential, a 
barrier method must be used while on treatment with birtamimab from the time of Screening 
through at least 90 days after the last dose of the study drug to prevent pregnancy of the female 
partner. In addition, a highly effective physician-approved method of birth control should be 
used by the female partner of childbearing potential. 
Pregnancy in a subject or partner should be reported within 24 hours of the site becoming aware 
of the pregnancy by faxing or a scan and email of the Pregnancy Form in the study reference 
materials to the Sponsor or their designee. Any abnormal outcome of pregnancy that occurs 
during the study shall be reported as an SAE. The Investigator must make every effort to follow 
the subject through resolution of the pregnancy (delivery or termination) and to report the 
resolution on the Pregnancy Form in the study reference materials. In the event of pregnancy in 

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the partner of a study subject, the Investigator should make every reasonable attempt to obtain 
the woman’s consent for release of protected health information. 
Any subject who becomes pregnant during the study must be withdrawn from study drug and 
will be followed for the outcome of the pregnancy. The Investigator must follow-up and 
document the course and the outcome of all pregnancies even if the clinical study has ended. 
Pregnancies must be followed until birth, termination of the pregnancy, or loss of the subject to 
follow-up. If applicable, follow-up of a pregnancy will occur beyond the end of the study (e.g., 
clinical database lock) to observe for any significant safety issues. 
9.9. 
Urgent Safety Measures  
The Sponsor is required to follow global regulations including EU regulations which state that 
the appropriate regulatory bodies, including IRBs/ ECs /Research Ethics Boards, be notified 
according to their respective regulations of any new event resulting in the Sponsor and 
Investigator taking urgent safety measures to protect subjects against any immediate hazards.  
For each phase of the study, the reporting period for these events, which may require the 
implementation of urgent safety measures, is the period from the first dose of study drug 
administration through the completion of the EOT/ETD Visit or for 28 days after the last dose of 
study drug, whichever is later. Investigators are required to report any events which may require 
the implementation of urgent safety measures to Sponsor within 24 hours. Examples of situations 
that may require urgent safety measures include the following: 
• Immediate need to revise the study drug administration (e.g., modified dose amount 
or frequency not defined in protocol) 
• Change in the study which has a significant impact on the scientific value of the 
clinical study 
• Detrimental study conduct or management  
• Discovery that the quality or safety of the study drug does not meet established safety 
requirements 

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10.8. 
Data Monitoring Committee  
The primary objective of the independent DMC is to safeguard the interests of subjects in the 
study and to help ensure the integrity and credibility of the study. The DMC abides by the 
principles set forth in applicable regulatory guidance documents. The DMC is composed of 
individuals external to the study Sponsor, and those involved with organizing, conducting, and 
regulating the trial, and Investigators, and operates under the DMC’s written Charter, which 
includes standard operating guidelines on its procedures and monitoring plans.  
The DMC members will review safety reports on a periodic basis. This will include review of 
aggregated data to assess SAEs. The DMC will meet at least twice a year starting when the first 
subject is exposed to study medication and continuing until the Double-blind Phase is complete 
and the database for that phase is locked and finalized, after which the DMC will be disbanded.  
The DMC will review the study data at the interim analysis (after approximately 
events have 
occurred) and recommend either continuing the study or stopping early for overwhelming 
efficacy.  

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11. 
DATA RECORDING, RETENTION, AND MONITORING  
11.1. 
Case Report Forms  
The clinical sites participating in this study are required to submit clinical data for each subject 
via an electronic data capture (EDC) system, using an eCRF. Site personnel will be trained on 
the EDC system before receiving access to it. The Sponsor or its designee is responsible for 
maintaining a record of all system users. The participants of the study will not be identified by 
name or initials on any study documents to be collected by the Sponsor. 
All clinical information requested in this protocol will be recorded on the eCRFs provided by the 
Sponsor or their designee (or via other data collection methods, e.g., electronic laboratory data 
transfer). The Principal Investigator is responsible for reviewing all eCRFs for their subjects, 
verifying them for accuracy, and approving them via an electronic signature. Copies of the 
completed eCRFs, saved to disk in pdf format, will be sent to the Investigator’s site at the 
completion of the study. 
11.2. 
Availability and Retention of Records  
The Investigator must make study data accessible to the Study Monitor, other authorized 
representatives of the Sponsor, and regulatory agency inspectors upon request. A file for each 
subject must be maintained that includes the signed ICF and the Investigator’s copies of all 
source documentation related to that subject. The Investigator must ensure the reliability and 
availability of source documents from which the information on the eCRF was derived. 
Investigators are required to maintain all study documentation, including documents created or 
modified in electronic format, for the maximum period required by applicable regulations and 
guidelines, institution procedures, or at least 25 years, whichever is longer, following the 
completion of the study. ICFs, as well as all other study documents as specified as essential 
documents in ICH GCP, and adequate records for the receipt and disposition of all study drug 
must be retained for a period of 2 years following the date a marketing application is approved 
for the drug for the indication for which it is being investigated, or if no application is to be filed 
or if the application is not approved for such indication, until 2 years after the investigation is 
discontinued and FDA and other applicable regulatory authorities are notified, unless a longer 
period is required by applicable law or regulation. The Investigator must not discard any records 
unless given written authorization by the Sponsor. 
Study subjects’ names and directly identifying personal information will be maintained by the 
Investigator for the maximum period required by institution procedures or at least 25 years, 
whichever is longer, unless applicable law or regulation requires a longer period. 
Subject data will be collected, processed, and stored securely in the originating source systems 
(i.e., validated vendor systems maintained on secure data servers). Electronic records will be 
maintained per the requirements of Eudralex Volume 4 Annex 11, FDA 21 CFR Part 11, and the 
respective FDA Guidance Documents. Paper records and documents will be maintained under 
secure, controlled access, fireproof conditions (e.g., fireproof cabinet in locked room) to prevent 
theft, damage, or deterioration. Vendors will transfer encrypted data securely to the 
Sponsor/designee(s) according to written data transfer agreements. All study data, regardless of 

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format, will be collected, processed, stored, and transferred in accordance with applicable laws 
and regulations.  
11.3. 
Quality Control and Quality Assurance  
Sponsor representatives and regulatory authority inspectors are responsible for contacting and 
visiting the Investigator for the purpose of inspecting the facilities and, upon request, inspecting 
the various records of the study (e.g., eCRFs and other pertinent data), provided that subject 
confidentiality is respected. 
The Study Monitor is responsible for inspecting the eCRFs at regular intervals throughout the 
study to verify the following: adherence to the protocol; completeness, accuracy, and consistency 
of the data; and adherence to local regulations on the conduct of clinical research. The Monitor 
should have access to subject medical records and other study-related records needed to verify 
the entries on the eCRFs. The Investigator must agree to cooperate with the Monitor to ensure 
that any problems detected in the course of these monitoring visits are resolved. 
In accordance with ICH GCP and Sponsor’s (or designee’s) audit plans, this study may be 
selected for an audit. Inspection of site facilities (e.g., pharmacy, drug storage areas, laboratories, 
etc.) and review of study-related records may occur in order to evaluate the study conduct and 
compliance with the protocol, ICH GCP, and applicable regulatory requirements. 
Source documentation may be accessed remotely for monitoring or audit purposes, if permitted 
by local regulations. 
11.4. 
Subject Confidentiality  
The Investigator must ensure that each subject’s anonymity is maintained as described below. On 
the eCRFs or other documents submitted to the Sponsor or its designee, subjects must be 
identified by no more than year of birth or age, sex, and a unique Subject Identification Number.  
Documents that are not for submission to the Sponsor (e.g., signed ICFs) shall be kept in strict 
confidence by the Investigator in compliance with applicable regulations and ICH GCP 
Guidelines. The Investigator and site must permit authorized representatives and agents of the 
Sponsor, study monitors and auditors, independent safety and expert oversight committees, 
regulatory agencies, and the IRB/EC direct access to review the subject’s original medical 
records for verification of study-related procedures and data. Direct access includes examining, 
analyzing, verifying, and reproducing any records and reports that are needed for the evaluation 
of the study. The Investigator shall inform each subject and further, secure each subject’s consent 
in the ICF that the above-named persons and entities may have such direct access to the subject’s 
study related records. 

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12. 
ETHICAL AND LEGAL ISSUES  
12.1. 
Ethical Conduct of the Study  
The Investigator and Sponsor will ensure that this study is conducted in full compliance with the 
“Declaration of Helsinki” ICH guidelines, the CFR, Regulation (EU) No. 536/2014 as 
applicable, and/or with the laws and regulations of the country in which the research is 
conducted, whichever affords the greater protection to the study subject.  
12.2. 
Regulatory Approval  
The Sponsor/designee will make the appropriate applications to the Regulatory Authority in each 
participating country for regulatory approval of the study and, if necessary, approval to import 
Investigational Product. The study will not start in a given region until the required regulatory 
approvals have been obtained in the appropriate jurisdiction. 
12.3. 
Independent Review Board / Ethics Committee (EC) Approval  
The Investigator at the site is responsible for obtaining IRB/EC approval for the final protocol, 
the Sponsor-approved ICF, and any materials provided to or used to recruit subjects. Written 
approval of these documents must be obtained from the IRB/EC before any subject may be 
enrolled at the site. 
The Investigator is also responsible for the following interactions with the IRB/EC: 
• Obtaining IRB/EC approval for any protocol amendments and ICF revisions before 
implementing the changes 
• Providing the IRB/EC with any required information before or during the study 
• Submitting progress reports to the IRB/EC, as required during the conduct of the 
study, requesting re-review and approval of the study, as needed, and for providing 
copies of all IRB/EC re-approvals and relevant communication to the Sponsor or its 
designee 
• Notifying the IRB/EC of all serious and unexpected AEs related to the study 
medication reported by the Sponsor or its designee, as required by local regulations 
12.4. 
Subject Informed Consent  
The Sponsor will prepare the master ICF for each phase of the study, which will be provided to 
the Investigator. The Sponsor or its designee must review and approve in writing, any amended 
ICFs prepared by the Investigator prior to submission to the IRB/EC for approval. An IRB/EC 
approved copy of each ICF and all amendments will be forwarded to Prothena or its designee for 
written approval prior to use by a site. 
The ICFs document the study-specific information the Investigator provides to the subject and 
the subject’s agreement to participate. Among other things, the Investigator will fully explain in 
layman’s terms the nature of the study, along with the aims, methods, potential risks, and any 
discomfort participation in the study may entail. The subject will be informed that his/her 
participation is voluntary and that he/she may withdraw consent to participate at any time. In 

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France, patients will be allowed a 48-hour reflection period during which they can make a 
decision regarding their participation in the study. The subject must voluntarily, personally sign 
and date the ICF for each study phase before any study-related procedures for that phase are 
performed. The original and any amended, signed and dated ICFs must be retained in the 
subject’s file at the study site and copies of the signed ICFs must be provided to the subject. 
12.5. 
Privacy of Personal Data  
The collection and processing of personal data from subjects enrolled in the study will be limited 
to those data that are necessary to fulfill the objectives of the study. Subject data will be stored 
according to Section 11.2.  
Such data must be collected and processed with adequate precautions to ensure compliance with 
applicable data privacy protection laws and regulations. Appropriate technical and organizational 
measures must be in place to protect the personal data against unauthorized access, disclosure, 
dissemination, alteration, or loss, such as being stored at the study site in encrypted electronic 
and/or paper form and password protected or secured in a locked room to ensure that only 
authorized study staff have access. With respect to information technology systems owned or 
controlled by the Sponsor, the Sponsor maintains policies and procedures on how to respond in 
the event of unauthorized access, use, or disclosure of Sponsor information or systems.   
The informed consent obtained from the subject shall include explicit consent for the processing 
of his or her personal data by the study site, Sponsor and representatives and agents of the 
Sponsor, and for the Investigator and study site to allow direct access to the subject’s medical 
records for study-related monitoring, audits, regulatory inspections, and IRB/EC review. The 
informed consent shall also provide for the subjects’ explicit consent for the transfer of their 
personal data to the Sponsor and to other entities who may be located in other countries, where 
different data privacy laws apply. 
12.6. 
Subject Compensation for Adverse Effects on Health  
The Sponsor or its designee will adhere to local regulations regarding clinical study 
compensation guidelines to subjects whose health is adversely affected by taking part in the 
study. 
12.7. 
Protocol Amendments and Study Termination  
The Sponsor or its designee may amend the protocol as needed to ensure that the clinical 
investigation is being conducted as intended. The Sponsor or its designee will initiate protocol 
amendments in writing if any change significantly affects the safety of subjects, the scope of the 
investigation, or the scientific quality of the study. Protocol changes must be submitted to the 
IRB/EC as a protocol amendment. If necessary, the ICF(s) will be revised to reflect the changes 
in the amendment and will be submitted to the IRB/EC for review and approval. A copy of the 
amendment signature page must be signed by the Investigator and returned to the Sponsor or its 
designee. Written documentation of IRB/EC approval is required before the amendment is 
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Both the Sponsor and the Investigator reserve the right to terminate the study, according to the 
study contract. The Investigator should notify the IRB/EC in writing of the study’s completion or 
early termination and send a copy of the notification to the Sponsor and/or their designee. 
12.8. 
Finance, Insurance, and Indemnity  
A study site will not initiate study participation until a fully executed Clinical Study Agreement 
is in place between the study site and the Sponsor. All details associated with finance, insurance, 
and indemnity will be delineated in the Clinical Study Agreement. 
12.9. 
Serious Breaches of the Protocol or ICH GCP  
The Investigator will inform Prothena immediately of any serious breaches of this protocol or of 
the ICH GCP guidelines that the Investigator becomes aware of, reporting the serious breach to 
seriousbreachGCP@prothena.com. 

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13. 
PUBLICATION  
All publication rights are delineated in the Clinical Study Agreement. The study results will be 
posted in clinical trial databases in accordance with local requirements. 

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14. 
REFERENCES  
American Heart Association. Classes of heart failure (last reviewed 06Apr2015). Available from: 
http://www.heart.org/HEARTORG/Conditions/HeartFailure/AboutHeartFailure/Classes-of-
Heart-Failure_UCM_306328_Article.jsp. Accessed 31 Oct 2015. 
Bokhari S, Castaño A, Pozniakoff T, et al. (99m)Tc-pyrophosphate scintigraphy for 
differentiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile 
cardiac amyloidoses. Circ Cardiovasc Imaging. 2013;6(2):195-201. 
Buss SJ, Emami M, Mereles D, et al. Longitudinal left ventricular function for prediction of 
survival in systemic light-chain amyloidosis: incremental value compared with clinical and 
biochemical markers. J Am Coll Cardiol. 2012;60(12):1067-76. 
Chuy KL, Drill E, Yang JC, et al. Incremental value of global longitudinal strain for predicting 
survival in patients with advanced AL amyloidosis. JACC CardioOncol. 2020;2(2):223-31.  
Cibeira MT, Sanchorawala V, Seldin DC, et al. Outcome of AL amyloidosis after high-dose 
melphalan and autologous stem cell transplantation: long term results in a series of 421 patients. 
Blood. 2011;118(16):4346-52. 
Cohen AD, Zhou P, Chou J, et al. Risk-adapted autologous stem cell transplantation with 
adjuvant dexamethasone+/-thalidomide for systemic light-chain amyloidosis: results of a phase II 
trial. Br J Haematol. 2007;139(2):224-33. 
Cohen OC, Sathyanath A, Petrie A, et al. Prognostic importance of the 6 min walk test in light 
chain (AL) amyloidosis. Heart. 2022;108(20):1616-22.  
Falk RH, Dubrey SW. Amyloid heart disease. Prog Cardiovasc Dis. 2010;52(4):347-61. 
Galat A, Rosso J, Guellich A, et al. Usefulness of (99m)Tc-HMDP scintigraphy for the etiologic 
diagnosis and prognosis of cardiac amyloidosis. Amyloid. 2015(4):210-20. 
Gertz MA, Cohen AD, Comenzo RL, et al. Birtamimab plus standard of care in light-chain 
amyloidosis: the phase 3 randomized placebo-controlled VITAL trial. Blood. 
2023;142(14):1208-18. 
Gertz MA, Lacy MQ, Dispenzieri A, et al. Autologous stem cell transplant for immunoglobulin 
light chain amyloidosis: a status report. Leuk Lymphoma. 2010;51(12):2181-7. 
Gertz MA, Landau H, Comenzo RL, et al. First-in-human phase I/II study of NEOD001 in 
patients with light chain amyloidosis and persistent organ dysfunction. J Clin Oncol. 
2016;34(10):1097-103. 
Goodman HJ, Gillmore JD, Lachmann HJ, et al. Outcome of autologous stem cell transplantation 
for AL amyloidosis in the UK. Br J Haematol. 2006;134(4):417-25. 
Hemminki K, Li X, Försti A, et al. Incidence and survival in non-hereditary amyloidosis in 
Sweden. BMC Public Health. 2012;12:974. 
Kumar S, Dispenzieri A, Lacy MQ, et al. Revised prognostic staging system for light chain 
amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin 
Oncol. 2012;30(9):989-95. 

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Kyle R, Linos A, Beard C, et al. Incidence and natural history of primary systemic amyloidosis 
in Olmsted County, Minnesota, 1950 through 1989. Blood. 1992;79(7):1817-22. 
Merlini G, Seldin DC, Gertz MA. Amyloidosis: pathogenesis and new therapeutic options. J Clin 
Oncol. 2011;29(14):1924-33. 
Michael M, Kastritis E, Delimpassi S, et al. Clinical characteristics and outcome of primary 
systemic light-chain amyloidosis in Greece. Clin Lymphoma Myeloma Leuk. 2010;10(1):56-61. 
Milani P, Merlini G, Palladini G. Light chain amyloidosis. Mediterr J Hematol Infect Dis. 
2018;10(1):e2018022. 
Palladini G, Kyle RA, Larson DR, et al. Multicentre versus single centre approach to rare 
diseases: the model of systemic light chain amyloidosis. Amyloid. 2005;12(2):120-6. 
Palladini G, Merlini G. What is new in diagnosis and management of light chain amyloidosis? 
Blood. 2016;128(2):159-68. 
Quock TP, Yan T, Chang E, et al. Epidemiology of AL amyloidosis: a real-world study using US 
claims data. Blood Adv. 2018;2(10):1046-53. 
Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group 
updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538-48. 
Rapezzi C, Quarta CC, Guidalotti PL, et al. Role of (99m)Tc-DPD scintigraphy in diagnosis and 
prognosis of hereditary transthyretin-related cardiac amyloidosis. JACC Cardiovasc Imaging. 
2011;4(6):659-70. 
Renz M, Torres R, Dolan PJ, et al. 2A4 binds soluble and insoluble light chain aggregates from 
AL amyloidosis patients and promotes clearance of amyloid deposits by phagocytosis. Amyloid. 
2016;23(3): 168-77. 
Salinaro F, Meier-Ewert HK, Miller EJ, et al. Longitudinal systolic strain, cardiac function 
improvement, and survival following treatment of light-chain (AL) cardiac amyloidosis. Eur 
Heart J Cardiovasc Imaging. 2017;18(9):1057-64. 
Shams P, Ahmed I. Cardiac Amyloidosis. In: StatPearls [internet]. Treasure Island (FL): 
StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK580521/ 
Siddiqi OK, Ruberg FL. Cardiac amyloidosis: An update on pathophysiology, diagnosis, and 
treatment. Trends Cardiovasc Med. 2018;28(1):10-21.  
Skinner M, Sanchorawala V, Seldin DC, et al. High-dose melphalan and autologous stem-cell 
transplantation in patients with AL amyloidosis: an 8-year study. Ann Intern Med. 
2004;140(2):85-93. 
US Food and Drug Administration. Update: the FDA warns that biotin may interfere with lab 
tests: FDA safety communication. 05 November 2019. 
https://public4.pagefreezer.com/content/FDA/16-06-2022T13:39/https:/www.fda.gov/medical-
devices/safety-communications/update-fda-warns-biotin-may-interfere-lab-tests-fda-safety-
communication. Accessed 22 May 2023. 
Weiss BM, Lund SH, Bjorkholm M, et al. Improved survival in AL amyloidosis: a 
population-based study on 1,430 patients diagnosed in Sweden 1995-2013. Blood. 
2016;128(22):4448. 

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15. 
APPENDICES  

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APPENDIX 2. EXAMPLES OF HIGHLY EFFECTIVE 
CONTRACEPTION METHODS  
Contraception methods that can achieve a failure rate of <1% per year when used consistently 
and correctly are considered to be highly effective. Such methods include: 
• Combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation1: 
− Oral 
− Intravaginal 
− Transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation1: 
− Oral 
− Injectable 
− Implantable2 
• Intrauterine device (IUD)2 
• Intrauterine hormone-releasing system (IUS)2 
• Bilateral tubal occlusion2 
• Vasectomized partner2,3 
• Sexual abstinence4 
 
1 
Hormonal contraception may be susceptible to interaction with the Investigational Medicinal Product (IMP), 
which may reduce the efficacy of the contraception method. 
2 
Contraception methods that in the context of this guidance are considered to have low user dependency. 
3 
Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner 
of the WOCBP trial participant and that the vasectomised partner has received medical assessment of the 
surgical success. 
4 
In the context of this guidance sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the 
preferred and usual lifestyle of the subject. 
 
Source:  Clinical Trial Facilitation Group (CTFG): Recommendations related to contraception and pregnancy testing 
in clinical trials (Final Version 15Sep2014). Available from: 
http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-
About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf. Accessed 02Aug2015. 

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APPENDIX 3. REVISED INTERNATIONAL MYELOMA WORKING 
GROUP DIAGNOSTIC CRITERIA FOR MULTIPLE 
MYELOMA  
Definition of Multiple Myeloma 
Clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary 
plasmacytoma1 and any one or more of the following myeloma deﬁning events: 
Myeloma deﬁning events: 
• Evidence of end organ damage that can be attributed to the underlying plasma cell 
proliferative disorder, speciﬁcally: 
− Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper 
limit of normal (ULN) or >2.75 mmol/L (>11 mg/dL) 
− Renal insufficiency: creatinine clearance <40 mL per min2 or serum creatinine 
>177 μmol/L (>2 mg/dL) 
− Anemia: hemoglobin value of >20 g/L below the lower limit of normal, or a 
hemoglobin value <100 g/L 
− Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or 
PET-CT3 
• Any one or more of the following biomarkers of malignancy: 
− Clonal bone marrow plasma cell percentage1 ≥60% 
− Involved/uninvolved serum free light chain ratio4 ≥100 
− >1 focal lesions on magnetic resonance imaging studies5 
CT = computed tomography; PET = positron emission tomography; PET-CT = 18F-ﬂuorodeoxyglucose PET with 
CT; ULN = upper limit of normal. 
1 
Clonality should be established by showing κ/λ-light-chain restriction on ﬂow cytometry, 
immunohistochemistry, or immunoﬂuorescence. Bone marrow plasma cell percentage should preferably be 
estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the highest 
value should be used. 
2 
Measured or estimated by validated equations.  
3 
If bone marrow has less than 10% clonal plasma cells, more than 1 bone lesion is required to distinguish from 
solitary plasmacytoma with minimal marrow involvement. 
4 
These values are based on the serum Freelite assay (The Binding Site Group, Birmingham, UK). The involved 
free light chain must be ≥100 mg/L.  
5 
Each focal lesion must be 5 mm or more in size. 
Source: Rajkumar 2014. 

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APPENDIX 4. SHORT FORM-36 QUESTIONNAIRE (SF-36V2)  
 
 
 
SAMPLE 

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APPENDIX 6. PACKAGE INSERTS FOR CHEMOTHERAPEUTIC 
AGENTS COMMONLY PRESCRIBED FOR 
INDIVIDUALS WITH AL AMYLOIDOSIS  
Package Inserts for many chemotherapeutic agents commonly prescribed for individuals with AL 
amyloidosis and which have been approved by the US Food and Drug Administration (FDA) 
may be found at the FDA website, Drugs@FDA, at the following link:  
http://www.accessdata.fda.gov/scripts/cder/drugsatfda/  
The Summary of Product Characteristics for all products approved via the Centralized procedure 
in the European Union (EU) can be found on the European Medicines Agency (EMA) website as 
follows: https://www.ema.europa.eu/en/medicines 
The above website states that EMA does not evaluate all medicines currently in use in Europe. If 
a specific medicine cannot be found on the website, it may be found on that of the national health 
authority of a specific EU country. For example, in the United Kingdom, refer to the electronic 
Medicines Compendium (https://www.medicines.org.uk/emc/about-the-emc). 
For countries outside of the US and EU, the package inserts may be found on the website of the 
country’s national health authority. 
 

Signature Page for NEOD001-301 Protocol Version 5.0
RDMS Document Number: VV-CLIN-001247 v5.0
Signature Page for NEOD001-301 Protocol Version 5.0
RDMS Document Number: VV-CLIN-001247 v5.0
Approval Task Task
Verdict: Approved
28-Mar-2024 01:57:59 GMT+0000