Clinical trial NCT02613182
Conditions: AL Amyloidosis
Sponsor: Prothena Biosciences Ltd.
Start date: 2016-02-01; Completion date: 2018-05-01
Enrollment: 34 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The rationale for this study is to provide additional treatment with NEOD001 for subjects who complete Study NEOD001-001, and to continue to evaluate long term safety and tolerability. All subjects in the current NEOD001 trials are being dosed at 24 mg/kg, which will be continued in this study.

Detailed description:
The rationale for this study is to provide additional treatment with NEOD001 for subjects who complete Study NEOD001-001, and to continue to evaluate long term safety and tolerability. All subjects in the current NEOD001 trials are being dosed at 24 mg/kg, which will be continued in this study. The primary objective of the study is to evaluate long-term safety and tolerability of NEOD001 and the secondary objectives are to assess the immunogenicity of NEOD001 and to incorporate serum NEOD001 concentrations in a population pharmacokinetic (PK) analysis.

Arms: arm 1: Open Label Study Drug NEOD001
Interventions: intervention 1: NEOD001
Intervention descriptions: intervention 1: NEOD001

Protocol documents:
Prot_000.pdf: 
 
Document Type: Study Protocol 
Official Title: 
Open-label Extension Study to Evaluate the Long-term Safety and 
Tolerability of NEOD001 in Subjects with Light Chain (AL) 
Amyloidosis 
NCT Number: 
NCT02613182 
Document Date: 
09 March 2017 
 


The protocol for Study NEOD001-OLE001 was amended one time. 
Date of Original Protocol: 
16 October 2015 
Date of Protocol Amendment 1: 
09 March 2017 
 
The following key changes were made: 
Overview of Major/Substantial Changes in Amendment 1: 
• 
Extended study participation duration from 14 to 38 months or until the study is 
terminated, whichever occurs first 
• 
Eliminated collection of archive samples 
• 
Eliminated routine collection of citrated plasma samples for coagulation indices (samples 
only to be collected in cases of relevant serious adverse events) 
• 
Reduced frequency of SF-36 and 6MWT from every 3 months to every 6 months 
• 
Reduced postdose monitoring time beginning with the third infusion 
 


CLINICAL RESEARCH PROTOCOL 
Study Title: 
Open-label Extension Study to Evaluate the Long-
term Safety and Tolerability of NEOD001 in 
Subjects with Light Chain (AL) Amyloidosis 
Protocol Number: 
NEOD001-OLE001 
Investigational Product: 
NEOD001 
IND Number: 
113495 
Indication: 
AL Amyloidosis 
Sponsor: 
Prothena Therapeutics Limited 
Adelphi Plaza, Upper George's Street 
Dún Laoghaire, Co. Dublin  
A96 T927, Ireland 
Sponsor Representative: 
Prothena Biosciences Inc 
331 Oyster Point Boulevard 
South San Francisco, CA 94080  USA 
Sponsor’s Chief Medical Officer: 
Development Phase: 
2 
Date of Original Protocol: 
16 October 2015 
Date of Protocol Amendment 1: 
09 March 2017 
CONFIDENTIAL 
The information contained in this document and all information provided to you related to NEOD001 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. 
______________________________
______________________________
______________________________




Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 3 of 83 
INVESTIGATOR SIGNATURE PAGE 
 
Protocol Title: A Phase 2 Open-label Extension Study to Evaluate the Long-term Safety and 
Tolerability of NEOD001 in Subjects with Light Chain (AL) Amyloidosis 
Protocol Number:   
 
NEOD001-OLE001 
Sponsor:  
 
 
 
Prothena Therapeutics Limited 
Date of Original Protocol:   
16 October 2015 
Date of Protocol Amendment 1: 
09 March 2017 
 
 
I have read the forgoing protocol and agree to conduct this study in accordance with the current 
protocol. 
 
 
 
 
 
 
Investigator Signature 
 
Date 
 
Investigator Print Name 
 
 
 
Please return the form to Prothena or its designee. Contact details will be provided to the 
Investigator. Please retain a copy for your study files. 


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 4 of 83 
TABLE OF CONTENTS 
PROTOCOL SYNOPSIS ..............................................................................................................9 
GLOSSARY OF TERMS ............................................................................................................17 
1 
INTRODUCTION...............................................................................................................20 
1.1 
LIGHT CHAIN (AL) AMYLOIDOSIS ......................................................................20 
1.2 
STUDY RATIONALE ................................................................................................21 
1.3 
BACKGROUND ON NEOD001 ................................................................................21 
1.3.1 
Nonclinical Safety ..........................................................................................22 
1.3.2 
Clinical Safety ................................................................................................25 
1.4 
RATIONALE FOR STUDY CONDUCT AND DOSE SELECTION .......................26 
2 
OBJECTIVES .....................................................................................................................27 
2.1 
PRIMARY ...................................................................................................................27 
2.2 
SECONDARY .............................................................................................................27 
2.3 
EXPLORATORY ........................................................................................................27 
3 
STUDY PLAN .....................................................................................................................28 
3.1 
STUDY DESIGN.........................................................................................................28 
3.2 
STUDY ENDPOINTS .................................................................................................28 
3.2.1 
Primary ...........................................................................................................28 
3.2.2 
Secondary .......................................................................................................28 
3.2.3 
Exploratory .....................................................................................................28 
3.3 
NUMBER OF SITES AND SUBJECTS .....................................................................28 
3.4 
RANDOMIZATION AND BLINDING......................................................................28 
3.5 
ESTIMATED STUDY AND TREATMENT DURATION ........................................28 
3.6 
DEFINITION OF END OF STUDY ...........................................................................28 
4 
SELECTION, DISCONTINUATION, AND WITHDRAWAL OF SUBJECTS .........29 
4.1 
INCLUSION CRITERIA .............................................................................................29 
4.2 
EXCLUSION CRITERIA ...........................................................................................29 
4.3 
EARLY TREATMENT DISCONTINUATION .........................................................31 
4.4 
EARLY TERMINATION FROM STUDY .................................................................31 
4.5 
TERMINATION OF THE CLINICAL STUDY, INVESTIGATOR, OR STUDY 
SITE .............................................................................................................................32 


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 5 of 83 
4.6 
REPLACEMENT OF SUBJECTS ..............................................................................32 
5 
TREATMENT OF SUBJECTS .........................................................................................33 
5.1 
STUDY THERAPY .....................................................................................................33 
5.1.1 
Formulation, Packaging, and Labeling ...........................................................33 
5.1.2 
Shipping, Storage, and Handling ....................................................................33 
5.2 
ACCOUNTABILITY AND RETURN OF STUDY SUPPLIES ................................33 
5.3 
DOSAGE, PREPARATION, AND ADMINISTRATION .........................................34 
5.4 
DOSE ADJUSTMENTS ..............................................................................................35 
5.4.1 
Withholding of Study Drug ............................................................................35 
5.4.2 
Management of Suspected Infusion-Related/Hypersensitivity Adverse 
Events .............................................................................................................35 
5.4.3 
Dose Reductions .............................................................................................36 
5.5 
TREATMENT COMPLIANCE ..................................................................................36 
5.6 
PRIOR AND CONCOMITANT MEDICATION/THERAPY ....................................36 
5.6.1 
Allowed Concomitant Medication/Therapy ...................................................36 
5.6.2 
Prohibited Concomitant Medication/Therapy ................................................36 
6 
STUDY PROCEDURES ....................................................................................................38 
6.1 
EVALUATIONS BY VISIT........................................................................................38 
6.1.1 
Screening Period:  Days -28 to -1 ..................................................................38 
6.1.1.1 
Assessments for Subjects Whose Previous Visit in Study 
NEOD001-001 was Within 60 Days of Screening ........................38 
6.1.1.2 
Assessments for Subjects Whose Previous Visit in Study 
NEOD001-001 was ≥60 Days from Screening ..............................39 
6.1.2 
Treatment Period:  Months 1 through 36, Day 1 (±5 Days) ...........................41 
6.1.3 
End of Study (EOS): 30 (±5) Days After Final Dose .....................................45 
6.1.4 
90-day Postdose Pregnancy Test ....................................................................46 
6.1.5 
Vital Status Telephone Call ............................................................................47 
6.2 
ORDER OF ASSESSMENTS OF SPECIFIC TESTS ................................................47 
6.3 
METHODS OF ASSESSMENT FOR SAFETY AND EFFICACY ...........................48 
6.3.1 
Clinical Laboratory Evaluations .....................................................................48 
6.3.2 
Vital Signs ......................................................................................................48 
6.3.3 
Physical Examination .....................................................................................48 


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 6 of 83 
6.3.4 
12-Lead ECGs ................................................................................................49 
6.3.5 
Peripheral Neuropathy Assessment ................................................................49 
6.3.6 
6-Minute Walk Test ........................................................................................49 
6.4 
PHARMACOKINETIC AND IMMUNOGENICITY ASSESSMENTS ...................50 
7 
ADVERSE EVENTS/SERIOUS ADVERSE EVENTS AND REPORTING ................51 
7.1 
ADVERSE EVENTS—DEFINITION ........................................................................51 
7.2 
ADVERSE EVENTS—SEVERITY RATING ...........................................................52 
7.3 
ADVERSE EVENTS—CAUSALITY RATING ........................................................52 
7.4 
SERIOUS ADVERSE EVENTS AND UNEXPECTED ADVERSE EVENTS ........53 
7.4.1 
Elective Procedures and Surgeries .................................................................55 
7.4.2 
Other Reportable Information ........................................................................55 
7.4.3 
Disease Progression and Death ......................................................................56 
7.4.4 
Serious Adverse Events—Reporting ..............................................................56 
8 
STATISTICAL METHODS AND CONSIDERATIONS ...............................................58 
8.1 
ANALYSIS POPULATIONS .....................................................................................58 
8.2 
ANALYSIS OF STUDY POPULATION AND SUBJECT CHARACTERISTICS ..58 
8.3 
ANALYSIS OF SAFETY ENDPOINTS ....................................................................58 
8.4 
ANALYSIS OF EFFICACY ENDPOINTS ................................................................58 
8.5 
ANALYSIS OF OTHER ENDPOINTS ......................................................................59 
8.5.1 
Pharmacokinetic .............................................................................................59 
8.5.2 
Immunogenicity ..............................................................................................59 
8.6 
DETERMINATION OF SAMPLE SIZE ....................................................................59 
8.7 
HANDLING OF DROPOUTS AND MISSING DATA .............................................59 
9 
DATA RECORDING, RETENTION, AND MONITORING ........................................60 
9.1 
CASE REPORT FORMS ............................................................................................60 
9.2 
AVAILABILITY AND RETENTION OF RECORDS ..............................................60 
9.3 
QUALITY CONTROL AND QUALITY ASSURANCE ...........................................60 
9.4 
SUBJECT CONFIDENTIALITY ................................................................................61 
10 
ETHICAL AND LEGAL ISSUES .....................................................................................62 
10.1 ETHICAL CONDUCT OF THE STUDY ...................................................................62 
10.2 REGULATORY APPROVAL ....................................................................................62 


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 7 of 83 
10.3 ETHICS COMMITTEE APPROVAL .........................................................................62 
10.4 SUBJECT INFORMED CONSENT ...........................................................................62 
10.5 SUBJECT COMPENSATION FOR ADVERSE EFFECTS ON HEALTH ...............63 
10.6 PROTOCOL AMENDMENTS AND STUDY TERMINATION ..............................63 
10.7 FINANCE, INSURANCE AND INDEMNITY ..........................................................63 
10.8 PUBLICATION POLICY ...........................................................................................63 
11 
REFERENCES ....................................................................................................................64 
12 
APPENDICES .....................................................................................................................66 
 
 
 


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 8 of 83 
LIST OF TABLES 
Table 1 
Schedule of Events ...................................................................................................14 
Table 2 
Common Terminology Criteria for Adverse Events Grade 1-5 for Peripheral 
Neuropathy ...............................................................................................................49 
 
LIST OF FIGURES 
Figure 1 
NEOD001-OLE001 Study Design ...........................................................................16 
Figure 2 
Proposed Mechanism of Action for NEOD001 .......................................................22 
 
LIST OF APPENDICES 
Appendix 1 Examples of Highly Effective Contraception Methods ...........................................67 
Appendix 2 Short Form-36 Health Survey ..................................................................................68 
Appendix 3 Laboratory Tests ......................................................................................................79 
Appendix 4 Coagulation Indices ..................................................................................................80 
Appendix 5 Peripheral Neuropathy Assessment .........................................................................81 
Appendix 6 Eastern Cooperative Oncology Group (ECOG) Performance Status ......................82 
Appendix 7 New York Heart Association (NYHA) Functional Classification ...........................83 
 
 
 


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 9 of 83 
PROTOCOL SYNOPSIS 
Title 
A Phase 2 Open-label Extension Study to Evaluate the Long-
term Safety and Tolerability of NEOD001 in Subjects with 
Light Chain (AL) Amyloidosis 
Study Phase 
2 
Indication 
AL amyloidosis 
Objectives 
Primary: 
• To evaluate long-term safety and tolerability of NEOD001 
Secondary: 
• To assess the immunogenicity of NEOD001 
• To incorporate serum NEOD001 concentrations in a 
population pharmacokinetics (PK) analysis 
Exploratory: 
• To evaluate overall survival 
• To evaluate change in 6-Minute Walk Test (6MWT) 
• To evaluate general health-related quality of life using the 
Short Form-36 (SF-36) 
Study Design 
This is an open-label study for subjects previously enrolled 
and treated for at least 9 months in Study NEOD001-001. 
Number of Sites and 
Subjects 
Multicenter study in approximately 70 subjects 
Estimated Study and 
Treatment Duration 
A subject’s study duration may be up to 38 months or until the 
study is terminated (per Section 4.5), whichever occurs first. 
The study consists of a Screening Phase (1 month), Treatment 
Phase (36 months), and the End of Study (EOS) Visit 30 (±5) 
days after the last dose. 
Summary of Subject 
Eligibility Criteria 
Inclusion Criteria (subject must meet all of the following): 
1. Previously enrolled and treated for at least 9 months in 
Study NEOD001-001 
2. Ability to understand and willingness to sign an informed 
consent form prior to initiation of any study procedures  
3. Has adequate bone marrow reserve, hepatic and renal 
function, as demonstrated by: 
o Absolute neutrophil count (ANC) ≥1.0 ×109/L 


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 10 of 83 
o Platelet count ≥75 × 109/L 
o Hemoglobin ≥9 g/dL 
o Total bilirubin ≤2 times the upper limit of normal 
(× ULN) 
o Aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) ≤3 × ULN 
o Estimated glomerular filtration rate ≥30 mL/minute 
4. Seated systolic blood pressure 90 to 180 mmHg 
5. ECOG Performance Status 0 to 2 
6. Women of childbearing potential (WOCBP) must have a 
negative serum pregnancy test within 28 days prior to the 
first administration of study drug and agree to use highly 
effective physician-approved contraception (Appendix 1) 
from 30 days prior to the first study drug administration to 
90 days following the last study drug administration  
7. Male subjects must be surgically sterile or must agree to 
use highly effective physician-approved contraception 
(Appendix 1) from 30 days prior to the first study drug 
administration to 90 days following the last study drug 
administration 
 
Exclusion Criteria (subject must not meet any of the 
following): 
1. Any new medical contraindication or clinically significant 
abnormality on physical, neurological, laboratory, vital 
signs, or electrocardiogram (ECG) examination (e.g., atrial 
fibrillation; with the exception of subjects for whom the 
ventricular rate is controlled) that precludes continued or 
initiation of treatment with NEOD001 or participation in 
the study 
2. History of Grade ≥3 infusion-associated adverse events 
(AEs) or hypersensitivities to NEOD001 or any of its 
excipients 
3. Treatment with any anticancer therapy (standard or 
investigational) within the 14 days prior to the first dose of 
study drug. In addition, subjects must have fully recovered 
(i.e., National Cancer Institute Common Terminology 
Criteria for Adverse Events [CTCAE] Grade 1 [exception: 
subjects with prior bortezomib may have CTCAE Grade 2 
neuropathy]) from the clinically significant toxic effects of 


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 11 of 83 
that treatment  
4. Received any of the following within the specified time 
frame prior to the first administration of study drug: 
o Hematopoietic growth factors, transfusions of blood 
or blood products within 1 week 
o Major surgery within 2 weeks 
o Radiotherapy within 2 weeks 
o Transplant within 8 weeks 
o Investigational drug other than NEOD001 within 
4 weeks 
o Another experimental anti-amyloid therapy other 
than NEOD001 within 2 years  
5. Uncontrolled symptomatic orthostatic hypotension 
6. Myocardial infarction, uncontrolled angina, severe 
uncontrolled ventricular arrhythmias, or 
electrocardiographic evidence of acute ischemia, within 
6 months prior to the first dose of study drug 
7. Uncontrolled infection 
8. Secondary malignancy, with the exception of: 
o Adequately treated basal cell carcinoma, squamous 
cell carcinoma, or in situ cervical cancer 
o Adequately treated stage I cancer from which the 
subject is currently in remission 
o Any other cancer from which the subject has been 
disease-free for ≥3 years 
9. Uncontrolled human immunodeficiency virus (HIV), 
hepatitis B, or hepatitis C infection  
10. Women who are lactating 
Drug, Drug Dosage, 
Formulation, and Route of 
Administration 
NEOD001 is supplied as a sterile, lyophilized dosage form in a 
20/25-mL vial containing 500 mg NEOD001. Each vial will be 
reconstituted with 9.6 mL sterile water for injection (WFI) to a 
concentration of 50 mg/mL resulting in a buffered, isotonic, 
preservative-free solution. 
NEOD001, 24 mg/kg (not to exceed 2500 mg), will be 
administered once every 28 (±5) days using the infusion 
duration established in Study NEOD001-001 or over 


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 12 of 83 
60 (±10) minutes. The length of the infusion may be extended 
over a longer period of time if and when it is clinically indicated 
per Section 5.3. If an infusion-related reaction occurs, for all 
subsequent dosing sessions the subject will be premedicated per 
Section 5.4.2. 
Control Group 
Not applicable 
Procedures 
See Schedule of Events Table 1.  
Of note, two pretreatment 6MWTs are required before the first 
administration of study drug, with a minimum of 4 days in 
between the two tests. The second test must be completed 1 to 
2 days before the Month 1-Day 1 Visit. The SF-36 must be 
administered before performing any other study assessments on 
the day it is administered. The N-terminal pro B-type natriuretic 
peptide (NT-proBNP) must be drawn before conducting 
6MWT, if performed on the same calendar day.  
Endpoints 
Primary: 
• Assessment of the safety and tolerability of NEOD001 as 
assessed by vital signs, duration of therapy, 12-lead ECGs, 
routine laboratory assessments, and frequency and severity 
of AEs 
Secondary: 
• Assessment of immunogenicity by measurement of anti-
NEOD001 antibodies 
• Serum NEOD001 concentrations (sparse sampling) will be 
pooled with similar samples from other studies in a 
population PK analysis 
Exploratory: 
• Time to all-cause mortality from baseline in Study 
NEOD001-001 
• Change from baseline (of this study) in the 6MWT  
• Change from baseline (of this study) in the SF-36 


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
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Statistical Considerations 
and Methods 
Analysis Populations: 
The Safety Population, which will include all subjects who 
receive at least one NEOD001 infusion, will be used for all 
analyses. 
Safety Analyses: 
Adverse Events - AEs will be coded using the Medical 
Dictionary of Regulatory Activities (MedDRA). The incidence 
of treatment-emergent adverse events (TEAEs) occurring on or 
after treatment on Study Day 1 will be tabulated by MedDRA 
System Organ Class and Preferred Term, and by severity and 
relationship to treatment. TEAEs leading to discontinuation and 
serious adverse events (SAEs) will be summarized. 
Clinical Laboratory Evaluations - Descriptive statistics 
summarizing central laboratory data will be presented for all 
study visits. Changes from baseline to each study visit will also 
be summarized.  
Additional Safety Assessments - Additional safety assessments 
include vital signs and ECGs. Descriptive statistics of the vital 
sign and ECG parameters will be presented by study visit, as 
well as the change from baseline at each visit.  
Efficacy Analyses: 
Overall survival will be summarized using the Kaplan-Meier 
method. The change from baseline in the 6MWT will be 
summarized using the mean, standard deviation, median, and 
minimum and maximum values.  
Other Analyses: 
Immunogenicity - Serum anti-NEOD001 antibody titers will be 
listed. 
Population PK - Serum NEOD001 concentrations (sparse 
sampling) will be pooled with similar samples from other 
studies in a population PK analysis (details will be provided in a 
separate document) 
Determination of Sample Size: 
Not applicable as this is an extension study for subjects 
previously enrolled and treated for at least 9 months in Study 
NEOD001-001. 
Sponsor 
Prothena Therapeutics Limited 
 
 


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 14 of 83 
Table 1 
Schedule of Events 
 
 
Screening1 
Treatment 
Termination 
 
 
Days -28 to -1 
Months 1- 36 
Day 1 (±52) 
EOS3 
30 (±5) days 
after last dose 
 
Assessment or Procedure 
<60 days since 
last visit in 
Study 
NEOD001-001 
≥60 days since 
last visit in 
Study 
NEOD001-001 
 
Written Informed Consent  
X 
X 
 
 
Eligibility Review 
X 
X 
 
 
Clinical 
Medical History4 
X 
X 
 
 
Historical NT-proBNP Levels 
X 
X 
 
 
Prior/Concomitant Medication/Therapy5 
X 
X 
X 
X 
Adverse Event Assessment6 
X 
X 
X 
X 
Physical Examination7 
X 
X 
X 
X 
Vital Signs8 
X 
X 
X 
X 
ECOG PS/NYHA Class 
 
X 
X 
X 
Peripheral Neuropathy Assessment9 
X 
X 
Every 3 months10 
X 
SF-36 Health Survey11 
X 
X 
Every 6 months12 
X 
6MWT13 
X14 
X14 
Every 6 months12 
X 
Echocardiogram 
 
X 
Every 12 months15 
X16 
ECG (12-lead in triplicate; local)  
X 
X 
Every 3 months10,17 
X 
Vital Status Telephone Call 
 
 
 
Every 
3 months18 
Laboratory21 
Hematology & Chemistry19 
X 
X 
X 
X 
Amylase 
X 
X 
X 
X 
Coagulation20 
X 
X 
X 
X 
Troponin T 
X 
X 
X 
X 
NT-proBNP13  
X 
X 
X 
X 
Pregnancy (WOCBP)22 
X 
X 
X 
X, X23 
Serum Free Light Chain 
 
X 
Every 3 months10 
X 
SPEP & 24-hour UPEP24 
 
X 
Every 3 months10,25 
X 
SIFE & UIFE 
 
X 
Every 3 months 10,25 
X 
Urinalysis (dip stick)26 
 
X 
Every 3 months10 
X 
24-hr Urine Protein Excretion24 
 
X 
Every 3 months10 
X 
Other 
Serum NEOD001 Sample27 
X 
X 
Every 3 months10 
X 
Serum anti-NEOD001 Antibody 
Sample28 
X 
X 
Every 3 months10 
X 
 
NEOD001 Infusion29 
 
 
X 
 
ECG = electrocardiogram; ECOG PS = Eastern Cooperative Oncology Group performance status; EOI = end of infusion; 
EOS = End of Study; INR = international normalized ratio; NT-proBNP = N-terminal pro B-type natriuretic peptide; 
NYHA = New York Heart Association; PK = pharmacokinetic; PT = prothrombin time; PTT = partial thromboplastin time; 
SF-36 = Short form-36; SIFE = serum immunofixation electrophoresis; 6MWT = 6-Minute Walk Test; SPEP = serum 
protein electrophoresis; UIFE = urine immunofixation electrophoresis; UPEP = urine protein electrophoresis; 
WOCBP = women of childbearing potential. 
1. 
Rescreening is allowed once per subject. Only repeat tests that did not meet eligibility requirements.  
2. 
Day 1 assessments may be conducted ±5 days from Day 1, with the exception of Month 1-Day 1 (i.e., no window is allowed 
at Month 1). 


Study Drug: NEOD001  
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Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
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3. 
Conduct the EOS Visit 30 (±5) days after last administration of study drug. Two additional evaluations are to be conducted 
beyond this time point, see Footnotes 18 and 23. 
4. 
Obtain medical history since subject’s last visit in Study NEOD001-001 (including all major hospitalizations and surgeries), 
as well as the subject’s current medical status and prior therapies for AL amyloidosis. Adverse events that resolved prior to 
the subject’s last visit in Study NEOD001-001 and prior to signing the ICF for this study should be assessed as possible 
medical history in this study. 
5. 
Record all prior therapies for AL amyloidosis taken prior to signing ICF for this study and since last visit in Study 
NEOD001-001. Record all prior/concomitant medications taken or received by a subject within the 28 days prior to the 
Month 1-Day 1 Visit through the EOS Visit, and any changes to concomitant medications during the study. See Study 
Manual for more information. 
6. 
Adverse events will be collected from the time that the informed consent form is signed through 30 days after the last dose 
of study drug or last study visit, whichever is later. Record any adverse events that were ongoing from the subject’s last visit 
in Study NEOD001-001 and at the time of the NEOD001-OLE001 Screening Visit. 
7. 
Physical examination will include weight, height (Screening only), and examination of the following:  general appearance; 
head, ears, eyes, nose, and throat; neck; skin; cardiovascular system; respiratory system; abdominal system; and nervous 
system. A complete physical examination will be done at Screening and EOS; at all other visits, the components of the 
physical examination will be as clinically indicated. However, at all time points the following should be assessed:  
macroglossia, submandibular nodes/fullness, adenopathy, ecchymoses, liver/spleen size (palpable +/-), ascites (+/-), and 
edema (which should be quantified on a scale of 0-4). 
8. 
Vital signs include heart rate (HR), blood pressure (BP), respiratory rate (RR), and body temperature; assess per Section 
6.3.2. Month 1-Day 1: Predose, halfway through infusion, immediately at EOI (+5 minutes), and 30 (±5) minutes and 
60 (±10) minutes after EOI. All Other Months-Day 1: Predose, EOI (+5 minutes), and 60 (±10) minutes after EOI. 
9. 
Peripheral neuropathy assessment: only for subjects previously enrolled in Cohort C of Study NEOD001-001. 
10. Perform every 3 months (Months 3, 6, 9, 12, etc.). 
11. Administer SF-36 before performing any other study assessments on the day it is administered (Appendix 2). 
12. Perform every 6 months (Months 6, 12, 18, etc.). 
13. NT-proBNP must be drawn before conducting 6MWT, if performed on the same calendar day. Collect blood pressure and 
heart rate pre- and post-6MWT administration. 
14. Two pretreatment 6MWTs are required before the first administration of study drug, with a minimum of 4 days in between 
the two tests. The second test must be completed 1 to 2 days before the Month 1-Day 1 Visit. 
15. Echocardiogram to be conducted every 12 months and may be conducted within 10 days before the visit.  
16. Repeat echocardiogram at EOS if not performed within 60 days prior to visit. 
17. For all post-Screening visits, ECGs are to be performed predose and within 15 minutes after the EOI.  
18. Conduct telephone call approximately 3 months after subject’s last study visit and approximately every 3 months thereafter 
for up to 5 years, death, or subject withdraws consent, whichever occurs first. 
19. Hematology and chemistry per Appendix 3. At Screening, include Screen for Infectious Diseases per Appendix 3. Within 3 
days before the first day of a new regimen of chemotherapy, conduct an unscheduled central laboratory collection (including 
hematology, chemistry, PT/INR, and PTT). 
20. Coagulation per Appendix 3. Collect unscheduled citrated plasma samples for subjects with relevant serious adverse 
event(s); if defects are identified, additional analytes will be analyzed, as indicated (see Appendix 4). 
21. All laboratory tests to be done centrally, unless otherwise noted. 
22. Perform pregnancy tests for WOCBP as follows: Screening: serum test (central) within 28 days before Month 1-Day 1; 
Monthly starting with Month 2: urine test (local) predose; EOS: serum test (central).A positive urine pregnancy test (local 
laboratory) is to be confirmed with a serum pregnancy test (central laboratory). 
23. Perform serum pregnancy test (local; WOCBP only) 90 (±5) days after the last study drug administration. 
24. Begin urine collections 24 hours prior to the study visit. 
25. After Baseline, use to confirm initial within-study hematologic complete response only. 
26. Urinalysis per Appendix 3. 
27. NEOD001 serum samples (for population PK analysis): collect predose, at EOI (record the time, but the sample can be 
collected at any time after the infusion on Day 1), and at other times as clinically indicated, such as when significant toxicity 
occurs. 
28. Anti-NEOD001 antibody samples: collect predose and at other times as clinically indicated, such as when significant 
toxicity occurs. 
29. NEOD001 will be administered every 28 (±5) days. Subjects should be closely monitored for 90 (±10) minutes following 
completion of the study drug infusion. Beginning with the third infusion, the Investigator may decrease the postdose 
monitoring time to no less than 60 minutes, if no infusion-related reactions were observed in the previous infusions and 
allowed per the IRB/IEC. The Investigator may increase the monitoring time if deemed appropriate or per local standards. In 
the event of any clinical concerns or suspicious signs or symptoms after the infusion, the subject will remain under 
observation for as long as the Investigator deems it appropriate. If parenteral chemotherapy is administered on the same day 
as NEOD001, the chemotherapy must be administered after the observation period. 


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Treatment
Termination
Days -28 to -1
Months 1 through 36
Day 1 (±5 days2)
30 (±5) Days
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Study
NEOD001-001
ICF &
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Assessments
ICF & 
Screening 
Assessments
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EOS Visit
EOS Visit
EOS = end of study; ICF = informed consent form.
1 Maximum dose not to exceed 2500 mg.
2 ±5-day window applicable to Months 2+.


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date:  09 March 2017 
Page 17 of 83 
GLOSSARY OF TERMS  
Abbreviation/Acronym 
Definition 
AA 
Amyloid A 
ADA(s) 
Anti-drug antibody(ies) 
AE 
Adverse event 
AEF 
Amyloid-enhancing factor 
AL 
Amyloid light chain 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
ASCT 
Autologous stem cell transplant 
AST 
Aspartate aminotransferase 
BP 
Blood pressure 
BSA 
Bovine serum albumin 
BUN 
Blood urea nitrogen 
CTCAE 
Common Terminology Criteria for Adverse Events 
(E) 
Eligibility (i.e., a test that may be used to determine eligibility) 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
EOI 
End of infusion 
EOS 
End of Study 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GGT 
Gamma-glutamyl transpeptidase 
HIV 
Human immunodeficiency virus 
HR 
Heart rate 


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 18 of 83 
Abbreviation/Acronym 
Definition 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Institutional Ethics Committee 
IFE 
Immunofixation electrophoresis 
IgG1 
Immunoglobulin G1 
INR 
International normalized ratio 
IRB 
Institutional Review Board 
IV 
Intravenous(ly) 
LDH 
Lactate dehydrogenase 
NT-proBNP 
N-terminal pro B-type natriuretic peptide  
NYHA 
New York Heart Association 
PCD 
Plasma cell dyscrasia 
PEP 
Protein electrophoresis 
PK 
Pharmacokinetic(s) 
PS 
Performance status 
PT 
Prothrombin time 
PTT 
Partial thromboplastin time 
QTc 
Corrected QT interval 
RBC 
Red blood cell 
RR 
Respiratory rate 
SAE 
Serious adverse event 
SFLC 
Serum free light chain 
SIFE 
Serum immunofixation electrophoresis 
6MWT 
Six-Minute Walk Test 
SPEP 
Serum protein electrophoresis 
TRIAD 
Transgenic Rapidly Inducible Amyloid Disease 
UIFE 
Urine immunofixation electrophoresis 


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 19 of 83 
Abbreviation/Acronym 
Definition 
ULN 
Upper limit of normal 
UPEP 
Urine protein electrophoresis 
US 
United States 
WBC 
White blood cell 
WFI 
Water for injection 
WOCBP 
Women of childbearing potential 
 


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 20 of 83 
1 
INTRODUCTION 
1.1 
LIGHT CHAIN (AL) AMYLOIDOSIS 
Systemic amyloidoses are a complex group of diseases caused by tissue deposition of misfolded 
proteins that result in progressive organ damage. The most common type, light chain (AL) 
amyloidosis or primary systemic amyloidosis, involves a hematologic disorder caused by clonal 
plasma cells that produce misfolded immunoglobulin light chains. Overproduction of misfolded 
light chains by plasma cells results in both soluble, aggregated forms of light chains and 
insoluble, fibrillar deposits of abnormal AL protein (amyloid), in the tissues and organs of 
individuals with AL amyloidosis. Clinical features of AL amyloidosis include a constellation of 
symptoms and organ dysfunction including cardiac, renal, and hepatic dysfunction, 
gastrointestinal involvement, neuropathy and macroglossia. The mechanisms by which 
amyloidogenic immunoglobulin light chains result in organ dysfunction are not well 
characterized; however, it is hypothesized that both amyloid deposits and prefibrillar aggregates 
may contribute to cytotoxic effects on organs observed in patients with AL amyloidosis. 
AL amyloidosis is a rare disorder. Although the exact incidence of AL amyloidosis in the United 
States (US) is unknown, a weighted average from 5 sources (Kyle et al, 1992; Simms et al, 
1994; Kyle et al, 2002; Kyle et al, 2006; Junicon Study) estimates the incidence to be 7.6 new 
cases per million population per year, which is approximately 2300 new cases per year. 
Approximately, two thirds of AL amyloidosis patients present with one or two major organ 
systems involved (e.g., cardiac, renal, gastrointestinal tract, hepatic, autonomic nervous system, 
peripheral nervous system, soft tissues) while a third of patients present with more than two 
systems involved (Kyle et al, 1992). AL amyloidosis is most commonly associated with cardiac 
and/or renal dysfunction, with overt restrictive cardiomyopathy observed in approximately 50% 
of all cases, and subclinical cardiac involvement detected in almost every case at autopsy or on 
endomyocardial biopsy (Falk and Dubrey, 2010). 
AL amyloidosis has two 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. While there are no approved 
treatments for AL amyloidosis, the current standard of care for these patients is aimed at 
reducing or eliminating the bone marrow disorder, 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 and 
proteasome inhibitors (e.g., bortezomib), in an attempt to reduce light chain production. There 
are no currently approved treatments for AL amyloidosis, and none that directly target 
potentially toxic forms of the amyloidogenic proteins. 


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 21 of 83 
1.2 
STUDY RATIONALE 
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 AL amyloidosis patients is the extent of 
cardiac involvement; 75% of the deaths are due to cardiac amyloidosis (Merlini et al, 2011). The 
process of amyloid formation results in cellular injury, tissue damage, and organ dysfunction 
through mechanisms that are not completely understood. Because the current 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 (Cibeira et al, 2011; Cohen et al, 2007; Michael et al, 2010). 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 et al, 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 four single-
center studies ranged from 21% to 39% (Falk and Dubrey, 2010). Therefore, there is an urgent 
need to develop a treatment that can directly target the misfolded proteins to increase their 
clearance and to alleviate direct organ toxicity. Treatments that reduce or eliminate PCD in 
conjunction with treatments that target toxic soluble aggregates and insoluble amyloid may be of 
great clinical benefit in the treatment of AL amyloidosis. 
1.3 
BACKGROUND ON NEOD001 
Prothena Therapeutics Limited (Prothena) is developing NEOD001, a humanized 
immunoglobulin G1 (IgG1), kappa version of 2A4, the parent murine monoclonal antibody, 
which is directed against a cryptic epitope on amyloid fibrils. NE0D001 specifically targets 
misfolded light chain aggregates and amyloid deposits. Nonclinical studies to date suggest little 
cross-reactivity of the antibody with normal immunoglobulins of the immune system. 
NEOD001, administered by intravenous (IV) infusion, is proposed for use to target the misfolded 
light chain protein in subjects with AL amyloidosis. See the current NEOD001 Investigator’s 
Brochure for detailed nonclinical and clinical information.  
The proposed mechanism of action for NEOD001 is thought to be two-pronged (Figure 2). First, 
is the direct interaction of NEOD001 with soluble aggregates resulting in the neutralization of 
the soluble, toxic aggregated moieties. The second is clearing the insoluble toxic amyloid 
deposited in organs/tissues. Here, it is believed that NEOD001 attaches to the amyloid deposits 
and the intact Fc portion of NEOD001 signals monocytes/macrophages to the area; and via 
phagocytosis, clearance of the insoluble, toxic deposits occurs (e.g., opsonization of the 
deposited amyloid). It is believed that both mechanisms may contribute to potential clinical 
benefit. 


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Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 23 of 83 
Cynomolgus monkey: Important amino acid contributions to the epitope in AL amyloidosis are 
glutamic acid (E) and aspartic acid (D) at positions 81 and 82, respectively, on IgG light chain 
and these are conserved in this species; i.e., the incidence of E and D at these positions is >90% 
in both cynomolgus monkey and human. Though the aspartic acid is buried in the normally 
folded light chain, if physiologic conditions arise that result in the revealing of this epitope, or if 
there is binding to similar epitopes on other proteins, then the consequence would be evaluable in 
this species.  
In a 28-day, weekly IV dose study of NEOD001 in cynomolgus monkeys with a 28-day 
dose-free period for control and high dose animals, treatment was well tolerated at all dose levels 
(10, 50, and 100 mg/kg/week). There were no NEOD001-related changes in any of the study 
parameters evaluated and thus the no-observable-adverse-effect-level for NEOD001 in this 
species was 100 mg/kg. Serum levels of NEOD001 were maintained throughout the treatment 
period. The data suggest a low risk of off-target toxicity. 
H2/hIL-6 TRIAD mice:  The TRIAD mouse model of AA amyloidosis has limitations relative 
to safety assessment for AL amyloidosis; e.g., (1) this transgenic model overexpresses human 
interleukin-6 (IL-6), creating a proinflammatory baseline state that is important for disease 
progression but can confound safety evaluation, (2) the disease state is also promoted by 
injection with an amyloid extract, called amyloid-enhancing factor (AEF), intended to seed tissue 
with amyloid, and (3) it involves an amyloid protein (AA) that is different than the one targeted 
in this population (AL), despite the fact that 2A4 recognizes both proteins. However, this model 
contributes to the safety assessment of NEOD001 as it is the only nonclinical model available 
that offers the ability to assess the potential hazards of antibody binding to amyloid embedded in 
various vital organs, primarily liver, spleen, and kidney. The murine homologue of NEOD001, 
2A4, maintains full effector function and was used in these studies. 
Two TRIAD mouse studies were used in the nonclinical safety assessment: a 22-day toxicity 
study by the IV route of administration and a 28-day toxicity study by IV and subcutaneous 
routes of administration. In addition, a 22-day special immunogenicity/toxicity study in H2/hIL-
6 mice (no AEF) was conducted to compare 2A4 against the immunogenic potential of an 
unrelated protein, bovine serum albumin (BSA). These are detailed in the Investigator’s 
Brochure and the key points are summarized below. 
As intended for this disease model, the TRIAD mouse has background pathology. Appropriate 
controls demonstrated the effect of the IL-6 transgene (plasmacytosis in spleen, thrombus 
formation in mesenteric vessels) and the effect of the IL-6 transgene with AEF added (amyloid 
deposition in kidney, liver, spleen, and other tissues; inflammatory infiltrates in the heart; and 
renal pathology, including tubular degenerative changes and papillary necrosis). Importantly, no 
additional pathology was observed that was attributable to 2A4 treatment at the doses studied, 
4 and 40 mg/kg/week. 


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 24 of 83 
In both toxicity studies, mortality was observed acutely following the third weekly dose 
(Study Day 15) when 2A4 was administered by bolus IV administration. No pathology was 
present to indicate mechanism of the cause of death. The timing of the adverse reaction being 
within minutes to hours of the third weekly dose, and the presence of anti-drug antibodies 
(ADAs), suggest that the effect is an ADA-mediated phenomenon in this model. In animals that 
survived, there were no adverse effects described surrounding deposited amyloid, or in other 
tissues. ADA reactions in animal species are not predictive of human responses and therefore 
these effects are not considered to contribute to human risk assessment (Bugelski et al, 2004; 
Pimm et al, 1992). Additionally, while it is possible that ADAs might develop, it is not known 
whether or not this would be associated with any clinical significance.  
A special immunogenicity/toxicity study was conducted to explore whether the mortality 
observed following IV dosing of 2A4 in the TRIAD mouse can be observed with an unrelated, 
but immunogenic, protein. Nontransgenic/wild-type (WT) mice and H2/hIL-6 transgenic mice 
(no AEF administered) were treated once weekly by IV administration with 2A4 at 4 mg/kg. The 
nontransgenic mice showed no systemic effects; however, the IL-6 overproducing mice 
developed profound signs (decreased motor activity, hunched posture, ataxia, cold to touch) 
immediately after dosing on Days 15 and 22, replicating what was observed in the TRIAD 
mouse safety studies above. Mortality and moribundity occurred post dosing on Day 22. Another 
group of H2/hIL-6 transgenic mice was treated once weekly by IV administration with BSA at 
50 mg/kg. A similar clinical course occurred although signs began one week earlier; i.e. after 
dosing on Day 8 (the second dose). Again, mortality was observed in some animals after dosing 
on Day 22. This study demonstrates the importance of elevated IL-6 in the morbidity and 
mortality observed in this model and further demonstrates that the mortality is not unique to 2A4 
but can be seen with other proteins that are immunogenic in this mouse model. 
Human tissue cross-reactivity:  In a human tissue cross-reactivity study of NEOD001 designed 
to examine potential off-target effects, a limited number of tissues demonstrated any binding. 
Cytoplasmic staining was observed in the heart, kidney, pancreas, pituitary, and testis. 
Cytoplasmic staining is generally not considered to be relevant to IV dosing as these sites are not 
accessible to the administered antibody. Rare to occasional, mild-intensity membrane staining 
was observed on ductular and tubular epithelial cells of the pancreas and testis, respectively. No 
pathologic changes were observed in these organs in the repeat-dose studies suggesting limited 
safety liabilities from potential binding in these tissues. Overall, these data confirm the 
prediction of a low potential for binding of NEOD001 to normal tissue. 
In summary, the available nonclinical data support clinical development of NEOD001 for the 
treatment of AL amyloidosis. No target organ toxicity has been described. Based on available 
models, there are limitations on the ability to assess the interaction of NEOD001 with deposited 
or soluble AL amyloid. The investigations in an AA amyloidosis model (the TRIAD mouse) 
provide some reassurance that binding of 2A4, an antibody with full effector function, does not 
appear to adversely react with deposited amyloid in tissue. Nevertheless, monitoring for changes 
in disease pathology, as would typically be performed in clinical development, is warranted. 


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 25 of 83 
1.3.2 
Clinical Safety 
The safety and tolerability of NEOD001 have been investigated in the Phase 1/2 study (Study 
NEOD001-001) in the US, and are being investigated in the following ongoing global studies: 
• 
Phase 1/2 open-label extension study (Study NEOD001-OLE001) 
• 
Phase 2b study (Study NEOD001-201) 
• 
Phase 3 study (Study NEOD001-CL002) 
Study NEOD001-001 was a Phase 1/2 open-label, dose escalation study of the IV administration 
of single-agent NEOD001 in subjects with AL amyloidosis, which enrolled 27 subjects in the 
Escalation Phase in 7 cohorts (evaluating dose levels from 0.5 mg/kg to 24.0 mg/kg) and 
enrolled an additional 42 subjects in the Expansion Phase. The most frequently reported 
treatment-emergent adverse events (TEAEs) overall in Study NEOD001-001 (occurring in ≥10% 
of subjects [N=69], regardless of relationship to NEOD001) were fatigue, nausea, upper 
respiratory tract infection, diarrhea, anemia, blood creatinine increased, dizziness, constipation, 
cough, headache, edema peripheral, vomiting, pain in extremity, back pain, dyspnea, edema, 
muscle spasms, rash, and urinary tract infection (Gertz et al, 2016). No confirmed anti-
NEOD001 antibodies were detected. No dose-limiting toxicities (DLTs) or related serious 
adverse events (SAEs) were reported. 
Study NEOD001-201 (PRONTO) is an ongoing Phase 2b, multicenter, global, randomized, 
double-blind, placebo-controlled, two-arm, parallel group efficacy and safety study of NEOD001 
as a single agent administered intravenously in adults with AL amyloidosis who had a 
hematologic response to first-line treatment for their amyloidosis (e.g., chemotherapy, ASCT) 
and have persistent cardiac dysfunction. Subjects are randomized in a 1:1 ratio to receive either 
NEOD001 (24 mg/kg) or placebo. Eligible subjects from Study NEOD001-201 may be enrolled 
in the open-label extension study (NEOD001-OLE251). As of the data lock point of 
30 September 2016, 23 subjects were enrolled in Study NEOD001-201 and received 24 mg/kg 
NEOD001 or placebo (treatment remains blinded). One subject experienced a serious TEAE and 
no deaths were reported. A 64-year-old male experienced vasovagal syncope (characterized by 
bradycardia, hypotension, and syncope), which the Investigator assessed as Common 
Terminology Criteria for Adverse Events (CTCAE) Grade 3, serious, and related to study drug 
(treatment remains blinded). The subject recovered from the event of vasovagal syncope and 
discontinued the study on the day of the event. 


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 26 of 83 
Study NEOD001-CL002 (VITAL) is an ongoing Phase 3, multicenter, international, randomized, 
double-blind, placebo-controlled, two-arm efficacy and safety study in subjects with AL 
amyloidosis. Newly diagnosed subjects with AL amyloidosis are randomized in a 1:1 ratio to 
received either NEOD001 (24 mg/kg) plus standard of care or placebo plus standard of care, 
administered once every 28 days as a 1- to 2-hour IV infusion. All subjects are premedicated 
with 25 mg diphenhydramine (or an equivalent dose of an H1 antihistamine) and 650 mg 
acetaminophen (or an equivalent dose of paracetamol) within 30 to 90 minutes prior to the start 
of the infusion. As of 30 September 2016, 129 subjects were enrolled in Study NEOD001-CL002 
and received NEOD001 24 mg/kg plus standard of care or placebo plus standard of care 
(treatment remains blinded). Sixty-five (50.4%) subjects experienced at least 1 serious TEAE, 
none of which were considered by the Investigator to be related to study drug treatment 
(blinded). As of the data lock point, 19 (14.7%) subjects had died; none of the deaths were 
considered by the Investigator to be related to study drug treatment (blinded). Five (3.9%) 
subjects had TEAEs that lead to study drug discontinuation. 
Due to the limited number of infusion-site related reactions reported to date, premedication of 
subjects prior to the start of NEOD001 infusion is not required in the NEOD001-OLE001, 
NEOD001-201, and NEOD001-OLE251 protocols. As of 30 September 2016, 221 subjects had 
been dosed in the 4 completed or ongoing studies. In Study NEOD001-CL002 (VITAL), 
129 subjects received a total of 534 infusions of blinded study drug (24 mg/kg NEOD001 plus 
standard of care or placebo plus standard of care). In Study NEOD001-201 (PRONTO), 
23 subjects received a total of 51 infusions of blinded study drug (24 mg/kg NEOD001 or 
placebo). In Study NEOD001-001, 69 subjects received 994 infusions of NEOD001 (up to doses 
of 24 mg/kg). In the completed Study NEOD001-001, 9 infusion-site reactions were reported 
(6 subjects) and most (n=7; 78%) were classified as Grade 1. As noted above, 1 subject in the 
ongoing Study NEOD001-201 experienced an event of vasovagal syncope (characterized by 
bradycardia, hypotension, and syncope). Another aspect of safety monitoring in studies of 
NEOD001 has been a required postinfusion observation time ranging from 60 to 120 minutes. In 
addition to this study, Studies NEOD001-201 and NEOD001-OLE251 allow for flexibility in 
monitoring time if no reactions are seen after the first 2 infusions, as described in Section 5.3. 
Based on the data available to date, NEOD001 has been well tolerated as single-agent therapy in 
subjects with AL amyloidosis and no clinically significant safety signals have been identified. 
See the current NEOD001 Investigator’s Brochure for detailed clinical information. 
1.4 
RATIONALE FOR STUDY CONDUCT AND DOSE SELECTION 
The rationale for this study is to provide additional treatment with NEOD001 for subjects who 
complete Study NEOD001-001, and to continue to evaluate long-term safety and tolerability. All 
subjects in the current NEOD001 trials are being dosed at 24 mg/kg, which will be continued in 
this study. 


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 27 of 83 
2 
OBJECTIVES 
2.1 
PRIMARY 
• To evaluate long-term safety and tolerability of NEOD001 
2.2 
SECONDARY 
• To assess the immunogenicity of NEOD001 
• To incorporate serum NEOD001 concentrations in a population pharmacokinetic (PK) 
analysis 
2.3 
EXPLORATORY 
• To evaluate overall survival 
• To evaluate change in Six Minute Walk Test (6MWT) 
• To evaluate general health-related quality of life using the Short Form-36 (SF-36) 


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 28 of 83 
3 
STUDY PLAN 
3.1 
STUDY DESIGN 
This is a multicenter, Phase 2, open-label extension study. The purpose of the study is to evaluate 
the long-term safety and tolerability of NEOD001 in subjects with AL amyloidosis who were 
previously enrolled and treated for at least 9 months in Study NEOD001-001.  
3.2 
STUDY ENDPOINTS 
3.2.1 
Primary 
• Assessment of the safety and tolerability of NEOD001 as assessed by vital signs, duration of 
therapy, 12-lead electrocardiograms (ECGs), routine laboratory assessments, and frequency 
and severity of AEs 
3.2.2 
Secondary 
• Assessment of immunogenicity by measurement of anti-NEOD001 antibodies  
• Serum NEOD001 concentrations (sparse sampling) will be pooled with similar samples from 
other studies in a population PK analysis 
3.2.3 
Exploratory 
• Time to all-cause mortality from baseline in Study NEOD001-001 
• Change from baseline (of this study) in the 6MWT 
• Change from baseline (of this study) in the SF-36 
3.3 
NUMBER OF SITES AND SUBJECTS 
Multi-center study in approximately 70 subjects. 
3.4 
RANDOMIZATION AND BLINDING 
Not applicable. 
3.5 
ESTIMATED STUDY AND TREATMENT DURATION 
A subject’s study duration may be up to 38 months or until the study is terminated (per Section 
4.5), whichever occurs first. The study consists of a Screening Phase (1 month), Treatment Phase 
(36 months), and the End of Study (EOS) Visit 30 (±5) days after the last dose. 
3.6 
DEFINITION OF END OF STUDY 
The study is expected to be completed approximately 3 years after the last subject is enrolled. 
The study is considered completed with the last study visit for the last subject participating in the 
study or if the study is terminated, whichever occurs first, see Section 4.5. 


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4 
SELECTION, DISCONTINUATION, AND WITHDRAWAL OF 
SUBJECTS 
4.1 
INCLUSION CRITERIA 
Subject must meet all of the following: 
1. Previously enrolled and treated for at least 9 months in Study NEOD001-001  
2. Ability to understand and willingness to sign an informed consent form (ICF) prior to 
initiation of any study procedures  
3. Has adequate bone marrow reserve, hepatic and renal function, as demonstrated by:  
o Absolute neutrophil count (ANC) ≥1.0 ×109/L 
o Platelet count ≥75 × 109/L 
o Hemoglobin ≥9 g/dL 
o Total bilirubin ≤2 times the upper limit of normal (× ULN) 
o Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤3 × ULN 
o Estimated glomerular filtration rate ≥30 mL/minute  
4. Seated systolic blood pressure (BP) 90 to 180 mmHg 
5. ECOG PS 0 to 2 
6. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test 
within 28 days prior to the first administration of study drug and agree to use highly effective 
physician-approved contraception (Appendix 1) from 30 days prior to the first study drug 
administration to 90 days following the last study drug administration  
7. Male subjects must be surgically sterile or must agree to use highly effective physician-
approved contraception (Appendix 1) from 30 days prior to the first study drug 
administration to 90 days following the last study drug administration 
4.2 
EXCLUSION CRITERIA 
Subject must not meet any of the following: 
1. Any new medical contraindication or clinically significant abnormality on physical, 
neurological, laboratory, vital signs, or ECG examination (e.g., atrial fibrillation; with the 
exception of subjects for whom the ventricular rate is controlled) that precludes continued or 
initiation of treatment with NEOD001 or participation in the study 
2. History of Grade ≥3 infusion-associated adverse events (AEs) or hypersensitivities to 
NEOD001 or any of its excipients 


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3. Treatment with any anticancer therapy (standard or investigational) within the 14 days prior 
to the first dose of study drug. In addition, subjects must have fully recovered (i.e., National 
Cancer Institute Common Terminology Criteria for Adverse Events [CTCAE] Grade 1 
[exception: subjects with prior bortezomib may have CTCAE Grade 2 neuropathy]) from the 
clinically significant toxic effects of that treatment  
4. Received any of the following within the specified time frame prior to the first administration 
of study drug: 
o Hematopoietic growth factors, transfusions of blood or blood products within 1 week 
o Major surgery within 2 weeks 
o Radiotherapy within 2 weeks 
o Transplant within 8 weeks 
o Investigational drug other than NEOD001 within 4 weeks 
o Another experimental anti-amyloid therapy other than NEOD001 within 2 years  
5. Uncontrolled symptomatic orthostatic hypotension 
6. Myocardial infarction, uncontrolled angina, uncontrolled ventricular arrhythmias, or 
electrocardiographic evidence of acute ischemia, within 6 months prior to the first dose of 
study drug 
7. Uncontrolled infection 
8. Secondary malignancy, with the exception of: 
o Adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ cervical 
cancer 
o Adequately treated stage I cancer from which the subject is currently in remission  
o Any other cancer from which the subject has been disease-free for ≥3 years 
9. Uncontrolled human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection  
10. Women who are lactating 


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4.3 
EARLY TREATMENT DISCONTINUATION 
If the subject discontinues study drug prior to completing 36 months of treatment, they should 
return for an EOS Visit 30 (± 5) days after their final administration of study drug as per Section 
6.1.3. If a subject fails to return for the scheduled visit, a documented effort must be made to 
determine the reason. If the subject cannot be reached by telephone after 2 attempts, a certified 
letter will be sent to the subject (or the subject’s legally authorized representative, if appropriate) 
requesting contact with the Investigator. This information will be recorded in the study records. 
Reasons for early discontinuation from study drug treatment may include, but are not limited to: 
• A suspected NEOD001-related immunologic reaction – collect additional serum samples, if 
possible, during the period following the treatment stoppage to allow for the determination of 
the persistence of anti-NEOD001 antibodies. Samples should be collected at the EOS Visit 
and 3 months after the EOS Visit, if the subject agrees to return to the clinic.  
• Occurrence of an AE or clinically significant laboratory abnormality that, in the opinion of 
the Investigator, warrants the subject’s permanent discontinuation from study drug treatment; 
the Medical Monitor should be notified as soon as possible of any discontinuation of study 
drug due to an AE. 
• Suspected or confirmed pregnancy or nursing during study treatment period. Female subjects 
whose pregnancy test is positive at the EOS Visit must be followed to term or until 
termination of the pregnancy (Section 7.4.2). 
• Subject requests to withdraw from the study treatment 
• Subject requires or has taken medication prohibited by the protocol 
4.4 
EARLY TERMINATION FROM STUDY 
Subject participation in this study will continue until EOS. Early termination occurs if the subject 
fails to complete the entire study, through the EOS Visit. 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 or its designee should be notified in a timely manner of all subject 
discontinuations. When possible, the tests and evaluations listed for the EOS Visit should be 
carried out. 
Early termination from the study may occur if: 
• 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 


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Vital status will be collected within legal and ethical boundaries for all randomized subjects 
receiving at least one dose of study drug and will be searched in public sources. During the study 
close-out period, survival status will be collected within legal and ethical boundaries for all 
randomized subjects who withdrew participation from the study. If vital status is determined, the 
subject will not be considered lost to follow-up. 
4.5 
TERMINATION OF THE CLINICAL STUDY, INVESTIGATOR, OR 
STUDY SITE 
The Sponsor reserves the right to terminate the study, participation of an individual Investigator, 
or a study site at any time for any reason. Conditions that may warrant termination include, but 
are not limited to: 
• Clinical or administrative reasons 
• Discovery of an unexpected, relevant, or unacceptable risk to subjects  
• Sponsor’s discontinuation of further development of the study drug  
• Study drug becomes commercially available  
• Failure of the Investigator to comply with the protocol, the requirements of the Institutional 
Ethics Committee/Institutional Review Board (IEC/IRB) or Competent Authority, the 
Sponsor’s procedures, or Good Clinical Practice (GCP) guidelines  
• Inadequate recruitment of subjects by the Investigator  
According to the study contract, the Investigator also reserves the right to terminate participation 
in the study.  
4.6 
REPLACEMENT OF SUBJECTS 
As this is an open-label study for subjects previously enrolled and treated for at least 9 months in 
Study NEOD001-001, no subjects will be replaced. 


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5 
TREATMENT OF SUBJECTS 
5.1 
STUDY THERAPY 
5.1.1 
Formulation, Packaging, and Labeling 
The active study drug, NEOD001, is supplied as a sterile, lyophilized dosage form in a 20/25-mL 
vial containing 500 mg NEOD001. After reconstitution with 9.6 mL of sterile water for injection 
(WFI), the vial will contain 50 mg/mL of NEOD001, 25 mM L-Histidine, 230 mM Trehalose, 
and 0.02% Polysorbate 20. The labeling will comply with applicable regulatory requirements. 
5.1.2 
Shipping, Storage, and Handling 
NEOD001 will be shipped to clinical sites in individual cartons (one vial per carton). Upon 
receipt, a study staff member will place the study drug in a refrigerator at a temperature ranging 
from 2°C to 8°C in a secure, locked location. Access to the study drug should be strictly limited 
to the study staff. Neither the Investigator nor any member of the study staff will distribute any 
of the study supplies to any person who is not participating in this study. 
If a study staff member becomes aware that the study drug has not been properly handled (e.g., 
physical damage to carton/vial, temperature outside the 2°C to 8°C range in transit, or not stored 
at 2°C to 8°C in the clinic), follow the procedure outlined in the Pharmacy Manual or 
immediately contact the Study Monitor (contact information available in the Study Manual). In 
such an event, study drug should be quarantined in a 2°C to 8°C refrigerator and must not be 
administered to any subject until the drug has been approved for use. 
It is expected that the site staff will maintain refrigerator temperature logs in the investigational 
product storage area, recording the temperature at least once each working day. 
See Section 5.3 and the Pharmacy Manual for further details about shipping, storage and 
handling of NEOD001. 
5.2 
ACCOUNTABILITY AND RETURN OF STUDY SUPPLIES 
The study drug will be dispensed at the discretion of the Investigator in accordance with the 
conditions specified in this protocol. It is the Investigator’s responsibility to ensure that accurate 
records of study drug issuance and return are maintained. 
All study drug provided by the Sponsor should be retained at the site until otherwise instructed in 
writing by the Sponsor. Upon completion of the study or termination of the investigational site, 
all unused vials of study drug supplied by the Sponsor can be destroyed locally as per local 
institutional guidelines and a copy of the destruction certificate supplied to the Sponsor or may 
be shipped to a depot designated by the Sponsor. Refer to the Pharmacy Manual for additional 
information. 


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5.3 
DOSAGE, PREPARATION, AND ADMINISTRATION  
Study drug consists of NEOD001. The NEOD001 dose is 24 mg/kg; however, the maximum 
dose administered is not to exceed 2500 mg. Therefore, subjects with a weight of 104.2 kg or 
greater will receive the maximum dose of 2500 mg. The subject’s weight during Screening may 
be used for calculation of the first dose. Subsequent doses may be calculated based on the current 
weight at that visit or using the baseline weight, based on the site’s institutional guidelines. A 
change of ±10% from the weight being used for dosing should trigger recalculation of the dose 
based on the new weight unless thought to be exclusively due to fluid fluctuation (e.g., edema). 
Each vial of 500 mg of NEOD001 will be reconstituted with 9.6 mL sterile WFI to a 
concentration of 50 mg/mL resulting in a buffered, isotonic, preservative-free solution with a 
total extractable volume of 10 mL. Study drug will be prepared in a 250-mL IV bag of 
0.9% saline. The equivalent volume of reconstituted NEOD001 will be withdrawn prior to 
transferring the drug solution into the IV bag, such that the total IV bag volume will be 250 mL. 
Refer to the Pharmacy Manual for complete information on preparing and administering the 
study drug. 
The study drug should only be administered in settings where emergency resuscitative equipment 
and personnel trained in the management of anaphylaxis are immediately available to treat 
systemic reactions under the direct supervision of a physician.  
The study drug will be administered once every 28 (±5) days at the infusion duration established 
in Study NEOD001-001 or over 60 (±10) minutes. The length of the infusion may be extended 
over a longer period of time as clinically indicated.  
NEOD001 contains no antimicrobial preservatives. Once reconstituted, storage of study drug, 
inclusive of dilution and administration, should be limited to 24 hours under refrigerated 
conditions or 4 hours at room temperature. If it is anticipated that the infusion will extend 
beyond 4 hours, the reconstituted study drug should be split into multiple bags to ensure that no 
amount of reconstituted study drug will be at room temperature for longer than 4 hours (i.e., 
from the time of reconstitution of the vial to end of the infusion of a bag). The additional bag(s) 
should remain refrigerated until ready for use. The volume contained in the administration tubing 
should be completely flushed using 30 mL of 0.9% Sodium Chloride Injection (USP) after 
administration of study drug. The infusion line should NOT be used for blood draws. 
Postdose Monitoring Period: All subjects will be closely monitored after completion of the 
study drug infusion as follows: 
• Subjects will be closely monitored for possible infusion-associated AEs and/or 
hypersensitivities for approximately 90 (±10) minutes after completion of the study drug 
infusion to assess for possible infusion-associated AEs and/or hypersensitivities.  
• Beginning with the third infusion, the Investigator may decrease the postdose monitoring 
time to no less than 60 minutes, if no infusion-related reactions were observed in the previous 
infusions and allowed per the IRB/IEC. 


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• The Investigator may increase the postdose monitoring time if deemed appropriate or per 
local standards. In the event of any clinical concerns or suspicious signs or symptoms after 
the infusion, the subject will remain under observation for as long as the Investigator deems 
it appropriate. 
5.4 
DOSE ADJUSTMENTS  
5.4.1 
Withholding of Study Drug 
Subjects with symptomatic orthostatic hypotension or systolic BP <85 mmHg, which in the 
medical judgment of the Investigator would interfere with subject’s ability to safely receive 
treatment, will have study drug withheld. 
5.4.2 
Management of Suspected Infusion-Related/Hypersensitivity Adverse 
Events 
In the event of a suspected infusion-related and/or hypersensitivity AE, the infusion should be 
immediately discontinued and appropriate supportive therapy should be administered, which 
may include epinephrine, IV fluids, corticosteroids, vasopressors, oxygen, bronchodilators, 
antihistamines, or acetaminophen. Subjects should be evaluated and carefully monitored until 
there is complete resolution of the AE or hypersensitivity signs and symptoms. In addition to the 
institution’s recommended assessments, blood samples should be obtained in the event of a 
suspected infusion-related and/or hypersensitivity AE for assessment of the following: tryptase, 
complements C3 and C4, serum NEOD001, and anti-NEOD001 antibody levels. 
For subjects who have an infusion-related reaction, any subsequent infusion must be given with 
premedication. Within the 30-60 minutes before the start of each infusion, administer 25 mg 
diphenhydramine (or an equivalent H1 antihistamine) and 650 mg acetaminophen. All 
premedications will be recorded in the electronic case report forms (eCRFs). 
For subjects with a Grade 2 infusion-related AE, if it is appropriate to restart the infusion, it 
should be done at 50% of the original rate (e.g., if the initial infusion is administered over 
60 minutes, the new rate should be based on administering 250 mL over at least 90 minutes). If 
the subject is to receive additional infusions in subsequent weeks, the rate of these infusions 
should be discussed with and agreed upon prospectively by the Investigator and the Medical 
Monitor. 
If a subject experiences a Grade 3 infusion-related and/or hypersensitivity AE, the infusion 
should not be restarted. The decision to continue dosing at the subject’s next scheduled 
administration should be discussed with the Medical Monitor. If the decision is made to proceed 
with dosing, the dose will be reduced by 50%, in addition to a 50% reduction of the original 
infusion rate. Subjects who have an infusion-related and/or hypersensitivity AE at the subsequent 
scheduled study drug administration must have study drug permanently discontinued and have an 
EOS Visit per Section 6.1.3. 
Subjects who experience a Grade 4 infusion-related and/or hypersensitivity AE must have study 
drug permanently discontinued and have an EOS Visit per Section 6.1.3. 


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5.4.3 
Dose Reductions 
Dose reductions may be allowed in the event that observed AEs are believed to be related to 
study drug, and which in consultation between the Investigator and the Medical Monitor, may be 
managed by a 50% reduction in dose. The duration of the dose reduction will be at the 
Investigator’s discretion. 
5.5 
TREATMENT COMPLIANCE 
Treatment compliance will be documented in the eCRF by recording the date, time, and whether 
or not each IV dose of study drug was completely infused. 
5.6 
PRIOR AND CONCOMITANT MEDICATION/THERAPY 
Prior and concomitant medications include any drug (prescription or over-the-counter) or 
biological product (such as vaccines, blood or blood components) including herbal remedies or 
preparations. All prior/concomitant medications taken or received by a subject within the 28 days 
prior to the Month 1-Day 1 Visit through the EOS Visit, and any changes to concomitant 
medications during the study will be recorded in the appropriate eCRF. In addition, all prior 
therapies for AL amyloidosis taken prior to signing ICF for this study and since last visit in 
Study NEOD001-001 will be recorded. See Study Manual for more information. 
5.6.1 
Allowed Concomitant Medication/Therapy 
The following are allowed during the study: 
• Radiation therapy for the removal of local amyloid deposits 
• Concomitant chemotherapy 
o The Investigator may prescribe chemotherapy as per standard of care 
o Particular care must be taken to accurately report chemotherapy administration, including 
missed or delayed doses, and dose reductions 
o If parenteral chemotherapy is administered on the same day as NEOD001, the 
chemotherapy must be administered after the 90-minute NEOD001 observation period 
o Within 3 days before the first day of a new regimen of chemotherapy, conduct an 
unscheduled central laboratory collection (including hematology, chemistry, PT/INR, and 
PTT) 
o Routine medications should not be administered in the 15 minutes after the completion of 
the NEOD001 infusion. Medications such as anti-emetics required for prophylaxis of 
emesis for the subsequent chemotherapy should be given after the ECG has been done. 
5.6.2 
Prohibited Concomitant Medication/Therapy 
The following are not allowed during the study: 
• Other investigational agents 


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• Myeloablative chemotherapy with ASCT 
• Gadolinium contrast agents are only permitted in exceptional circumstances. If a subject 
requires the use of gadolinium contrast agents, contact the Medical Monitor. 


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6 
STUDY PROCEDURES 
6.1 
EVALUATIONS BY VISIT 
6.1.1 
Screening Period:  Days -28 to -1 
A signed ICF must be obtained before any study-specific screening evaluations are performed 
and should be documented in the subject’s medical chart. 
Screening evaluations and procedures will be performed within 28 days prior to the first study 
drug administration on Month 1-Day 1. 
Rescreening is allowed once per subject. Repeat only tests that did not meet eligibility 
requirements. All laboratory evaluations to be done centrally, unless otherwise noted. Refer to 
the Central Laboratory Manual for complete instructions on collection of samples. 
6.1.1.1 
Assessments for Subjects Whose Previous Visit in Study NEOD001-001 was 
Within 60 Days of Screening  
• Signed informed consent 
• Review eligibility, including discontinuation of prior therapies according to the Exclusion 
Criteria 
• Medical History - Obtain medical history since subject’s last visit in Study NEOD001-001 
(including all major hospitalizations and surgeries), as well as the subject’s current medical 
status and prior therapies for AL amyloidosis. Adverse events that resolved prior to the 
subject’s last visit in Study NEOD001-001 and prior to signing ICF for this study should be 
assessed as possible medical history in this study. 
• Historical NT-proBNP levels – any NT-proBNP results available since participation in 
Study NEOD001-001 must be recorded 
• Prior and concomitant medications/therapy (per Section 5.6) 
• Assessment of AEs; record any AEs that were ongoing from the subject’s last visit in Study 
NEOD001-001 and at the time of the NEOD001-OLE001 Screening Visit 
• Complete physical examination - including height, weight, and examination of general 
appearance; head, ears, eyes, nose, and throat; neck; skin; cardiovascular system; respiratory 
system; abdominal system; and nervous system. The following should be assessed:  
macroglossia, submandibular nodes/fullness, adenopathy, ecchymoses, liver/spleen size 
(palpable +/-), ascites (+/-), and edema (which should be quantified on a scale of 0-4). 
• Vital signs including heart rate (HR), BP, respiratory rate (RR), and body temperature 
(Section 6.3.2) 
o Note: subjects with uncontrolled hypotension or systolic BP <85 mmHg are not eligible 
for the study 


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• Peripheral Neuropathy Assessment (Section 6.3.5 and Appendix 5) 
o Note: only for subjects previously enrolled in Cohort C of Study NEOD001-001 
• SF-36 Health Survey (Appendix 2) 
o Note: administer SF-36 before performing any other study assessments on the day it is 
administered 
• 6MWT (Section 6.3.6): Two pretreatment 6MWTs are required before the first 
administration of study drug, with a minimum of 4 days in between the two tests. The second 
test must be completed 1 to 2 days before the Month 1-Day 1 Visit. Also collect HR and BP 
pre- and post-6MWT administration. 
o Note: NT-proBNP must be drawn before conducting 6MWT, if performed on the same 
calendar day 
• 12-lead ECG in triplicate (perform locally) 
• Laboratory Assessments: 
o Hematology, chemistry (including amylase), and Screen for Infectious Diseases per 
Appendix 3 
o Coagulation per Appendix 3; collect unscheduled citrated plasma samples for subjects 
with relevant SAEs; if defects are identified, additional analytes will be analyzed, as 
indicated (see Appendix 4) 
o Cardiac biomarkers per Appendix 3 
o Serum pregnancy tests (WOCBP only): Perform a serum pregnancy test (central) within 
28 days before Month 1-Day 1 study drug administration 
• Other Assessments (see Laboratory Manual): 
o Serum NEOD001 concentration 
o Serum anti-NEOD001 antibodies 
6.1.1.2 
Assessments for Subjects Whose Previous Visit in Study NEOD001-001 was 
≥60 Days from Screening 
• Signed informed consent 
• Begin urine collection 24 hours prior to the study visit 
• Review eligibility, including discontinuation of prior therapies according to the Exclusion 
Criteria 


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• Medical History - Obtain medical history since subject’s last visit in Study NEOD001-001 
(including all major hospitalizations and surgeries), as well as the subject’s current medical 
status and prior therapies for AL amyloidosis. Adverse events that resolved prior to the 
subject’s last visit in Study NEOD001-001 and prior to signing ICF in this study should be 
assessed as possible medical history in this study. 
• Historical NT-proBNP levels – any NT-proBNP results available since participation in 
Study NEOD001-001 must be recorded 
• Prior and concomitant medications/therapy (per Section 5.6) 
• Assessment of AEs; record any AEs that were ongoing from the subject’s last visit in Study 
NEOD001-001 and at the time of the NEOD001-OLE001 Screening Visit.  
• Complete physical examination - including height, weight, and examination of general 
appearance; head, ears, eyes, nose, and throat; neck; skin; cardiovascular system; respiratory 
system; abdominal system; and nervous system. The following should be assessed:  
macroglossia, submandibular nodes/fullness, adenopathy, ecchymoses, liver/spleen size 
(palpable +/-), ascites (+/-), and edema (which should be quantified on a scale of 0-4). 
• Vital signs including HR, BP, RR, and body temperature (Section 6.3.2) 
o Note: subjects with uncontrolled hypotension or systolic BP <85 mmHg are not eligible 
for the study 
• ECOG PS (Appendix 6) 
• New York Heart Association (NYHA) functional status (Appendix 7) 
• Peripheral Neuropathy Assessment (Section 6.3.5 and Appendix 5) 
o Note: only for subjects previously enrolled in Cohort C of Study NEOD001-001  
• SF-36 Health Survey (Appendix 2) 
o Note: administer SF-36 before performing any other study assessments on the day it is 
administered 
• 6MWT (Section 6.3.6): Two pretreatment 6MWTs are required before the first 
administration of study drug, with a minimum of 4 days in between the two tests. The second 
test must be completed 1 to 2 days before the Month 1-Day 1 Visit. Also collect HR and BP 
pre- and post-6MWT administration. 
o Note: NT-proBNP must be drawn before conducting 6MWT, if performed on the same 
calendar day 
• Echocardiogram 


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• 12-lead ECG in triplicate (perform locally) 
• Laboratory Assessments: 
o Hematology and chemistry (including amylase) per Appendix 3 
o Coagulation per  Appendix 3; collect unscheduled citrated plasma samples for subjects 
with relevant SAEs; if defects are identified, additional analytes will be analyzed, as 
indicated (see Appendix 4) 
o Cardiac biomarkers per Appendix 3 
o Serum pregnancy tests (WOCBP only): Perform a serum test (central) within 28 days 
before Month 1-Day 1 study drug administration 
o Serum free light chain (SFLC) 
o Serum protein electrophoresis (SPEP) and 24-hour urine protein electrophoresis (UPEP) 
o Serum immunofixation (SIFE) and urine immunofixation (UIFE) 
o Urinalysis (dip stick) per Appendix 3 
o 24-hour urine protein excretion 
• Other Assessments (see Laboratory Manual): 
o Serum NEOD001 concentration 
o Serum anti-NEOD001 antibodies 
6.1.2 
Treatment Period:  Months 1 through 36, Day 1 (±5 Days) 
Day 1 assessments may be conducted ±5 days from Day 1, with the exception of Month 1-Day 1 
(i.e., no window is allowed at Month 1). 
Subjects will receive 24 mg/kg of NEOD001 as an IV infusion every 28 (±5) days, i.e., on Day 1 
of Months 1 through 36.  
All laboratory tests to be done centrally, unless otherwise noted. Refer to the Central Laboratory 
Manual for complete instructions on collection of samples. 
Although central laboratory assessments will be performed each month for study analysis, local 
laboratory assessments including hematology, chemistry, and urinalysis will be performed for 
subject management. Results will be reviewed prior to dosing at each month’s Day 1 visit to 
confirm that continued dosing is appropriate. 


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Subjects who present with symptomatic orthostatic hypotension or systolic BP <85 mmHg, 
which in the medical judgment of the Investigator would interfere with the subject’s ability to 
safely receive treatment, will have the study drug withheld. If the study drug is withheld and 
subsequently rescheduled, central laboratory assessments required for that visit will need to be 
repeated if they were drawn >7 days prior to the rescheduled dosing date. However, a symptom-
directed physical examination and vital signs need to be repeated prior to each dosing.  
An unscheduled central laboratory collection (i.e., hematology, chemistry, PT/INR, and PTT) 
will be conducted within 3 days before the first day of a new regimen of chemotherapy. 
Prior to Infusion: 
The following assessments will be done prior to study drug administration on Day 1 of every 
month, unless otherwise indicated. Because questionnaires and laboratory samples should be 
completed prior to the 6MWT, all of the following assessments, at a minimum, should be 
completed 1 to 2 days prior to Day 1: 
• Begin urine collection 24 hours prior to the study visit 
• Concomitant medications/therapies 
• Assessment of AEs 
• Directed physical examination - including weight and examination of the following:  general 
appearance; head, ears, eyes, nose, and throat; neck; skin; cardiovascular system; respiratory 
system; abdominal system; and nervous system. The components of the physical examination 
will be as clinically indicated. However, at all time points the following should be assessed:  
macroglossia, submandibular nodes/fullness, adenopathy, ecchymoses, liver/spleen size 
(palpable +/-), ascites (+/-), and edema (which should be quantified on a scale of 0-4).  
• Vital signs including HR, BP, RR, and body temperature; assess in the same position for all 
time points (Section 6.3.2) 
• ECOG PS (Appendix 6) 
• NYHA functional status (Appendix 7) 
• Peripheral Neuropathy Assessment (Section 6.3.5 and Appendix 5) – every 3 months 
o Note: only for subjects previously enrolled in Cohort C of Study NEOD001-001  
• SF-36 Health Survey (Appendix 2) – every 6 months 
o Note: administer SF-36 before performing any other study assessments on the day it is 
administered 


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• 6MWT (Section 6.3.6) – every 6 months; also collect HR and BP pre- and post-6MWT 
administration 
o Notes: NT-proBNP must be drawn before conducting 6MWT, if performed on the same 
calendar day. The 6MWT must be performed 1-2 days prior to administration of study 
drug; it should not be administered on the same day as study drug administration (i.e., 
Day 1). 
• Echocardiogram – every 12 months  
o Note: May be conducted within 10 days before the visit 
• 12-lead ECG in triplicate (perform locally) – every 3 months 
• Laboratory Assessments: 
o Hematology and chemistry (including amylase) per Appendix 3 
o Coagulation per  Appendix 3; collect unscheduled citrated plasma samples for subjects 
with relevant SAEs; if defects are identified, additional analytes will be analyzed, as 
indicated (see Appendix 4) 
o Cardiac biomarkers per Appendix 3 
o Urine pregnancy test (WOCBP only; local laboratory) – Monthly starting with Month 2 
o SFLC – every 3 months 
o SPEP and 24-hour UPEP – every 3 months 
 Note: During the Treatment Phase, SPEP and UPEP are used to confirm the initial 
within-study hematologic complete response only 
o SIFE and UIFE – every 3 months 
 Note: During the Treatment Phase, SIFE and UIFE are used to confirm the initial 
within-study hematologic complete response only 
o Urinalysis (dip stick) per Appendix 3 – every 3 months 
o 24-hour collection for urine protein excretion – every 3 months 
• Other Assessments (Laboratory Manual) – every 3 months 
o Serum NEOD001 concentration 
o Serum anti-NEOD001 antibodies 


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o Additional samples for anti-NEOD001 antibodies and serum NEOD001 should be 
collected if a significant toxicity is observed 
NEOD001 Administration: 
Note: Subjects who present with symptomatic orthostatic hypotension or systolic BP <85 mmHg 
will have the study drug held  
• Month 1-Day 1:  
o Administer NEOD001 IV using the infusion duration established during Study 
NEOD001-001 or over 60 (±10) minutes (Section 5.3) 
o Assess vital signs including HR, BP, RR, and body temperature, halfway through the 
infusion (Section 6.3.2)  
• All Other Months:  
o If the Month 1-Day 1 infusion was well tolerated without infusion-associated AEs, 
administer NEOD001 IV using the infusion duration established during Study 
NEOD001-001 or over 60 (±10) minutes. If needed, see Section 5.4 for dose adjustment 
instructions. 
After Infusion: 
• Monitor subjects for 90 (±10) minutes following completion of the study drug infusion. 
Beginning with the third infusion, the Investigator may decrease the postdose monitoring 
time to no less than 60 minutes, if no infusion-related reactions were observed in the previous 
infusions and allowed per the IRB/IEC (per Section 5.3). The Investigator may increase the 
monitoring time if deemed appropriate or per local standards. In the event of any clinical 
concerns or suspicious signs or symptoms after the infusion, the subject will remain under 
observation for as long as the Investigator deems it appropriate.  
• Routine medications should not be administered in the 15 minutes after the completion of the 
NEOD001 infusion 
• Vital signs including HR, BP, RR, and body temperature (Section 6.3.2): 
o Month 1-Day 1: 
 Immediately at end of infusion (EOI) (+5 minutes) 
 30 (±5) minutes after EOI 
 60 (±10) minutes after EOI 
o All Other Months: 
 Immediately at EOI (+5 minutes) 


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 60 (±10) minutes after EOI 
• 12-lead ECG in triplicate (perform locally) 
o Within 15 minutes after EOI 
• Serum NEOD001 concentration – every 3 months 
o EOI (record the time, but the sample can be collected at any time after the infusion on 
Day 1) 
• Discharge subject from clinic if no immediate safety concerns and/or hypersensitivities are 
present after the postdose assessments and observation period. In the event of any clinical 
concerns or suspicious signs or symptoms after the infusion, the subject will remain with the 
Investigator and study staff for further observation until the Investigator deems the subject 
can safely leave the clinic. 
6.1.3 
End of Study (EOS): 30 (±5) Days After Final Dose 
A final visit should be scheduled 30 (±5) days after the last administration of NEOD001. The 
following procedures must be conducted: 
• Begin urine collection 24 hours prior to the study visit 
• Concomitant medications/therapy 
• Assessment of AEs  
• Complete physical examination - including weight and examination of general appearance; 
head, ears, eyes, nose, and throat; neck; skin; cardiovascular system; respiratory system; 
abdominal system; and nervous system. The following should be assessed:  macroglossia, 
submandibular nodes/fullness, adenopathy, ecchymoses, liver/spleen size (palpable +/-), 
ascites (+/-), and edema (which should be quantified on a scale of 0-4). 
• Vital signs including HR, BP, RR, and body temperature (Section 6.3.2) 
• ECOG PS (Appendix 6) 
• NYHA functional status (Appendix 7) 
• Peripheral Neuropathy Assessment (Section 6.3.5 and Appendix 5) 
o Note: only for subjects previously enrolled in Cohort C of Study NEOD001-001  
• SF-36 Health Survey (Appendix 2) 
o Note: administer SF-36 before performing any other study assessments on the day it is 
administered 


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• 6MWT (Section 6.3.6); also collect HR and BP pre- and post-6MWT administration 
o Note: NT-proBNP must be drawn before conducting 6MWT, if performed on the same 
calendar day 
• Echocardiogram 
o Note: repeat echocardiogram at EOS if not performed within 60 days prior to visit 
• 12-lead ECG in triplicate (perform locally) 
• Laboratory Assessments: 
o Hematology and chemistry (including amylase) per Appendix 3 
o Coagulation per  Appendix 3; collect unscheduled citrated plasma samples for subjects 
with relevant SAEs; if defects are identified, additional analytes will be analyzed, as 
indicated (see Appendix 4) 
o Cardiac biomarkers per Appendix 3 
o Serum pregnancy test (WOCBP only; central laboratory) 
o SFLC 
o SPEP and 24-hour UPEP 
o SIFE and UIFE 
o Urinalysis (dip stick) per Appendix 3 
o 24-hour urine protein excretion 
• Other Assessments (see Laboratory Manual): 
o Serum NEOD001 concentration 
o Serum anti-NEOD001 antibodies 
o Additional samples for anti-NEOD001 antibodies and serum NEOD001 should be 
collected if a significant toxicity is observed 
6.1.4 
90-day Postdose Pregnancy Test 
For WOCBP only: Obtain a local laboratory serum pregnancy test 90 (±5) days after the last 
administration of study drug. 


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6.1.5 
Vital Status Telephone Call 
Conduct a vital status telephone call approximately 3 months after the subject’s last study visit 
and approximately every 3 months thereafter for up to 5 years, death, or subject withdraws 
consent, whichever occurs first. 
6.2 
ORDER OF ASSESSMENTS OF SPECIFIC TESTS 
SF-36: 
• Must be administered prior to any other visit assessments on the day it is administered 
6MWT: 
• Must be performed 1-2 days prior to administration of study drug 
• Should not be administered on Day 1 (i.e., the same day as NEOD001 administration) 
• Blood samples must be collected for local (if applicable) and central laboratory assessments 
before the 6MWT is administered, if being performed on the same calendar day 
• Collect BP and HR pre- and post-6MWT administration 
ECGs: 
• When ECGs are scheduled to be performed at the same visit as PK blood collection, the ECG 
must be done first 
• For subject receiving chemotherapy, medications such as anti-emetics required for 
prophylaxis of emesis for the subsequent chemotherapy should be given after the ECG has 
been done 
Chemotherapy and Routine Medications:  
• Routine medications should not be administered in the 15 minutes after the completion of 
the NEOD001 infusion 
• If parenteral chemotherapy is administered on the same day as NEOD001, the chemotherapy 
must be administered after the 90-minute NEOD001 observation period 
• Within 3 days before the first day of a new regimen of chemotherapy, conduct an 
unscheduled central laboratory collection (including hematology and chemistry, PT/INR, and 
PTT) 


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6.3 
METHODS OF ASSESSMENT FOR SAFETY AND EFFICACY 
6.3.1 
Clinical Laboratory Evaluations 
A central laboratory will be used for this study for analysis of hematology, chemistry (including 
amylase), PT/INR, PTT, troponin T, NT-proBNP, SFLC, SPEP, SIFE, UPEP, UIFE, urinalysis, 
and 24-hour urine assessment. Details for the processing of laboratory specimens will be 
provided in the Laboratory Manual. Local hematology, chemistry, and urinalysis laboratory 
results will be obtained at the Investigator’s discretion for subject management when necessary 
for obtaining results on a more immediate basis. Local laboratory results should also be obtained 
and reviewed for a safety assessment prior to each administration of chemotherapy. Central and 
local pregnancy testing will be conducted as shown in Table 1 and Section 6. A positive urine 
pregnancy test (local laboratory) is to be confirmed with a serum pregnancy test (central 
laboratory). Results from local laboratory tests will not be collected in the eCRFs or the clinical 
database (exception: local laboratory pregnancy test results will be collected via an eCRF and in 
the clinical database).  
In addition, a bioanalytical laboratory will be used for this study for the analysis of PK and anti-
NEOD001 antibody samples, as well as for the storage of serum samples for future correlative 
testing (Section 6.4).  
6.3.2 
Vital Signs 
Heart rate will be measured from the radial pulse counted manually or with an automatic BP 
monitor over at least 15 seconds and adjusted per minute.  
Blood pressure (systolic and diastolic) will be measured after the subject has rested in a semi-
recumbent position ≥5 minutes. Blood pressure measurements should be taken from the same 
arm throughout the study using an automated BP monitor that uses an oscillometric method. At 
Screening, BP measurements may be repeated twice. If there is a clinically important change in 
BP from the previous reading, measurements will be repeated immediately to confirm the 
change. 
Respiratory rate will be measured over at least 15 seconds and adjusted per minute. 
Measurement can be made using either oral or tympanic methods, but the method should be 
consistent throughout the study for a given subject. 
6.3.3 
Physical Examination 
Any unfavorable findings considered by the Investigator as clinically significant, especially 
changes occurring between Screening and EOS, will be documented in the eCRF as an AE. 
Physical examinations must be performed by the Investigator or a medically qualified delegate. 


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All physical examinations should include weight and examination of the following:  general 
appearance; head, ears, eyes, nose, and throat; neck; skin; cardiovascular system; respiratory 
system; abdominal system; and nervous system. The specific components of the physical 
examination will be as clinically indicated. However, at all time points the following should be 
assessed:  macroglossia, submandibular nodes/fullness, adenopathy, ecchymoses, liver/spleen 
size (palpable +/-), ascites (+/-), and edema (which should be quantified on a scale of 0-4). The 
Screening physical examination will also include a measurement of height. 
6.3.4 
12-Lead ECGs 
Measurements will be made in triplicate, 5 to 10 minutes apart and taken after the subject has 
rested in a supine position for ≥5 minutes. Heart rate, PQ/PR duration, QRS duration, QT 
duration, QTcF - Fridericia's correction formula, QTcB - Bazett's correction formula, and the 
Investigator’s overall interpretation will be recorded. When ECGs are scheduled to be performed 
at the same time as PK blood collection, the ECG must be done before the PK blood collection. 
6.3.5 
Peripheral Neuropathy Assessment 
The Peripheral Neuropathy Assessment form (Appendix 5), will be used to assess reflexes, 
sensation, and motor strength to determine a peripheral neuropathy score in subjects previously 
enrolled in Cohort C of Study NEOD001-001. A peripheral neuropathy grade based on the 
CTCAE scale (Table 2) will be determined at each assessment. 
Table 2 
Common Terminology Criteria for Adverse Events Grade 1-5 for Peripheral 
Neuropathy 
 
CTCAE Grade 
 
1 
2 
3 
4 
5 
Peripheral 
sensory 
neuropathya 
Asymptomatic; 
loss of deep 
tendon reflexes 
or paresthesia 
Moderate 
symptoms; limiting 
instrumental ADL 
Severe 
symptoms; 
limiting self-
care ADL 
Life-threatening 
consequences; 
urgent 
intervention 
indicated 
Death 
Abbreviations: ADL = activities of daily living (e.g., preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc.); CTCAE = Common Terminology Criteria for Adverse Events. 
a 
Definition: a disorder characterized by inflammation or degeneration of the peripheral sensory nerves. 
Source: National Cancer Institute, 2009. 
6.3.6 
6-Minute Walk Test 
The 6MWT will be assessed according to Table 1. As part of the 6MWT, BP and HR will be 
collected pre- and post-6MWT administration. The 6MWT should not be administered on the 
same day that study drug is administered, but may be performed 1-2 days prior to the Day 1 visit 
at each required assessment. The SF-36 must be administered and clinical laboratory samples 
(local and central) must be drawn prior to administering the 6MWT, if being performed on the 
same calendar day. 
Details regarding the requirements for proper administration of the 6MWT are described in a 
separate manual. 


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6.4 
PHARMACOKINETIC AND IMMUNOGENICITY ASSESSMENTS 
All subjects enrolled in the study will undergo sparse sampling for serum NEOD001 according 
to Table 1. Serum NEOD001 concentrations from this study will be pooled with similar samples 
from other studies in a population PK analysis. Details will be provided in a separate document. 
Serum anti-NEOD001 antibody levels will be measured according to Table 1. An 
electrochemiluminescent assay will be used to detect serum anti-NEOD001 antibodies. Any 
screening positives will be run at increasing dilutions to and a titer determined (expressed as the 
reciprocal of the dilution that generates a positive response. Additionally, all positives will be run 
in a confirmatory assay to determine the response is specific to NEOD001. 
Additional samples for anti-NEOD001 antibodies and serum NEOD001 should be collected if a 
significant toxicity is observed (e.g., an infusion reaction in the clinic, anaphylaxis, etc.) and if 
possible, should be collected while the acute symptoms persist.  
Refer to the Laboratory Manual for additional details. 


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7 
ADVERSE EVENTS/SERIOUS ADVERSE EVENTS AND 
REPORTING 
7.1 
ADVERSE EVENTS—DEFINITION 
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether 
or not considered drug related. An AE can therefore be any unfavorable and unintended sign 
(including a laboratory finding, for example), symptom, syndrome, or disease temporally 
associated with the use of a medicinal product, whether or not considered related to the 
medicinal product. Examples include: 
• Any treatment-emergent signs and symptoms (events that are marked by a change from the 
subject’s baseline/entry status [e.g., an increase in severity or frequency of preexisting 
abnormality or disorder]) 
• All reactions from study drug, abuse of drug, withdrawal phenomena, sensitivity, or toxicity 
to study drug 
• Apparently unrelated illnesses 
• Injury or accidents 
• Exacerbations of the underlying disease (indication) 
• Extensions or exacerbations or symptomatology, subjective events reported by the subject, 
new clinically significant abnormalities in clinical laboratory, physiological testing, or 
physical examination 
The reporting period for AEs is from the time that the ICF is signed through 30 days after the last 
dose of study drug or last study visit, whichever is later. All AEs, whether or not related to the 
study drug, must be fully and completely documented in the eCRF and in the subject’s medical 
notes. The following attributes must be assigned:  description, dates of onset and resolution, 
severity, assessment of relatedness to study drug (either related or not related), and action taken. 
The Investigator may be asked to provide additional follow-up information. 
In the event that a subject is withdrawn from the study because of an AE, it must be recorded in 
the eCRF. The subject should be followed and treated by the Investigator until the AE has 
resolved, stabilized, or a new chronic baseline has been established. 
The Investigator must report all AEs. At each visit the Investigator will ask the subject a 
nonspecific question (e.g., “Have you noticed anything different since your last visit?”) to assess 
whether any AEs have been experienced since the last report or visit. AEs will be identified and 
documented in the eCRF in appropriate medical terminology. The severity and the relationship to 
the study drug will be determined and reported in the eCRF (see Sections 7.2 and 7.3). 
Note that any intermittent or as-needed (“PRN”) use of medication (and specifically any newly 
prescribed medication) during the course of a study may indicate the occurrence of an AE that 
may need to be recorded on multiple eCRFs (e.g., AE and Concomitant Medication eCRFs). 


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7.2 
ADVERSE EVENTS—SEVERITY RATING 
AEs will be assessed according to CTCAE version 4.0 (National Cancer Institute, 2009). AEs 
that do not have a corresponding CTCAE term will be assessed according to their impact on the 
participant’s ability to perform daily activities as listed below. 
The severity of each AE should be characterized and then classified into one of five clearly 
defined categories as follows: 
• Mild (Grade 1):  the AE does not interfere in a significant manner with the subject’s normal 
functioning level—it may be an annoyance 
• Moderate (Grade 2): the AE produces some impairment of functioning, but is not hazardous 
to health—it is uncomfortable or an embarrassment 
• Severe (Grade 3):  the AE produces significant impairment of functioning or incapacitation 
and is a definite hazard to the subject’s health 
• Life threatening (Grade 4): Life threatening or disabling 
• Fatal (Grade 5): Causes death of the participant 
These five categories are based on the Investigator’s clinical judgment, which in turn depends on 
consideration of various factors such as the subject’s reports, the Investigator’s observations, and 
the Investigator’s prior experience. The severity of the AE should be recorded in the appropriate 
eCRF. The evaluation of severity is distinguished from the evaluation of “seriousness.” A severe 
event might not meet the criteria for seriousness and a serious event might be evaluated as mild. 
For example, a subject might have a severe headache that does not require hospitalization and is 
consequently not serious; or a subject might have a mild myocardial infarction that requires 
hospitalization and is therefore serious. 
7.3 
ADVERSE EVENTS—CAUSALITY RATING 
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). 
• Related:  An Investigator should consider an AE related to the study drug if there is a 
reasonable possibility that the event may have been caused by the study drug. 
• Not Related:  An Investigator should consider an AE not related to the study drug if there is 
another reasonable explanation for the event to occur. 
Consider the following when assessing causality: 
• Temporal associations between the agent and the event 


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• Effect of dechallenge and/or rechallenge 
• Compatibility with known class effect 
• Known effects of concomitant medications 
• Preexisting risk factors 
• A plausible mechanism 
• Concurrent illnesses 
7.4 
SERIOUS ADVERSE EVENTS AND UNEXPECTED ADVERSE 
EVENTS 
In addition to the severity rating, each AE is to be classified by the Investigator as “serious” or 
“not serious.” The seriousness of an event is defined according to the applicable regulations and 
generally refers to the outcome of an event. An SAE is one that meets one or more of the 
following: 
• Is fatal 
• Is life-threatening 
• Is persistent or significantly incapacitating or causes substantial disruption of the ability to 
conduct normal life functions 
• Requires inpatient hospitalization 
• Prolongs existing hospitalization 
• Is a congenital anomaly or birth defect  
• Is an important medical event that may jeopardize the subject and may require medical or 
surgical intervention to prevent on of the outcomes listed above 
Definition of Life-threatening 
An AE or suspected adverse reaction is considered "life-threatening" if, in the view of either the 
Investigator or Sponsor (and/or designee), its occurrence places the subject at immediate risk of 
death. It does not include an AE or suspected adverse reaction that, had it occurred in a more 
severe form, might have caused death. 


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Definition of 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. Hospitalization 
may include social hospitalization, defined as inadequate family support/care at subject’s 
primary residence, which results in subject being admitted to the hospital (i.e. wound care, 
nutrition, etc.). 
Examples of visits to a hospital facility that do not meet the serious criteria for hospitalization 
include: 
• Emergency room visits hat last for a period of <24 hours and do not result in a full hospital 
admission 
• Outpatient surgery 
• Preplanned or elective procedures (Section 7.4.1) 
• Protocol procedures 
The above events would not be reported as SAEs unless the event triggering the hospital visit is 
an SAE as defined by other SAE criteria such as life-threatening, results in persistent or 
significant disability/incapacity or as per medical judgment of Investigator. 
Any other event fulfilling the definition of serious that develops as a result of the in-hospital 
procedure or extends the hospital stay is an SAE. 
Definition of Disability 
Disability is defined as a persistent or significant incapacity or substantial disruption of the 
ability to conduct normal life functions. 
Definition of Medically Significant 
Important medical events (medically significant events) that may not result in death, be life-
threatening or require hospitalization may be considered to be an SAE when, based upon 
appropriate medical judgment, they may jeopardize the subject or may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. Examples of such 
events are intensive treatment in an emergency room or at home for allergic bronchospasm, 
blood dyscrasias, or convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse. 
An SAE may also include any other event that the Investigator or medical monitor judges to be 
serious, or that suggests a significant hazard, contraindication, side effect, or precaution. 


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Definition of Unexpected AEs or Unexpected Suspected Adverse Reactions 
An AE or suspected adverse reaction is considered “unexpected” if it is not listed in the 
Investigator Brochure or is not listed at the specificity or severity that has been observed. 
“Unexpected,” as used in this definition, also refers to AEs or suspected adverse reactions that 
are mentioned in the Investigator Brochure as occurring with a class of drugs or as anticipated 
from the pharmacological properties of the drug, but are not specifically mentioned as occurring 
with the particular drug under investigation. 
7.4.1 
Elective Procedures and Surgeries 
For the purposes of this protocol, the following conventions will apply for SAE reporting of 
elective procedures, and surgeries: 
A prescheduled 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 prescheduled 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 prescheduled elective procedure or routinely scheduled treatment is the sole reason for 
admission and intervention 
An untoward medical event occurring during the prescheduled elective procedure or routinely 
scheduled treatment should be recorded as an AE or a SAE. Any concurrent medications should 
also be recorded on the eCRF. 
7.4.2 
Other Reportable Information 
In addition, and for the purposes of monitoring, the following should be reported via the SAE 
form, regardless of seriousness, according to the directions in Section 7.4.4: 
• A new diagnosis of cancer 
• Any occurrence of pregnancy (with or without AEs) 
Note: Any subject who becomes pregnant during the study must be withdrawn from 
treatment, and will be followed to term. A Pregnancy Follow-up Form may be used to obtain 
information on the outcome of the pregnancy/status of the infant. 


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7.4.3 
Disease Progression and Death 
Disease progression (including progression of hematologic condition and/or organ dysfunction of 
AL amyloidosis, and death due to disease progression) is generally recorded as part of the 
efficacy evaluation and should not be reported as a specific AE or SAE. 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 instance, a subject with pleural effusion presents with shortness of breath. The 
cause of the shortness of breath is a pleural effusion resulting from disease progression. The 
event term may be reported as “pleural effusion” instead of disease progression.  
Death should not be reported as an SAE, but as a clinical outcome of a specific SAE. The cause 
of death, reported on a source document such as the Death Certificate or autopsy report, should 
be used as the event term for the SAE. For example, in a subject with acute heart failure that 
results in death, the SAE is reported as “acute heart failure” with an outcome of “death.” 
7.4.4 
Serious Adverse Events—Reporting 
It is the responsibility of the Principal Investigator to report SAEs to the Sponsor or its designee 
within 24 hours. 
All SAEs must be reported immediately (within 24 hours of discovery) to the Sponsor or its 
designee (see Study Manual for details). Do not delay in the reporting of a suspected SAE in 
order to obtain additional information. Any additional information, if collected, can be reported 
to the Sponsor or its designee as a follow-up to the initial report. SAEs will be reported using the 
SAE forms provided as part of the Study Manual. Please remember to give details of the study-
specific site and subject numbers or other appropriate terminology and ensure the narrative is 
comprehensive and includes a chronology and assessment of the event. 
Reporting of SAEs to the Institutional Review Board/Institutional Ethics Committee (IRB/IEC) 
will be done in compliance with the standard operating procedures and policies of the IRB/IEC 
and with applicable regulatory requirements. Adequate information must be obtained by the 
Sponsor or its designee showing that the IRB/IEC was properly and promptly notified as 
required. 
The process for reporting an SAE, pregnancy or new cancer is as follows: 
• Complete the appropriate eCRF(s) 
• Complete an SAE form—this must include the subject’s date of birth or age, sex, and study-
specific site and subject numbers 
• Complete the narrative, which should be comprehensive and include a chronological 
description and assessment of the event 
• Complete the SAE fax cover sheet 
• Call the Sponsor Medical Monitor for life-threatening or fatal events (see contact information 
on Team Roster in Study Manual) 


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• Fax the cover sheet and the SAE form (within 24 hours of discovery) to the Safety 
Representative number listed on the Team Roster in the Study Manual 
The Investigator is encouraged to discuss any AEs with the Sponsor Medical Monitor for which 
the issue of seriousness is unclear or questioned. Contact information for the Medical Monitor is 
listed on the Team Roster in the Study Manual. 
The reporting period for SAEs is the period from signing of the ICF through 30 days after the 
last administration of study drug or last study visit, whichever is later. SAEs reported to the 
Investigator outside of this reporting period will be reported to the Sponsor or its designee if, in 
the judgment of the Investigator, there is “a reasonable possibility” that the event may have been 
caused by the product. 
All SAEs will continue to be followed until the end of the study or until such events have 
resolved or the Investigator, in conjunction with the Sponsor or its designee, deems them to be 
chronic or stable. 


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8 
STATISTICAL METHODS AND CONSIDERATIONS 
The final analyses will be based on all subject data collected through study discontinuation. 
8.1 
ANALYSIS POPULATIONS 
The Safety Population, which will include all subjects who receive at least one NEOD001 
infusion, will be used for all analyses. 
8.2 
ANALYSIS OF STUDY POPULATION AND SUBJECT 
CHARACTERISTICS 
Enrollment, major protocol violations, and discontinuations from the study will be summarized. 
Demographic and baseline characteristics, such as age, sex, race, weight, and markers of organ 
function at Screening will be summarized using means, standard deviations, medians, ranges for 
continuous variables, and proportions for categorical variables.  
Study drug administration data will be listed by study site, subject number, and visit; and any 
dose modifications will be flagged. Means and standard deviations will be used to summarize the 
total dose of NEOD001 received.  
8.3 
ANALYSIS OF SAFETY ENDPOINTS 
Safety will be assessed through summaries of AEs, changes in laboratory test results, and 
changes in vital signs. All subjects who receive one NEOD001 infusion will be included in the 
safety analysis.  
All AE data will be listed by study site, subject number, and visit. Adverse events will be coded 
using the Medical Dictionary of Regulatory Activities (MedDRA). The incidence of TEAEs 
occurring on or after treatment on Study Day 1 will be tabulated by MedDRA System Organ 
Class and Preferred Term, and by severity and relationship to treatment. TEAEs leading to 
discontinuation and SAEs, including deaths, will be listed separately and summarized. 
Descriptive statistics summarizing central laboratory data will be presented for all study visits. 
Changes from baseline to each study visit will also be summarized. 
Additional safety assessments include vital signs and ECGs. Descriptive statistics of the vital 
sign and ECG parameters will be presented by study visit, as well as the change from baseline at 
each visit. 
The incidence of anti-NEOD001 antibodies will be summarized. 
8.4 
ANALYSIS OF EFFICACY ENDPOINTS 
Overall survival will be summarized using the Kaplan-Meier method. The change from baseline 
in the 6MWT will be summarized using the mean, standard deviation, median, and minimum and 
maximum value.  


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Date: 09 March 2017 
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8.5 
ANALYSIS OF OTHER ENDPOINTS 
8.5.1 
Pharmacokinetic 
Serum NEOD001 concentrations from this study will be pooled with similar samples from other 
studies in a population PK analysis. Details will be provided in a separate document. 
8.5.2 
Immunogenicity 
Serum anti-NEOD001 antibody titers will be listed and correlated with clinical toxicity. Anti-
NEOD001 antibody levels will be correlated with NEOD001 exposure level to assess potential 
dose concentration related associations when anti-NEOD001 antibody and corresponding PK 
data are available. 
8.6 
DETERMINATION OF SAMPLE SIZE 
Not applicable as this is an extension study for subjects previously enrolled and treated for at 
least 9 months in Study NEOD001-001.  
8.7 
HANDLING OF DROPOUTS AND MISSING DATA 
Observed data will be included in listings and summary tables. There will be no imputation of 
missing data. 


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9 
DATA RECORDING, RETENTION, AND MONITORING 
9.1 
CASE REPORT FORMS 
The clinical site(s) participating in this study is (are) required to submit clinical data for each 
enrolled subject via an electronic data capture (EDC) system, using an eCRF. Site personnel will 
be trained on the EDC system before receiving access to the system. 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 on any study documents to be collected by the Sponsor. 
All clinical information requested in this protocol will be recorded in the eCRFs provided by the 
Sponsor or its designee (or via other data collection methods, e.g., electronic laboratory data 
transfer). The Principal Investigator is responsible for reviewing all eCRFs, 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. 
9.2 
AVAILABILITY AND RETENTION OF RECORDS 
The Investigator must make study data accessible to the Sponsor, study monitor, other authorized 
representatives of the Sponsor, and Regulatory Authority inspectors upon request. A file for each 
subject must be maintained at the clinical site 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 at least 15 years following the completion of the study unless 
local regulations or institutional policies require a longer retention period or the Investigator is 
otherwise notified in writing by the Sponsor. Essential documents should be retained until at 
least 2 years after the last approval of a marketing application in an International Council for 
Harmonisation (ICH) region and until there are no pending or contemplated marketing 
applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of 
clinical development of the investigational product. These documents should be retained for a 
longer period, however, if required by the applicable regulatory requirements or by an agreement 
with the Sponsor. The Investigator must not discard any records unless given written 
authorization by the Sponsor. 
Subject identity information will be maintained for 15 years unless applicable law or regulation 
requires a longer period. 
9.3 
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. 


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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 in 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 the Sponsor’s (or its 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 trial conduct and 
compliance with the protocol, ICH GCP, and applicable regulatory requirements. 
9.4 
SUBJECT CONFIDENTIALITY 
The Investigator must ensure that each subject’s anonymity is maintained as described below. In 
the eCRFs or other documents submitted to the Sponsor or its designee, subjects must be 
identified by no more than their date of birth or age, sex, and study-specific site and subject 
numbers. Documents that are not for submission to the Sponsor (e.g., signed ICFs) should be 
kept in strict confidence by the Investigator in compliance with applicable regulations and ICH 
GCP Guidelines. The Investigator and institution must permit authorized representatives of the 
Sponsor, of regulatory agencies, and the IRB/IEC 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 is obligated to inform the subject in the ICF that the 
above named representatives may review study-related records from subjects. 


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10 
ETHICAL AND LEGAL ISSUES 
10.1 
ETHICAL CONDUCT OF THE STUDY 
This study will be conducted in compliance with the current ICH E6 GCP, the ethical principles 
of the Declaration of Helsinki, current FDA GCP guidelines, and any additional local, national, 
or IRB/IEC or CA-required procedures, whichever represents the greater protection for the 
individual. 
10.2 
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 until the required regulatory approvals have been 
obtained in the appropriate jurisdiction. 
10.3 
ETHICS COMMITTEE APPROVAL 
The Investigator at the site is responsible for obtaining IRB/IEC approval for the final protocol, 
the Sponsor-approved ICF, and any materials used to recruit subjects. Written approval of these 
documents must be obtained from the IRB/IEC before any subject is enrolled at a site. 
The Principal Investigator is also responsible for the following interactions with the IRB/IEC: 
• Obtaining IRB/IEC approval for any protocol amendments and ICF revisions before 
implementing the changes 
• Providing the IRB/IEC with any required information before or during the study 
• Submitting progress reports to the IRB/IEC, as required, during the conduct of the study; 
requesting re-review and approval of the study, as needed; providing copies of all IRB/IEC 
re-approvals and relevant communication to the Sponsor or its designee 
• Notifying the IRB/IEC of all serious and unexpected AEs related to the study medication 
reported by the Sponsor or its designee, as required by local regulations 
10.4 
SUBJECT INFORMED CONSENT 
The Sponsor or its designee must review and approve the draft ICF and any amended ICFs 
prepared by the Investigator prior to submission to the IRB/IEC for approval. An 
IRB/IEC-approved copy of the ICF and all amendments will be forwarded to Prothena. 
The ICF documents 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 must personally sign and date the 
ICF before any study-related procedures are performed. The original and any amended, signed 
and dated ICF(s) must be retained in the subject’s file at the study site and a copy of the signed 
ICF must be given to the subject. 


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10.5 
SUBJECT COMPENSATION FOR ADVERSE EFFECTS ON HEALTH 
The Sponsor or its designee will adhere to local regulations regarding clinical trial compensation 
guidelines to subjects whose health is adversely affected by taking part in the study. 
10.6 
PROTOCOL AMENDMENTS AND STUDY TERMINATION 
Protocol amendments and amendment to the Informed Consent must be made only with the prior 
approval of the Sponsor and/or its designee. The IRB/IEC must be informed of all amendments 
and give approval for any amendments likely to affect the safety of the subjects or the conduct of 
the trial. The Investigator must send a copy of the approval letter from the IRB/IEC to Sponsor 
and/or designee. 
Both the Sponsor and the Investigator reserve the right to terminate the study, according to the 
study contract. The Investigator should notify the IRB/IEC in writing of the trial’s completion or 
early termination and send a copy of the notification to the Sponsor and/or designee. 
10.7 
FINANCE, INSURANCE AND INDEMNITY 
A study center will not initiate study participation until a fully executed Clinical Study 
Agreement is in place between the study center and the Sponsor. All details associated with 
finance, insurance, and indemnity are delineated in the Clinical Study Agreement. 
10.8 
PUBLICATION POLICY 
All publication rights are delineated in the Clinical Study Agreement. 


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11 
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 21 Oct 2015. 
Bugelski PJ, Treacy G. Predictive power of preclinical studies in animals for the immunogenicity 
of recombinant therapeutic proteins in humans. Cur Opin Mol Ther. 2004;6(1):10-6. 
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. 
Clinical Trial Facilitation Group. 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 
21 Oct 2015. 
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. 
Comenzo RL, Reece D, Palladini G, et al. Consensus guidelines for the conduct and reporting of 
clinical trials in systemic light-chain amyloidosis. Leukemia. 2012;26(11):2317-25. 
Falk RH, Dubrey SW. Amyloid heart eisease. Prog Cardiovasc Dis. 2010;52(4):347-61. 
Gertz MA, Comenzo RL, Landau H, et al. NEOD001 demonstrates organ biomarker responses in 
patients with light chain amyloidosis and persistent organ dysfunction: final results from a phase 
1/2 study. Oral presentation at the 58th Annual American Society of Hematology (ASH) 
Meeting; 15th International Symposium on Amyloidosis (ISA); 03 06 Dec 2016; San Diego, 
California. 
Junicon Study: Relatively little published data exists on the incidence or prevalence of AL 
amyloidosis. Prothena contracted Juniper Consulting Group to conduct an amyloidosis 
opportunity evaluation and clinical landscape assessment. This study was completed in 
September 2011 and the review of the available literature was the basis for the estimated 
amyloidosis populations in the United States and Europe that formed the basis of the Orphan 
Drug Designation granted by the US FDA’s Office of Orphan Drug Products on 17 February 
2012 for NEOD001 in the treatment of AA and AL Amyloidosis and by the European 
Committee on Orphan Medicinal Products (COMP) on 9 January 2013 for NEOD001 for the 
treatment of AL Amyloidosis. 
Kyle RA, Linos A, Beard CM, et al. Incidence and natural history of primary systemic 
amyloidosis in Olmsted County, Minnesota, 1950 through 1989. Blood. 1992;79(7):1817-22. 
Kyle RA, Therneau TM, Rajkumar SV, et al. A long-term study of prognosis in monoclonal 
gammopathy of undetermined significance. NEJM. 2002;346(8):564-69. 


Study Drug: NEOD001  
CONFIDENTIAL 
Study Protocol: NEOD001-OLE001 
Date: 09 March 2017 
Page 65 of 83 
Kyle RA, Therneau TM, Rajkumar SV, et al. Prevalence of monoclonal gammopathy of 
undetermined significance. NEJM. 2006;354(13):1362-69. 
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(1);10:56-61. 
National Cancer Institute. Common Terminology Criteria for Adverse Events v4.0 NCI, NIH, 
DHHS. NIH publication # 09-7473. 28 May 2009. 
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern 
Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-55. 
Palladini G, Hegenbart U, Milani P, et al. A staging system for renal outcome and early markers 
of renal response to chemotherapy in AL amyloidosis. Blood. 2014;124(15):2325-32. 
Pimm MV, Gribben SJ. Toxicity associated with the formation and clearance of immune 
complexes between antitumour monoclonal antibodies and syngeneic anti idiotypic antibodies in 
mice. J Cancer Res Clin Oncol. 1992;119(1):41-5. 
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. 
Simms RW, Prout MN, Cohen AS. The epidemiology of AL and AA amyloidosis. Baillieres 
Clinical Rheumatology. 1994;8(3):627-34. 


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12 
APPENDICES 


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Appendix 1 
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: 
o Oral 
o Intravaginal 
o Transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation1: 
o Oral 
o Injectable 
o 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 women of childbearing potential (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, 2014. 
 
 


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Appendix 2 
Short Form-36 Health Survey 
 
 


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Appendix 3 
Laboratory Tests 
Serum Chemistry: 
• 
ALP 
• 
ALT (E) 
• 
AST (E) 
• 
Bilirubin - total  (E) and direct 
• 
GGT 
• 
BUN 
• 
LDH 
• 
Creatinine (E) 
• 
Glucose 
• 
Cholesterol 
• 
Triglycerides 
• 
Calcium 
• 
Phosphate 
• 
Protein - total 
• 
Albumin 
• 
Sodium 
• 
Potassium 
• 
Chloride 
• 
Bicarbonate 
• 
Magnesium 
• 
Amylase 
• 
Uric acid 
• 
Estimated glomerular filtration rate (E) 
• 
Estimated creatinine clearance  
• 
Creatine kinase 
Hematology: 
• 
Hemoglobin (E) 
• 
Hematocrit 
• 
RBC 
• 
WBC 
• 
Neutrophils (absolute, %) (E) 
• 
Lymphocytes (absolute, %) (E) 
• 
Monocytes (absolute, %) 
• 
Eosinophils (absolute, %) 
• 
Basophils (absolute, %) 
• 
Platelet count (E) 
Coagulation: 
• 
PT 
• 
INR 
• 
PTT 
• 
See also Appendix 4 
 
Cardiac Biomarkers: 
• 
Troponin T 
• 
NT-proBNP  
 
Urinalysis (dip stick): 
• 
Color & clarity 
• 
Specific gravity 
• 
pH 
• 
Protein 
• 
Glucose 
• 
Ketones 
• 
Bilirubin 
• 
Urobilinogen 
• 
Blood 
• 
Nitrite 
• 
Leukocyte esterase 
• 
Microscopic 
Other: 
• 
Serum beta hCG and urine pregnancy tests 
for women of childbearing potential only (E) 
 
• 
Serum anti-NEOD001 antibodies 
• 
Serum NEOD001 concentration 
 
• 
Serum free light chains 
• 
24-hr urine protein excretion 
• 
Serum & 24-hour urine PEP 
• 
Serum & urine IFE  
Screen for Infectious Diseases: 
• 
HIV antibody  (E) 
• 
Hepatitis B surface antigen (HBsAg) (E) 
• 
Hepatitis C antibody (E) 
Abbreviations: ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood 
urea nitrogen; (E) = may be used for eligibility; GGT = gamma-glutamyl transpeptidase; hCG = human chorionic 
gonadotropin; HIV = human immunodeficiency virus; IFE = immunofixation electrophoresis; INR = international 
normalized ratio; LDH = lactate dehydrogenase; NT-proBNP = N-terminal pro B-type natriuretic peptide; PEP = protein 
electrophoresis; PT = prothrombin time; PTT = partial thromboplastin time; RBC = red blood cell; WBC = white blood cell. 


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Appendix 4 
Coagulation Indices 
In addition to PT/INR and PTT, citrated plasma samples will be collected for subjects with 
relevant SAEs. If defects are identified, additional analytes will be analyzed; these analyses may 
include, but may not be limited to, the indices listed in the following table. 
Test Name 
Antithrombin Activity (ATIII Activity) 
Fibrinogen Antigen 
Partial Thromboplastin Time Mixing Studies 
High-Molecular Weight Kininogen 
D-dimer, quantitative 
Prekallikrein 
Euglobulin Lysis Time  
Plasminogen Activator Inhibitor-1 Antigen 
Factor II Activity 
Plasminogen Activator Inhibitor-1 Activity 
Factor V Activity 
Plasmin-antiplasmin Complex 
Factor VII Activity 
Plasminogen Activity 
Factor VIII Activity  
Protein C Activity 
Factor VIII Antigen Quantitation 
Protein S Antigen Free 
Factor IX Activity 
Thrombin Time 
Factor X Activity 
Tissue Plasminogen Activator Activity 
Factor XI Activity 
Tissue Plasminogen Activator Antigen 
Factor XII Activity 
von Willebrand Factor Activity (Ristocetin Cofactor) 
Factor XIII Activity 
von Willebrand Factor Antigen 
Fibrin Monomer 
von Willebrand Factor Multimers 
Fibrinogen Activity 
 


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Appendix 5 
Peripheral Neuropathy Assessment 
 
 


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Appendix 6 
Eastern Cooperative Oncology Group (ECOG) Performance Status 
Grade 
Description 
0 
Fully active, able to carry on all predisease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of 
a light or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. Up 
and about more than 50% of waking hours. 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking 
hours. 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 
5 
Dead 
Source: Oken et al, 1982. 


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Appendix 7 
New York Heart Association (NYHA) Functional Classification 
NYHA Class 
Symptoms 
I 
No symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when 
walking, climbing stairs etc. 
II 
Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary 
activity. 
III 
Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. 
walking short distances (20–100 m). Comfortable only at rest. 
IV 
Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients. 
Source: American Heart Association, 2015. 

SAP_001.pdf: 
Document Type:
Statistical Analysis Plan
Official Title:
Open-label Extension Study to Evaluate the Long-term Safety and 
Tolerability of NEOD001 in Subjects with Light Chain (AL) 
Amyloidosis
NCT Number:
NCT02613182
Document Date:
14 May 2018


TITLE PAGE 
 
 
Statistical Analysis Plan for Protocol NEOD001-OLE001 
Open-label Extension Study to Evaluate the Long-term Safety and 
Tolerability of NEOD001 in Subjects with Light Chain (AL) Amyloidosis 
 
 
Investigational Product: 
NEOD001 
US IND Number: 
113495 
EudraCT Number: 
N/A 
Protocol Version and Date: 
Amendment 1; 09 March 2017 
Phase: 
Phase 2 
Methodology: 
Open-label Study 
Sponsor: 
Prothena Therapeutics Limited 
Adelphi Plaza, Upper George’s Street 
Dún Laoghaire, Co. Dublin 
A96 T927, Ireland 
Sponsor Representative: 
Prothena Biosciences Inc 
331 Oyster Point Boulevard 
South San Francisco, CA 94080 USA 
Analysis Plan Date: 
14 May 2018 
Analysis Plan Version: 
Final, Version 1 
 
 
CONFIDENTIAL 
This document and its contents are confidential and proprietary to Prothena. Any unauthorized 
use, disclosure, or copying of this document is prohibited. 
 
 


Statistical Analysis Plan 
 
Prothena Therapeutics Limited 
NEOD001-OLE001 
 
14 May 2018 
 
 
CONFIDENTIAL 
 
Page 2of 52 
TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
TABLE OF CONTENTS .................................................................................................................2 
LIST OF TABLES ...........................................................................................................................5 
LIST OF FIGURES .........................................................................................................................5 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ....................................................6 
1. 
INTRODUCTION ........................................................................................................9 
2. 
INFORMATION FROM THE STUDY PROTOCOL ...............................................10 
2.1. 
Study Objective ..........................................................................................................10 
2.1.1. 
Primary Objective .......................................................................................................10 
2.1.2. 
Secondary Objectives .................................................................................................10 
2.1.3. 
Exploratory Objectives ...............................................................................................10 
2.2. 
Study Design ...............................................................................................................10 
2.2.1. 
Overall Study Design ..................................................................................................10 
2.2.2. 
Study Drug ..................................................................................................................11 
2.2.3. 
Study Procedures ........................................................................................................11 
2.2.4. 
Definition of Baseline .................................................................................................14 
2.2.4.1. 
NEOD001 Baseline ....................................................................................................14 
2.2.4.2. 
OLE Baseline ..............................................................................................................14 
2.3. 
Study Endpoints ..........................................................................................................14 
2.3.1. 
Primary Endpoints ......................................................................................................14 
2.3.2. 
Secondary Endpoints ..................................................................................................14 
2.3.2.1. 
Immunogenicity ..........................................................................................................14 
2.3.2.2. 
Pharmacokinetics (PK) ...............................................................................................14 
2.3.3. 
Exploratory Efficacy Endpoints .................................................................................14 
2.3.3.1. 
Time to Event Endpoints ............................................................................................14 
2.3.3.2. 
Quality of Life Endpoints: Change from OLE Baseline in SF-36v2 Scores ..............15 
2.3.3.3. 
Functional Endpoint: Change from OLE Baseline in the 6-Minute Walk Test 
(6MWT) Distance (meters) .........................................................................................16 
2.3.3.4. 
Cardiac Endpoints .......................................................................................................16 
2.3.3.5. 
Renal Endpoints ..........................................................................................................16 
2.3.3.6. 
Peripheral Neuropathy Endpoints ...............................................................................17 
3. 
SAMPLE SIZE JUSTIFICATION .............................................................................18 


Statistical Analysis Plan 
 
Prothena Therapeutics Limited 
NEOD001-OLE001 
 
14 May 2018 
 
 
CONFIDENTIAL 
 
Page 3of 52 
4. 
GENERAL STATISTICAL METHODS ...................................................................19 
4.1. 
Reporting Conventions ...............................................................................................19 
4.2. 
Computing Environment ............................................................................................19 
4.3. 
Partial Dates and Unknown Times .............................................................................20 
4.4. 
Data Conventions ........................................................................................................21 
4.5. 
Standard Calculations .................................................................................................21 
4.6. 
Analysis Visit Windows .............................................................................................22 
4.6.1. 
NEOD001 Therapy Visit Windows ............................................................................22 
4.6.2. 
OLE Therapy Visit Windows .....................................................................................24 
5. 
ANALYSIS POPULATIONS ....................................................................................25 
6. 
EXAMINATION OF SUBGROUPS .........................................................................26 
7. 
STUDY POPULATION .............................................................................................27 
7.1. 
Subject Disposition .....................................................................................................27 
7.2. 
Demographics and Baseline Characteristics ...............................................................27 
7.3. 
Baseline AL Amyloidosis Disease Characteristics .....................................................28 
7.4. 
General Medical History .............................................................................................28 
7.5. 
Pre-Treatment, Prior, and New Concomitant Medications ........................................28 
7.6. 
Premedication .............................................................................................................29 
7.7. 
Chemotherapy .............................................................................................................29 
7.8. 
Concurrent Procedures ................................................................................................29 
8. 
EFFICACY ANALYSES ...........................................................................................30 
8.1. 
Adjustments for Covariates ........................................................................................30 
8.2. 
Handling of Dropouts or Missing Data ......................................................................30 
8.3. 
Interim Analyses and Data Monitoring ......................................................................30 
8.4. 
Multicenter Studies .....................................................................................................30 
8.5. 
Multiple Comparisons/Multiplicity ............................................................................30 
9. 
SAFETY ANALYSES ...............................................................................................31 
9.1. 
Extent of Exposure .....................................................................................................31 
9.2. 
Adverse Events ...........................................................................................................32 
9.2.1. 
Types of Incidence Rates ............................................................................................33 
9.2.1.1. 
Crude Incidence Rates ................................................................................................33 
9.2.1.2. 
Cumulative Incidence Rates .......................................................................................34 


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9.2.2. 
Overall Summary of Adverse Events .........................................................................35 
9.2.3. 
Treatment-Emergent Adverse Events .........................................................................36 
9.2.4. 
Severity of Adverse Events ........................................................................................36 
9.2.5. 
Relationship to Study Drug as Assessed by Investigator ...........................................36 
9.2.6. 
Adverse Events Leading to Dosing Changes ..............................................................36 
9.2.7. 
Serious Adverse Events and Deaths ...........................................................................37 
9.2.8. 
Adverse Events Leading to Study Drug Withdrawal .................................................37 
9.2.9. 
Other Adverse Events:  Infusion Reactions ................................................................37 
9.3. 
Clinical Laboratory Evaluations .................................................................................38 
9.3.1. 
Serum Chemistry, Hematology, and Coagulation ......................................................38 
9.3.2. 
Shifts in CTCAE Grade ..............................................................................................38 
9.3.3. 
Shifts in Normal Range ..............................................................................................38 
9.3.4. 
Pregnancy Testing and Urinalysis Dipstick ................................................................39 
9.4. 
Weight and BMI .........................................................................................................39 
9.5. 
Vital Signs ..................................................................................................................39 
9.6. 
Electrocardiograms .....................................................................................................39 
9.7. 
Physical Examination .................................................................................................40 
9.8. 
Immunogenicity ..........................................................................................................40 
10. 
PHARMACOKINETIC ANALYSES ........................................................................41 
11. 
CHANGES TO PROTOCOL PLANNED ANALYSES ...........................................42 
12. 
REFERENCES ...........................................................................................................43 
13. 
APPENDICES ............................................................................................................44 
APPENDIX 1. EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) 
PERFORMANCE STATUS .......................................................................................45 
APPENDIX 2. NEW YORK HEART ASSOCIATION (NYHA) FUNCTIONAL 
CLASSIFICATION ....................................................................................................46 
APPENDIX 3. LABORATORY TESTS ....................................................................................47 
APPENDIX 4. COAGULATION INDICES ..............................................................................48 
APPENDIX 5. ANAPHYLACTIC REACTION SMQ ..............................................................49 
 
 
 


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LIST OF TABLES 
Table 1: 
Schedule of Study Procedures ....................................................................................12 
Table 2: 
NEOD001 Therapy 1-Month Interval Visit Windows (Days) ...................................23 
Table 3: 
NEOD001 Therapy 3-Month Interval Visit Windows (Days) ...................................23 
Table 4: 
OLE Therapy 1-Month Interval Visit Windows (Days) .............................................24 
Table 5: 
OLE Therapy 3-Month Interval Visit Windows (Days) .............................................24 
Table 6: 
Treatment Group Schema ...........................................................................................33 
Table 7: 
Example of Computing Cumulative Incidence Rates Using the Life Table 
Method ........................................................................................................................35 
 
LIST OF FIGURES 
Figure 1 
NEOD001-OLE001 Study Design .............................................................................11 
 


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation 
Term 
6MWT 
6-minute walk test 
AE 
adverse event 
AL 
amyloid light chain 
ALP 
alkaline phosphatase 
ATC  
Anatomical Therapeutic Chemical 
BMI 
body mass index 
BP 
blood pressure 
C 
Celsius 
CI 
confidence interval 
cm 
centimeter 
CRF 
case report form 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DOB 
date of birth 
DOIC 
date of informed consent 
eCRF 
electronic case report form 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eGFR 
estimated glomerular filtration rate 
EOI 
end of infusion 
EOS 
end of study 
FLC 
free light chain 
g/24 hours 
grams per day (24 hours) 
g 
gram 
HR 
heart rate 
ICH 
International Council for Harmonisation 
ID 
identification 
IFE 
immunofixation electrophoresis  
in 
inches 


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Abbreviation 
Term 
IQR 
interquartile range 
IV 
intravenous  
kg 
kilogram  
L 
liter 
lb 
pounds 
m 
meter 
m2 
meters squared 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram  
mg/dL 
milligrams per deciliter 
min 
minimum 
mL 
milliliters 
mmHg 
millimeters of mercury 
msec 
milliseconds 
NCS 
not clinically significant 
ng 
nanogram 
ng/L 
nanograms per liter 
NT-proBNP 
N-terminal pro-brain natriuretic peptide 
NYHA 
New York Heart Association 
PE 
physical examination 
PEP 
protein electrophoresis 
PK 
pharmacokinetic 
pg/mL 
picogram per milliliter 
PN 
peripheral neuropathy 
PS 
performance status 
PT 
preferred term 
PT/INR 
prothrombin time/international normalized ratio 
PTT 
partial thromboplastin time 
QT 
measure of time between start of Q wave and end of T wave  
QTcB 
QT formula corrected by Bazett’s formula 


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Abbreviation 
Term 
QTcF 
QT interval corrected by Fridericia’s formula 
RR 
respiratory rate or time between 2 consecutive R waves 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SF-36v2 
Short Form-36 version 2 Health Survey   
sFLC 
serum free light chains 
SI 
Système International unit 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
temp 
temperature 
ULN 
upper limit of normal 
vs 
versus 
WHO 
World Health Organization 
WOCBP 
women of childbearing potential 
 


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1. 
INTRODUCTION 
This document outlines the statistical methods to be implemented during the analyses of Study 
NEOD001-OLE001 (Open-label Extension [OLE] Study to Evaluate the Long-term Safety and 
Tolerability of NEOD001 in Subjects with Light Chain [AL] Amyloidosis). The purpose of this 
plan is to provide specific guidelines from which the analyses will proceed. Any deviations from 
this statistical analysis plan (SAP) will be documented in the clinical study report (CSR). 
 


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2. 
INFORMATION FROM THE STUDY PROTOCOL 
2.1. 
Study Objective 
2.1.1. 
Primary Objective 
The primary objective of this study is to evaluate the long-term safety and tolerability of 
NEOD001. 
2.1.2. 
Secondary Objectives 
The secondary objectives of this study are: 
x To assess the immunogenicity of NEOD001 
x To incorporate serum NEOD001 concentrations in a population pharmacokinetic 
(PK) analysis 
2.1.3. 
Exploratory Objectives 
The exploratory objectives of this study are: 
x To evaluate overall survival 
x To evaluate general health-related quality of life using the Short Form-36 version 2 
(SF-36v2) health survey 
x To evaluate change in 6-minute walk test (6MWT) 
x To evaluate cardiac, renal, peripheral neuropathy, and hepatic response 
x To evaluate time to organ response and progression 
2.2. 
Study Design 
2.2.1. 
Overall Study Design 
This is a multicenter, Phase 2, open-label extension (OLE) study. The purpose of the study is to 
evaluate the long-term safety and tolerability of NEOD001 in up to approximately 70 subjects 
with AL amyloidosis who were previously enrolled and treated for at least 9 months in 
Study NEOD001-001. 
A subject’s participation in this extension study may be up to 38 months or until the study is 
terminated, whichever occurs first. The extension study consists of a Screening Phase (1 month), 
Treatment Phase (36 months), and an End of Study (EOS) Visit 30 (±5) days after the last dose. 
NEOD001 will be administered once every 28 (±5) days using the infusion duration that subject 
has been established in Study NEOD001-001 or over 60 (±10) minutes. Vital status telephone 
calls are to occur approximately 3 months after the subject’s last study visit and approximately 
every 3 months thereafter for up to 5 years, death, or until the subject withdraws consent, 
whichever occurs first. 


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Study visits will include collection of adverse events (AEs), vital signs, 12-lead 
electrocardiograms (ECGs), routine laboratory assessments, immunogenicity testing, 6-minute 
walk (6MWT) distance, and the SF-36 health-related quality of life survey results. 
Figure 1 
NEOD001-OLE001 Study Design 
 
2.2.2.
Study Drug 
Study drug consists of NEOD001. The NEOD001 dose is 24 mg/kg (not to exceed 2500 mg) and 
will be administered once every 28 (±5) days using the infusion duration established in 
Study NEOD001-001 or over 60 (±10) minutes. The length of the infusion may be extended over 
a longer period of time when it is clinically indicated. Each vial of 500 mg of NEOD001 will be 
reconstituted with 9.6 mL sterile water for injection to a concentration of 50 mg/mL, resulting in 
a buffered, isotonic, preservative-free solution with a total extractable volume of 10 mL. Study 
drug will be prepared in a 250 mL intravenous (IV) bag of 0.9% saline. The equivalent volume 
of reconstituted NEOD001 will be withdrawn from the IV bag prior to transferring the drug 
solution into the IV bag, such that the total IV bag volume will be 250 mL.  
Please refer to the protocol for complete product details. 
2.2.3.
Study Procedures 
The schedule of assessments, as outlined in the study protocol, is presented in Table 1. 
Screening
Treatment
Termination
Days -28 to -1
Months 1 through 36
Day 1 (±5 days2)
30 (±5) Days
After Last Dose
Completed 
9 months in 
Study
NEOD001-001
ICF &
Screening
Assessments
ICF & 
Screening 
Assessments
24 mg/kg1 NEOD001 every 28 days
EOS Visit
EOS Visit
EOS = end of study; ICF = informed consent form.
1 Maximum dose not to exceed 2500 mg.
2 ±5-day window applicable to Months 2+.


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Table 1: 
Schedule of Study Procedures  
 
 
Screening1 
Treatment 
Termination 
 
 
Days -28 to -1 
Months 1- 36 
Day 1 (±52) 
EOS3 
30 (±5) days 
after last dose 
 
Assessment or Procedure 
<60 days since 
last visit in 
Study 
NEOD001-001 
≥60 days since 
last visit in 
Study 
NEOD001-001 
 
Written Informed Consent  
X 
X 
 
 
Eligibility Review 
X 
X 
 
 
Clinical 
Medical History4 
X 
X 
 
 
Historical NT-proBNP Levels 
X 
X 
 
 
Prior/Concomitant Medication/Therapy5 
X 
X 
X 
X 
Adverse Event Assessment6 
X 
X 
X 
X 
Physical Examination7 
X 
X 
X 
X 
Vital Signs8 
X 
X 
X 
X 
ECOG PS/NYHA Class 
 
X 
X 
X 
Peripheral Neuropathy Assessment9 
X 
X 
Every 3 months10 
X 
SF-36 Health Survey11 
X 
X 
Every 6 months12 
X 
6MWT13 
X14 
X14 
Every 6 months12 
X 
Echocardiogram 
 
X 
Every 12 months15 
X16 
ECG (12-lead in triplicate; local)  
X 
X 
Every 3 months10,17 
X 
Vital Status Telephone Call 
 
 
 
Every 
3 months18 
Laboratory Assessments21 
Hematology & Chemistry19 
X 
X 
X 
X 
Amylase 
X 
X 
X 
X 
Coagulation20 
X 
X 
X 
X 
Troponin T 
X 
X 
X 
X 
NT-proBNP13  
X 
X 
X 
X 
Pregnancy (WOCBP)22 
X 
X 
X 
X, X23 
Serum Free Light Chain 
 
X 
Every 3 months10 
X 
SPEP & 24-hour UPEP24 
 
X 
Every 3 months10,25  
X 
SIFE & UIFE 
 
X 
Every 3 months 10,25 
X 
Urinalysis (dip stick)26 
 
X 
Every 3 months10 
X 
24-hr Urine Protein Excretion24 
 
X 
Every 3 months10 
X 
Other 
Serum NEOD001 Sample27 
X 
X 
Every 3 months10 
X 
Serum anti-NEOD001 Antibody Sample28 
X 
X 
Every 3 months10 
X 
 
NEOD001 Infusion29 
 
 
X 
 
ECG = electrocardiogram; ECOG PS = Eastern Cooperative Oncology Group performance status; EOI = end of infusion; 
EOS = End of Study; INR = international normalized ratio; NT-proBNP = N-terminal pro B-type natriuretic peptide; 
NYHA = New York Heart Association; PK = pharmacokinetic; PT = prothrombin time; PTT = partial thromboplastin time; SF-
36 = Short form-36; SIFE = serum immunofixation electrophoresis; 6MWT = 6-Minute Walk Test; SPEP = serum protein 
electrophoresis; UIFE = urine immunofixation electrophoresis; UPEP = urine protein electrophoresis; WOCBP = women of 
childbearing potential. 
1. 
Rescreening is allowed once per subject. Only repeat tests that did not meet eligibility requirements.  


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2. 
Day 1 assessments may be conducted ±5 days from Day 1, with the exception of Month 1-Day 1 (i.e., no window is allowed 
at Month 1). 
3. 
Conduct the EOS Visit 30 (±5) days after last administration of study drug. Two additional evaluations are to be conducted 
beyond this time point, see Footnotes 18 and 23. 
4. 
Obtain medical history since subject’s last visit in Study NEOD001-001 (including all major hospitalizations and surgeries), 
as well as the subject’s current medical status and prior therapies for AL amyloidosis. Adverse events that resolved prior to 
the subject’s last visit in Study NEOD001-001 and prior to signing the ICF for this study should be assessed as possible 
medical history in this study. 
5. 
Record all prior therapies for AL amyloidosis taken prior to signing ICF for this study and since last visit in Study 
NEOD001-001. Record all prior/concomitant medications taken or received by a subject within the 28 days prior to the 
Month 1-Day 1 Visit through the EOS Visit, and any changes to concomitant medications during the study. See Study 
Manual for more information. 
6. 
Adverse events will be collected from the time that the informed consent form is signed through 30 days after the last dose 
of study drug or last study visit, whichever is later. Record any adverse events that were ongoing from the subject’s last visit 
in Study NEOD001-001 and at the time of the NEOD001-OLE001 Screening Visit. 
7. 
Physical examination will include weight, height (Screening only), and examination of the following:  general appearance; 
head, ears, eyes, nose, and throat; neck; skin; cardiovascular system; respiratory system; abdominal system; and nervous 
system. A complete physical examination will be done at Screening and EOS; at all other visits, the components of the 
physical examination will be as clinically indicated. However, at all time points the following should be assessed:  
macroglossia, submandibular nodes/fullness, adenopathy, ecchymoses, liver/spleen size (palpable +/-), ascites (+/-), and 
edema (which should be quantified on a scale of 0-4). 
8. 
Vital signs include heart rate (HR), blood pressure (BP), respiratory rate (RR), and body temperature; assess per protocol 
Section 6.3.2. Month 1-Day 1: Predose, halfway through infusion, immediately at EOI (+5 minutes), and 30 (±5) minutes 
and 60 (±10) minutes after EOI. All Other Months-Day 1: Predose, EOI (+5 minutes), and 60 (±10) minutes after EOI. 
9. 
Peripheral neuropathy assessment: only for subjects previously enrolled in Cohort C of Study NEOD001-001. 
10. Perform every 3 months (Months 3, 6, 9, 12, etc.). 
11. Administer SF-36 before performing any other study assessments on the day it is administered (see protocol Appendix 2). 
12. Perform every 6 months (Months 6, 12, 18, etc.). 
13. NT-proBNP must be drawn before conducting 6MWT, if performed on the same calendar day. Collect blood pressure and 
heart rate pre- and post-6MWT administration. 
14. Two pretreatment 6MWTs are required before the first administration of study drug, with a minimum of 4 days in between 
the two tests. The second test must be completed 1 to 2 days before the Month 1-Day 1 Visit. 
15. Echocardiogram to be conducted every 12 months and may be conducted within 10 days before the visit.  
16. Repeat echocardiogram at EOS if not performed within 60 days prior to visit. 
17. For all post-Screening visits, ECGs are to be performed predose and within 15 minutes after the EOI.  
18. Conduct telephone call approximately 3 months after subject’s last study visit and approximately every 3 months thereafter 
for up to 5 years, death, or subject withdraws consent, whichever occurs first. 
19. Hematology and chemistry per Appendix 3. At Screening, include Screen for Infectious Diseases per Appendix 3. Within 3 
days before the first day of a new regimen of chemotherapy, conduct an unscheduled central laboratory collection (including 
hematology, chemistry, PT/INR, and PTT). 
20. Coagulation per Appendix 3. Collect unscheduled citrated plasma samples for subjects with relevant serious adverse 
event(s); if defects are identified, additional analytes will be analyzed, as indicated (see Appendix 4). 
21. All laboratory tests to be done centrally, unless otherwise noted. 
22. Perform pregnancy tests for WOCBP as follows: Screening: serum test (central) within 28 days before Month 1-Day 1; 
Monthly starting with Month 2: urine test (local) predose; EOS: serum test (central). A positive urine pregnancy test 
(local laboratory) is to be confirmed with a serum pregnancy test (central laboratory). 
23. Perform serum pregnancy test (local; WOCBP only) 90 (±5) days after the last study drug administration. 
24. Begin urine collections 24 hours prior to the study visit. 
25. After Baseline, use to confirm initial within-study hematologic complete response only. 
26. Urinalysis per Appendix 3. 
27. NEOD001 serum samples (for population PK analysis): collect predose, at EOI (record the time, but the sample can be 
collected at any time after the infusion on Day 1), and at other times as clinically indicated, such as when significant toxicity 
occurs. 
28. Anti-NEOD001 antibody samples: collect predose and at other times as clinically indicated, such as when significant 
toxicity occurs. 
29. NEOD001 will be administered every 28 (±5) days. Subjects should be closely monitored for 90 (±10) minutes following 
completion of the study drug infusion. Beginning with the third infusion, the Investigator may decrease the postdose 
monitoring time to no less than 60 minutes, if no infusion-related reactions were observed in the previous infusions and 
allowed per the IRB/IEC. The Investigator may increase the monitoring time if deemed appropriate or per local standards. In 
the event of any clinical concerns or suspicious signs or symptoms after the infusion, the subject will remain under 
observation for as long as the Investigator deems it appropriate. If parenteral chemotherapy is administered on the same day 
as NEOD001, the chemotherapy must be administered after the observation period. 


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2.2.4. 
Definition of Baseline 
2.2.4.1. 
NEOD001 Baseline 
The NEOD001 Baseline will be derived using one of the two following methods:  
1. Last assessment prior to first infusion in the original parent study (NEOD001-001) if the 
time from last dose in the original parent study (NEOD001-001) to first dose in the OLE 
(NEOD001-OLE001) is less than or equal to 60 days. 
2. Last assessment prior to first infusion in the OLE if the time from last dose in the original 
parent study (NEOD001-001) to first dose in the OLE is greater than 60 days. The initial 
OLE visit can be included as a baseline evaluation. 
2.2.4.2. 
OLE Baseline 
The OLE Baseline for the 6MWT distance (meters) will be defined as the longest distance 
walked prior to the first infusion in the OLE. Otherwise, OLE Baseline is defined as the last 
assessment prior to first infusion in the OLE.  
2.3. 
Study Endpoints 
2.3.1. 
Primary Endpoints 
The primary study endpoints are the frequency and severity of AEs, changes in laboratory 
assessments from OLE baseline, and change in vital signs and 12-lead ECGs from NEOD001 
baseline and OLE baseline. 
2.3.2. 
Secondary Endpoints  
2.3.2.1. 
Immunogenicity  
Immunogenicity of NEOD001 will be assessed by anti-NEOD001 antibody levels. Serum 
anti-NEOD001 antibody levels and change from the OLE Baseline will be listed. Serum 
anti-NEOD001 antibody levels may be correlated with serum NEOD001 concentrations and 
select safety endpoints, if sufficient data exist.  
2.3.2.2. 
Pharmacokinetics (PK)  
Data on serum NEOD001 concentrations from this study will be provided in a by-subject line 
listing.  
2.3.3. 
Exploratory Efficacy Endpoints  
The following are the exploratory efficacy endpoints.  
2.3.3.1. 
Time to Event Endpoints 
x Time to all-cause mortality from first infusion of study drug in the original parent 
study (NEOD001-001)  
x Cardiac progression-free survival from first infusion of study drug in the original 
parent study (NEOD001-001)  


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x Time to derived organ progression from first infusion of study drug in the original 
parent study (NEOD001-001), and from first OLE NEOD001 infusion of study drug  
x Time to first organ response from first infusion of study drug in the original parent 
study (NEOD001-001), and from first OLE NEOD001 infusion of study drug 
x Duration of organ response from first derived organ response  
2.3.3.2. 
Quality of Life Endpoints: Change from OLE Baseline in SF-36v2 Scores  
The SF-36v2 is a 36-item self-report instrument that measures generic health-related quality of 
life in 8 specific dimensions plus 1 additional question that asks respondents to rate the amount 
of change experienced in their health in general (Maruish, 2011). It allows for the scoring of 2 
component summary indices: the Physical Component Summary (PCS) score and the Mental 
Component Summary (MCS) score. The SF-36v2 is scored as 8 subscales representing separate 
domains of functional health and well-being:  
x Physical Functioning (PF: 10 questions, # 3a to 3j)  
x Role-Physical (RP; role limitations due to physical problems: 4 questions, # 4a to 4d)  
x Bodily Pain (BP: 2 questions, # 7 to 8)  
x General Health Perceptions (GH: 5 questions, # 1, 11a to 11d)  
x Vitality (VT: 4 questions, # 9a, 9e, 9g, and 9i)  
x Social Functioning (SF: 2 questions, # 6 and 10)  
x Role-Emotional (RE; role limitations due to emotional problems: 3 questions, # 5a to 
5c)  
x Mental Health (MH: 5 questions, # 9b to 9d, 9f, 9h)  
Responses to items allow for direct calculation of subscales for each of the 8 dimensions, while 
PCS and MCS scores are computed from weighted subscale scores (Maruish, 2011). The lower 
the score the more disability, the higher the score the less disability. A score of 50 is the mean in 
the US General Population. The standard deviation is 10 for all scales and both summary 
measures. The SF-36v2 will be scored using the algorithm provided by Optum with the 
instrument license (Health Outcomes™ Scoring Software 4.5). Algorithms that allow for the 
evaluation of summary component scores in the presence of missing data have been developed 
using Item Response Theory (IRT) and regression methods. Scores for respondents with 
incomplete answers can be derived using the maximum data recovery approach for the missing 
data estimation for all scales except the PF scale. For the PF scale, an estimated score based on 
an IRT model is utilized as long as at least one of its items has valid data, otherwise the scale 
score will be missing. Both the PCS score and the MCS score can be calculated if (1) at least 
seven scale scores are available, (2) the PF scale is not missing when evaluating the PCS, and (3) 
the MH scale is not missing when calculating the MCS. The scoring algorithm to apply to the 
calculation of the summary scores depends upon which particular scale score is missing from the 
8-scale profile. 


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2.3.3.3. 
Functional Endpoint: Change from OLE Baseline in the 6-Minute Walk Test 
(6MWT) Distance (meters)  
The 6MWT is a practical simple test that requires a minimum walking length of 25 m and no 
exercise equipment or advanced training for technicians. The walking track or area should be the 
same for all tests for a subject. This test measures the distance that a subject can quickly walk on 
a flat, hard surface in a period of 6 minutes.  
2.3.3.4. 
Cardiac Endpoints 
The following endpoints will be evaluated in the Cardiac Evaluable Population (see Section 5).  
For these subjects, cardiac response, as assessed by N-terminal pro-brain natriuretic peptide 
(NT-proBNP), categories are defined as (modified from Table 2 in Comenzo, 2012):   
Response 
Stable Disease 
Progression 
Decrease in NT-proBNP from 
baseline of >30% and >300 ng/L or 
decrease in NYHA class of ≥2 in 
subjects with baseline NYHA class 
III or IV 
Assessment was neither 
Response nor Progression 
Increase in NT-proBNP from 
baseline of >30% and >300 ng/L 
Best response is defined as the most favorable category (response, stable, or progression) across 
all visits. Subjects will be classified as responders or non-responders. Non-response is defined as 
either stable or progression.  
x Cardiac response from NEOD001 and OLE baselines (see Section 2.2.4), as assessed by 
NT-proBNP response criteria, at each visit  
x Cardiac best response from NEOD001 and OLE baselines (see Section 2.2.4), as assessed 
by NT-proBNP response criteria. Best response will be over the course of the study. 
x Change and percent change from NEOD001 and OLE baselines (see Section 2.2.4) to 
each visit in NT-proBNP 
2.3.3.5. 
Renal Endpoints 
The following endpoints will be evaluated in the Renal Evaluable Population (see Section 5).  
For these subjects, renal response categories (modified from Palladini, 2014) are defined as:  
Response 
Stable  
Progression 
≥ 30% decrease from baseline or < 
0.5g/24 hours post-baseline result 
of proteinuria (measured by 24-
hour urine total protein excretion) 
in the absence of renal progression 
Assessment was neither 
Response nor Progression 
≥ 25% decrease in eGFR from 
baseline 
Note: if assessment qualifies as 
both Response and Progression, 
then assessments will be counted as 
progression 
Best response is defined as the most favorable category (response, stable, or progression) across 
all visits. Subjects will be classified as responders or non-responders. Non-response is defined as 
either stable or progression. 


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x Renal response from NEOD001 and OLE baselines (see Section 2.2.4) at each visit 
x Renal best response from NEOD001 and OLE baselines (see Section 2.2.4). Best 
response will be evaluated over the course of the study.  
x Change and percent change from NEOD001 and OLE baselines (see Section 2.2.4) to 
each visit in creatinine, proteinuria, and estimated glomerular filtration rate (eGFR)  
x Time to eGFR ≤15 mL/min/1.73 m2 (Chronic Kidney Stage 5) from NEOD001 and 
OLE baselines (see Section 2.2.4) 
2.3.3.6. 
Peripheral Neuropathy Endpoints 
The following endpoints will be evaluated in the Peripheral Neuropathy Evaluable Population 
(see Section 5). Peripheral neuropathy response and progression as defined in Coelho, 2012, are 
those with an increase from baseline in Neuropathy Impairment Score in the Lower Limbs 
(NIS-LL) total score of <2 points and those with an increase from baseline in NIS-LL of 
≥2 points, respectively. 
x Change and percent change from NEOD001 and OLE baselines (see Section 2.2.4) to 
each visit in the NIS-LL total score to each visit 
x Peripheral neuropathy response from NEOD001 and OLE baselines (see 
Section 2.2.4) at each visit  
x Change and percent change from NEOD001 and OLE baselines (see Section 2.2.4)in 
the 3 NIS-LL component scores (sensory function, reflexes, muscle strength) to each 
visit  
 


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3. 
SAMPLE SIZE JUSTIFICATION 
Not applicable as this is an extension study for subjects previously enrolled and treated for at 
least 9 months in Study NEOD001-001. 


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4. 
GENERAL STATISTICAL METHODS 
4.1. 
Reporting Conventions 
Individual subject data obtained from electronic case report forms (eCRFs), central laboratories, 
external sources, and any derived data will be presented in data listings by subject. The primary 
data source will be used for all analyses. All data listings that contain an evaluation date will 
contain a relative study day. Pre-treatment and on-treatment study days are numbered relative to 
the day of the first dose of study drug in the OLE which is designated as Day 1. The preceding 
day is Day -1, the day before that is Day -2, etc.  
All output will be incorporated into Microsoft Word rich text format (.rtf) files, sorted and 
labeled according to the International Council for Harmonisation (ICH) recommendations, and 
formatted to the appropriate page size(s). 
For categorical variables, summary tabulations of the number and percentage of subjects within 
each category (with a category for missing data) of the parameter will be presented. Percentage 
calculations will be based on non-missing data, unless otherwise specified. Percentages are 
rounded to 1 decimal place, unless otherwise specified.  
For frequency counts of categorical variables, categories whose counts are zero will be displayed 
for the sake of completeness. For example, if none of the subjects discontinue due to “lost to 
follow-up,” this reason will be included in the table with a count of 0. Percentages based on 
frequency counts will be presented to one decimal place, and values less than 1% will be 
presented as “<1%.” Values less than 100% but greater than 99% will be presented as “>99%.”   
For continuous variables, the number of subjects, mean, standard deviation (SD), median, 25th 
quartile (Q1), 75th quartile (Q3), minimum, and maximum values will be presented. The 
precision of summary statistics, unless otherwise, specified will be as follows:  mean and median 
to 1 more decimal place than the raw data, and SD to 2 decimal places more than the raw data. In 
general, the number of decimal places should not exceed 3 decimal places unless appropriate. 
Confidence intervals (CIs) will be provided and will be rounded to 1 decimal place, unless 
otherwise specified, in the table and listing shell.  
For tables where rounding is required, rounding will be done to the nearest round-off unit. For 
example, when rounding to the nearest integer, values ≥XX.5 will be rounded up to XX+1 (e.g., 
97.5 will round up to 98), while values <XX.5 will be rounded down to XX (e.g., 97.4 will round 
down to 97). 
4.2. 
Computing Environment 
All descriptive statistical analyses will be performed using SAS statistical software Version 9.4 
or higher, unless otherwise noted. Medical history and AEs will be coded using Medical 
Dictionary for Regulatory Activities (MedDRA) version 19.0. Concomitant medications will be 
coded using World Health Organization (WHO) Drug Dictionary, B2 Enhanced September 
2015. 


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4.3. 
Partial Dates and Unknown Times 
If only a partial date is available and is required for calculation, the following standards will be 
applied: 
x Death Date  
 The last date that each subject was known to be alive will be identified as the 
greatest date associated with the subject’s completed assessments, including 
telephone contacts at which the subject was confirmed to be alive.  
 For missing day only – Day will be imputed as the first day of the month (i.e., 1) 
with the following exception: if the partial date falls in the same month as the last 
known alive date, then the partial date will be imputed to equal the last known 
alive date. 
 For missing day and month – Day and month will be imputed as the first day of 
the year (i.e., 1 January) with the following exception: if the partial date falls in 
the same year as the last known alive date, then the partial date will be imputed to 
equal the last known alive date.  
x Start Dates (e.g., event date, AE onset date, start date of medication, or 
hospitalization admission date) 
 For missing start day only – Day will be imputed as the first day of the month 
(i.e., 1) with the following exception:  if the partial date falls in the same month 
and year as the date being used in the calculation (e.g., first infusion date, 
informed consent date), then the partial date will be imputed to equal the date 
being used for the calculation. 
 For missing start day and month – Day and month will be imputed as the first day 
of the year (i.e., 1 January) with the following exception:  if the partial date falls 
in the same year as the date being used in the calculation (e.g., first infusion date, 
informed consent date), then the partial date will be imputed to equal the date 
being used for the calculation. 
 When applicable, imputed start dates must be prior to the stop date. 
x Stop Dates (e.g., AE resolution date or stop date of medication) 
 For missing stop day only – Day will be imputed as the last day of the month (i.e., 
28, 29, 30, or 31). 
 For missing stop day and month – Day and month will be imputed as the last day 
of the year (i.e., 31 December). 
 Imputed stop dates must be on or after the start date. 
If a time required for calculation related to exposure is missing, the following standards will be 
applied: 
x If start time is missing for an infusion where the volume recorded on the eCRF is greater 
than 0 mL then start time will be imputed as the pre-dose time of vital signs at the same 


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visit + 1 minute. This should only be done for the first dose time within a given visit 
should there be more than one record. 
x If stop time is missing for an infusion where the volume is greater than 0 mL then stop 
time will be imputed as the ‘immediately after infusion’ time of the vital signs at the 
same visit - 1 minute. This will only be done for the last dose time within a given visit 
should there be more than one record. 
x If vital sign assessment times are not available, infusion start date/time is missing, and 
infusion stop date/time is non-missing then the start date/time will be imputed as stop 
date/time - 2 hours at the Month 1 Day 1 visit or as the stop date/time - 1 hour for all 
other visits.  
x If vital sign assessment times are not available, infusion stop date/time is missing, and 
infusion start date/time is non-missing then the stop date/time will be imputed as start 
date/time + 2 hours at the Month 1 Day 1 visit or as the start date/time + 1 hour for all 
other visits.  
All data recorded on the case report form will be included in data listings that will accompany 
the CSR. 
4.4. 
Data Conventions 
The precision of original measurements will be maintained in summaries, when possible. 
Quantitative laboratory tests containing less than (<) and greater than (>) symbols are test results 
that are below and above quantifiable limits, respectively. In order to retain these values for 
analysis purpose, the numeric portion of the result will be imputed and stored within the analysis 
datasets. 
4.5. 
Standard Calculations 
Variables requiring calculation will be derived using the following formulas: 
x Days – A duration expressed in days between one date (date1) and another later date 
(date2) will be calculated using the following formulas:  
duration in days = date2 – date1 + 1, where date1 ≥first infusion date 
duration in days = date2 – date1, where date1 <first infusion date 
x Months – A duration expressed in months is calculated as the number of days divided 
by 30.4375 
x Years – A duration expressed in years between one date (date1) and another date 
(date2) is calculated using the following formulas: 
duration in years = (date2 – date1 + 1)/365.25, where date1 ≥first infusion date 
duration in years = (date2 – date1)/365.25, where date1<first infusion date 


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x Age – Age is calculated as the number of years from the date of birth (DOB) to the 
specified date, e.g., date of informed consent (DOIC):  
age (years) = (DOIC –DOB + 1) / 365.25 
x Height – Height entries made in inches (in) are converted to centimeters (cm) using 
the following formula: 
height (cm) = height (in) × 2.54 
x Weight – Weight entries made in pounds (lb) are converted to kilograms (kg) using 
the following formula: 
weight (kg) = weight (lb) / 2.2046 
x Temperature – Temperature entries in degrees Fahrenheit are converted to degrees 
Celsius using the following formula: 
temp (degrees Celsius) = 5 / 9 × (temp [degrees Fahrenheit] – 32) 
x Body Mass Index (BMI) – BMI is calculated using height (cm) and weight (kg) using 
the following formula: 
BMI (kg/m2) = weight (kg) / ([height (cm)/100]2) 
x Change from baseline – Change from baseline will be calculated as: 
Change = post baseline value – baseline value 
x Percent change from baseline – Change from baseline will be calculated as: 
Percent change from baseline = ([post baseline value – baseline value] / baseline 
value) × 100 
4.6. 
Analysis Visit Windows   
Each visit will be denoted by its “month” and “day” such that the first dose day is denoted as 
Month 1-Day 1; subsequent months will use sequential numbers (e.g., the second dose is 
administered on Month 2-Day 1). Each infusion is scheduled to be 28 days from the previous 
infusion (±2 days for Months 2 and 3; ±5 days for Months 4 and beyond).  
“Cycle” is reserved to denote administration of chemotherapy. It is expected that all visits should 
occur according to the protocol schedule.  
In data listings, the relative study day from first infusion of all dates will be presented. 
4.6.1. 
NEOD001 Therapy Visit Windows 
Table 2 defines the visit windows for assessments taken at 1-month intervals to be established 
with respect to relative day from the start of NEOD001 therapy.  


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Table 2: 
NEOD001 Therapy 1-Month Interval Visit Windows (Days) 
Months 
Target Study 
Daya 
Analysis Window Study Daya 
Low 
High 
NEOD001 Baselineb 
1 
Closest visit to Day 1, prior to first NEOD001 dose 
NEOD001 Month 1 
28 
2 
42 [= 28 + 28/2] 
NEOD001 Month 2 
56 
43 [= (28 + 28/2 + 1] 
70 [= 56 + 28/2] 
NEOD001 Month x 
28*x 
(x-1)*28 + 28/2 + 1 
x*28 + 28/2 
a Study day will be calculated from first dose date according to Section 2.2.4.1. 
b NEOD001 Baseline is defined in Section 2.2.4.1. 
Table 3 defines the visit windows for assessments taken at 3-month intervals to be established 
with respect to relative day from the start of NEOD001 therapy.  
Table 3: NEOD001 Therapy 3-Month Interval Visit Windows (Days) 
Months 
Target Study 
Daya 
Analysis Window Study Daya 
Low 
High 
NEOD001 Baselineb 
1 
Closest visit to Day 1, prior to first NEOD001 dose 
NEOD001 Month 3 
84 
2 
126 [= 84 + 84/2] 
NEOD001 Month 6 
168 
127 [= (84 + 84/2) +1] 
210 [= (168 +84/2)] 
NEOD001 Month x 
28*x 
(x-3)*28 + 84/2 + 1 
x*28 + 84/2 
a Study day will be calculated from first dose date according to Section 2.2.4.1. 
b NEOD001 Baseline is defined in Section 2.2.4.1. 
The duration of 60 days between the time from last dose in the original parent study 
(NEOD001-001) to first dose in the OLE was chosen based on PK experience of elimination of 
study drug.  
Note that the assessment used in the analyses is chosen step by step as follows in cases when 
multiple records exist within the same analysis window: 
1. Choose the assessments with shortest distance from the target day. 
2. If multiple assessments are the same distance from the target day for a particular analysis 
window, the later assessments are chosen. 
3. If there are 2 or more assessments taken on the same date or same date and time, the rules 
for choosing the assessment are: 
a. First take the assessment from the scheduled visit, then take the assessment from the 
re-test visit (applicable to laboratory tests), then take the assessment from the 
discontinuation visit, then take the assessment from the unscheduled visit. 
b. Take the assessment with the most abnormal value. 
 Most abnormal value is determined by taking the value that is the further from the 
lower limit of normal (LLN) or ULN. 


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4.6.2. 
OLE Therapy Visit Windows 
Table 4 defines the visit windows for assessments taken at 1-month intervals to be established 
with respect to relative day from the start of NEOD001 therapy in the OLE.  
Table 4: 
OLE Therapy 1-Month Interval Visit Windows (Days) 
Months 
Target 
Study Daya 
Analysis Window Study Daya 
Low 
High 
OLE Baselineb 
1 
Closest visit to Day 1, prior to first OLE NEOD001 dose 
OLE Month 1 
28 
2 
42 [= 28 + 28/2] 
OLE Month 2 
56 
43 [= (28 + 28/2) + 1] 
70 [= 56 + 28/2] 
OLE Month x 
28*x 
(x-1)*28 + 28/2 + 1 
x*28 + 28/2 
OLE = open-label extension. 
a Study day will be calculated from first OLE dose date. 
b OLE Baseline is defined in Section 2.2.4.2. 
Table 5 defines the visit windows for assessments taken at 3-month intervals to be established 
with respect to relative day from the start of NEOD001 therapy in the OLE.  
Table 5: 
OLE Therapy 3-Month Interval Visit Windows (Days) 
Months 
Target 
Study Daya 
Analysis Window Study Daya 
Low 
High 
OLE Baselineb 
1 
Closest visit to Day 1, prior to first OLE NEOD001 dose 
OLE Month 3 
84 
2 
126 [= 84 + 84/2] 
OLE Month 6 
168 
127 [= (84 + 84/ 2) +1] 
210 [= (168 + 84/2)] 
OLE Month x 
28*x 
(x-3)*28 + 84/2 + 1 
x*28 + 84/2 
OLE = open-label extension. 
a Study day will be calculated from first OLE dose date. 
b OLE Baseline is defined in Section 2.2.4.2. 
Note that same scheme will be applied as described Section 4.6.1 when multiple records exist 
within the same analysis window.  


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5. 
ANALYSIS POPULATIONS  
The NEOD001 Safety Population will include all subjects who received any amount of 
NEOD001 in the original parent study (NEOD001-001). 
The OLE Safety Population will include all subjects who received any amount of NEOD001 in 
the OLE study.  
The Cardiac Evaluable Population will include subjects who had cardiac involvement in the 
original parent study (NEOD001-001), defined as subjects who had an NT-proBNP ≥ 650 ng/L 
at Screening and at least one post-baseline assessment of NT-proBNP. 
The Renal Evaluable Population will include subjects who had renal involvement in the original 
parent study (NEOD001-001), defined as proteinuria >0.5g/day in a 24-hour urine collection (the 
value reported as Total Protein on the Disease Specific Urine Laboratory Tests CRF) at 
Screening and at least one post-baseline assessment of proteinuria. 
The Peripheral Neuropathy Evaluable Population will include subjects who had peripheral nerve 
involvement in the original parent study (NEOD001-001), defined as subjects who were marked 
as having had peripheral nerve involvement at baseline per the Amyloidosis Baseline Disease 
Assessment AND had a Screening peripheral neuropathy assessment score of 2 or greater from 
the Peripheral Neuropathy Assessment CRF and at least one post-baseline peripheral neuropathy 
assessment from the Peripheral Neuropathy Assessment CRF. 


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6. 
EXAMINATION OF SUBGROUPS 
No prespecified evaluation of subgroups will be performed.  


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7. 
STUDY POPULATION 
7.1. 
Subject Disposition 
Subject disposition will be tabulated for all screened subjects and will include: 
x the number of subjects dosed in the original parent study (NEOD001-001; NEOD001 
Safety Population) 
x the number of subjects screened in the OLE 
x the number screened but not enrolled in the OLE 
x the number enrolled in the OLE (OLE Safety Population) 
x the number in each analysis organ evaluable population 
x the number who discontinued treatment early in the OLE and reason(s) for 
discontinuation of treatment as recorded on the OLE eCRF 
x the number who withdraw from OLE study prior to completing the study and 
reason(s) for withdrawal as recorded on the OLE eCRF 
Time on study will be calculated as last known date of contact minus date of first infusion in 
NEOD001-OLE001 plus one.  
By-subject data listings of all the above study disposition data including study completion and 
any reasons for premature treatment and/or study withdrawal will be presented. 
7.2. 
Demographics and Baseline Characteristics 
Demographic and baseline characteristics from as reported on the OLE Demographics eCRF will 
be summarized for the OLE Safety Population. 
Demographic variables will include the following: 
x Age at informed consent including the subgroups <65 vs ≥65 years and <75 vs ≥75 
years 
x Sex 
x Race 
x Ethnicity 
Other baseline characteristics will include the following: 
x Weight (kg) 
x Height (cm) 
x BMI (kg/m2) including frequency of the following subgroups: <20, ≥20 to <30, 
≥30 kg/m2 
Both conventional BMI and modified BMI (mBMI [kg/m2×g/L], defined as subject’s weight 
(kg)/subjects squared height (meters) × serum albumin (g/L)) will be presented.  


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No inferential statistical comparisons will be performed.  
All demographic and baseline characteristics data will be presented in by-subject data listings. 
7.3. 
Baseline AL Amyloidosis Disease Characteristics 
The following disease histories from the original parent study (NEOD001-001) will be 
summarized for the OLE Safety Population: 
x Age (years) at AL amyloidosis diagnosis 
x Duration (months) since AL amyloidosis diagnosis 
x Number of derived involved organs (1, 2, 3, or 4 organs: cardiac, renal, peripheral 
neuropathy, and hepatic) based on the organ evaluable populations defined in 
Section 5 
x Number of physician assessed involved organs (gastrointestinal, autonomic nervous 
system, lung, soft tissue/lymphatic, or other) as recorded on the eCRF 
x Total number of involved organs (derived plus physician assessed; range 1-9) 
x Screening NT-proBNP:  <1800 ng/L, ≥1800 ng/L 
x NYHA Class:  I, II, III, IV 
x Baseline FLC Ratio: Low (<0.26), Normal (0.26 – 1.65), High (>1.65) 
In addition, from the OLE Baseline 6MWT distance (meters) will be summarized including 
frequency of the subgroups:  <300 meters vs. ≥300 meters. 
No inferential statistical comparisons will be performed.  
Baseline disease characteristics will be presented in by-subject data listings. 
7.4. 
General Medical History  
Medical history verbatim terms as recorded on the OLE eCRFs will be mapped to preferred 
terms (PTs) and system organ classes (SOCs) using MedDRA version 19.0.  
Medical history collected during NEOD001-OLE001 will be summarized by SOC and PT using 
the OLE Safety Population. Summaries will be ordered by descending order of 
NEOD001-OLE001 24 mg/kg incidence of SOC and PT within each SOC.  
General medical history will be presented in a by-subject data listing. 
7.5. 
Pre-Treatment, Prior, and New Concomitant Medications 
Medication verbatim terms as recorded on the OLE eCRFs will be mapped to 
Anatomical Therapeutic Chemical (ATC) class and Preferred Name using the WHO Drug 
Dictionary, B2 Enhanced December 2015.  
Pretreatment medications, recorded on the Concomitant Medications eCRF, are those 
medications with start and stop dates prior to the first infusion of study drug in the OLE. Prior 
concomitant medications are those medications started prior and continued after the first infusion 
of study drug in the OLE. New concomitant medications are those medications that were started 


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on or after the first infusion of study drug in OLE. Concomitant chemotherapy is described in 
Section 7.7. If it cannot be determined whether the medication was a new concomitant 
medication due to a partial start or stop date or if the medication is taken on the same date as the 
first infusion of study drug, then it will be counted as a new concomitant medication. 
Pretreatment medications will be listed only. Prior and new concomitant medications will be 
summarized by WHO ATC level 3, WHO ATC level 4, and preferred name using the OLE 
Safety Population. Prior and new concomitant medications will also be summarized separately as 
well. These summaries will present the number and percentage of subjects using each 
medication. Subjects may have more than one medication per ATC level and preferred name. At 
each level of subject summarization, a subject is counted once if he/she reported one or more 
medications at that level. Each summary will be ordered by descending order of NEOD001 
incidence of ATC level and preferred name within each ATC level. 
7.6. 
Premedication 
Subjects may be premedicated with 25 mg diphenhydramine (or an equivalent dose of a H1 
antihistamine) and 650 mg acetaminophen (or an equivalent paracetamol dose) within 
30-90 minutes prior to study drug administration. Premedications will be mapped to ATC class 
and Preferred Name using the WHO Drug Dictionary, B2 Enhanced December 2015 and listed. 
7.7. 
Chemotherapy 
Chemotherapy regimens may be prescribed as per standard of care at the Investigator’s 
discretion. All chemotherapy recorded on the Prescribed Chemotherapy Regimens and 
Concomitant Chemotherapy Treatment Medications eCRFs will be listed for OLE Safety 
Population.  
7.8. 
Concurrent Procedures 
Data will be collected for concurrent procedures will be mapped to PTs and SOCs using 
MedDRA version 19.0. and will include name of procedure, ongoing status, indication, 
relationship to an AE or medical history, and frequency of the procedure. Concurrent procedures 
will be displayed in a subject data listing only for OLE Safety Population.  


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8. 
EFFICACY ANALYSES  
All recorded efficacy endpoint data will be presented in by-subject data listings for the OLE 
Safety Population. No summary tables or figures will be produced for the efficacy endpoints. 
8.1. 
Adjustments for Covariates 
Not applicable.  
8.2. 
Handling of Dropouts or Missing Data 
For the SF-36v2, missing data conventions for partially completed questionnaires are specified in 
Section 2.3.3.2. 
No imputations will be performed on missing data. 
8.3. 
Interim Analyses and Data Monitoring 
Not applicable.  
8.4. 
Multicenter Studies 
This is a multicenter study and data collected from all study centers will be listed. 
8.5. 
Multiple Comparisons/Multiplicity 
No adjustments for multiplicity will be made. 


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9. 
SAFETY ANALYSES 
Safety analyses will be conducted using the NEOD001 and OLE Safety Populations as specified 
below.  
No inferential comparison of safety endpoints will be performed, unless otherwise specified.  
9.1. 
Extent of Exposure 
Study drug exposure during the OLE and separately for the original parent study 
(NEOD001-001) and OLE combined will be summarized including: 
x Total Number of Infusions received will be determined for each subject by number of 
times the start time of drug infused is reported. If multiple infusion start times are 
reported on a single day, then only 1 infusion will be counted for that day. If the start 
time of drug infused is missing but total volume infused is greater than 0 mL, 
1 infusion will be counted for that day.  
x Total Number of Dose Interruptions will be determined for each subject by the 
number of times the IV was not completed in OLE, or segment outcome of the 
infusion was interrupted in parent study. 
x Dose Strength (mg/kg) will be calculated for each subject at each OLE visit and each 
visit in parent study separately as follows: 
- 
For each OLE visit, dose (mg) recorded on the Study Drug Exposure CRF will be 
divided by the weight (kg) at that visit (Vital Signs CRF). If the dose (mg) is 
missing but the total duration of infusion is at least 50 minutes which is the lower 
limit of the protocol specified time (i.e. 60 min – 10 min), and IV completed is 
marked “Yes” then dose strength will be imputed to be equal to the planned dose 
strength (described below).  
- 
For each visit in parent study, the total dose (mg) reported will be divided by the 
weight used to calculate dose strength for that visit. If Current Visit is marked for 
Weight Used to determine dose and no corresponding weight is available from the 
vital sign page then the screening/baseline weight will be assigned as the weight 
used to calculate total dose. Dose strength will only be calculated where both the 
total dose and weight used are available.  
Once visit/individual specific dose strengths are determined, subjects will be assigned a 
single average dose strength value across all visits to be used for summary statistics in the 
table.  
x Percent of Planned Dose Strength will be determined by dividing the average dose 
strength per visit by the average planned dose strength per visit for each subject. 
Calculation of average dose strength is described above. Planned dose strength will 
be assigned by visit based on NEOD001 dose level. The average of planned dose 
strength will be the average of the individual planned dose strength calculated at each 
visit.  


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Once visit/individual specific percent of planned dose strength are determined, subjects will 
be assigned a single average percent of planned dose strength value across all visits to be 
used for summary statistics in the table.  
x Total Number of Dose Reductions will be determined for each subject by the number 
of times the percent of planned dose was less than 100. 
In addition, duration of exposure (months) will be calculated including treatment delays and 
interruptions as: (last dose date – first dose date+1)/30.4375. Duration will be calculated from the 
first infusion in the original parent study (NEOD001-001) and separately from the first infusion 
in the OLE. Each duration of exposure will be summarized using descriptive statistics. The 
number and percentage of subjects with duration of exposure in the following categories will be 
summarized:  
x <3 months 
x ≥3 and <6 months 
x ≥6 and <9 months 
x ≥9 and <12 months 
x ≥12 and <15 months 
x ≥15 months and <18 months 
x ≥18 months and <21 months 
x ≥21 months and <24 months 
x ≥24 months 
Additional 3-month intervals may be added based on the available data. The number of total 
infusions will be summarized with similar categories, replacing months with infusions. 
All recorded and derived exposure data will be presented in a by-subject data listing. 
9.2. 
Adverse Events 
Verbatim terms on the OLE Adverse Event eCRFs will be mapped to PT and SOC using 
MedDRA version 19.0. AEs will be reported and severity will be categorized using the Common 
Terminology Criteria for Adverse Events (CTCAE, Version 4.03).  
AE summaries will use the OLE Safety Population. 
All AE summaries will be restricted to treatment-emergent adverse events (TEAEs), which are 
defined as any AE that newly appears, increases in frequency, or worsens in severity following 
initiation of study drug and up to 30 days after date of last dose or last study visit, whichever is 
later. If it cannot be determined whether the AE is treatment emergent due to a partial onset date, 
then it will be counted as such.  
Each AE summary will be displayed by treatment group. Summaries that are displayed by SOC 
and PT will be ordered by descending order of NEOD001-OLE001 24 mg/kg incidence of SOC 
and PT within each SOC.  


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The following listings will be presented by subject, with non-TEAEs flagged: 
x All AEs 
x Serious adverse events (SAEs) (this is a subset of the AEs where serious is marked as 
“Yes”) 
x CTCAE Grade 3 or higher AEs (this is a subset of AEs where severity is missing or 
marked as CTCAE Grade 3, 4, or 5) 
x Related AEs (this is a subset of the AEs where relationship marked as “Related” or 
relationship is missing) 
x AEs leading to Study Drug Withdrawal (this is a subset of the AEs where Action 
Taken with Study Treatment is checked as “Drug Discontinued”) 
x Fatal AEs (this is a subset of the AEs where outcome is indicated as “Fatal” or the 
CTCAE grade is 5) 
x AEs resulting in any dose change (i.e., interruption, reduction, held, or prolongation)  
x AEs assessed by the investigator as infusion-associated (this is a subset of the AEs 
where infusion-associated AE was reported as "Yes.") 
x AEs within one day of any infusion (this is a subset of the AEs where AE onset date 
was the same day as the date of any infusion) 
9.2.1. 
Types of Incidence Rates 
9.2.1.1. 
Crude Incidence Rates 
The crude rate for a particular AE is defined as the number of subjects with the AE divided by 
the number of subjects exposed to the study drug. All crude incidence tables will be repeated 
only for MedDRA PT, excluding MedDRA SOC. 
To assess the long-term treatment effects overall and relative to shorter term treatment, the crude 
incidence of TEAEs will be summarized by combined study from the original parent study and 
OLE study (NEOD001-001), followed by the OLE only (NEOD001-OLE001). TEAEs that 
started in the original parent study will be summarized for subjects who initiated at 24 mg/kg, 
subjects who ever took 24 mg/kg, and subjects who took any dose of NEOD001. TEAEs that 
start on or after the first dose of OLE NEOD001 (i.e., OLE TEAEs) will be summarized using 
the OLE dose 24 mg/kg. The treatment group schema is shown in Table 6 using the NEOD001 
Safety Population.  
Table 6: 
Treatment Group Schema  
NEOD001-001 + NEOD001-OLE001 
NEOD001-OLE001 
Initiated at 24 mg/kg 
(N=xx) 
All 24 mg/kg 
(N=xx) 
Any Dose 
(N=xx) 
24 mg/kg 
(N=xx) 


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9.2.1.2. 
Cumulative Incidence Rates 
The cumulative incidence rate is the probability that a particular AE occurs by a specified time. 
To compute the cumulative rate using the life table method, exposure time intervals from the first 
NEOD001 dose of the original parent study (NEOD001-001) (i.e., ≤1 month, >1 month to 
≤3 months, >3 month to ≤6 months, >6 months to ≤1 year, >1 to ≤1.5 years, >1.5 to ≤2 years, >2 
to ≤3 years, …, and > maximum years) are specified, and the number of subjects at risk of 
experiencing an AE in each time interval is determined by taking the average number of subjects 
at risk at the start and end of each time interval. As subjects leave the study over time, the 
number of subjects at risk of experiencing the AE in each time interval decreases. The 
cumulative incidence rate over each time intervals is as follows:  
1 − {[1 − P(t1)][1 − P(t2)] … [1 − P(tk)]} 
where P(ti) is the number of subjects with the AE divided by the number of subjects at risk in 
time interval ti and where i ranges from 1 to k. 
To illustrate the difference between crude and cumulative incidence rates and how these are 
computed, an example is provided (O'Neill, 1988). Suppose that 3000 subjects are initially 
exposed to a drug and followed for up to 1 year with varying durations of exposure (see Table 7). 
Assume further that 30 subjects experience SAEs, most of which occur later in the study as 
duration of exposure increases. The crude rate is 30/3000 = 0.01 and the 12-month cumulative 
rate is 0.055. When AEs occur later in time as fewer subjects are at risk due to discontinuations 
or tolerability, the crude rate underestimates the longer-term risk and overestimates the shorter-
term risk. 
Using the example in Table 7, the number of subjects at the start of a time interval is the number 
of subjects at the start of the previous time interval minus the number of subjects lost to follow-
up or who dropped out minus the number of subjects with SAEs. For instance, the number of 
subjects at the start of the 3rd time interval is equal to  
[1800 – 399 – 1] = 1400 
The proportion of subjects with SAEs at each time interval P(ti) is computed by dividing the 
number of subjects with SAEs by the number of subjects at risk in the time interval. For 
example, the number of subjects at risk for the 2nd time interval is as follows:   
[1800 + (1800 – 399)] 
 
—————————— 
= 1600.5 
2 
 
The proportion of subjects with SAEs in the 2nd time interval, P(t2) is therefore 1/1600.5 or 
0.0006. The 12-month cumulative SAE incidence rate is 
P(t) = 1 – [(1 – 0.0000) u (1 – 0.0006) u (1 – 0.000) u (1 – 0.0021) u …  
u (1 – 0.0100)] = 0 .055 
which is 1 minus the cumulative probability of not having any SAE up to the 12th time interval. 


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Table 7: 
Example of Computing Cumulative Incidence Rates Using the Life Table 
Method  
Interval 
(months) 
Number 
Entering 
Interval 
Number 
Lost to 
Follow-Up 
Number 
with SAE 
Number 
at Risk 
Proportion 
with SAE 
Cumulative 
Incidence 
Rate 
0–1 
3000 
1200 
0 
2400 
0.0000 
0.0000 
1–2 
1800 
399 
1 
1600.5 
0.0006 
0.0006 
2–3 
1400 
400 
0 
1200 
0.0000 
0.0006 
3–4 
1000 
98 
2 
951 
0.0021 
0.0027 
4–5 
900 
100 
0 
850 
0.0000 
0.0027 
5–6 
800 
95 
5 
752.5 
0.0066 
0.0094 
6–7 
700 
92 
8 
654 
0.0122 
0.0215 
7–8  
600 
91 
9 
554.5 
0.0162 
0.0374 
8–9 
500 
98 
2 
451 
0.0044 
0.0416 
9–10 
400 
100 
0 
350 
0.0000 
0.0416 
10–11 
300 
99 
1 
250.5 
0.0040 
0.0454 
11–12 
200 
0 
2 
200 
0.0100 
0.0550 
Source: O'Neill, 1988. 
Summaries of cumulative incidence rates will be presented for the OLE Safety Population, based 
on TEAEs experienced from the start of the original parent study (NEOD001-001). Cumulative 
incidence rates will be computed separately for each MedDRA SOC and each MedDRA PT 
within SOC. 
9.2.2. 
Overall Summary of Adverse Events 
An overall summary of crude AE incidences will be presented according to Table 7, including 
the number and percent of subjects with at least one of: 
x Any TEAE 
x TEAE by maximum CTCAE Grade 
x CTCAE Grade ≥3 TEAE 
x Serious TEAE 
x Fatal TEAEs (outcome=“Fatal” or severity=CTCAE Grade 5) 
x Treatment-related TEAE 
x Treatment-related serious TEAE 
x Treatment-related TEAE of CTCAE ≥Grade 3 
x TEAE leading to infusion interruption  


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x TEAE leading to dose reduction  
x TEAE leading to dose being held 
x TEAE leading to prolongation of infusion time (>2.5 hours) 
x Infusion associated TEAE as determined by the Investigator 
x TEAE leading to study drug withdrawal  
9.2.3. 
Treatment-Emergent Adverse Events 
The crude and cumulative incidences of TEAEs will be summarized. The following summaries 
will be presented: 
x Subject incidence of TEAEs by MedDRA SOC and PT 
x Subject incidence of TEAEs by MedDRA SOC and PT occurring in ≥5% of subjects  
9.2.4. 
Severity of Adverse Events 
The crude and cumulative incidences of TEAEs by maximum severity will be summarized. At 
each level of subject summarization, a subject is classified according to the highest severity if the 
subject reported 1 or more events. AEs with missing severity (CTCAE grade) will be considered 
Grade 3 (severe) for these summaries. The following summaries will be presented: 
x Subject incidence of TEAEs by MedDRA SOC, PT, and highest severity (CTCAE 
grade) 
x Subject incidence of CTCAE Grade 3 or higher TEAEs by MedDRA SOC and PT.  
9.2.5. 
Relationship to Study Drug as Assessed by Investigator 
The crude and cumulative incidences of TEAEs by strongest relationship to study drug 
(Related/Not Related) will be summarized. At each level of subject summarization, a subject is 
classified according to the closest relationship to study drug if the subject reported 1 or more 
events. AEs with a missing relationship will be considered related for this summary. The 
following summaries will be presented: 
x Subject incidence of related TEAEs by MedDRA SOC and PT 
x Subject incidence of related CTCAE Grade 3 or higher TEAEs by MedDRA SOC 
and PT 
9.2.6. 
Adverse Events Leading to Dosing Changes 
The crude and cumulative incidences of TEAEs leading to dosing changes will be summarized. 
The following summaries will be presented: 
x Subject incidence of TEAEs leading to infusion interruption by MedDRA SOC and 
PT. This is a subset of the AEs where Action Taken with Study Treatment is checked 
as “Dose Interrupted” is checked. 


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x Subject incidence of TEAEs leading to dose reduction by MedDRA SOC and PT. 
This is a subset of the AEs where Action Taken with Study Treatment is checked as 
“Dose Reduced” is checked. 
x Subject incidence of TEAEs leading to dose held by MedDRA SOC and PT. This is a 
subset of the AEs where Action Taken with Study Treatment is checked as “Dose 
Held” is checked. 
x Subject incidence of TEAEs leading to prolongation of infusion time (>2.5 hours) by 
MedDRA SOC and PT. 
9.2.7. 
Serious Adverse Events and Deaths 
The crude incidences of serious TEAEs will be summarized. The incidence of fatal TEAEs will 
be summarized separately. In addition, the cumulative incidences of serious TEAEs and deaths 
will be summarized. The following summaries will be presented: 
x Subject incidence of serious TEAEs by MedDRA SOC and PT 
x Subject incidence of serious related TEAEs by MedDRA SOC and PT 
x Subject incidence of fatal TEAEs by MedDRA SOC and PT 
9.2.8. 
Adverse Events Leading to Study Drug Withdrawal  
AEs leading to study drug withdrawal are those AEs where Action Taken with Study Treatment 
is checked as “Drug Discontinued”. The crude and cumulative incidences of AEs leading to 
study drug withdrawal will be summarized. The following summaries will be presented: 
x Subject incidence of TEAEs leading to study drug withdrawal by MedDRA SOC and 
PT 
9.2.9. 
Other Adverse Events:  Infusion Reactions 
The crude incidence of infusion associated TEAEs by MedDRA SOC and PT will be 
summarized. This is a subset of the AEs where the question “Was the event an 
infusion-associated adverse event?” is checked “Yes”. In addition, the cumulative incidences of 
TEAEs will be summarized.  
If applicable, the crude incidence anaphylactic reaction, defined as the broad algorithmic 
standardized MedDRA query (SMQ) of “Anaphylactic reaction”, defined in Appendix 5, will be 
summarized. 
In order to explore the temporal relationship of TEAEs that may be associated with the infusion, 
the crude incidence of all TEAE occurring within 1 day (AE start date – infusion date + 1 = 1) of 
an infusion will be summarized.  


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9.3. 
Clinical Laboratory Evaluations 
Laboratory parameters will be presented in Système International (SI) units. 
Local laboratories were used during the original parent study NEOD001-001. A central 
laboratory (Covance Central Laboratory Services) was used for this open-label extension, 
NEOD001-OLE001. Data from the local and central labs will not be pooled. Summaries will 
only present data from the central laboratory for OLE Safety Population. 
All clinical laboratory data will be presented in by-subject data listings. In addition, separate 
listings will be presented for any subject with a post OLE baseline CTCAE Grade 3 or 4 
laboratory value. 
The following normal ranges will be used where not provided in the central laboratory data: 
x INR Upper Limit of Normal (ULN) = 1.1 
x eGFR LLN = 90 mL/min/1.73m2 
9.3.1. 
Serum Chemistry, Hematology, and Coagulation 
Quantitative serum chemistry, hematology, and coagulation results will be summarized using 
descriptive statistics at OLE baseline, each post OLE baseline visit, minimum OLE value, and 
maximum OLE value. The change and percentage change from OLE baseline will also be 
summarized. 
9.3.2. 
Shifts in CTCAE Grade 
Quantitative laboratory tests will be assigned grades based on CTCAE Version 4.03, where 
applicable. Shifts in CTCAE grade of laboratory tests will be presented from OLE baseline to 
worst post OLE baseline value, last post OLE baseline value, best post OLE baseline value, and 
at each post OLE baseline visit. Summaries will present the number and percentage of subjects 
with shifts in laboratory grade. Denominators for percentages will be the number of subjects with 
non-missing data at the specific assessment and OLE baseline. 
In addition, the number and percent of subjects with a lab value with CTCAE Grade ≥3 and the 
number and percent of subjects with a CTCAE shift of ≥2 grades will be presented. 
Where applicable, if the quantitative criteria for grading are equivalent for two grades, only 
differentiated by clinical interventions, the clinical intervention will be ignored and the highest 
CTCAE grade will be used. 
9.3.3. 
Shifts in Normal Range 
In addition, for laboratory tests that cannot be graded via CTCAE, shift tables (i.e., low-normal-
high at baseline versus low-normal-high at post-baseline visit in a 3-by-3 contingency table) 
from OLE baseline to worst post OLE baseline value, last post OLE baseline value and at each 
post OLE baseline visit will be presented. Denominators for percentages will be the number of 
subjects with non-missing data at the specific assessment and baseline. 


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9.3.4. 
Pregnancy Testing and Urinalysis Dipstick 
Pregnancy test results and urinalysis dipstick results will not be summarized and will be provided 
in a by-subject data listing. 
9.4. 
Weight and BMI 
Weight (kg), BMI (kg/m2), and mBMI (kg/m2 g/L), defined as a subject’s weight (kg) ÷ subjects 
squared height (meters) × serum albumin (g/L), will be summarized using descriptive statistics at 
NEOD001 baseline, OLE baseline, at each post NEOD001 baseline visit, and at each post OLE 
baseline visit. In addition, changes and percent changes from NEOD001 and OLE baselines will 
be presented. 
9.5. 
Vital Signs  
Vital sign parameters including temperature (C), systolic and diastolic pressure (mmHg), pulse 
(beats/min), and respiratory rate (breaths/min) will be presented in a data listing. Method of 
collection will be provided in the listing; however, summaries will be generated without regard 
to the method of collection. Summaries of vital sign parameter results, change from NEOD001 
baseline, change from OLE baseline, percent change from NEOD001 baseline, and percent 
change from OLE baseline, will be summarized using descriptive statistics at baseline and at 
each post-baseline visit. In addition, change and percent change from baseline will be presented 
from pre-dose to post-dose at infusion visit. 
9.6. 
Electrocardiograms 
ECGs measurements will be made in triplicate, 5 to 10 minutes apart and assessed by a central 
reader. For summary purposes, the mean of the three measurements will be used. ECG 
parameters including, time between 2 consecutive R waves [RR], PR interval, QRS duration, QT 
(uncorrected) interval, QT interval corrected by the Bazett’s formula [QTcB], and QT interval 
corrected by the Fridericia’s formula [QTcF], will be summarized using descriptive statistics will 
be presented for observed values, change from NEOD001 baseline, change from OLE baseline, 
at each NEOD001 post-baseline time point, and at each OLE post-baseline time point. 
A categorical summary of the following abnormal maximum mean triplicate QTcF values will be 
presented: >450 msec, >480 msec, and >500 msec. Change from NEOD001 baseline and OLE 
baseline summaries will also be presented for measurements that represent a change from 
baseline >30 msec and >60 msec. Three separate listings for those subjects with any QTcF 
>450 msec or a QTcF change from either baseline >30 msec, any QTcF >480 msec or a QTcF 
change from either baseline >30 msec, and any QTcF >500 msec or a QTcF change from 
baseline >60 msec will be presented. The observation(s) meeting criteria for inclusion will be 
flagged in the listing.  
Overall interpretation results for ECGs and the investigator interpretation results are collected as 
normal, abnormal not clinically significant, and abnormal clinically significant. Subjects whose 
interpretation shifts from normal to abnormal clinically significant or not clinically significant 
will be listed separately including description of the abnormality and any associated comments. 
All ECG results will be presented in by-subject data listings.  


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9.7. 
Physical Examination 
Physical examination findings based on body systems entered on the eCRF will be included in a 
data listing only. 
9.8. 
Immunogenicity  
Immunogenicity of NEOD001 will be assessed by anti-NEOD001 antibody levels. Any sample 
found to be confirmed positive for anti-NEOD001 antibodies will be further evaluated by a 
neutralizing antibody assay. Serum anti-NEOD001 antibody levels will be listed.  


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10. 
PHARMACOKINETIC ANALYSES 
Serum NEOD001 concentrations and elapsed time from the preceding NEOD001 dose will be 
listed.  


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11. 
CHANGES TO PROTOCOL PLANNED ANALYSES 
Additional analyses of safety endpoints are included in this SAP. 
Due to the discontinuation of the NEOD001 program, no summary tables or figures will be 
produced for the efficacy endpoints. 
 


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12. 
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 21 Oct 2015. 
Comenzo RL, Reece D, Palladini G, et al. Consensus guidelines for the conduct and reporting of 
clinical trials in systemic light-chain amyloidosis. Leukemia. 2012;26(11):2317-25. 
Maruish ME. User’s manual for the SF36v2 health survey (3rd ed.). Lincoln, RI:  QualityMetric, 
Inc.; 2011. 
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern 
Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-55. 
O’Neill RT. 1988. Section 13, Chapter VII, Postmarketing Safety Assessment and Surveillance. 
In Peace KE, editor. Biopharmaceutical Statistics for Drug Development. New York and Basel: 
Marcel Dekker, Inc. pp. 543–573. 
Palladini G, Hegenbart U, Milani P, et al. A staging system for renal outcome and early markers 
of renal response to chemotherapy in AL amyloidosis. Blood. 2014;124(15):2325-32. 
 


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13. 
APPENDICES 


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APPENDIX 1. EASTERN COOPERATIVE ONCOLOGY GROUP 
(ECOG) PERFORMANCE STATUS 
Grade 
Eastern Cooperative Oncology Group 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of 
a light or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. Up 
and about more than 50% of waking hours. 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking 
hours. 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 
5 
Dead 
Source:  Oken, 1982. 


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APPENDIX 2. NEW YORK HEART ASSOCIATION (NYHA) 
FUNCTIONAL CLASSIFICATION 
NYHA Class 
Symptoms 
I 
No symptoms and no limitation in ordinary physical activity, e.g., shortness of 
breath when walking, climbing stairs etc. 
II 
Mild symptoms (mild shortness of breath and/or angina) and slight limitation during 
ordinary activity. 
III 
Marked limitation in activity due to symptoms, even during less-than-ordinary 
activity, e.g., walking short distances (20–100 m). Comfortable only at rest. 
IV 
Severe limitations. Experiences symptoms even while at rest. Mostly bedbound 
subjects. 
Source:  American Heart Association, 2015. 
 
 


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APPENDIX 3. LABORATORY TESTS 
Serum Chemistry: 
x 
ALP 
x 
ALT (E) 
x 
AST (E) 
x 
Bilirubin - total  (E) and direct 
x 
GGT 
x 
BUN 
x 
LDH 
x 
Creatinine (E) 
x 
Glucose 
x 
Cholesterol 
x 
Triglycerides 
x 
Calcium 
x 
Phosphate 
x 
Protein - total 
x 
Albumin 
x 
Sodium 
x 
Potassium 
x 
Chloride 
x 
Bicarbonate 
x 
Magnesium 
x 
Amylase 
x 
Uric acid 
x 
Estimated glomerular filtration rate (E) 
x 
Estimated creatinine clearance  
x 
Creatine kinase 
Hematology: 
x 
Hemoglobin (E) 
x 
Hematocrit 
x 
RBC 
x 
WBC 
x 
Neutrophils (absolute, %) (E) 
x 
Lymphocytes (absolute, %) (E) 
x 
Monocytes (absolute, %) 
x 
Eosinophils (absolute, %) 
x 
Basophils (absolute, %) 
x 
Platelet count (E) 
Coagulation: 
x 
PT 
x 
INR 
x 
PTT 
x 
See also Appendix 4 
 
Cardiac Biomarkers: 
x 
Troponin T 
x 
NT-proBNP  
 
Urinalysis (dip stick): 
x 
Color & clarity 
x 
Specific gravity 
x 
pH 
x 
Protein 
x 
Glucose 
x 
Ketones 
x 
Bilirubin 
x 
Urobilinogen 
x 
Blood 
x 
Nitrite 
x 
Leukocyte esterase 
x 
Microscopic 
Other: 
x 
Serum beta hCG and urine pregnancy tests for 
women of childbearing potential only (E) 
x 
Serum anti-NEOD001 antibodies 
x 
Serum NEOD001 concentration 
x 
Serum free light chains 
x 
24-hr urine protein excretion 
x 
Serum & 24-hour urine PEP 
x 
Serum & urine IFE  
Screen for Infectious Diseases: 
x 
HIV antibody (E) 
x 
Hepatitis B surface antigen (HBsAg) (E) 
x 
Hepatitis C antibody (E) 
Abbreviations: ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood 
urea nitrogen; (E) = may be used for eligibility; GGT = gamma-glutamyl transpeptidase; hCG = human chorionic gonadotropin; 
HIV = human immunodeficiency virus; IFE = immunofixation electrophoresis; INR = international normalized ratio; 
LDH = lactate dehydrogenase; NT-proBNP = N-terminal pro B-type natriuretic peptide; PEP = protein electrophoresis; 
PT = prothrombin time; PTT = partial thromboplastin time; RBC = red blood cell; WBC = white blood cell. 


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APPENDIX 4. COAGULATION INDICES 
In addition to PT/INR and PTT, citrated plasma samples will be collected for subjects with 
relevant SAEs. If defects are identified, additional analytes will be analyzed; these analyses may 
include, but may not be limited to, the indices listed in the following table. 
Test Name 
Antithrombin Activity (ATIII Activity) 
Fibrinogen Antigen 
Partial Thromboplastin Time Mixing Studies 
High-Molecular Weight Kininogen 
D-dimer, quantitative 
Prekallikrein 
Euglobulin Lysis Time  
Plasminogen Activator Inhibitor-1 Antigen 
Factor II Activity 
Plasminogen Activator Inhibitor-1 Activity 
Factor V Activity 
Plasmin-antiplasmin Complex 
Factor VII Activity 
Plasminogen Activity 
Factor VIII Activity  
Protein C Activity 
Factor VIII Antigen Quantitation 
Protein S Antigen Free 
Factor IX Activity 
Thrombin Time 
Factor X Activity 
Tissue Plasminogen Activator Activity 
Factor XI Activity 
Tissue Plasminogen Activator Antigen 
Factor XII Activity 
von Willebrand Factor Activity (Ristocetin Cofactor) 
Factor XIII Activity 
von Willebrand Factor Antigen 
Fibrin Monomer 
von Willebrand Factor Multimers 
Fibrinogen Activity 
 
 


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APPENDIX 5. ANAPHYLACTIC REACTION SMQ 
An Adverse Event or group of Adverse Events occurring on the same day should be flagged as 
Anaphylactic Reaction per SMQ if the AE(s) meets one or more of the following criteria: 
x Any term from group A 
x Any two terms, with one from group B and one from group C 
x Any two terms, with one from group D and one from either group B or group C 
Group A Terms 
Preferred Term 
Preferred Term Code 
Anaphylactic reaction 
10002198 
Anaphylactic shock 
10002199 
Anaphylactic transfusion reaction 
10067113 
Anaphylactoid reaction 
10002216 
Anaphylactoid shock 
10063119 
Circulatory collapse 
10009192 
Dialysis membrane reaction 
10076665 
Kounis syndrome 
10069167 
Shock 
10040560 
Shock symptom 
10040581 
Type I hypersensitivity 
10045240 
 
Group B Terms 
Preferred Term 
Preferred Term Code 
Acute respiratory failure 
10001053 
Asthma 
10003553 
Bronchial oedema 
10056695 
Bronchospasm 
10006482 
Cardio-respiratory distress 
10049874 
Chest discomfort 
10008469 
Choking 
10008589 
Choking sensation 
10008590 


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Group B Terms 
Preferred Term 
Preferred Term Code 
Circumoral oedema 
10052250 
Cough 
10011224 
Cyanosis 
10011703 
Dyspnoea 
10013968 
Hyperventilation 
10020910 
Irregular breathing 
10076213 
Laryngeal dyspnoea 
10052390 
Laryngeal oedema 
10023845 
Laryngospasm 
10023891 
Laryngotracheal oedema 
10023893 
Mouth swelling 
10075203 
Nasal obstruction 
10028748 
Oedema mouth 
10030110 
Oropharyngeal oedema 
10078783 
Oropharyngeal spasm 
10031111 
Oropharyngeal swelling 
10031118 
Pharyngeal oedema 
10034829 
Respiratory arrest 
10038669 
Respiratory distress 
10038687 
Respiratory failure 
10038695 
Reversible airways obstruction 
10062109 
Sensation of foreign body 
10061549 
Sneezing 
10041232 
Stridor 
10042241 
Swollen tongue 
10042727 
Tachypnoea 
10043089 
Throat tightness 
10043528 
Tongue oedema 
10043967 
Tracheal obstruction 
10044291 


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Group B Terms 
Preferred Term 
Preferred Term Code 
Tracheal oedema 
10044296 
Upper airway obstruction 
10067775 
Wheezing 
10047924 
 
Group C Terms 
Preferred Term 
Preferred Term Code 
Allergic oedema 
10060934 
Angioedema 
10002424 
Erythema 
10015150 
Eye oedema 
10052139 
Eye pruritus 
10052140 
Eye swelling 
10015967 
Eyelid oedema 
10015993 
Face oedema 
10016029 
Flushing 
10016825 
Generalised erythema 
10051576 
Injection site urticaria 
10022107 
Lip oedema 
10024558 
Lip swelling 
10024570 
Nodular rash 
10075807 
Ocular hyperaemia 
10030041 
Oedema 
10030095 
Periorbital oedema 
10034545 
Pruritus 
10037087 
Pruritus allergic 
10063438 
Pruritus generalised 
10052576 
Rash 
10037844 
Rash erythematous 
10037855 
Rash generalised 
10037858 


Statistical Analysis Plan 
 
Prothena Therapeutics Limited 
NEOD001-OLE001 
 
14 May 2018 
 
 
CONFIDENTIAL 
 
Page 52of 52 
Group C Terms 
Preferred Term 
Preferred Term Code 
Rash pruritic 
10037884 
Skin swelling 
10053262 
Swelling 
10042674 
Swelling face 
10042682 
Urticaria 
10046735 
Urticaria papular 
10046750 
 
Group D Terms 
Preferred Term 
Preferred Term Code 
Blood pressure decreased 
10005734 
Blood pressure diastolic decreased 
10005737 
Blood pressure systolic decreased 
10005758 
Cardiac arrest 
10007515 
Cardio-respiratory arrest 
10007617 
Cardiovascular insufficiency 
10065929 
Diastolic hypotension 
10066077 
Hypotension 
10021097