Clinical trial NCT03154047
Conditions: AL Amyloidosis
Sponsor: Prothena Biosciences Ltd.
Start date: 2017-06-14; Completion date: 2018-05-30
Enrollment: 80 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The objective of this study is to evaluate the long-term safety and efficacy of NEOD001 in subjects with AL amyloidosis who have completed Study NEOD001-201.

Detailed description:
Global, multicenter, Phase 2b, open-label extension study of subjects with AL amyloidosis who had a hematologic response to first-line treatment for their amyloidosis (e.g., chemotherapy, autologous stem cell transplant \[ASCT\]) and completed Study NEOD001-201. Subjects in this study may receive concomitant chemotherapy. Subject screening will occur during the 28 days prior to the first administration of study drug, which may overlap with the last visit in Study NEOD001-201. If all eligibility requirements are met, the subject will be enrolled and Screening assessments will be completed. Study visits will occur every 28 days based on scheduling from Month 1 Day 1. A ±5-day window is allowed for visits starting after Month 1. Subjects who discontinue study drug before the End of Study Visit (EOS) should have an Early Treatment Discontinuation Visit 30 (±5) days after their final administration of study drug. Each subject's study participation may be up to 38 months or until the study is terminated, whichever occurs first. The study consists of a Screening Phase (1 month), Treatment Phase (36 months), and EOS Visit (30 \[±5\] days after the last dose).

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

Protocol documents:
Prot_001.pdf: 
 
Document Type: Study Protocol 
Official Title: 
A Phase 2b Open-label Extension Study to Evaluate the Long-term Safety 
and Efficacy of NEOD001 in Subjects with Light Chain (AL) 
Amyloidosis who were previously enrolled in Study NEOD001-201 
(PRONTO) 
NCT Number: 
NCT03154047 
Document Date: 
09 January 2017 
 


Study Drug: NEOD001 
CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 1 of 100 
CLINICAL RESEARCH PROTOCOL 
Study Title: 
A Phase 2b Open-label Extension Study to Evaluate the 
Long-term Safety and Efficacy of NEOD001 in Subjects 
with Light Chain (AL) Amyloidosis who were 
previously enrolled in Study NEOD001-201 (PRONTO) 
Protocol Number: 
NEOD001-OLE251 
Investigational Product: 
NEOD001 
US IND Number: 
122,912 
EudraCT Number: 
2016-004664-18 
Indication: 
Light Chain (AL) Amyloidosis 
Sponsor: 
Prothena Therapeutics Limited 
Adelphi Plaza, Upper George's Street 
Dun Laoghaire, Co. Dublin  
A96 T927, Ireland 
Sponsor Representative: 
Prothena Biosciences Inc 
331 Oyster Point Boulevard  
South San Francisco, California 94080 USA 
Sponsor’s Chief Medical Officer: 
_____________________ 
Development Phase: 
2b 
Date of Original Protocol: 
09 January 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-OLE251 
Original Protocol:  09 January 2017 
Page 3 of 100 
INVESTIGATOR SIGNATURE PAGE 
 
Protocol Title:  
A Phase 2b Open-label Extension Study to Evaluate the Long-term 
Safety and Efficacy of NEOD001 in Subjects with Light Chain 
(AL) Amyloidosis who were previously enrolled in Study 
NEOD001-201 (PRONTO) 
Protocol Number: 
 
NEOD001-OLE251 
Sponsor:  
 
 
Prothena Therapeutics Limited 
Date of Original Protocol: 09 January 2017 
 
 
 
 
I have read the foregoing protocol and agree to conduct this study in accordance with the current 
protocol. 
 
 
 
Investigator Signature 
 
Date 
 
Investigator Name (Print) 
 
Please sign, date, and return this form to your Study Monitor. Please retain a copy for your 
study files. 


Study Drug: NEOD001 
CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 4 of 100 
TABLE OF CONTENTS 
TABLE OF CONTENTS ..............................................................................................................4 
1 
INTRODUCTION............................................................................................................24 
1.1 
Light Chain (AL) Amyloidosis ..............................................................................24 
1.2 
Background on NEOD001 .....................................................................................25 
1.2.1 
Nonclinical Safety .................................................................................26 
1.2.2 
Clinical Experience ...............................................................................28 
1.3 
Rationale for Study Conduct, Design, and Dose Selection ...................................31 
2 
OBJECTIVES ..................................................................................................................32 
3 
STUDY PLAN ..................................................................................................................33 
3.1 
Study Design ..........................................................................................................33 
3.2 
Endpoints ...............................................................................................................33 
3.2.1 
Safety Endpoints ...................................................................................33 
3.2.2 
Efficacy Endpoints ................................................................................33 
3.3 
Number of Sites and Subjects ................................................................................35 
3.4 
Randomization and Blinding .................................................................................35 
3.5 
Safety Monitoring Committee ...............................................................................35 
3.6 
Estimated Treatment Duration ...............................................................................35 
3.7 
Definition of End of Study .....................................................................................35 
4 
SELECTION, DISCONTINUATION, AND WITHDRAWAL OF SUBJECTS ......36 
4.1 
Inclusion Criteria ...................................................................................................36 
4.2 
Exclusion Criteria ..................................................................................................36 
4.3 
Early Treatment Discontinuation ...........................................................................38 
4.4 
Early Termination from the Study .........................................................................39 
4.5 
Replacement of Subjects ........................................................................................39 
4.6 
Termination of the Clinical Study, Investigator, or Study Site ..............................40 
5 
TREATMENT OF SUBJECTS ......................................................................................41 
5.1 
Study Drug .............................................................................................................41 
5.1.1 
Formulation and Packaging of NEOD001 ............................................41 
5.1.2 
Shipping, Storage, and Handling of NEOD001 ....................................41 
5.2 
Accountability and Return of Study Supplies ........................................................41 
5.3 
Dosage, Preparation, and Administration ..............................................................42 
5.4 
Dosage Adjustments ..............................................................................................43 
5.4.1 
Withholding of Study Drug ...................................................................43 
5.4.2 
Management of Suspected Systemic Infusion-
Related/Hypersensitivity Adverse Events .............................................43 


Study Drug: NEOD001 
CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
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5.4.3 
Dose Reductions ...................................................................................44 
5.5 
Treatment Compliance ...........................................................................................44 
5.6 
Prior and Concomitant Medication/Therapy .........................................................44 
5.6.1 
Allowed Concomitant Medication/Therapy ..........................................44 
5.6.2 
Prohibited Concomitant Medication/Therapy .......................................45 
6 
STUDY PROCEDURES .................................................................................................46 
6.1 
Evaluations by Visit ...............................................................................................46 
6.1.1 
Screening Period: Days -28 to -1 ..........................................................46 
6.1.2 
Treatment Period: Monthly X-Day 1 (±5 days starting with Month 
2) ...........................................................................................................49 
6.1.3 
End of Study/Early Treatment Discontinuation (EOS/ETD):  
30 (±5) Days After Final Dose ..............................................................53 
6.2 
90-day Postdose Pregnancy Test ...........................................................................55 
6.3 
Vital Status Follow-Up Phone Call........................................................................55 
6.4 
Order of Assessments of Specific Tests .................................................................55 
6.5 
Methods of Assessment .........................................................................................56 
6.5.1 
Safety ....................................................................................................56 
6.5.2 
Efficacy .................................................................................................58 
6.5.3 
Pharmacokinetics ..................................................................................59 
6.5.4 
Immunogenicity ....................................................................................59 
7 
ADVERSE EVENTS/SERIOUS ADVERSE EVENTS AND REPORTING .............61 
7.1 
Adverse Events—Definition ..................................................................................61 
7.2 
Adverse Events—Severity Rating .........................................................................62 
7.3 
Adverse Events—Causality Rating........................................................................62 
7.4 
Serious Adverse Events and Unexpected Adverse Events ....................................63 
7.4.1 
Elective Procedures and Surgeries ........................................................65 
7.4.2 
Other Reportable Information ...............................................................66 
7.4.3 
Disease Progression and Death .............................................................66 
7.4.4 
Serious Adverse Events—Reporting.....................................................66 
8 
STATISTICAL METHODS AND CONSIDERATIONS ............................................68 
8.1 
Analysis Populations ..............................................................................................68 
8.2 
Analysis of Study Population and Subject Characteristics ....................................68 
8.3 
Analysis of Safety Endpoints .................................................................................68 
8.4 
Analysis of Efficacy Endpoints .............................................................................69 
8.5 
Analysis of Other Endpoints ..................................................................................69 
8.5.1 
Pharmacokinetics ..................................................................................69 
8.5.2 
Immunogenicity ....................................................................................69 


Study Drug: NEOD001 
CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 6 of 100 
8.6 
Determination of Sample Size ...............................................................................69 
8.7 
Handling of Dropouts and Missing Data ...............................................................69 
9 
DATA RECORDING, RETENTION, AND MONITORING .....................................70 
9.1 
Case Report Forms .................................................................................................70 
9.2 
Availability and Retention of Records ...................................................................70 
9.3 
Quality Control and Quality Assurance .................................................................70 
9.4 
Subject Confidentiality ..........................................................................................71 
10 
ETHICAL AND LEGAL ISSUES ..................................................................................72 
10.1 
Ethical Conduct of the Study .................................................................................72 
10.2 
Regulatory Approval ..............................................................................................72 
10.3 
Ethics Committee Approval ...................................................................................72 
10.4 
Subject Informed Consent......................................................................................72 
10.5 
Subject Compensation for Adverse Effects on Health ..........................................73 
10.6 
Protocol and ICF Amendments ..............................................................................73 
10.7 
Finance, Insurance, and Indemnity ........................................................................73 
10.8 
Publication Policy ..................................................................................................73 
11 
REFERENCES .................................................................................................................74 
12 
APPENDICES ..................................................................................................................76 
Appendix 1 
Hematologic Response and Progression Criteria ..................................77 
Appendix 2 
Examples of Highly Effective Contraception Methods ........................78 
Appendix 3 
Organ Response and Progression Criteria ............................................79 
Appendix 4 
Eastern Cooperative Oncology Group (ECOG) Performance Status ...80 
Appendix 5 
New York Heart Association (NYHA) Functional Classification ........81 
Appendix 6 
Neuropathy Impairment Scale – Lower Limbs (NIS-LL).....................82 
Appendix 7 
Visual Analog Scale – Pain Intensity (VASPI).....................................83 
Appendix 8 
Short Form-36 Health Survey Version 2 (SF-36v2) .............................84 
Appendix 9 
Kansas City Cardiomyopathy Questionnaire (KCCQ) .........................95 
Appendix 10 
Laboratory Tests....................................................................................99 
Appendix 11 
Other Coagulation Indices ..................................................................100 
 
 
 


Study Drug: NEOD001 
CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
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LIST OF TABLES 
Table 1 
Schedule of Assessments ...........................................................................16 
Table 2 
Common Terminology Criteria for Adverse Events (CTCAE) Grade 1-
5 for Peripheral Neuropathy and Neuropathic Pain ...................................59 
 
LIST OF FIGURES 
Figure 1 
NEOD001-OLE251 Design .......................................................................19 
Figure 2 
Proposed Mechanism of Action for NEOD001 .........................................26 
 
 
 


Study Drug: NEOD001 
CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 8 of 100 
NEOD001-OLE 251 PROTOCOL SYNOPSIS 
Title 
A Phase 2b Open-label Extension Study to Evaluate the Long-
term Safety and Efficacy of NEOD001 in Subjects with Light 
Chain (AL) Amyloidosis who were previously enrolled in Study 
NEOD001-201 (PRONTO) 
Phase 
2b 
Planned Number of Study 
Sites 
Approximately 40 sites globally 
Objective 
The objective of this study is to evaluate the long-term safety and 
efficacy of NEOD001 in subjects with AL amyloidosis who have 
completed Study NEOD001-201. 
Study Design 
This is a global, multicenter, Phase 2b, open-label extension study 
of subjects with AL amyloidosis who had a hematologic response 
(Appendix 1) to first-line treatment for their amyloidosis (e.g., 
chemotherapy, autologous stem cell transplant [ASCT]) and 
completed Study NEOD001-201. Subjects in this study may 
receive concomitant chemotherapy. 
Subject screening will occur during the 28 days prior to the 
first administration of study drug (i.e., Month 1-Day 1 Visit), 
which may overlap with the last visit in Study NEOD001-201. 
If all eligibility requirements are met, the subject will be 
enrolled and Screening assessments (Table 1) will be 
completed.  
Study visits will occur every 28 days based on scheduling from 
Month 1-Day 1. A ±5-day window is allowed for visits starting 
after Month 1. Subjects who discontinue study drug before the 
End of Study (EOS) Visit should have an Early Treatment 
Discontinuation (ETD) Visit 30 (±5) days after their final 
administration of study drug. 
Number of Subjects 
Approximately 100 subjects will be enrolled. 
Study Drug, Dose, and 
Mode of Administration 
Study drug consists of NEOD001 24 mg/kg (dose not to exceed 
2500 mg). NEOD001 will be administered as an intravenous (IV) 
infusion once every 28 days (a ±5-day window is allowed for 
visits starting after Month 1) over 60 (±10) minutes unless a 
longer infusion duration was established for the individual subject 
in Study NEOD001-201. A minimum of 21 days between doses is 
required. Subjects should be closely monitored per Section 5.3 
following completion of the study drug infusion. 
Control Group 
Not applicable 


Study Drug: NEOD001 
CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 9 of 100 
Estimated Treatment 
Duration 
Each subject’s study participation may be up to 38 months or until 
the study is terminated (per Section 4.6), whichever occurs first. 
The study consists of a Screening Phase (1 month), Treatment 
Phase (36 months), and EOS Visit (30 [±5] days after the last 
dose). 
Subject Eligibility Criteria Inclusion Criteria (subjects must meet all of the following 
criteria): 
1. Completed the EOS Visit in Study NEOD001-201 
2. 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 × upper limit of normal (ULN) 
o Aspartate aminotransferase (AST) ≤3 × ULN  
o Alanine aminotransferase (ALT) ≤3 × ULN 
o Alkaline phosphatase (ALP) ≤5 × ULN (except for 
subjects with hepatomegaly and isozymes specific to 
liver, rather than bone) 
o Estimated glomerular filtration rate (eGFR) 
≥25 mL/min/1.73 m2 as estimated by the Chronic Kidney 
Disease Epidemiology Collaboration (CKD-EPI) 
equation, or measured GFR ≥25 mL/min/1.73 m2 
3. Systolic blood pressure 80-180 mmHg 
4. Women of childbearing potential (WOCBP) must have 
a negative pregnancy test during Screening and must agree 
to use highly effective physician-approved contraception 
(Appendix 2) from Screening to 90 days following the last 
study drug administration  
5. Male subjects must be surgically sterile or must agree to use 
highly effective physician-approved contraception 
(Appendix 2) from Screening to 90 days following the last 
study drug administration 
6. Ability to understand and willingness to sign an informed 
consent form (ICF) prior to initiation of any study 


Study Drug: NEOD001 
CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 10 of 100 
procedures 
Exclusion Criteria (subjects must not meet any of the following 
criteria): 
1. Any new medical contraindication or clinically significant 
abnormality on physical, neurological, laboratory, vital 
signs, or electrocardiographic (ECG) examination (e.g., 
atrial fibrillation; with the exception of subjects for whom 
the ventricular rate is controlled) that precludes continuation 
or initiation of treatment with NEOD001 or participation in 
the study 
2. Symptomatic orthostatic hypotension that in the medical 
judgment of the Investigator would interfere with subject’s 
ability to safely receive treatment or complete study 
assessments 
3. Myocardial infarction, uncontrolled angina, uncontrolled 
ventricular arrhythmias, or ECG evidence of acute ischemia, 
within 6 months prior to the Month 1-Day 1 Visit 
4. Severe valvular stenosis (e.g., aortic or mitral stenosis with a 
valve area <1.0 cm2) or severe congenital heart disease 
5. ECG evidence of acute ischemia or active conduction 
system abnormalities with the exception of any of the 
following: 
o First degree atrioventricular (AV) block 
o Second degree AV block Type 1 (Mobitz Type 1/ 
Wenckebach type) 
o Right or left bundle branch block 
o Atrial fibrillation with a controlled ventricular rate 
(uncontrolled [i.e., >110 bpm] ventricular rate is not 
allowed [determined by an average of three beats in 
Lead II or 3 representative beats if Lead II is not 
representative of the overall ECG]) 
6. Has not recovered (i.e., equivalent to a Common 
Terminology Criteria for Adverse Events [CTCAE] 
≥Grade 2) from the clinically significant toxic effects of 
prior anticancer therapy. Exception: subjects who have 
received treatment with a proteasome inhibitor such as 
bortezomib may have CTCAE Grade 2 neuropathy. 
7. Received any of the following within the specified time 
frame prior to the Month 1-Day 1 Visit: 


Study Drug: NEOD001 
CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 11 of 100 
o Oral or IV antibiotics, antifungals, or antivirals within 
1 week, with the exception of prophylactic oral agents. 
Note:  In the event that a subject requires the chronic use 
of antivirals, Medical Monitor permission is required for 
entry into the study. 
o Hematopoietic growth factors, transfusions of blood or 
blood products within 1 week 
o Chemotherapy, radiotherapy, HDAC inhibitors, or other 
plasma cell directed therapy within 2 weeks 
o ASCT within 4 weeks (i.e., ASCT is allowed if it 
occurred before enrollment in Study NEOD001-201 or 
after completion of Study NEOD001-201 if it was at least 
4 weeks before Month 1-Day 1 of this study) 
o Major surgery within 4 weeks (or within 2 weeks 
following consultation with and approval of Medical 
Monitor) 
o Planned organ transplant during the study 
o Any investigational agent, other than NEOD001, within 
4 weeks 
o Any experimental imaging agent directed at amyloid 
within 2 weeks 
8. Active malignancy with the exception of any of the 
following: 
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 and has been in remission for 
≥2 years 
o Low-risk prostate cancer with Gleason score <7 and 
prostate-specific antigen <10 mg/mL 
o Any other cancer from which the subject has been 
disease-free for ≥2 years 
9. History of Grade ≥3 infusion-related adverse events (AEs) 
or hypersensitivity to NEOD001 
10. History of severe allergy to any of the components of 


Study Drug: NEOD001 
CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 12 of 100 
NEOD001 such as histidine/L-Histidine, Trehalose, or 
Polysorbate 20 
11. Currently known uncontrolled bacterial, viral, fungal, HIV, 
hepatitis B, or hepatitis C infection 
12. Women who are breastfeeding 
13. Any condition which could interfere with, or the treatment 
for which might interfere with, the conduct of the study or 
which would, in the opinion of the Investigator, 
unacceptably increase the subject’s risk by participating in 
the study 
14. Unable or unwilling to adhere to the study-specified 
procedures and restrictions 
15. Subject is under legal custodianship 
Study Procedures and 
Assessments 
See Schedule of Assessments (Table 1) 
Endpoints 
Safety Endpoints: 
• Long-term safety and tolerability as assessed by vital signs, 
12-lead ECGs, routine clinical laboratory assessments, and 
AEs 
• Immunogenicity 
Efficacy Endpoints: 
• N-terminal pro-brain natriuretic peptide (NT-proBNP): 
o Response (Appendix 3) 
o Best response from baseline 
o Change from baseline 
• Change from baseline in troponin T 
• Change from baseline in the Short Form-36 Health Survey 
version 2 (SF-36v2) Physical Component Score (PCS), 
Mental Component Score (MCS), and the 8 subscales 
• Change from baseline in the 6-Minute Walk Test (6MWT) 
distance (meters) 
• Progression-free survival 
• For renal-evaluable subjects: 
o Renal response (Appendix 3) 


Study Drug: NEOD001 
CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 13 of 100 
o Renal best response from baseline 
o Change from baseline in creatinine, proteinuria, and 
eGFR 
o Time to eGFR:  
 ≤15 mL/min/1.73 m2 (Chronic Kidney Disease 
[CKD] Stage 5) 
 <30 mL/min/1.73 m2 (CKD Stage 4) 
 <60 mL/min/1.73 m2 (CKD Stage 3) 
o Time to any worsening in CKD Stage 
o Time to 40% reduction in eGFR 
o Time to doubling of creatinine  
• For peripheral neuropathy-evaluable subjects: 
o Change from baseline in Neuropathy Impairment 
Score–Lower Limbs (NIS-LL) total score  
o Peripheral neuropathy best response 
o Peripheral neuropathy response (Appendix 3) 
o For subjects with painful peripheral neuropathy in 
Study NEOD001-201 (i.e., baseline Visual Analog 
Scale – Pain Intensity [VASPI] score >0) change from 
baseline in the VASPI score  
• For hepatic-evaluable subjects: 
o Hepatic response (Appendix 3)  
o Hepatic best response from baseline 
• Time to all-cause mortality (overall survival) 
• Frequency and duration of hospitalizations over the course of 
the study 
• Change from baseline in the Kansas City Cardiomyopathy 
Questionnaire (KCCQ) subscores and overall summary score 
• Time to progression for each organ (cardiac/NT-proBNP, 
renal, peripheral neuropathy, hepatic) separately and to any 
organ progression 
• Eastern Cooperative Oncology Group (ECOG) Performance 
Status and New York Heart Association (NYHA) Class at 
each visit including any changes from baseline  
• Change from baseline in serum free light chains (sFLCs), 
serum and 24-hour urine protein electrophoresis (PEP), and 


Study Drug: NEOD001 
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Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 14 of 100 
serum and urine immunofixation electrophoresis (IFE)  
• Severity of disease-related symptoms including any changes 
from baseline 
• Pharmacokinetics (PK) 
Statistical Considerations 
and Methods 
Analysis Populations: 
All analyses will be based on the Safety Population, defined as all 
subjects who receive any amount of study drug. 
Select analyses will use efficacy subsets, defined as: 
• Renal Evaluable Population: subjects who had renal 
involvement in Study NEOD001-201 
• Peripheral Neuropathy Evaluable Population: subjects who 
had peripheral nerve involvement in Study NEOD001-201   
• Hepatic Evaluable Population: subjects who had hepatic 
involvement in Study NEOD001-201 
Safety Analyses: 
Safety will be assessed through changes in vital signs, 12-lead 
ECGs, laboratory test results, and summaries of AEs. All 
treatment-emergent adverse events (TEAEs) and serious adverse 
events (SAEs) will be summarized.  
Efficacy Analyses: 
Response rates will be summarized including 95% confidence 
intervals. The distributions of time-to-event endpoints 
(progression-free survival, overall survival) will be summarized 
using the Kaplan-Meier method.  
All quantitative endpoints, except 6MWT distance, defined as the 
change from baseline will be analyzed using linear mixed models 
for repeated measurements (MMRM). The dependent variable 
will be the change from baseline at each time point. The model 
will include fixed effects for time point and treatment-by-time 
interaction. The baseline value of the corresponding endpoint will 
be included as a covariate and the unstructured covariance model 
will be used. The denominator degrees of freedom will be 
estimated using the Kenward-Roger approximation. The 6MWT 
distance change from baseline will be analyzed using a Wilcoxon 
signed rank test. 


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CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 15 of 100 
Sample Size Justification 
 
Not applicable as this is an open-label extension study for subjects 
who completed Study NEOD001-201. 
Sponsor 
Prothena Therapeutics Limited 
 
 


Study Drug: NEOD001 
CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 16 of 100 
Table 1 
Schedule of Assessments 
  
Screening1 
Treatment2 
Termination 
  
Days -28 through -1 
 
 
 
Assessment or Procedure 
<60 days 
since last 
visit in 
Study 
NEOD001-
201 
≥60 days 
since last 
visit in 
Study 
NEOD001-
201 
Monthly 
Day 1 (±5 days)3 
EOS/ETD4 
 
Written Informed Consent  
X 
X 
 
 
Eligibility Review 
X 
X 
 
 
Clinical 
Medical History5 
X 
X 
 
 
Prior/Concomitant Medications/Therapy6 
X 
X 
X 
X 
Adverse Event Assessment7 
X 
X 
X 
X 
Physical Exam8 
X 
X 
X 
X 
Vital Signs9 
X 
X 
X 
X 
ECOG PS/NYHA Class10 
 
X 
Every 6 months 
X 
NIS-LL11 
X 
X 
Every 6 months 
X 
VASPI12 
X 
X 
Every 6 months 
X 
SF-36v213 
X 
X 
Every 6 months 
X 
KCCQ14 
X 
X 
Every 6 months 
X 
6MWT15,16 
X, X17 
X, X17 
Every 6 months18 
X 
ECG (12-lead triplicate) 
X 
X 
Every 3 months19 
X 
Laboratory20 
Hematology & Chemistry (including 
amylase and creatine kinase)21 
X 
X 
X 
X 
Coagulation – PT/INR, PTT 
X 
X 
X 
X 
Coagulation – other indices22 
 
 
Months 1, 12 
X 
Troponin T  
X 
X 
X 
X 
NT-proBNP15  
X 
X 
X 
X 
Pregnancy (WOCBP)23 
X 
X 
X 
X, X24 
sFLCs 
 
X 
Every 6 months 
X 
Serum IFE & PEP25 
 
X 
Every 6 months 
X 
Urinalysis – Dipstick26 
 
X 
Every 6 months 
X 
24-hour Urine Collection: 
 
 
 
 
Urine IFE & PEP24 
 
X 
Every 6 months  
X 
Urine Protein Excretion 
 
X 
Every 6 months 
X 
 
Serum NEOD001 Sample27 
 
 
Every 6 months28 
X 
Anti-NEOD001 Serum Sample29 
X 
X 
Every 3 months28 
X 
 Study Drug Infusion30 
 
 
X 
 
 Vital Status Phone Call 
 
 
 
Every 3 months31 


Study Drug: NEOD001 
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Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 17 of 100 
BP = blood pressure; ECG = electrocardiogram; ECOG PS = Eastern Cooperative Oncology Group performance 
status; EOI = end of infusion; EOS = End of Study; ETD = Early Treatment Discontinuation; HR = heart rate; 
ICF = informed consent form; IFE = immunofixation electrophoresis; KCCQ = Kansas City Cardiomyopathy 
Questionnaire; nAb = neutralizing antibody; NIS-LL = Neuropathy Impairment Score – Lower Limbs; 
NT-proBNP = N-terminal pro-brain natriuretic peptide; NYHA = New York Heart Association; PEP = protein 
electrophoresis; PK = pharmacokinetic; PT/INR = prothrombin time/international normalized ratio; 
PTT = partial thromboplastin time; RR = respiratory rate; 6MWT = 6-Minute Walk Test; SF-36v2 = Short 
Form-36 Health Survey version 2; VASPI = Visual Analog Scale – Pain Intensity; vWF = von Willebrand 
Factor; WOCBP = women of childbearing potential. 
1. 
Individual test results that do not meet eligibility requirements may be repeated; full rescreening is allowed once 
per subject. Laboratory tests results from Study NEOD001-201 that were performed within 28 days of Month 1-
Day 1 may be used for screening in this study. 
2. 
See Sections 6.1.2 and 6.4 for details regarding timing (e.g., pre- vs. postdose) and order of assessments, 
respectively. 
3. 
Study visits will occur every 28 days based on scheduling from Month 1-Day 1. A ±5-day window is allowed 
for visits starting after Month 1. The predose assessments for each visit may be performed within the 3 days 
before the visit unless a different timeframe is specified in Section 6.1. 
4. 
Conduct the EOS Visit 30 (±5) days after last administration of study drug. Subjects who discontinue study 
drug before the end of the study should have an ETD Visit 30 (±5) days after their final administration of study 
drug. The assessments shown for EOS/ETD should also be conducted for any unscheduled visit (i.e., a visit not 
specified by the protocol) as clinically indicated or if deemed necessary.  
5. 
Medical History - Obtain medical history since the subject’s last visit in Study NEOD001-201 (including all 
major hospitalizations and surgeries), as well as the subject’s current medical status and therapy for AL 
amyloidosis. 
6. 
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/ETD Visit, and any changes to concomitant medications during the study. 
7. 
Adverse events will be collected 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. 
8. 
Screening and EOS/ETD: conduct a complete physical examination per Section 6.5.1.3. All Other Visits: 
conduct a directed physical examination per Section 6.5.1.3.  
9. 
Vital signs (HR, BP, RR, and body temperature) - collect after the subject has been at rest for ≥5 minutes; 
within a visit, assess in the same position for all time points. Month 1: Within 30 minutes before start of 
dosing, at EOI (+5 minutes), 30 (±5) minutes after EOI, and 60 (±10) minutes after EOI. All Other Months: 
Within 30 minutes before start of dosing, at EOI (+5 minutes), and 60 (±10) minutes after EOI. 
10. See Appendix 4 (ECOG) and Appendix 5 (NYHA). 
11. See Appendix 6; NIS-LL is for all subjects who had peripheral neuropathy in Study NEOD001-201. 
12. See Appendix 7; VASPI is for subjects who had painful peripheral neuropathy in Study NEOD001-201. 
13. See Appendix 8; SF-36v2 should be administered before performing any other study assessments on the same 
calendar day it is administered. 
14. See Appendix 9; administer KCCQ after the SF-36v2, but before conducting any other assessments on the same 
calendar day it is administered. 
15. NT-proBNP should be drawn before conducting 6MWT if being performed on the same calendar day.  
16. Collect blood pressure and heart rate pre- and post-6MWT administration.  
17. Two pretreatment 6MWTs are required before the first administration of study drug, with a minimum of 4 days 
between the two tests. The first Screening 6MWT is required to be performed between Days -28 and -5, at least 
4 days prior to the second Screening 6MWT, which should be performed within 2 days prior to Month 1-Day 1 
(i.e., on Day -2 or Day -1). 
18. The postbaseline 6MWTs may be administered on the same calendar day that study drug is administered as long 
as the NT-proBNP sample is drawn before conducting the 6MWT and the 6MWT is completed before initiation 
of the study drug infusion. 
19. Perform ECGs centrally within 30 minutes before start of dosing and within 15 minutes after EOI.  
20. All laboratory tests to be done centrally, unless otherwise noted. Please refer to Laboratory Manual for details. 
Laboratory tests conducted within 28 days of Month 1-Day 1 may be used for screening. 
21. Hematology and chemistry per Appendix 10. 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). 


Study Drug: NEOD001 
CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 18 of 100 
22. Collect citrated plasma samples, which will be frozen for potential analysis of coagulation indices at a later 
date; see Appendix 11. Month 1: EOS/ETD results from Study NEOD001-201 will serve as baseline for this 
study. Collect sample for vWF activity and antigen assays before dosing on Month 1-Day 1 if they were not 
tested at EOS/ETD in Study NEOD001-201. Month 12: Subjects with defects identified at EOS/ETD in Study 
NEOD001-201: collect sample and test analytes that were abnormal. All other subjects: collect sample. 
EOS/ETD: Subjects with defects identified at Month 12: collect sample and test analytes that were abnormal. 
All other subjects: collect sample. Unscheduled Samples: collect sample in case of relevant serious adverse 
events. At any time, if defects are identified, additional analytes will be evaluated, as indicated. 
23. Urine pregnancy tests (local) for WOCBP: Screening: within 28 days before Month 1-Day 1; Monthly: 
preinfusion; EOS/ETD: any time during visit. A positive urine pregnancy test (local laboratory) is to be 
confirmed with a serum pregnancy test (central laboratory). 
24. 90 (±5) days after last study drug administration (any time during visit) perform urine pregnancy test (local) for 
WOCBP. 
25. The serum and urine PEP must be conducted before the NEOD001 infusion, if being performed on the same 
calendar day. 
26. Urinalysis dipstick per Appendix 10. 
27. NEOD001 serum samples (for population PK analysis): Every 6 months (±1 month): within 2 hours before 
infusion and within 4 hours after EOI; EOS/ETD: any time during visit. 
28. Collect additional samples as clinically indicated, such as when significant toxicity occurs per Section 5.4.2. 
29. Anti-NEOD001 serum samples: Screening: any time during visit; Every 3 months: preinfusion; EOS/ETD: 
any time during visit.  
30. Administer over 60 (±10) minutes unless a longer infusion duration was established for the individual subject in 
Study NEOD001-201 or during a previous infusion on this study. A minimum of 21 days between doses is 
required. Subjects should be closely monitored per Section 5.3 following completion of the study drug infusion. 
If chemotherapy is administered on the same day as NEOD001, it must be administered after the NEOD001 
observation period. 
31. Conduct vital status telephone call approximately 3 months after last study visit and approximately every 
3 months thereafter for up to 5 years, death, or subject withdraws consent, whichever occurs first.


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Screening
Treatment (N = ~100)
Follow-up/Termination
Days -28 to -1
Monthlyc
Day 1 (±5 daysd)
30 (±5) Days 
After Last 
Dose
Population:
Completed
 Study
NEOD001-201
Hematologic 
response to first-
line treatment for 
AL amyloidosis
Persistent
cardiac
dysfunction
ICF &
Screening
Assessments
ICF & 
Screening 
Assessments
24 mg/kga IV NEOD001 every 28 days
EOS/ETD 
Visit
EOS/ETD 
Visit
EOS/ETD = End of Study/Early Treatment Discontinuation; ICF = informed consent form; IV = intravenous; NIS-LL = Neuropathy Impairment Score–Lower Limbs; NT-proBNP = N-terminal pro-brain 
natriuretic peptide; PCS=Physical Component Score; SF-36v2 = Short Form-36 Health Survey version 2; 6MWT = 6-Minute Walk Test.
a  Maximum dose not to exceed 2500 mg.
b  Conduct vital status telephone call approximately 3 months after last study visit and approximately every 3 months thereafter for up to 5 years, death, or subject withdraws consent, 
 
whichever occurs first.
c  For up to 36 months or until the study is terminated, whichever occurs first. 
d  ±5-day window applicable to Months 2+.
e  In Efficacy Subset Populations: Renal-evaluable subjects, peripheral neuropathy-evaluable subjects, and hepatic-evaluable subjects, respectively.
Primary Endpoint:
x
Safety
Primary Endpoint: 
x
Safety
Select Efficacy Endpoints:
x
NT-proBNP response, best response, change from baseline
x
SF-36v2 PCS change from baseline
x
6MWT distance change from baseline
x
Progression-free survival
Select Efficacy Endpoints: 
x
NT-proBNP response, best response, change from baseline
x
SF-36v2 PCS change from baseline
x
6MWT distance change from baseline
x
Progression-free survival
Follow-up 
Phone
Callsb
Follow-up 
Phone 
Callsb
Every
3 months
x
Renal best responsed
x
NIS-LL total score change from baselined
x
Hepatic best responsed
x
Renal best responsed
x
NIS-LL total score change from baselined
x
Hepatic best responsed


Study Drug: NEOD001 
CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 20 of 100 
GLOSSARY OF TERMS 
Abbreviation/Acronym 
Definition 
AA 
Amyloid A 
ADA(s) 
Anti-drug antibody(ies) 
ADCP 
Antibody-dependent cellular phagocytosis 
ADL 
Activities of daily living 
AE(s) 
Adverse event(s) 
AEF 
Amyloid-enhancing factor 
ALP 
Alkaline phosphatase 
AL 
Amyloid light chain 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
ASCT 
Autologous stem cell transplant 
A-SAA 
Acute phase serum amyloid A 
AST 
Aspartate aminotransferase 
AV 
Atrioventricular 
BP 
Blood pressure 
BPM 
Beats per minute 
BSA 
Bovine serum albumin 
BUN 
Blood urea nitrogen 
CA 
Competent Authority 
CKD 
Chronic Kidney Disease 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
CR 
Complete response 
CRP 
C-reactive protein 
CTCAE 
Common Terminology Criteria for Adverse Events  
D 
Aspartic acid 
DLTs 
Dose-limiting toxicities 


Study Drug: NEOD001 
CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 21 of 100 
Abbreviation/Acronym 
Definition 
E 
Glutamic acid 
ECG 
Electrocardiogram 
ECL 
Electrochemiluminescent 
ECOG PS 
Eastern Cooperative Oncology Group performance status 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
eGFR 
Estimated glomerular filtration rate 
EOI 
End of infusion 
EOS 
End of Study 
ETD 
Early Treatment Discontinuation 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIV 
Human immunodeficiency virus 
HR 
Heart rate 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Institutional Ethics Committee 
IFE 
Immunofixation electrophoresis 
Ig 
Immunoglobulin 
IgG1 
Immunoglobulin G1 
IL-6 
Interleukin-6 
IRB 
Institutional Review Board 
IV 
Intravenous or intravenously 
KCCQ 
Kansas City Cardiomyopathy Questionnaire 
LDH 
Lactate dehydrogenase 
MCS 
Mental Component Score 
MMRM 
Mixed models for repeated measurements 


Study Drug: NEOD001 
CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 22 of 100 
Abbreviation/Acronym 
Definition 
nAb 
Neutralizing antibody 
NIS-LL 
Neuropathy Impairment Score–Lower Limbs 
NOAEL 
No-observable-adverse-effect-level 
NR 
No response 
NT-proBNP 
N-terminal pro-brain natriuretic peptide 
NYHA 
New York Heart Association 
PCD 
Plasma cell dyscrasia 
PCS 
Physical Component Score 
PEP 
Protein electrophoresis 
PK 
Pharmacokinetic(s) 
PR 
Partial response 
PT/INR 
Prothrombin time/international normalized ratio 
PTT 
Partial thromboplastin time 
RR 
Respiratory rate 
SAA 
Serum amyloid A 
SAE(s) 
Serious adverse event(s) 
SC 
Subcutaneous(ly) 
SF-36v2 
Short Form-36 Health Survey version 2 
sFLC 
Serum free light chain 
6MWT 
6-Minute Walk Test 
TEAE(s) 
Treatment-emergent adverse event(s) 
TRIAD 
Transgenic Rapidly Inducible Amyloid Disease 
ULN 
Upper limit of normal 
US(A) 
United States (of America) 
USP 
United States Pharmacopeial Convention 
VASPI 
Visual Analog Scale – Pain Intensity 
VGPR 
Very good partial response 


Study Drug: NEOD001 
CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 23 of 100 
Abbreviation/Acronym 
Definition 
vWF 
von Willebrand Factor 
WFI 
Water for injection 
WOCBP 
Women of childbearing potential 
WT 
Wild-type 
 


Study Drug: NEOD001 
CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 24 of 100 
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, is a rare disease that 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, and gastrointestinal involvement, neuropathy, and macroglossia. The mechanisms 
by which amyloidogenic immunoglobulin light chains result in organ dysfunction are not well 
characterized, however, it is believed that both amyloid deposits and prefibrillar aggregates may 
contribute to cytotoxic effects on organs observed in patients with AL amyloidosis.  
Approximately three-fourths of AL amyloidosis patients present with 1 or 2 major organ systems 
involved (e.g., cardiac, renal, hepatic, peripheral nervous system, autonomic nervous system, 
gastrointestinal tract, soft tissues) while a quarter of patients present with >2 systems involved 
(Palladini et al, 2005; Gertz et al, 2010). 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. Currently, there are no approved 
treatments for AL amyloidosis and no existing treatments that directly neutralize the toxic 
soluble aggregates or remove the deposited misfolded amyloid that are thought to cause organ 
dysfunction (Falk and Dubrey, 2010). The current standard of care for patients with AL 
amyloidosis 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.  
The incidence of treatment-related mortality following ASCT is high, although variable and 
treatment center dependent, with the greatest mortality occurring in patients with cardiac 
involvement (Falk and Dubrey, 2010). Falk and colleagues noted that although complete 
hematologic responses could be achieved in approximately 40% of treated patients (Falk and 
Dubrey, 2010), the rate of any organ function improvement or stabilization (“organ response”) 
after achieving hematologic response from ASCT or chemotherapy regimens is highly variable 
(Cibeira et al, 2011; Cohen et al, 2007; Michael et al, 2010). Hematologic response in the 
absence of organ benefit provides limited, if any, clinical benefit to patients with AL amyloidosis 


Study Drug: NEOD001 
CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 25 of 100 
(Kaufman et al, 2015), underscoring that the major determinant of morbidity and mortality is end 
organ damage. 
Unlike other hematologic disorders such as multiple myeloma, the morbidity and mortality of 
AL amyloidosis is related to organ dysfunction rather than the PCD. In all patients with AL 
amyloidosis, disease outcome is highly dependent on the severity of organ involvement, 
especially cardiac involvement; and prognosis can be defined by N-terminal pro-brain natriuretic 
peptide (NT-proBNP). NT-proBNP was chosen as the primary endpoint for the Phase 2b 
Study NEOD001-201 because it is a clinically validated cardiac functional biomarker of injury 
and dysfunction and decreasing NT-proBNP levels predict lower mortality rates (Comenzo et al, 
2012). NT-proBNP can also be used for early assessment of cardiac response, allowing treatment 
modification (Palladini et al, 2014). In Study NEOD001-001, the Phase 1/2 study of NEOD001 
in subjects with AL amyloidosis, monthly infusions of NEOD001 resulted in clinically 
meaningful reductions in NT-proBNP (Gertz et al, 2016). 
AL amyloidosis is a rare disorder. NEOD001 was designated as an Orphan Medicinal Product in 
the European Union on 08 February 2013 for the treatment of AL amyloidosis and in the US on 
17 February 2012 for the treatment of AA amyloidosis and AL amyloidosis.  
1.2 
Background on NEOD001 
Prothena Therapeutics Limited (Prothena) is developing NEOD001, a humanized 
immunoglobulin G1 (IgG1), kappa version of 2A4, the parent murine monoclonal antibody. 
NEOD001 and 2A4 bind specifically and with nanomolar affinity to a cryptic epitope only 
exposed on AL amyloid fibrils and soluble aggregates, but not available for binding on normally 
folded light chains that compose immunoglobulins (Ig) or on free non-amyloid light chain in 
circulation. NEOD001, administered by intravenous (IV) infusion, is proposed for use to target 
the misfolded light chain protein in subjects with AL amyloidosis. Refer to 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). The 
first is the direct interaction of NEOD001 with misfolded, soluble light chain aggregates 
resulting in the neutralization of these cytotoxic moieties. The second is the clearing of insoluble 
toxic light chain amyloid deposited in organs/tissues via an antibody-dependent cellular 
phagocytosis (ADCP) mechanism. It is believed that NEOD001 binds (opsonizes) amyloid 
deposits, and signals monocytes/macrophages to initiate the phagocytosis process that ultimately 
removes the amyloid deposits from affected organs. Both mechanisms may contribute to 
potential clinical benefit. 


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Study Drug: NEOD001 
CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 27 of 100 
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 (NOAEL) 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 an exaggerated pro-inflammatory 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 in periphery, 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 SC 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). 
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.  
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 identified 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. Anti-drug antibody reactions in animal species are not predictive of human 
responses and, therefore, these effects are not considered to contribute to human risk assessment 
(Bugelski and Treacy, 2004; Pimm and Gribben, 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.  


Study Drug: NEOD001 
CONFIDENTIAL 
Study Protocol: NEOD001-OLE251 
Original Protocol:  09 January 2017 
Page 28 of 100 
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 the safety and efficacy for the continued 
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. 
1.2.2 
Clinical Experience 
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) 


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Study NEOD001-001 was an 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, peripheral edema, diarrhea, anemia, increased blood creatinine, 
dizziness, cough, constipation, headache, vomiting, dyspnea, pain in extremity, back pain, 
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. 
Efficacy data from the completed Study NEOD001-001 were reported by Gertz et al. (2016) and 
are summarized herein. Cardiac response was assessed by the clinically relevant cardiac 
biomarker, NT-proBNP, using Comenzo et al, 2012 criteria (Appendix 3). Thirty-six subjects 
were considered cardiac evaluable (i.e., baseline NT-proBNP ≥650 pg/mL). Among cardiac-
evaluable subjects, 53% (n=19) met the criteria for cardiac best response and 47% (n=17) met 
cardiac best response category of stable disease. Renal response was defined according to 
Palladini et al (2014) criteria (Appendix 3). Thirty-six subjects were considered renal evaluable 
(i.e., baseline proteinuria ≥0.5 g/24 hours). Among renal-evaluable subjects, 64% (n=23) met the 
criteria for renal best response and 36% (n=13) met renal best response category of stable 
disease. Peripheral neuropathy response was defined according to Coelho et al (2012) criteria 
(Appendix 3). Eleven subjects in the Peripheral Neuropathy Expansion Cohort were considered 
peripheral neuropathy evaluable. Among peripheral neuropathy-evaluable subjects, 82% (n=9) 
met the criteria for neuropathy response (i.e., <2-point increase in Neuropathy Impairment 
Score–Lower Limbs [NIS-LL] score [88-point scale] from baseline) and 18% (n=2) were 
progressors. Two of the responders had complete resolution of peripheral neuropathy. 
Eligible subjects from Study NEOD001-001 are being enrolled in Study NEOD001-OLE001, an 
open-label extension study to evaluate the long-term safety and tolerability of NEOD001 in 
subjects with AL amyloidosis. Subjects receive 24 mg/kg NEOD001 once every 28 days using 
the infusion duration established for the individual subject in Study NEOD001-001 or over 
60 (±10) minutes. 


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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 this open-label extension study (NEOD001-OLE251). As 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/resolved from the event of vasovagal syncope and discontinued the study on the day of 
the event. 
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 the Phase 3 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) and 31 of these subjects had gone on to receive 59 infusions of 24 mg/kg 
NEOD001 in the open-label extension study (NEOD001-OLE001). In the completed Study 
NEOD001-001, 6 subjects experienced 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. 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. 


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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. 
1.3 
Rationale for Study Conduct, Design, and Dose Selection 
Study NEOD001-OLE251 is an open-label extension study, designed to allow subjects who 
completed Study NEOD001-201 to receive active treatment and to evaluate the long-term safety 
and efficacy of NEOD001 as a single agent in subjects with AL amyloidosis who were 
previously treated with PCD therapies. The selected dose of NEOD001, 24 mg/kg (dose not to 
exceed 2500 mg), was used in Study NEOD001-201 and will be continued in this study and the 
other ongoing studies of NEOD001. 
NEOD001 is currently being studied in 3 other ongoing studies. Study NEOD001-201 is a 
double-blinded, randomized, controlled Phase 2b study designed to evaluate the efficacy and 
safety of NEOD001 as a single agent in patients with AL amyloidosis whose underlying PCD is 
stable but who still exhibit significant cardiac impairment. Study NEOD001-CL002 is a double-
blinded, randomized, placebo-controlled Phase 3 study in patients with newly diagnosed AL 
amyloidosis disease who are receiving chemotherapy to treat the underlying PCD. In addition, 
Study NEOD001-OLE001, an open-label extension study for subjects previously enrolled in the 
Phase 1/2 Study NEOD001-001, allows subjects to receive NEOD001 and concomitant 
chemotherapy for treatment of their underlying PCD.  


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2 
OBJECTIVES 
The objective of this study is to evaluate the long-term safety and efficacy of NEOD001 in 
subjects with AL amyloidosis who completed Study NEOD001-201. 


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3 
STUDY PLAN 
3.1 
Study Design 
This is a global, multicenter, Phase 2b, open-label extension study of subjects with AL 
amyloidosis who had a hematologic response (Appendix 1) to first-line treatment for their 
amyloidosis (e.g., chemotherapy, ASCT) and completed Study NEOD001-201. Subjects in this 
study may receive concomitant chemotherapy (see Section 5.6.1). 
Subject screening will occur during the 28 days prior to the first administration of study drug 
(i.e., Month 1-Day 1 Visit), which may overlap with the last visit in Study NEOD001-201. If all 
eligibility requirements are met, the subject will be enrolled and Screening assessments will be 
completed. Screening assessments are listed in Table 1.  
Study visits will occur every 28 days based on scheduling from Month 1-Day 1. A ±5-day 
window is allowed for visits starting after Month 1. Subjects may receive up to 36 infusions of 
study drug. Subjects who discontinue study drug before the End of Study (EOS) Visit should 
have an Early Treatment Discontinuation (ETD) Visit 30 (±5) days after their final 
administration of study drug.  
3.2 
Endpoints 
3.2.1 
Safety Endpoints 
• Long-term safety and tolerability as assessed by vital signs, 12-lead ECGs, routine clinical 
laboratory assessments, and AEs 
• Immunogenicity 
3.2.2 
Efficacy Endpoints 
• N-terminal pro-brain natriuretic peptide (NT-proBNP): 
o Response (Appendix 3) 
o Best response from baseline 
o Change from baseline 
• Change from baseline in troponin T 
• Change from baseline in the Short Form-36 Health Survey version 2 (SF-36v2) Physical 
Component Score (PCS), Mental Component Score (MCS), and the 8 subscales 
• Change from baseline in the 6-Minute Walk Test (6MWT) distance (meters) 
• Progression-free survival 
• For renal-evaluable subjects: 
o Renal response (Appendix 3) 


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o Renal best response from baseline 
o Change from baseline in creatinine, proteinuria, and eGFR 
o Time to eGFR:  
 ≤15 mL/min/1.73 m2 (Chronic Kidney Disease [CKD] Stage 5) 
 <30 mL/min/1.73 m2 (CKD Stage 4) 
 <60 mL/min/1.73 m2 (CKD Stage 3) 
o Time to any worsening in CKD Stage 
o Time to 40% reduction in eGFR 
o Time to doubling of creatinine  
• For peripheral neuropathy-evaluable subjects: 
o Change from baseline in NIS-LL total score  
o Peripheral neuropathy best response 
o Peripheral neuropathy response (Appendix 3) 
o For subjects with painful peripheral neuropathy in Study NEOD001-201 (i.e., baseline 
Visual Analog Scale – Pain Intensity [VASPI] score >0) change from baseline in the 
VASPI score  
• For hepatic-evaluable subjects: 
o Hepatic response (Appendix 3)  
o Hepatic best response from baseline 
• Time to all-cause mortality (overall survival) 
• Frequency and duration of hospitalizations over the course of the study 
• Change from baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) subscores 
and overall summary score 
• Time to progression for each organ (cardiac/NT-proBNP, renal, peripheral neuropathy, 
hepatic) separately and to any organ progression 
• Eastern Cooperative Oncology Group (ECOG) Performance Status and New York Heart 
Association (NYHA) Class at each visit including any changes from baseline  


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• Change from baseline in serum free light chains (sFLCs), serum and 24-hour urine protein 
electrophoresis (PEP), and serum and urine immunofixation electrophoresis (IFE)  
• Severity of disease-related symptoms including any changes from baseline  
• Pharmacokinetics (PK) 
3.3 
Number of Sites and Subjects 
This is a global, multicenter study in approximately 40 sites and 100 subjects. 
3.4 
Randomization and Blinding 
Not applicable. 
3.5 
Safety Monitoring Committee 
Not applicable. 
3.6 
Estimated Treatment Duration 
Each subject’s study participation may be up to 38 months or until the study is terminated (per 
Section 4.6), whichever occurs first. The study consists of a Screening Phase (1 month), 
Treatment Phase (36 months), and EOS Visit (30 [±5] days after the last dose). 
3.7 
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 assessment for the last subject participating in 
the study or if the study is terminated, whichever occurs first, see Section 4.6. 


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4 
SELECTION, DISCONTINUATION, AND WITHDRAWAL OF SUBJECTS 
4.1 
Inclusion Criteria 
Subjects must meet all of the following criteria: 
1. Completed the EOS Visit in Study NEOD001-201 
2. 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 × upper limit of normal (ULN) 
o Aspartate aminotransferase (AST) ≤3 × ULN  
o Alanine aminotransferase (ALT) ≤3 × ULN 
o Alkaline phosphatase (ALP) ≤5 × ULN (except for subjects with hepatomegaly and 
isozymes specific to liver, rather than bone)  
o Estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2 as estimated by the 
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, or measured 
GFR ≥25 mL/min/1.73 m2 
3. Systolic blood pressure (BP) 80-180 mmHg 
4. Women of childbearing potential (WOCBP) must have a negative pregnancy test during 
Screening and must agree to use highly effective physician-approved contraception 
(Appendix 2) from Screening to 90 days following the last study drug administration  
5. Male subjects must be surgically sterile or must agree to use highly effective physician-
approved contraception (Appendix 2) from Screening to 90 days following the last study 
drug administration 
6. Ability to understand and willingness to sign an informed consent form (ICF) prior to 
initiation of any study procedures 
4.2 
Exclusion Criteria 
Subjects must not meet any of the following criteria: 
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 continuation 
or initiation of treatment with NEOD001 or participation in the study 


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2. Symptomatic orthostatic hypotension that in the medical judgment of the Investigator would 
interfere with subject’s ability to safely receive treatment or complete study assessments 
3. Myocardial infarction, uncontrolled angina, uncontrolled ventricular arrhythmias, or ECG 
evidence of acute ischemia, within 6 months prior to the Month 1-Day 1 Visit 
4. Severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area <1.0 cm2) or severe 
congenital heart disease 
5. ECG evidence of acute ischemia or active conduction system abnormalities with the 
exception of any of the following: 
o First degree atrioventricular (AV) block 
o Second degree AV block Type 1 (Mobitz Type 1/Wenckebach type) 
o Right or left bundle branch block 
o Atrial fibrillation with a controlled ventricular rate (uncontrolled [i.e., >110 bpm] 
ventricular rate is not allowed [determined by an average of three beats in Lead II or 
3 representative beats if Lead II is not representative of the overall ECG]) 
6. Has not recovered (i.e., equivalent to a CTCAE ≥Grade 2) from the clinically significant 
toxic effects of prior anticancer therapy. Exception: subjects who have received treatment 
with a proteasome inhibitor such as bortezomib may have CTCAE Grade 2 neuropathy. 
7. Received any of the following within the specified time frame prior to the Month 1-Day 1 
Visit: 
o Oral or IV antibiotics, antifungals, or antivirals within 1 week, with the exception of 
prophylactic oral agents. Note:  In the event that a subject requires the chronic use of 
antivirals, Medical Monitor permission is required for entry into the study. 
o Hematopoietic growth factors, transfusions of blood or blood products within 1 week 
o Chemotherapy, radiotherapy, HDAC inhibitors, or other plasma cell directed therapy 
within 2 weeks 
o ASCT within 4 weeks (i.e., ASCT is allowed if it occurred before enrollment in Study 
NEOD001-201 or after completion of Study NEOD001-201 if it was at least 4 weeks 
before Month 1-Day 1 of this study) 
o Major surgery within 4 weeks (or within 2 weeks following consultation with and 
approval of Medical Monitor) 
o Planned organ transplant during the study 
o Any investigational agent, other than NEOD001, within 4 weeks 


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o Any experimental imaging agent directed at amyloid within 2 years 
8. Active malignancy with the exception of any of the following: 
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 and 
has been in remission for ≥2 years 
o Low-risk prostate cancer with Gleason score <7 and prostate-specific antigen 
<10 mg/mL 
o Any other cancer from which the subject has been disease-free for ≥2 years 
9. History of Grade ≥3 infusion-related AEs or hypersensitivity to NEOD001 
10. History of severe allergy to any of the components of NEOD001 such as histidine/ 
L-histidine, Trehalose, or Polysorbate 20 
11. Currently known uncontrolled bacterial, viral, fungal, HIV, hepatitis B, or hepatitis C 
infection 
12. Women who are breastfeeding 
13. Any condition which could interfere with, or the treatment for which might interfere with, the 
conduct of the study or which would, in the opinion of the Investigator, unacceptably 
increase the subject’s risk by participating in the study 
14. Unable or unwilling to adhere to the study-specified procedures and restrictions 
15. Subject is under legal custodianship 
4.3 
Early Treatment Discontinuation 
If the subject discontinues study drug prior to the EOS Visit, they should return for an ETD 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: 
• Need for organ transplant 


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• A suspected NEOD001-related clinically significant 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. At a minimum, 
samples should be collected at the ETD Visit and 3 months after the ETD 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 ETD Visit must be followed to term or until 
termination of the pregnancy (Section 7.4.2). 
After the ETD Visit, vital status follow-up phone calls should be made per Section 6.3. 
4.4 
Early Termination from the Study 
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 ETD 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 
Vital status will be collected within legal and ethical boundaries for all screened subjects 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 subjects who withdrew participation from the 
study. If vital status is determined, the subject will not be considered lost to follow-up. 
4.5 
Replacement of Subjects 
As this is an open-label study for subjects who completed Study NEOD001-201, no subjects will 
be replaced. 


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4.6 
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, and/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 (CA), 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.  


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5 
TREATMENT OF SUBJECTS 
5.1 
Study Drug 
Study drug consists of NEOD001. 
5.1.1 
Formulation and Packaging of NEOD001 
The active study drug, NEOD001, is supplied as a sterile, lyophilized dosage form in a 20/25 mL 
vial containing 500 mg/vial 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 labelling will comply with applicable regulatory 
requirements. 
5.1.2 
Shipping, Storage, and Handling of NEOD001 
NEOD001 will be shipped to clinical sites in individual cartons (one vial per carton). Upon 
receipt, a study staff member will place the NEOD001 in a refrigerator at a temperature ranging 
from 2°C to 8°C in a secure, locked location. Access to the NEOD001 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 NEOD001 has not been properly handled (e.g., 
supply arrived at room temperature or was not placed in refrigerator upon receipt), 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, NEOD001 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. 
Refer to 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 disposition and return are maintained. 
All study drugs provided by the Sponsor or provided at the study center 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 Screening 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 Pharmacy Staff at each site will be responsible for preparing 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.  
NEOD001 will be administered once every 28 days (a ±5-day window is allowed for visits 
starting after Month 1) over 60 (±10) minutes unless a longer infusion duration was established 
for the individual subject in Study NEOD001-201. A minimum of 21 days between doses is 
required. The length of the infusion may be extended over a longer period of time if and when it 
is 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: 
• If it has been <60 days since the subject’s last visit in Study NEOD001-201, the subject 
should be monitored according to the observation time established for the individual subject 
in Study NEOD001-201 
• If it has been ≥60 days since the subject’s last visit in Study NEOD001-201, the subject 
should be monitored for 90 (±10) minutes for at least the first two infusions 


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• Beginning with the third infusion, the Investigator may decrease the 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.  
5.4 
Dosage Adjustments 
5.4.1 
Withholding of Study Drug 
Subjects with symptomatic orthostatic hypotension and/or systolic BP <85 mmHg, which in the 
medical judgment of the Investigator would interfere with subject’s ability to safely receive 
study drug, will have study drug withheld until the next scheduled monthly administration, but 
should still have all other study visit assessments completed. If 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. A symptom-directed 
physical exam and vital signs need to be repeated prior to each dosing.  
5.4.2 
Management of Suspected Systemic Infusion-Related/Hypersensitivity Adverse 
Events 
In the event of a suspected systemic infusion-related and/or hypersensitivity AE, the infusion 
should be immediately discontinued and appropriate supportive therapy should be administered 
per institutional practice, which may include, but is not limited to, epinephrine, IV fluids, 
corticosteroids, vasopressors, oxygen, bronchodilators, antihistamines, or 
acetaminophen/paracetamol. Subjects should be evaluated and carefully monitored until there is 
complete resolution of the AE (i.e., all hypersensitivity signs and symptoms have resolved). In 
addition to the institution’s recommended assessments, blood samples should be obtained in the 
event of a suspected systemic infusion-related and/or hypersensitivity AE for assessment of the 
following: cytokine levels (IL-6, IL-8, TNF-alpha, and INF-gamma) complements C3, C4, and 
CH50; C-reactive protein (CRP), serum amyloid A/acute phase serum amyloid A (SAA/A-
SAA); tryptase (serial levels: within 30 to 120 minutes of onset AND at 48 to 72 hours); serum 
NEOD001; and anti-NEOD001 antibody levels. If possible, samples should be collected while 
the acute symptoms persist. 
For subjects with a Grade 2 infusion-related AE, if it is appropriate to restart the infusion, the 
infusion rate should be decreased by 50% (e.g., if the infusion was previously 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. In addition, for all subsequent infusions, maximal premedication must be administered 
according to institutional practice and should include an H1 blocker, an H2 blocker, an 
antipyretic such as acetaminophen/paracetamol and a steroid (e.g., 25-50 mg hydrocortisone IV). 


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If a subject experiences a Grade 3 infusion-related and/or hypersensitivity AE, the infusion 
should not be restarted. The decision to continue dosing this subject at their next scheduled 
administration should be discussed with the Medical Monitor. If the decision is made to proceed 
with subsequent dosing, both the dose and infusion rate will be reduced by 50% from the 
original dose (i.e., 12.5 mg/kg in 250 mL) and infusion rate (e.g., over at least 90 minutes [if the 
previous infusion time was 60 minutes]). In addition, maximal premedication must be 
administered according to institutional practice and should include an H1 blocker, an H2 blocker, 
an antipyretic such as acetaminophen/paracetamol and a steroid (e.g., 25-50 mg hydrocortisone 
IV). 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 
ETD 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 ETD Visit per Section 6.1.3. 
5.4.3 
Dose Reductions 
Dose reductions may be allowed in the event that an observed AE is believed to be related to 
study drug, and upon consultation between the Investigator and the Medical Monitor, is 
considered to be manageable 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 electronic case report form (eCRF) by 
recording the date, time, and whether or not each IV dose of study drug was completely infused, 
along with reasons why treatment was adjusted or not administered, if applicable. 
5.6 
Prior and Concomitant Medication/Therapy 
Prior and concomitant medications include any drug (investigational, 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/ETD Visit, and any 
changes to concomitant medications during the study, will be recorded in the appropriate eCRF. 
5.6.1 
Allowed Concomitant Medication/Therapy 
• Radiation therapy for the treatment of local amyloid deposits 
• Concomitant chemotherapy: 
o The Investigator may prescribe chemotherapy as per standard of care 
o Monthly doses of NEOD001 should not be delayed or skipped due to adjustments made 
to chemotherapy dosing 
o If bortezomib is administered, antiviral prophylaxis is required 


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o Particular care must be taken to accurately report chemotherapy administration, 
including missed or delayed doses, and dose reductions 
o Blood samples for local laboratory assessments must be collected per institutional 
practice prior to administration of chemotherapy 
o Within 3 days before the first day of a new regimen of chemotherapy, conduct an 
unscheduled laboratory collection (including hematology, chemistry, prothrombin 
time/international normalized ratio [PT/INR], and partial thromboplastin time [PTT]) 
o If chemotherapy is administered on the same day as NEOD001, the chemotherapy must 
be administered after the NEOD001 observation period and postdose vital sign 
measurements 
o Medications such as anti-emetics required for prophylaxis of emesis for the subsequent 
chemotherapy should be given after the ECG has been completed. 
• Calcium channel blockers (if on stable dose) 
• Steroids 
5.6.2 
Prohibited Concomitant Medication/Therapy 
• Other investigational agents (e.g., drugs not approved for any indication) 
• Myeloablative chemotherapy with ASCT 
• Organ transplant 
• Histone deacetylase (HDAC) inhibitors 
• Experimental imaging agent directed at amyloid  
• Gadolinium contrast agents are only permitted in exceptional circumstances. If a patient 
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  
With the exception of the assessments to be considered standard of care (e.g., NT-proBNP), 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. Individual test results that do not meet eligibility 
requirements may be repeated; full rescreening is allowed once per subject.  
6.1.1.1 
Assessments for Subjects Whose Previous Visit in Study NEOD001-201 was 
Within 60 Days of Screening 
The following will be performed within the 28 days prior to the Month 1-Day 1 Visit: 
• Signed ICF 
• Review inclusion and exclusion criteria to assess eligibility 
• Medical History - Obtain medical history since the subject’s last visit in Study 
NEOD001-201 (including all major hospitalizations and surgeries), as well as the subject’s 
current medical status and therapy for AL amyloidosis 
• Prior and concomitant medications/therapy taken or received by a subject within the 28 days 
prior to the Month 1-Day 1 Visit 
• Assessment of AEs 
• Complete physical examination - including height (per Section 6.5.1.3) 
• Vital signs (HR, BP, RR, and body temperature; per Section 6.5.1.2) - collect after the 
subject has been at rest for ≥5 minutes 
• NIS-LL (Appendix 6 and Section 6.5.2.5) 
o Note: NIS-LL is for all subjects who had peripheral neuropathy in Study NEOD001-201 
• VASPI (Appendix 7 and Section 6.5.2.5) 
o Note: VASPI is for subjects with painful peripheral neuropathy in Study NEOD001-201 
• SF-36v2 (Appendix 8) 
o Note: Administer SF-36v2 before conducting any other assessments on the same 
calendar day it is administered 


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• KCCQ (Appendix 9)  
o Note: Administer KCCQ after the SF-36v2, but before conducting any other assessments 
on the same calendar day it is administered 
• 6MWT (Section 6.5.2.3); also collect HR and BP pre- and post-6MWT administration 
o Notes: Two pretreatment 6MWTs are required before the first administration of study 
drug, with a minimum of 4 days in between the two tests. The first Screening 6MWT is 
required to be performed between Days -28 and -5, at least 4 days prior to the second 
Screening 6MWT, which should be performed within 2 days prior to Month 1-Day 1 
(i.e., on Day -2 or Day -1). NT-proBNP should be drawn before conducting 6MWT if 
being performed on the same calendar day. 
• 12-lead ECG performed in triplicate (perform centrally) 
• Laboratory Assessments (central laboratory, unless otherwise noted) – Note: Laboratory tests 
results from Study NEOD001-201 that were performed within 28 days of Month 1-Day 1 
may be used for screening in this study: 
o Hematology and chemistry (including amylase and creatine kinase) per Appendix 10  
o Coagulation - PT/INR, PTT 
o Troponin T 
o NT-proBNP 
 Note: NT-proBNP should be drawn before 6MWT if being performed on the same 
calendar day 
o Urine pregnancy test for WOCBP  
 Note: Women with tubal ligations are considered to be of childbearing potential but 
women who are surgically sterile (hysterectomy) or postmenopausal ≥2 years are not 
considered to be of childbearing potential 
• Other Assessments (see Laboratory Manual): 
o Anti-NEOD001 serum sample 
6.1.1.2 
Assessments for Subjects Whose Previous Visit in Study NEOD001-201 was 
≥60 Days from Screening 
The following will be performed within the 28 days prior to the Month 1-Day 1 Visit: 
• Signed ICF 
• Review inclusion and exclusion criteria to assess eligibility 


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• Medical History - Obtain medical history since the subject’s last visit in Study 
NEOD001-201 (including all major hospitalizations and surgeries), as well as the subject’s 
current medical status and therapy for AL amyloidosis 
• Prior and concomitant medications/therapy taken or received by a subject within the 28 days 
prior to the Month 1-Day 1 Visit 
• Assessment of AEs 
• Complete physical examination - including height (per Section 6.5.1.3) 
• Vital signs (HR, BP, RR, and body temperature; per Section 6.5.1.2) - collect after the 
subject has been at rest for ≥5 minutes 
• Eastern Cooperative Oncology Group performance status (ECOG PS) (Appendix 4) 
• NYHA class (Appendix 5) 
• NIS-LL (Appendix 6) 
o Note: NIS-LL is for all subjects who had peripheral neuropathy in Study NEOD001-201 
• VASPI (Appendix 7) 
o Note: VASPI is for subjects who had painful peripheral neuropathy in 
Study NEOD001-201 
• SF-36v2 (Appendix 8) 
o Note: Administer SF-36v2 before conducting any other assessments on the same 
calendar day it is administered 
• KCCQ (Appendix 9)  
o Note: Administer KCCQ after the SF-36v2, but before conducting any other assessments 
on the same calendar day it is administered 
• 6MWT (Section 6.5.2.3); also collect HR and BP pre- and post-6MWT administration 
o Notes: Two pretreatment 6MWTs are required before the first administration of study 
drug, with a minimum of 4 days between the two tests. The first Screening 6MWT is 
required to be performed between Days -28 and -5, at least 4 days prior to the second 
Screening 6MWT, which should be performed within 2 days prior to Month 1-Day 1 
(i.e., on Day -2 or Day -1). NT-proBNP should be drawn before conducting 6MWT if 
being performed on the same calendar day. 
• 12-lead ECG performed in triplicate (perform centrally) 


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• Laboratory Assessments (central laboratory, unless otherwise noted): 
o Hematology and chemistry (including amylase and creatine kinase) per Appendix 10  
o Coagulation - PT/INR, PTT 
o Troponin T 
o NT-proBNP 
 Note: NT-proBNP should be drawn before 6MWT if being performed on the same 
calendar day 
o Urine pregnancy test for WOCBP 
 Note: Women with tubal ligations are considered to be of childbearing potential but 
women who are surgically sterile (hysterectomy) or postmenopausal ≥2 years are not 
considered to be of childbearing potential 
o sFLCs 
o Serum immunofixation electrophoresis (IFE) and protein electrophoresis (PEP) 
o Urinalysis - dipstick per Appendix 10  
o 24-hour urine collection for: 
 Urine IFE and PEP 
 Urine protein excretion 
• Other Assessments (see Laboratory Manual): 
o Anti-NEOD001 serum sample 
6.1.2 
Treatment Period: Monthly X-Day 1 (±5 days starting with Month 2) 
Study visits will occur every 28 days based on scheduling from Month 1-Day 1. A ±5-day 
window is allowed for visits starting after Month 1. A minimum of 21 days between doses is 
required. When chemotherapy is administered on same day as NEOD001, it must be 
administered after the NEOD001 observation period. 
Although central laboratory assessments will be performed each month for study analysis, local 
laboratory assessments may be performed for subject management when necessary for obtaining 
results on a more immediate basis. 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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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. An 
unscheduled sample will be taken in case of a relevant serious adverse event. If defects are 
identified, additional analytes will be evaluated, as indicated. 
Prior to Study Drug Infusion: 
The following assessments will be done monthly, unless otherwise specified, prior to dosing on 
Day 1. The predose assessments may be performed within the 3 days before the visit unless a 
different timeframe is specified: 
• Concomitant medications/therapies 
• Assessment of AEs 
• Directed physical examination (per Section 6.5.1.3) 
• Vital signs (HR, BP, RR, and body temperature; per Section 6.5.1.2) – within 30 minutes 
before start of dosing, after subject has been at rest ≥5 minutes; assess in same position for all 
time points 
• ECOG PS (Appendix 4) – every 6 months 
• NYHA class (Appendix 5) – every 6 months 
• NIS-LL (Appendix 6) – every 6 months 
o Note: NIS-LL is for all subjects who had peripheral neuropathy in Study NEOD001-201 
• VASPI (Appendix 7) – every 6 months 
o Note: VASPI is for subjects who had painful peripheral neuropathy in 
Study NEOD001-201 
• SF-36v2 (Appendix 8) – every 6 months 
o Note: administer SF-36v2 before performing any other study assessments on the same 
calendar day it is administered 
• KCCQ (Appendix 9) – every 6 months 
o Note: Administer after the SF-36v2, but prior to conducting any other assessments on 
the same calendar day it is administered 


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• 6MWT (Section 6.5.2.3) – every 6 months – also collect HR and BP pre- and post-6MWT 
administration  
o Notes: NT-proBNP should be drawn before conducting 6MWT if being performed on 
the same calendar day. If the 6MWT is conducted on the same calendar day as the study 
drug infusion, the 6MWT must be completed before initiation of the infusion 
• 12-lead ECG in triplicate (perform centrally) – within 30 minutes before start of dosing – 
every 3 months 
• Laboratory Assessments (central laboratory, unless otherwise noted): 
o Hematology and chemistry (including amylase and creatine kinase) per Appendix 10  
o Coagulation - PT/INR, PTT 
o Other coagulation indices – Month 1, Month 12 - per Appendix 11 
 Month 1: EOS/ETD results from Study NEOD001-201 will serve as baseline for this 
study. Collect sample for vWF activity and antigen assays before dosing on Month 1-
Day 1 if they were not tested at EOS/ETD in Study NEOD001-201. 
 Month 12: For subjects with defects identified at EOS/ETD in Study NEOD001-201: 
collect sample and test analytes that were abnormal. All other subjects: collect 
sample. If defects are identified, additional analytes will be evaluated, as indicated. 
o Troponin T 
o NT-proBNP 
 Note: NT-proBNP should be drawn before conducting 6MWT if being performed on 
the same calendar day 
o Urine pregnancy test (WOCBP only) 
o sFLCs – every 6 months 
o Serum IFE and PEP – every 6 months 
o Urinalysis - dipstick per Appendix 10 – every 6 months 
o 24-hour urine collection - every 6 months for: 
 Urine IFE and PEP 
 Urine protein excretion 


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• Other Assessments (see Laboratory Manual): 
o NEOD001 serum sample – within 2 hours before infusion – every 6 months (±1 month) 
o Anti-NEOD001 serum sample – preinfusion – every 3 months 
Study Drug Administration: 
Subjects who present with symptomatic orthostatic hypotension and/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 study drug withheld until the next scheduled monthly 
administration, but should still have all other study visit assessments completed. If 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. A symptom-
directed physical exam and vital signs need to be repeated prior to each dosing.  
• Month 1-Day 1: 
o Administer study drug IV over 60 (±10) minutes unless a longer infusion duration was 
established for the individual subject in Study NEOD001-201. See Section 5.3 for 
information on dosage, preparation, and administration of study drug. 
• All Other Months-Day 1: 
o If the Month 1-Day 1 infusion was well tolerated without infusion-associated AEs, 
administer NEOD001 IV over 60 (±10) minutes unless a longer infusion duration was 
established for the individual subject during Study NEOD001-201. See Section 5.3 for 
information on dosage, preparation, and administration of study drug; if needed, see 
Section 5.4 for dose adjustment instructions. 
Assessments After Infusion: 
• Monitor subjects per Section 5.3 following completion of the study drug infusion 
• Routine medications should not be administered for at least 15 minutes after the completion 
of the NEOD001 infusion and, if possible, should be delayed until completion of the 
postinfusion vital sign and ECG assessments 
• Vital signs (HR, BP, RR, and body temperature; per Section 6.5.1.2) – after subject has been 
at rest ≥5 minutes; assess in same position for all time point 
o Month 1-Day 1: 
 At end of infusion (EOI) (+5 minutes) 
 30 (±5) minutes after EOI 
 60 (±10) minutes after EOI 


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o All Other Months: 
 EOI (+5 minutes) 
 60 (±10) minutes after EOI 
• 12-lead ECG in triplicate (perform centrally) – every 3 months: 
o Within 15 minutes after EOI 
• Other Assessments (see Laboratory Manual): 
o NEOD001 serum sample within 4 hours after EOI – every 6 months (±1 month) 
o Collect additional blood samples if a significant toxicity is observed (e.g., a systemic 
infusion-related reaction, anaphylaxis, hypersensitivity reaction; Section 5.4.2) and if 
possible, samples should be collected while the acute symptoms persist 
• Discharge subject from clinic if no immediate safety concerns and/or hypersensitivities are 
present after the postdose assessments and monitoring 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/Early Treatment Discontinuation (EOS/ETD):  30 (±5) Days After 
Final Dose 
A final visit should occur 30 (±5) days after the last administration of NEOD001. The 
assessments shown for EOS/ETD should also be conducted for any unscheduled visit (i.e., a visit 
not specified by the protocol) as clinically indicated or if deemed necessary. 
• Concomitant medications/therapy 
• Assessment of AEs 
• Complete physical examination (per Section 6.5.1.3) 
• Vital signs (HR, BP, RR, and body temperature; per Section 6.5.1.2) - after subject has been 
at rest ≥5 minutes 
• ECOG PS (Appendix 4) 
• NYHA class (Appendix 5) 
• NIS-LL (Appendix 6) 
o Note: NIS-LL is for all subjects who had peripheral neuropathy in Study NEOD001-201 
• VASPI (Appendix 7) 


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o Note: VASPI is for subjects who had painful peripheral neuropathy in 
Study NEOD001-201 
• SF-36v2 (Appendix 8) 
o Note: Administer SF-36v2 before conducting any other assessments on the same 
calendar day it is administered 
• KCCQ (Appendix 9)  
o Note: Administer after the SF-36v2, but prior to conducting any other assessments on 
the same calendar day it is administered 
• 6MWT (Section 6.5.2.3); also collect HR and BP pre- and post-6MWT administration  
o Note: NT-proBNP should be drawn before conducting 6MWT if being performed on the 
same calendar day 
• 12-lead ECG performed in triplicate (perform centrally) 
• Laboratory Assessments (central laboratory, unless otherwise noted): 
o Hematology and chemistry (including amylase and creatine kinase) per Appendix 10 
o Coagulation - PT/INR, PTT 
o Other coagulation indices per Appendix 11 - For subjects with defects identified at 
Month 12: collect sample and test analytes that were abnormal. All other subjects: 
collect sample. If defects are identified, additional analytes will be evaluated, as 
indicated. 
o Troponin T 
o NT-proBNP 
 Note: NT-proBNP should be drawn before conducting 6MWT if being performed on 
the same calendar day 
o Urine pregnancy test (WOCBP only); see also Section 6.2 
o sFLCs 
o Serum IFE and PEP 
o Urinalysis - dipstick per Appendix 10 
o 24-hour urine collection for: 
 Urine IFE and PEP 


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 Urine protein excretion 
• Other Assessments (see Laboratory Manual): 
o NEOD001 serum sample 
o Anti-NEOD001 serum sample 
6.2 
90-day Postdose Pregnancy Test 
For WOCBP only: Obtain a local laboratory urine pregnancy test 90 (±5) days after the last 
administration of study drug. 
6.3 
Vital Status Follow-Up Phone Call 
Conduct vital status telephone call approximately 3 months after last study visit and 
approximately every 3 months thereafter for up to 5 years, death, or subject withdraws consent, 
whichever occurs first. 
6.4 
Order of Assessments of Specific Tests 
SF-36v2: 
Whenever the SF-36v2 is required, it should be administered prior to any other visit assessments 
on the calendar day it is administered. 
KCCQ: 
Administer the KCCQ after the SF-36v2, but prior to conducting any other assessments on the 
calendar day it is administered. 


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6MWT: 
• Questionnaires should be administered and clinical laboratory samples, including NT-
proBNP, should be drawn prior to administering the 6MWT, if being performed on the same 
calendar day.  
• Postbaseline 6MWTs must be completed before the study drug infusion is initiated, if being 
performed on the same calendar day. 
ECGs: 
• When ECGs are scheduled to be performed at the same visit as PK blood collection, the ECG 
should be performed before the PK blood collection  
Concomitant Medications: 
• Routine medications should not be administered for at least 15 minutes after the completion 
of the NEOD001 infusion and, if possible, should be delayed until completion of the 
postinfusion vital sign and ECG assessments 
• 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 completed 
• If chemotherapy is administered on the same day as NEOD001, the chemotherapy must be 
administered after the NEOD001 observation period and postdose vital sign measurements 
6.5 
Methods of Assessment 
6.5.1 
Safety 
6.5.1.1 
Clinical Laboratory Evaluations 
A central laboratory will be used for analysis of hematology, chemistry (including amylase), 
PT/INR, PTT, cardiac biomarkers, sFLCs, serum IFE/PEP, urinalyses, and 24-hour urine 
collection for urine IFE/PEP and urine protein excretion. Local urine pregnancy testing will be 
conducted as shown in Table 1. A positive urine pregnancy test (local laboratory) is to be 
confirmed with a serum pregnancy test (central laboratory). Local pregnancy test results will be 
collected via an eCRF and in the clinical database. 
Local laboratory results may 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. Results will be reviewed prior to dosing at each month’s Day 1 visit to confirm 
that continued dosing is appropriate. Results from local laboratory tests (Exception: pregnancy 
tests) will not be collected via an eCRF or the clinical database. 
Other Coagulation Indices: Citrated plasma samples will be collected and frozen for potential 
analysis of coagulation indices at a later date. These analyses may include but may not be limited 
to the indices listed in Appendix 11. 


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24-hour Urine Collection: The 24-hour urine IFE/PEP and 24-hour urine protein excretion tests 
will be performed using the same 24-hour urine collection sample when required at the same 
visit. Details regarding the 24-hour urine sample collection will be provided in the Laboratory 
Manual. 
Bioanalytical Samples: A bioanalytical laboratory will be used for the analysis of serum 
NEOD001 and anti-NEOD001 samples (Sections 6.5.3 and 6.5.4). 
Details for the processing of laboratory specimens will be provided in the Laboratory Manual. 
6.5.1.2 
Vital Signs 
Predose vital signs should be assessed within 30 minutes before start of dosing. Vital signs 
should be measured after the subject has been at rest ≥5 minutes. Within a single visit, assess in 
the same position for all time points. 
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) measurements should be taken from the same arm 
throughout the study using an automated BP monitor that uses an oscillometric method.  
Respiratory rate will be measured over at least 15 seconds and adjusted per minute. 
Body temperature can be measured using either oral or tympanic methods, but the method should 
be consistent throughout the study for a given subject. 
As part of the 6MWT, BP and HR will be collected pre- and post-6MWT administration. 
6.5.1.3 
Physical Examination 
Any unfavorable changes in physical examination findings considered by the Investigator as 
clinically significant will be documented on the eCRF as an AE. Other results of the physical 
examinations will not be collected via an eCRF or the clinical database. Physical examinations 
must be performed by the Investigator or a medically qualified delegate. 
A complete physical examination includes height (Screening only), weight, and examination of 
the following:  general appearance; head, ears, eyes, nose, and throat; neck; skin; cardiovascular 
system; respiratory system; gastrointestinal system; and nervous system. A directed physical 
examination includes weight and other components, which will be as clinically indicated. At all 
visits, the following are to 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+).  


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6.5.1.4 
12-Lead ECGs 
The ECGs will be performed centrally. Measurements will be made in triplicate, 1 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, and QTcF - Fridericia's correction formula, and the 
Investigator’s overall interpretation will be recorded. Refer to Section 6.4 for details regarding 
order of assessments in relation to conducting 12-lead ECGs.  
6.5.2 
Efficacy 
6.5.2.1 
Organ Response (i.e., cardiac, renal, peripheral nerve) 
See Appendix 3. 
6.5.2.2 
Short Form-36 Version 2 (SF-36v2) 
See Appendix 8. Details will be provided separately. 
6.5.2.3 
Kansas City Cardiomyopathy Questionnaire (KCCQ) 
See Appendix 9. Details will be provided in the Study Manual. 
6.5.2.4 
6-Minute Walk Test (6MWT) 
Details regarding the requirements for proper administration of the 6MWT are described in the 
Study Manual. As part of the 6MWT, BP and HR will be collected pre- and post-6MWT 
administration. 
6.5.2.5 
Peripheral Neuropathy Assessment 
Peripheral neuropathy will be assessed as follows: 
• The Neuropathy Impairment Score in Lower Limbs (NIS-LL; Appendix 6) assesses lower 
limb reflexes, sensation, and motor strength and will be administered to subjects who had 
peripheral neuropathy in Study NEOD001-201 
• The Visual Analog Scale – Pain Intensity (VASPI; sample tool in Appendix 7) assesses a 
subject’s level of pain related to peripheral neuropathy and will be administered to subjects 
who had painful peripheral neuropathy in Study NEOD001-201. Details regarding 
administration of the VASPI are described in the Study Manual.  
Peripheral neuropathy and neuropathic pain AEs will be assessed using CTCAE grading, as 
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Table 2 
Common Terminology Criteria for Adverse Events (CTCAE) Grade 1-5 for 
Peripheral Neuropathy and Neuropathic Pain 
 
CTCAE Grade 
 
1 
2 
3 
4 
5 
Peripheral 
motor 
neuropathy 
Asymptomatic; 
clinical or diagnostic 
observations only; 
intervention not 
indicated 
Moderate 
symptoms; limiting 
instrumental ADL 
Severe symptoms; 
limiting self-care 
ADL; assistive 
device indicated 
Life-threatening 
consequences; urgent 
intervention indicated 
Death 
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 
Neuralgia 
Mild pain 
Moderate 
symptoms; limiting 
instrumental ADL 
Severe pain; 
limiting self-care 
ADL 
 
 
Abbreviations: ADL = activities of daily living (e.g., preparing meals, shopping for groceries or clothes, using the 
telephone, managing money, etc.). 
a 
Definition: a disorder characterized by inflammation or degeneration of the peripheral sensory nerves. 
Source: National Cancer Institute, 2009. 
 
6.5.2.6 
ECOG 
See Appendix 4. 
6.5.2.7 
NYHA 
See Appendix 5. 
6.5.3 
Pharmacokinetics 
All subjects enrolled in the study will undergo sparse sampling for serum NEOD001 according 
to Table 1 and the Laboratory Manual. Additional samples should be collected if a significant 
toxicity is observed (per Section 5.4.2). 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. Refer to the Laboratory Manual for additional details. 
6.5.4 
Immunogenicity 
Serum ADA levels will be measured according to Table 1 and the Laboratory Manual. 
Additional samples should be collected if a significant toxicity is observed (per Section 5.4.2). 
ADA levels will be correlated with serum NEOD001 concentrations when ADA and 
corresponding serum NEOD001 concentrations are available.  
An electrochemiluminescent (ECL) assay will be used to detect serum anti-NEOD001 
antibodies. Any screening positives will be run at increasing dilutions 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. 
Any sample found to be confirmed positive for anti-NEOD001 antibodies may be further 
evaluated by a neutralizing antibody (nAb) assay. 


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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 on 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 on 
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. Adverse events will be 
identified and documented on the eCRF in appropriate medical terminology. The severity and the 
relationship to the study drug will be determined and recorded on the eCRF (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 the study may indicate the occurrence of an AE that 
may need to be recorded in more than one eCRF. 


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7.2 
Adverse Events—Severity Rating 
Adverse events will be assessed according to CTCAE v4.0 (National Cancer Institute, 2009). 
Adverse events 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: 
• Grade 1 (mild): Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated. 
• Grade 2 (moderate): Moderate; minimal, local or noninvasive intervention indicated; 
limiting age-appropriate instrumental activity of daily living (e.g., preparing meals, shopping 
for groceries or clothes, using the telephone, managing money). 
• Grade 3 (severe): Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
activities of daily living (e.g., bathing, dressing and undressing, feeding self, using the toilet, 
taking medications, and not bedridden). 
• Grade 4 (life threatening): Life-threatening consequences; urgent intervention indicated. 
• Grade 5 (fatal): Death related to AE. 
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 
section of the 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). 
Guidelines for “Related” Events 
• There is clear evidence to suggest a causal relationship, and other possible contributing 
factors can be ruled out. 
• There is evidence to suggest a causal relationship, and the influence of other factors is 
unlikely. 


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• There is some evidence to suggest a causal relationship (e.g., the event occurred within a 
reasonable time after administration of the study drug). However, the influence of other 
factors may have contributed to the event (e.g., the subject’s clinical condition, other 
concomitant events). 
Guidelines for “Not related” Events 
• There is little evidence to suggest there is a causal relationship. There is another reasonable 
explanation for the event. 
• An adverse event will be considered “not related” to the use of the product if any of the 
following tests are met: 
o An unreasonable temporal relationship between administration of the product and the 
onset on the AE (e.g., the event occurred either before, or too long after administration 
of the product for it to be considered product-related) 
o A causal relationship between the product and the AE is biologically implausible (e.g., 
death as a passenger in an automobile accident) 
o A clearly more likely alternative explanation for the AE is present (e.g., typical adverse 
reaction to a concomitant drug and/or typical disease-related event) 
Consider the Following When Assessing Causality 
• Temporal associations between the agent and the event 
• Effect of dechallenge and/or rechallenge 
• Compatibility with known class effect 
• 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 


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• 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/or may require medical or 
surgical intervention to prevent one 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. 
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.  
Examples of visits to a hospital facility that do not meet the serious criteria for hospitalization 
include: 
• Emergency room visits that 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 the 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. 


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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 and/or may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. Examples of such 
events are a new diagnosis of cancer, intensive treatment in an emergency room or at home for 
allergic bronchospasm, 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. 
Definition of Suspected Adverse Reactions 
Suspected adverse reaction is considered any AE for which there is a reasonable possibility that 
the drug caused the AE. 
Definition of Unexpected 
An AE or suspected adverse reaction is considered “unexpected” if it is not listed in the 
Investigator’s 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’s 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: 
o 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 
o 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. 


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7.4.2 
Other Reportable Information 
In addition, and for the purposes of monitoring, any occurrence of exposure through lactation 
and any pregnancy (with or without an AE) of a female subject or partner of a male subject 
should be reported, regardless of seriousness, according to the directions in Section 7.4.4. Any 
subject who becomes pregnant during the study must be withdrawn from study drug treatment, 
and will be followed to term. 
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 term. When an AE 
resulting from disease progression meets the requirements to be considered serious, the SAE 
verbatim term should be reported as the diagnosis 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 term, 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 Investigator to report SAEs to the Sponsor or its designee within 
24 hours of awareness of the event or safety information, whether initial or follow-up. 
All SAEs must be reported immediately (within 24 hours of awareness) 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 subject 
identification number 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. Please refer to the Study Manual for details on reporting SAEs. 
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. 


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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 only 
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 
A statistical analysis plan, providing details about the specific planned analyses and hypothesis 
tests, will be prepared and approved by the Sponsor prior to study database lock.  
Endpoints are listed in Section 3.2. 
8.1 
Analysis Populations 
All analyses will be based on the Safety Population, defined as all subjects who receive any 
amount of study drug. 
Select analyses will use efficacy subsets, defined as: 
• Renal Evaluable Population: subjects who had renal involvement in Study NEOD001-201  
• Peripheral Neuropathy Evaluable Population: subjects who had peripheral nerve involvement 
in Study NEOD001-201 
• Hepatic Evaluable Population: subjects who had hepatic involvement in Study NEOD001-
201 
8.2 
Analysis of Study Population and Subject Characteristics 
Enrollment, important 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 changes in vital signs, 12-lead ECGs, laboratory test results, and 
summaries of AEs. All TEAEs and SAEs will be summarized.  
Quantitative laboratory tests will be assigned toxicity grades based on CTCAE v4.0. Shifts in 
CTCAE toxicity grade of laboratory tests will be presented from baseline to worst value, last 
value, and at each postbaseline visit. Summaries will present the number and percentage of 
subjects with shifts in laboratory toxicity grade. 
Descriptive statistics of the quantitative laboratory, vital sign, and ECG parameters will be 
presented by study visit, as well as the change from baseline. 


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8.4 
Analysis of Efficacy Endpoints 
Response rates will be summarized including 95% confidence intervals. The distributions of 
time-to-event endpoints (progression-free survival, overall survival) will be summarized using 
the Kaplan-Meier method.  
All quantitative endpoints (except 6MWT distance) defined as the change from baseline will be 
analyzed using linear mixed models for repeated measurements (MMRM). The dependent 
variable will be the change from baseline at each time point. The model will include fixed effects 
for time point and treatment-by-time interaction. The baseline value of the corresponding 
endpoint will be included as a covariate and the unstructured covariance model will be used. The 
denominator degrees of freedom will be estimated using the Kenward-Roger approximation. The 
6MWT distance change from baseline will be analyzed using a Wilcoxon signed rank test. 
8.5 
Analysis of Other Endpoints 
8.5.1 
Pharmacokinetics 
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. 
8.5.2 
Immunogenicity 
Serum anti-NEOD001 titers will be listed and correlated with clinical toxicity and serum 
NEOD001 concentrations (where available). 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 open-label extension study for subjects who completed 
Study NEOD001-201. 
8.7 
Handling of Dropouts and Missing Data 
Observed data will be included in listings and summary tables. Sensitivity analyses imputing 
missing data may be conducted. 


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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 
screened 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 on the eCRFs provided by the 
Sponsor or its designee (or via other data collection methods, e.g., electronic laboratory data 
transfer). The Investigator is responsible for reviewing all eCRFs, verifying them for accuracy, 
and approving them via an electronic signature. An electronic copy of the completed eCRFs 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 CA 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 CA 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 on the eCRFs. The Investigator must agree to cooperate with the 
Monitor to ensure that any problems detected in the course of these monitoring visits are 
resolved. 
In accordance with ICH GCP and 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. On 
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, IRB/IEC, or CA 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 or its designee will make the appropriate applications to the CA 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 or CA 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 or CA before any subject is enrolled at a 
site. 
The Investigator is also responsible for the following interactions with the IRB/IEC or CA: 
• Obtaining IRB/IEC or CA approval for any protocol amendments and ICF revisions before 
implementing the changes 
• Providing the IRB/IEC or CA with any required information before or during the study 
• Submitting progress reports to the IRB/IEC or CA, as required, during the conduct of the 
study; requesting re-review and approval of the study, as needed; providing copies of all 
IRB/IEC or CA re-approvals and relevant communication to the Sponsor or its designee 
• Notifying the IRB/IEC or CA of all serious and unexpected AEs related to the study 
medication reported by the Sponsor or its designee, as required by local regulations 
• Notifying the IRB/IEC or CA in writing of the study’s completion or early termination and 
sending a copy of the notification to the Sponsor and/or designee 
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 or CA for approval. An 
IRB/IEC- or CA-approved copy of the ICF and all amendments will be forwarded to the 
Sponsor. 


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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. 
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 and ICF Amendments 
Protocol amendments and amendments to the ICF must be made only with the prior approval of 
the Sponsor and/or its designee. The IRB/IEC or CA must be informed of all amendments and 
give approval for any amendments related to the safety of the subjects or the conduct of the trial 
(Section 10.3). The Investigator must send a copy of the approval letter from the IRB/IEC or CA 
to the Sponsor and/or designee. The Sponsor or its designee will also obtain the appropriate 
approval from the CA in each participating country for any substantial amendments before 
implementing the changes in that country. 
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 April 2015). Available from: 
http://www.heart.org/HEARTORG/Conditions/HeartFailure/AboutHeartFailure/Classes-of-
Heart-Failure_UCM_306328_Article.jsp#. Accessed 02 Sep 2016. 
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 
28 Sep 2016. 
Coelho T, Maia LF, Martins da Silva A, et al. Tafamidis for transthyretin familial amyloid 
polyneuropathy: a randomized, controlled trial. Neurology. 2012;79(8):785-92. 
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. 
Dyck PJ, Litchy WJ, Lehman KA, et al. Variables influencing neuropathic endpoints: the 
Rochester Diabetic Neuropathy Study of Healthy Subjects. Neurology. 1995;45(6):1115-21. 
Falk RH, Dubrey SW. Amyloid heart disease. Prog Cardiovasc Dis. 2010;52(4):347-61. Erratum 
in: Prog Cardiovasc Dis. 2010 Mar-Apr;52(5):445-7. 
Gertz MA, Lacy MQ, Dispenzieri A, et al. Autologous stem cell transplant for immunoglobulin 
light chain amyloidosis: a status report. Leuk Lymphoma. 2010;51(12):2181-7. 
Gertz MA, 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. 
Kaufman GP, Dispenzieri A, Gertz MA, et al. Kinetics of organ response and survival following 
normalization of the serum free light chain ratio in AL amyloidosis. Am J Hematol. 
2015;90(3):181-6. 
Michael M, Kastritis E, Delimpassi S, et al. Clinical characteristics and outcome of primary 
systemic light-chain amyloidosis in Greece. Clin Lymphoma Myeloma Leuk. 2010;10(1):56-61. 


Study Drug: NEOD001 
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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, Kyle RA, Larson DR, et al. Multicentre versus single centre approach to rare 
diseases: the model of systemic light chain amyloidosis. Amyloid. 2005;12(2):120-6. 
Palladini G, 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. 


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12 
APPENDICES 


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Appendix 1 
Hematologic Response and Progression Criteria 
Response Subcategory 
Response Criteria 
Complete Response (CR) 
• Normalization of FLC levels and ratio, negative 
serum and urine immunofixation 
Very Good Partial Response (VGPR)* 
• Reduction in the dFLC to <40 mg/L (<4.0 mg/dL) 
Partial Response (PR)* 
• A greater than 50% reduction in the dFLC 
No Response (NR) 
• Less than a PR 
Progression 
• From CR: any detectable monoclonal protein or 
abnormal FLC ratio (light chain must double) 
• From PR, 50% increase in serum M protein to 
>0.5 g/dL or 50% increase in urine M protein to 
>200 mg/day (a visible peak must be present) or 
FLC increase of 50% to >10 mg/dL (100 mg/L) 
Abbreviations:  dFLC = difference between involved and uninvolved free light chains; FLC = free light chain. 
*Only applicable for subjects who had dFLC >50 mg/L (5 mg/dL) prior to treatment. 
Source: Comenzo et al, 2012. 


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Appendix 2 
Examples of Highly Effective Contraception Methods 
Contraception methods that can achieve a failure rate of <1% per year when used consistently 
and correctly are considered to be highly effective. Such methods include: 
• Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation1: 
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 
• Vasectomised 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 3 
Organ Response and Progression Criteria 
Organ 
Response 
Progression 
Hearta 
NT-proBNP response (>30% and 
>300 ng/L decrease in subjects with 
baseline NT-proBNP ≥650 ng/L)  
OR 
NYHA class response (≥2 class decrease in 
subjects with baseline NYHA class III or 
IV) 
NT-proBNP progression (>30% 
and >300 ng/L increase)b  
Renalc  
≥30% decrease in proteinuria or drop of 
proteinuria below 0.5 g/24 hours in the 
absence of renal progression 
≥25% decrease in eGFR 
Livera 
50% decrease in abnormal ALP value 
OR 
≥2 cm reduction in liver size 
radiographically 
≥50% increase in ALP above the 
lowest value 
Peripheral 
Nerved 
NIS-LL increase from baseline of <2 points 
NIS-LL increase from baseline of 
≥2 points 
ALP = alkaline phosphatase; eGFR = estimated glomerular filtration rate; NIS-LL = Neuropathy Impairment Score–Lower 
Limbs; NT-proBNP = N-terminal pro-brain natriuretic peptide; NYHA = New York Heart Association.  
a 
Modified from Table 2 in Comenzo et al, 2012. In addition to the progression criteria listed above, the investigators will use 
their best clinical judgment in circumstances that do not meet the specifically referenced criteria above in assessing the 
progression. A repeated assessment at an interval that is determined by the investigator is required to confirm the 
progression. 
b 
Subjects with progressively worsening renal function cannot be scored for NT-proBNP progression. 
c 
Palladini et al, 2014. 
d 
Coelho et al, 2012. 
 
 


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Appendix 4 
Eastern Cooperative Oncology Group (ECOG) Performance Status 
Grade 
Description 
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 et al, 1982. 


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Appendix 5 
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: adapted from American Heart Association, 2016. 


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Appendix 6 
Neuropathy Impairment Scale – Lower Limbs (NIS-LL) 
 
 


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Appendix 8 
Short Form-36 Health Survey Version 2 (SF-36v2) 
 


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Appendix 9 
Kansas City Cardiomyopathy Questionnaire (KCCQ) 
 


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Appendix 10 Laboratory Tests 
Serum Chemistry: 
• 
ALP (E)a 
• 
ALT (E) 
• 
AST (E) 
• 
Bilirubin - total (E) and direct 
• 
GGT 
• 
BUN 
• 
LDH 
• 
Creatinine 
• 
Glucose 
• 
Cholesterol 
• 
Triglycerides 
• 
Calcium 
• 
Phosphate 
• 
Protein - total 
• 
Albumin 
• 
Sodium 
• 
Potassium 
• 
Chloride 
• 
Bicarbonate 
• 
Magnesium 
• 
Amylase 
• 
Creatine kinase  
• 
Uric acid 
• 
eGFR (E)e 
• 
Estimated creatinine clearance 
• 
Cystatin C 
Hematology: 
• 
Hemoglobin (E) 
• 
Hematocrit 
• 
RBC 
• 
WBC 
• 
Neutrophils (absolute [E], %) 
• 
Lymphocytes (absolute, %) 
• 
Monocytes (absolute, %) 
• 
Eosinophils (absolute, %) 
• 
Basophils (absolute, %) 
• 
Platelet count (E) 
Otherb: 
• 
Serum anti-NEOD001 antibodiesc 
• 
Serum NEOD001 concentration 
• 
sFLCsd 
• 
24-hr urine protein excretion 
• 
Serum & 24-hour urine PEP 
• 
Serum & urine IFE 
Cardiac Biomarkers: 
• 
Troponin T 
• 
NT-proBNP 
Coagulation: 
• 
PT/INR 
• 
PTT 
• 
Other coagulation indices – see Appendix 11 
Urinalysis - Dipstick: 
• 
Color & clarity 
• 
Specific gravity 
• 
pH 
• 
Protein 
• 
Glucose  
• 
Ketones  
• 
Bilirubin 
 
• 
Urobilinogen 
• 
Blood 
• 
Nitrite  
• 
Leukocyte esterase 
• 
Microscopic 
• 
Pregnancy (WOCBP only) (E)f 
  
ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; 
(E) = may be used for eligibility; eGFR = estimated glomerular filtration rate; FLC = free light chain; GGT = gamma-
glutamyl transpeptidase; IFE = immunofixation electrophoresis; LDH = lactate dehydrogenase; nAb = neutralizing 
antibody; NT-proBNP = N-terminal pro-brain natriuretic peptide; PEP = protein electrophoresis; PT/INR = prothrombin 
time/international normalized ratio; PTT = partial thromboplastin time; RBC = red blood cell; sFLC = serum free light 
chains; WBC = white blood cell; WOCBP = women of childbearing potential. 
a 
Including isozymes for subjects with ALP >5 × upper limit of normal.  
b 
See details in Section 5.4.2 regarding collection of samples for inflammatory biomarkers in cases of suspected systemic 
infusion-related/hypersensitivity reactions. 
c 
Any sample found to be confirmed positive for anti-NEOD001 antibodies may be further evaluated by a nAb assay. 
d 
Including dFLC (difference between involved and uninvolved FLCs) and FLC ratio.  
e 
GFR = 141 × min (Scr /κ, 1)α × max(Scr /κ, 1)-1.209 × 0.993Age × 1.018 [if female] × 1.159 [if black] 
where: Scr = serum creatinine in mg/dL; κ = 0.7 for females, 0.9 for males; α = -0.329 for females, -0.411 for males; 
min = the minimum of Scr /κ or 1; max = the maximum of Scr /κ or 1. Measured GFR is allowed for eligibility purposes 
only; eGFR must be used throughout the study. 
f 
A positive urine pregnancy test (local laboratory) is to be confirmed with a serum pregnancy test (central laboratory). 


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Appendix 11 Other Coagulation Indices 
For each coagulation time point in Table 1 and Section 6.1.2, citrated plasma samples will be 
collected and frozen for potential analysis of coagulation indices at a later date; these analyses 
may include, but may not be limited to, the indices listed in the following table: 
Antithrombin Activity (ATIII Activity) 
Fibrin Monomer 
Partial Thromboplastin Time Mixing Studies 
Fibrinogen Activity 
D-dimer, quantitative 
Fibrinogen Antigen 
Euglobulin Lysis Time  
High-Molecular Weight Kininogen 
Factor II Activity 
Prekallikrein 
Factor IV Activity 
Plasminogen Activator Inhibitor-1 Antigen 
Factor V Activity 
Plasminogen Activator Inhibitor-1 Activity 
Factor VII Activity 
Plasmin-antiplasmin Complex 
Factor VIII Activity  
Plasminogen Activity 
Factor VIII Antigen Quantitation 
Protein C Activity 
Factor IX Activity 
Protein S Antigen Free 
Factor X Activity 
Thrombin Time 
Factor XI Activity 
Tissue Plasminogen Activator Activity 
Factor XII Activity 
Tissue Plasminogen Activator Antigen 
Factor XIII Activity 
von Willebrand Factor (vWF) Activity (Ristocetin Cofactor) 
 
vWF Antigen 
 
vWF Multimers 
 
 

SAP_000.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: 
NCT03154047 
Document Date: 
13 June 2018 
 


TITLE PAGE 
 
 
Statistical Analysis Plan for Protocol NEOD001-OLE251 
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: 
122,912 
EudraCT Number: 
2016-004664-18 
Protocol Version and Date: 
Original; 09 January 2017 
Phase: 
Phase 2b 
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: 
13 June 2018 
Analysis Plan Version: 
Final v1.0  
 
 
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-OLE251 
 
13 June 2018 
 
 
CONFIDENTIAL 
 
Page 2of 51 
TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
TABLE OF CONTENTS .................................................................................................................2 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ....................................................6 
1. 
INTRODUCTION ........................................................................................................9 
2. 
INFORMATION FROM THE STUDY PROTOCOL ...............................................10 
2.1. 
Study Objective ..........................................................................................................10 
2.2. 
Study Design ...............................................................................................................10 
2.2.1. 
Overall Study Design ..................................................................................................10 
2.2.2. 
Study Drug ..................................................................................................................10 
2.2.3. 
Study Procedures ........................................................................................................10 
2.2.4. 
Definition of Baseline .................................................................................................13 
2.2.4.1. 
PRONTO Baseline ......................................................................................................13 
2.2.4.2. 
OLE Baseline ..............................................................................................................13 
2.3. 
Study Endpoints ..........................................................................................................13 
2.3.1. 
Safety Endpoints .........................................................................................................13 
2.3.2. 
Efficacy Endpoints ......................................................................................................13 
2.3.2.1. 
NT-proBNP (Cardiac) Endpoints ...............................................................................13 
2.3.2.2. 
Quality of Life Endpoint – SF-36v2 ...........................................................................14 
2.3.2.3. 
Functional Endpoint -  6MWT Distance ....................................................................15 
2.3.2.4. 
Renal Endpoints ..........................................................................................................15 
2.3.2.5. 
Peripheral Neuropathy Endpoint - NIS-LL Total Score .............................................16 
2.3.2.6. 
Time to All-Cause Mortality (Overall Survival) ........................................................16 
2.3.2.7. 
Other Efficacy Data ....................................................................................................16 
3. 
SAMPLE SIZE JUSTIFICATION .............................................................................17 
4. 
GENERAL STATISTICAL METHODS ...................................................................18 
4.1. 
Reporting Conventions ...............................................................................................18 
4.2. 
Computing Environment ............................................................................................18 
4.3. 
Partial Dates and Unknown Times .............................................................................19 
4.4. 
Data Conventions ........................................................................................................20 
4.5. 
Standard Calculations .................................................................................................20 
4.6. 
Analysis Visit Windows .............................................................................................21 


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NEOD001-OLE251 
 
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4.6.1. 
PRONTO Visit Windows ...........................................................................................21 
4.6.2. 
OLE Therapy Visit Windows .....................................................................................22 
5. 
ANALYSIS POPULATIONS ....................................................................................24 
6. 
EXAMINATION OF SUBGROUPS .........................................................................25 
7. 
STUDY POPULATION .............................................................................................26 
7.1. 
Subject Disposition .....................................................................................................26 
7.2. 
Demographics and Baseline Characteristics ...............................................................26 
7.3. 
Baseline AL Amyloidosis Disease Characteristics .....................................................27 
7.4. 
General Medical History .............................................................................................27 
7.5. 
Prior and New Concomitant Medications ...................................................................28 
7.6. 
Protocol Deviations ....................................................................................................28 
7.7. 
Chemotherapy .............................................................................................................28 
7.8. 
Concurrent Procedures ................................................................................................28 
8. 
EFFICACY ANALYSES ...........................................................................................29 
8.1. 
Adjustments for Covariates ........................................................................................29 
8.2. 
Handling of Dropouts or Missing Data ......................................................................29 
8.2.1. 
Time to All-Cause Mortality ......................................................................................29 
8.2.2. 
Responder Endpoints ..................................................................................................30 
8.3. 
Interim Analyses and Data Monitoring ......................................................................30 
8.4. 
Multicenter Studies .....................................................................................................30 
8.5. 
Multiple Comparisons/Multiplicity ............................................................................30 
8.6. 
NT-proBNP (Cardiac) Endpoint Analyses .................................................................30 
8.6.1. 
Best Response from Baseline .....................................................................................30 
8.6.2. 
Response at Each Visit ...............................................................................................30 
8.6.3. 
NT-proBNP Endpoint:  Change from Baseline ..........................................................30 
8.7. 
Quality of Life Endpoint: SF-36V2 ............................................................................31 
8.8. 
Functional Endpoint: 6WMT Distance .......................................................................31 
8.9. 
Renal Endpoint Analyses ............................................................................................31 
8.9.1. 
Best Renal Response from Baseline ...........................................................................31 
8.9.2. 
Renal Response at Each Visit .....................................................................................31 
8.9.3. 
Creatinine, Proteinuria and eGFR:  Change from Baseline ........................................31 
8.10. 
Peripheral Neuropathy Endpoint: Change from Baseline in NIS-LL Total 
Score ...........................................................................................................................32 


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NEOD001-OLE251 
 
13 June 2018 
 
 
CONFIDENTIAL 
 
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8.11. 
All-Cause Mortality (Overall Survival) ......................................................................32 
8.12. 
Other Efficacy Data ....................................................................................................32 
9. 
SAFETY ANALYSES ...............................................................................................33 
9.1. 
Extent of Exposure .....................................................................................................33 
9.2. 
Use of Premedication ..................................................................................................33 
9.3. 
Adverse Events ...........................................................................................................33 
9.4. 
Clinical Laboratory Evaluations .................................................................................35 
9.4.1. 
Pregnancy Testing and Urinalysis Dipstick ................................................................35 
9.5. 
Weight and BMI .........................................................................................................35 
9.6. 
Vital Signs ..................................................................................................................35 
9.7. 
Electrocardiograms .....................................................................................................35 
9.8. 
Physical Examination .................................................................................................36 
9.9. 
Immunogenicity ..........................................................................................................36 
10. 
CHANGES TO PROTOCOL PLANNED ANALYSES ...........................................37 
11. 
REFERENCES ...........................................................................................................38 
12. 
APPENDICES ............................................................................................................39 
APPENDIX 1. HEMATOLOGIC RESPONSE AND PROGRESSION CRITERIA ................40 
APPENDIX 2. ORGAN RESPONSE AND PROGRESSION CRITERIA ...............................41 
APPENDIX 3. EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) 
PERFORMANCE STATUS .......................................................................................42 
APPENDIX 4. NEW YORK HEART ASSOCIATION (NYHA) FUNCTIONAL 
CLASSIFICATION ....................................................................................................43 
APPENDIX 5. NEUROPATHY IMPAIRMENT SCALE – LOWER LIMBS..........................44 
APPENDIX 6. VISUAL ANALOG SCALE – PAIN INTENSITY (VASPI) ...........................45 
APPENDIX 7. SF-36V2 HEALTH SURVEY ...........................................................................46 
APPENDIX 8. KANSAS CITY CARDIOMYOPATHY QUESTIONNAIRE (KCCQ) ...........47 
APPENDIX 9. LABORATORY TESTS ....................................................................................48 
APPENDIX 10. COAGULATION INDICES ............................................................................50 
APPENDIX 11. RENAL STAGE ...............................................................................................51 
 
 
 


Statistical Analysis Plan 
 
Prothena Therapeutics Limited 
NEOD001-OLE251 
 
13 June 2018 
 
 
CONFIDENTIAL 
 
Page 5of 51 
 
LIST OF TABLES 
Table 1: 
Schedule of Study Procedures ....................................................................................11 
Table 2: 
PRONTO 1-Month Interval Visit Windows (Days) ...................................................21 
Table 3: 
PRONTO 3-Month Interval Visit Windows (Days) ...................................................22 
Table 4: 
OLE Therapy 1-Month Interval Visit Windows (Days) .............................................22 
Table 5: 
OLE Therapy 3-Month Interval Visit Windows (Days) .............................................23 
Table 6: 
Treatment Group Schema ...........................................................................................34 
 
 


Statistical Analysis Plan 
 
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NEOD001-OLE251 
 
13 June 2018 
 
 
CONFIDENTIAL 
 
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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 
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 
IFE 
immunofixation electrophoresis  
in 
inches 
IQR 
interquartile range 
IV 
intravenous  


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Abbreviation 
Term 
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 
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 
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 
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   


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Abbreviation 
Term 
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-OLE251 (Open-label Extension [OLE] Study to Evaluate the Long-term Safety and 
Efficacy of NEOD001 in Subjects with Light Chain [AL] Amyloidosis Who were previously 
enrolled in Study NEOD001-201 (PRONTO)). 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 
The objective of this study is to evaluate the long-term safety and efficacy of NEOD001 in 
subjects with AL amyloidosis who completed Study NEOD001-201 (PRONTO). 
Safety and efficacy endpoints are detailed in Section 8 and Section 9. 
2.2. 
Study Design 
2.2.1. 
Overall Study Design 
This is a global, multicenter, Phase 2b, open-label extension study of subjects with AL 
amyloidosis who completed Study NEOD001-201. Subjects in this study may receive 
concomitant chemotherapy.  
Subject screening will occur during the 28 days prior to the first administration of study drug 
(i.e., Month 1-Day 1 Visit), which may overlap with the last visit in Study NEOD001-201. If all 
eligibility requirements are met, the subject will be enrolled and Screening assessments will be 
completed. Screening assessments are listed in Table 1 .  
Study visits will occur every 28 days based on scheduling from Month 1-Day 1. A ±5-day 
window is allowed for visits starting after Month 1. Subjects may receive up to 36 infusions of 
study drug. Subjects who discontinue study drug before the End of Study (EOS) Visit should 
have an Early Treatment Discontinuation (ETD) Visit 30 (±5) days after their final 
administration of study drug. 
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 (a ±5-day window is allowed for visits starting after Month 
1) over 60 (±10) minutes unless a longer infusion duration was established for the individual 
subject in Study NEOD001-201. 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 study 
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. 
 
 


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Table 1: 
Schedule of Study Procedures  
  
Screening1 
Treatment2 
Termination 
  
Days -28 through -1 
 
 
 
Assessment or Procedure 
<60 days 
since last 
visit in 
Study 
NEOD001-
201 
≥60 days 
since last 
visit in 
Study 
NEOD001-
201 
Monthly 
Day 1 (±5 days)3 
EOS/ETD4 
 
Written Informed Consent  
X 
X 
 
 
Eligibility Review 
X 
X 
 
 
Clinical 
Medical History5 
X 
X 
 
 
Prior/Concomitant Medications/Therapy6 
X 
X 
X 
X 
Adverse Event Assessment7 
X 
X 
X 
X 
Physical Exam8 
X 
X 
X 
X 
Vital Signs9 
X 
X 
X 
X 
ECOG PS/NYHA Class10 
 
X 
Every 6 months 
X 
NIS-LL11 
X 
X 
Every 6 months 
X 
VASPI12 
X 
X 
Every 6 months 
X 
SF-36v213 
X 
X 
Every 6 months 
X 
KCCQ14 
X 
X 
Every 6 months 
X 
6MWT15,16 
X, X17 
X, X17 
Every 6 months18 
X 
ECG (12-lead triplicate) 
X 
X 
Every 3 months19 
X 
Laboratory20 
Hematology & Chemistry (including 
amylase and creatine kinase)21 
X 
X 
X 
X 
Coagulation – PT/INR, PTT 
X 
X 
X 
X 
Coagulation – other indices22 
 
 
Months 1, 12 
X 
Troponin T  
X 
X 
X 
X 
NT-proBNP15  
X 
X 
X 
X 
Pregnancy (WOCBP)23 
X 
X 
X 
X, X24 
sFLCs 
 
X 
Every 6 months 
X 
Serum IFE & PEP25 
 
X 
Every 6 months 
X 
Urinalysis – Dipstick26 
 
X 
Every 6 months 
X 
24-hour Urine Collection: 
 
 
 
 
Urine IFE & PEP24 
 
X 
Every 6 months  
X 
Urine Protein Excretion 
 
X 
Every 6 months 
X 
 
Serum NEOD001 Sample27 
 
 
Every 6 months28 
X 
Anti-NEOD001 Serum Sample29 
X 
X 
Every 3 months28 
X 
 Study Drug Infusion30 
 
 
X 
 
 Vital Status Phone Call 
 
 
 
Every 3 months31 
 
BP = blood pressure; ECG = electrocardiogram; ECOG PS = Eastern Cooperative Oncology Group performance status; EOI = 
end of infusion; EOS = End of Study; ETD = Early Treatment Discontinuation; HR = heart rate; ICF = informed consent form; 
IFE = immunofixation electrophoresis; KCCQ = Kansas City Cardiomyopathy Questionnaire; nAb = neutralizing antibody; NIS-
LL = Neuropathy Impairment Score – Lower Limbs; NT-proBNP = N-terminal pro-brain natriuretic peptide; NYHA = New York 
Heart Association; PEP = protein electrophoresis; PK = pharmacokinetic; PT/INR = prothrombin time/international normalized 


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ratio; PTT = partial thromboplastin time; RR = respiratory rate; 6MWT = 6-Minute Walk Test; SF-36v2 = Short Form-36 Health 
Survey version 2; VASPI = Visual Analog Scale – Pain Intensity; vWF = von Willebrand Factor; WOCBP = women of 
childbearing potential. Rescreening is allowed once per subject. Only repeat tests that did not meet eligibility requirements.  
1. Individual test results that do not meet eligibility requirements may be repeated; full rescreening is allowed once per subject. 
Laboratory tests results from Study NEOD001-201 that were performed within 28 days of Month 1-Day 1 may be used for 
screening in this study.  
2. See Protocol sections 6.1.2 and 6.4 for details regarding timing (e.g., pre- vs. postdose) and order of assessments, respectively.  
3. Study visits will occur every 28 days based on scheduling from Month 1-Day 1. A ±5-day window is allowed for visits starting 
after Month 1. The predose assessments for each visit may be performed within the 3 days before the visit unless a different 
timeframe is specified in protocol section 6.1.  
4. Conduct the EOS Visit 30 (±5) days after last administration of study drug. Subjects who discontinue study drug before the 
end of the study should have an ETD Visit 30 (±5) days after their final administration of study drug. The assessments shown for 
EOS/ETD should also be conducted for any unscheduled visit (i.e., a visit not specified by the protocol) as clinically indicated or 
if deemed necessary.  
5. Medical History - Obtain medical history since the subject’s last visit in Study NEOD001-201 (including all major 
hospitalizations and surgeries), as well as the subject’s current medical status and therapy for AL amyloidosis.  
6. 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/ETD Visit, and any changes to concomitant medications during the study.  
7. Adverse events will be collected 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.  
8. Screening and EOS/ETD: conduct a complete physical examination per protocol section 6.5.1.3. All Other Visits: conduct a 
directed physical examination per protocol section 6.5.1.3.  
9. Vital signs (HR, BP, RR, and body temperature) - collect after the subject has been at rest for ≥5 minutes; within a visit, assess 
in the same position for all time points. Month 1: Within 30 minutes before start of dosing, at EOI (+5 minutes), 30 (±5) minutes 
after EOI, and 60 (±10) minutes after EOI. All Other Months: Within 30 minutes before start of dosing, at EOI (+5 minutes), 
and 60 (±10) minutes after EOI.  
10. See Appendix 3 (ECOG) and Appendix 4 (NYHA).  
11. See Appendix 5; NIS-LL is for all subjects who had peripheral neuropathy in Study NEOD001-201.  
12. See Appendix 6; VASPI is for subjects who had painful peripheral neuropathy in Study NEOD001-201.  
13. See Appendix 7 SF-36v2 should be administered before performing any other study assessments on the same calendar day it 
is administered.  
14. See Appendix 8 ; administer KCCQ after the SF-36v2, but before conducting any other assessments on the same calendar day 
it is administered.  
15. NT-proBNP should be drawn before conducting 6MWT if being performed on the same calendar day.  
16. Collect blood pressure and heart rate pre- and post-6MWT administration.  
17. Two pretreatment 6MWTs are required before the first administration of study drug, with a minimum of 4 days between the 
two tests. The first Screening 6MWT is required to be performed between Days -28 and -5, at least 4 days prior to the second 
Screening 6MWT, which should be performed within 2 days prior to Month 1-Day 1 (i.e., on Day -2 or Day -1).  
18. The postbaseline 6MWTs may be administered on the same calendar day that study drug is administered as long as the NT-
proBNP sample is drawn before conducting the 6MWT and the 6MWT is completed before initiation of the study drug infusion.  
19. Perform ECGs centrally within 30 minutes before start of dosing and within 15 minutes after EOI.  
20. All laboratory tests to be done centrally, unless otherwise noted. Please refer to Laboratory Manual for details. Laboratory 
tests conducted within 28 days of Month 1-Day 1 may be used for screening.  
21. Hematology and chemistry per Appendix 9. Within 3 days before the first day of a new regimen of chemotherapy, conduct an 
unscheduled central laboratory collection (including hematology, chemistry, PT/INR. 
22. Collect citrated plasma samples, which will be frozen for potential analysis of coagulation indices at a later date; see 
Appendix 10. Month 1: EOS/ETD results from Study NEOD001-201 will serve as baseline for this study. Collect sample for 
vWF activity and antigen assays before dosing on Month 1-Day 1 if they were not tested at EOS/ETD in Study NEOD001-201. 
Month 12: Subjects with defects identified at EOS/ETD in Study NEOD001-201: collect sample and test analytes that were 
abnormal. All other subjects: collect sample. EOS/ETD: Subjects with defects identified at Month 12: collect sample and test 
analytes that were abnormal. All other subjects: collect sample. Unscheduled Samples: collect sample in case of relevant serious 
adverse events. At any time, if defects are identified, additional analytes will be evaluated, as indicated.  
23. Urine pregnancy tests (local) for WOCBP: Screening: within 28 days before Month 1-Day 1; Monthly: preinfusion; 
EOS/ETD: any time during visit. A positive urine pregnancy test (local laboratory) is to be confirmed with a serum pregnancy 
test (central laboratory).  
24. 90 (±5) days after last study drug administration (any time during visit) perform urine pregnancy test (local) for WOCBP.  
25. The serum and urine PEP must be conducted before the NEOD001 infusion, if being performed on the same calendar day.  
26. Urinalysis dipstick per Appendix 9.  
27. NEOD001 serum samples (for population PK analysis): Every 6 months (±1 month): within 2 hours before infusion and 
within 4 hours after EOI; EOS/ETD: any time during visit.  
28. Collect additional samples as clinically indicated, such as when significant toxicity occurs per protocol section 5.4.2.  


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29. Anti-NEOD001 serum samples: Screening: any time during visit; Every 3 months: preinfusion; EOS/ETD: any time during 
visit.  
30. Administer over 60 (±10) minutes unless a longer infusion duration was established for the individual subject in Study 
NEOD001-201 or during a previous infusion on this study. A minimum of 21 days between doses is required. Subjects should be 
closely monitored per protocol section 5.3 following completion of the study drug infusion. If chemotherapy is administered on 
the same day as NEOD001, it must be administered after the NEOD001 observation period.  
31. Conduct vital status telephone call approximately 3 months after last study visit and approximately every 3 months thereafter 
for up to 5 years, death, or subject withdraws consent, whichever occurs first. 
2.2.4. 
Definition of Baseline 
2.2.4.1. 
PRONTO Baseline 
The PRONTO Baseline for the 6MWT distance (meters), as defined in the PRONTO SAP, is the 
longest distance walked prior to the first study drug infusion in the original parent study 
(NEOD001-201). For all other efficacy and safety parameters, PRONTO Baseline will be 
defined as the last non-missing assessment prior to the first study drug infusion in the original 
parent study. 
2.2.4.2. 
OLE Baseline 
The OLE Baseline for the 6MWT will use the PRONTO Baseline for 6MWT. Otherwise, OLE 
Baseline is defined as the last assessment prior to first infusion in the OLE.  
2.3. 
Study Endpoints 
2.3.1. 
Safety Endpoints 
Safety evaluations performed during the study include:  
• Vital signs 
• 12-lead ECGs 
• Routine laboratory assessments 
• AEs 
• Immunogenicity  
2.3.2. 
Efficacy Endpoints  
The following are the efficacy endpoints.  
2.3.2.1. 
NT-proBNP (Cardiac) Endpoints 
The following endpoints will be evaluated in the NEOD001 Safety Population and OLE Safety 
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; Appendix 
2):   


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Response 
Stable Disease 
Progression 
Decrease in NT-proBNP from 
baseline of >30% and >300 ng/L 
Assessment was neither 
Response nor Progression 
Increase in NT-proBNP from 
baseline of >30% and from 
baseline >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.  
• Cardiac best response from PRONTO 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. 
• Cardiac response from PRONTO and OLE baselines (see Section 2.2.4), as assessed 
by NT-proBNP response criteria, at each visit  
• Change and percent change from PRONTO and OLE baselines (see Section 2.2.4) to 
each visit in NT-proBNP 
2.3.2.2. 
Quality of Life Endpoint – SF-36v2 
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:  
• Physical Functioning (PF: 10 questions, # 3a to 3j)  
• Role-Physical (RP; role limitations due to physical problems: 4 questions, # 4a to 4d)  
• Bodily Pain (BP: 2 questions, # 7 to 8)  
• General Health Perceptions (GH: 5 questions, # 1, 11a to 11d)  
• Vitality (VT: 4 questions, # 9a, 9e, 9g, and 9i)  
• Social Functioning (SF: 2 questions, # 6 and 10)  
• Role-Emotional (RE; role limitations due to emotional problems: 3 questions, # 5a to 
5c)  
• 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 


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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. 
• Change and percent change from PRONTO and OLE baselines in SF-36v2 PCS to 
each visit  
2.3.2.3. 
Functional Endpoint -  6MWT Distance  
The 6MWT is a practical simple test that requires a minimum walking length of 25 m but 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.  
• Change and percent change from PRONTO and OLE baselines in the 6MWT distance 
(meters) to each visit  
2.3.2.4. 
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 ; Appendix 2) 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. 
• Renal best response from PRONTO and OLE baselines (see Section 2.2.4). Best 
response will be evaluated over the course of the study  
• Renal response from PRONTO and OLE baselines (see Section 2.2.4) at each visit 
• Change and percent change from PRONTO and OLE baselines (see Section 2.2.4) to 
each visit in creatinine, proteinuria, and estimated glomerular filtration rate (eGFR)  


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2.3.2.5. 
Peripheral Neuropathy Endpoint - NIS-LL Total Score 
• Change and percent change from PRONTO and OLE baselines (see Section 2.2.4) to 
each visit in NIS-LL total score will be evaluated in the Peripheral Neuropathy 
Evaluable Population (see Section 5). 
2.3.2.6. 
Time to All-Cause Mortality (Overall Survival) 
Any deaths after the first infusion of study drug (i.e. study day 1) through the study’s last subject 
last visit (LSLV). Time (months) to event will be calculated as: (date of death - the date of first 
study drug infusion + 1) / 30.4375. Subjects will be censored at their last assessment known to be 
alive prior to LSLV.  
2.3.2.7. 
Other Efficacy Data 
Below are the other efficacy data collected in NEOD001-OLE251 study: 
• Visual Analog Scale – Pain Intensity (VASPI) 
• Kansas City Cardiomyopathy Questionnaire (KCCQ) 
• Eastern Cooperative Oncology Group (ECOG) performance 
• Free light chains (sFLCs), serum and 24-hour urine protein electrophoresis (PEP), 
and serum and urine immunofixation electrophoresis (IFE)  
• Severity of disease-related symptoms including any changes from baseline  
• Pharmacokinetics (PK)  
 
 


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3. 
SAMPLE SIZE JUSTIFICATION 
Not applicable as this is an extension study for subjects who completed Study NEOD001-201. 


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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: 
• 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.  
• 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. 
• 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. 
All data recorded on the case report form will be included in data listings that will accompany 
the CSR. 


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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: 
• 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 
• Months – A duration expressed in months is calculated as the number of days divided 
by 30.4375 
• 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 
• 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 
• Height – Height entries made in inches (in) are converted to centimeters (cm) using 
the following formula: 
height (cm) = height (in) × 2.54 
• Weight – Weight entries made in pounds (lb) are converted to kilograms (kg) using 
the following formula: 
weight (kg) = weight (lb) / 2.205 
• Temperature – Temperature entries in degrees Fahrenheit are converted to degrees 
Celsius using the following formula: 
temp (degrees Celsius) = 5 / 9 × (temp [degrees Fahrenheit] – 32) 
• 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) 
• Change from baseline – Change from baseline will be calculated as: 
Change = post baseline value – baseline value 


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• 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 every 28 days (±5 days) based 
on the first infusion date. For reporting purposes, the nominal visits will be used for the by-visit 
analyses. Details of the protocol defined visits and visit windows are given in the protocol and 
Table 1. In the event of unscheduled visits, re-test assessments, or ETD assessments, these will 
be reassigned to a scheduled visit for analysis purposes according to Tables 2, 3, 4 and 5.   
below. If multiple visits occur within a single visit window, after reassignment of unscheduled 
visits and ETD visits, then the visit closest to the target day of the visit window will be used in 
the analysis. If there is a tie, the later visit will be used in the analysis. Unscheduled assessments 
that do not collect time will not be mapped to any scheduled visit/timepoint. 
In data listings, the relative study day from first infusion of all dates will be presented. 
4.6.1. 
 PRONTO Visit Windows 
PRONTO visit windows, a defined in PRONTO SAP, will be used to map the data collected in 
parent study (NEOD001-201). 
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 study drug in parent study.  
Table 2: 
PRONTO 1-Month Interval Visit Windows (Days) 
Months 
Target 
Study 
Day a 
Analysis Window Study Day a 
Low 
High 
PRONTO Baselineb 
1 
Closest visit to Day 1, prior to first NEOD001 dose 
PRONTO Month 2 
28 
14 
42 
PRONTO Month 3 
56 
43 
70 
PRONTO Month 4 
84 
71 
98 
PRONTO Month 5 
112 
99 
126 
PRONTO Month 6 
140 
127 
154 
PRONTO Month 7 
168 
155 
182 
PRONTO Month 8 
196 
183 
210 
PRONTO Month 9 
224 
211 
238 
PRONTO Month 10 
252 
239 
266 
PRONTO Month 11 
280 
267 
294 


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Months 
Target 
Study 
Day a 
Analysis Window Study Day a 
Low 
High 
PRONTO Month 12 
308 
295 
319 [EEOS Low – 1] 
PRONTO EEOSc 
338 
320 [Month 12 Low + 30 – 5] 
 
a Study day will be calculated from first dose date in parent study.  
b PRONTO Baseline is defined in Section 2.2.4. 
c PRONTO EEOS is defined as the visit occurring 30 (-5) days after the Month 12 infusion in parent study.  
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 study drug in parent study. 
Table 3: PRONTO 3-Month Interval Visit Windows (Days) 
Months 
Target 
Study 
Day a 
Analysis Window Study Day a 
Low 
High 
PRONTO Baselineb 
1 
Closest visit to Day 1, prior to first NEOD001 dose b 
PRONTO Month 3 
56 
14 
98 
PRONTO Month 6 
140 
99 
182 
PRONTO Month 9 
224 
183 
266 
PRONTO Month 12 
308 
267 
319 [EEOS Low – 1] 
PRONTO EEOSc 
338 
320 [Same definition as table 3] 
 
a Study day will be calculated from first dose date in parent study.  
b PRONTO Baseline is defined in Section 2.2.4.1  
c PRONTO EEOS is defined as the visit occurring 30 (-5) days after the Month 12 infusion in parent study. 
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 2 
28 
14 
42 [= 28 + 28/2] 
OLE Month 3 
56 
43 [= (28 + 28/2) + 1] 
70 [= 56 + 28/2] 
OLE Month x 
28*x 
(x-2)*28 + 28/2 + 1 
(x-1)*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. 


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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 
56 
14 
98 [= 56 + 84/2] 
OLE Month 6 
168 
99 [= (56 + 84/ 2) +1] 
182 [= (140 + 84/2)] 
OLE Month x 
28*x 
(x-4)*28 + 84/2 + 1 
(x-1)*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. 


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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 (NEOD001-201). 
The OLE Safety Population will include all subjects who received any amount of NEOD001 in 
the OLE study.  
The Renal Evaluable Population will include subjects who were in the Renal Evaluable 
Population in the original parent study (NEOD001-201), defined as subjects who had proteinuria 
>0.5g/24 hours (measured by 24-hour urine total protein excretion), at baseline and at least one 
post-baseline assessment of proteinuria in NEOD001-201. 
The Peripheral Neuropathy Evaluable Population will include subjects who were in the in the 
Peripheral Neuropathy Evaluable Population in the original parent study (NEOD001-201), 
defined as subjects who had ascending sensorimotor neuropathy due to AL amyloidosis 
etiologies at screening, had a baseline Neuropathy Impairment Score–Lower Limbs (NIS-LL) 
total score of 2 or greater and at least one post-baseline NIS-LL total score in NEOD001-201. 
 


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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: 
• the number of subjects dosed in the original parent study (NEOD001-201; NEOD001 
Safety Population) 
• the number of subjects screened in the OLE 
• the number screened but not enrolled in the OLE 
• the number enrolled in the OLE (OLE Safety Population) 
• the number in each organ evaluable population 
• the number who discontinued treatment early in the OLE and reason(s) for 
discontinuation of treatment as recorded on the OLE eCRF 
• the number who withdraw from OLE study prior to completing the study and 
reason(s) for withdrawal as recorded on the OLE eCRF 
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: 
• Age at informed consent including the subgroups <65 vs ≥65 years  
• Sex 
• Race 
• Ethnicity 
Other baseline characteristics will include the following: 
• Weight (kg) 
• Height (cm) 
• BMI (kg/m2) including frequency of the following subgroups: <20, ≥20 - <25, ≥25 - 
<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.  
No inferential statistical comparisons will be performed.  
All demographic and baseline characteristics data will be presented in by-subject data listings. 


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7.3. 
Baseline AL Amyloidosis Disease Characteristics 
The following disease histories from the original parent study (NEOD001-201) will be 
summarized for the OLE Safety Population: 
• Age at AL amyloidosis diagnosis 
• Duration (months) since AL amyloidosis diagnosis 
• Number of prior regimens for amyloidosis  
• Duration (months) since last reported therapy for amyloidosis  
• Response to last reported therapy for amyloidosis (CR, VGPR, PR, NR) 
• Best response to previously reported therapy (CR, VGPR, PR, NR) 
• Duration (months) since best response to previously reported therapy for amyloidosis  
• Number of derived involved organs (1or 2 organs:  renal, peripheral neuropathy) as 
defined in Section 5 
• Number of physician assessed involved organs:  The Investigator also assessed other 
organ involvement including gastrointestinal, autonomic nervous system, lung, soft 
tissue/lymphatic, or other. (1, 2, 3, 4, or 5 organs) 
• Total number of involved organs (derived plus physician assessed) 
• Screening and Baseline NT-proBNP (ng/L) 
• Baseline 6MWT distance (meters) 
• Renal Stage (Appendix 11):  I, II, III; I/II, III; I, II/III 
• Chronic Kidney Stage:  1, 2, 3, 4, 5 
• NYHA Class (Appendix 4):  I, II, III, IV; I/II vs III/IV 
• Baseline FLC Ratio:  Low (<0.26), Normal (0.26 – 1.65), High (>1.65) 
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.  
General medical history will be presented in a by-subject data listing. 
7.5. 
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.  


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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 on or after the first infusion of study drug in OLE. 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. 
Prior and new concomitant medications will be presented in a by-subject data listing. 
7.6. 
Protocol Deviations 
The Investigator is not permitted to deviate from the protocol in any significant way without 
prior notification to the Sponsor (or designee) as described in the protocol.  
All protocol deviations will be collected by the clinical research associates and presented in a by-
subject data listing. 
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.  
Analyses will be produced in both NEOD001 Safety Population and OLE Safety Population, 
unless otherwise specified. Data, visit window, and treatment group to be used for each 
population as below: 
1. NEOD001 Safety Population:  
• Data: Pooled data from parent and OLE study  
• Visit window: PRONTO visit window for data in parent study, OLE therapy visit 
window for OLE data with exclusion of OLE Baseline. 
• Treatment: Placebo and NEOD001 subjects received in NEOD001-201 study and 
Overall 
2. OLE Safety Population:  
 Using data from OLE study only 
 Visit window: OLE therapy visit window  
 Treatment:  NEOD001  
Analyses in Renal Evaluable Population or Peripheral Neuropathy Evaluable Population will be 
presented in the same manner described above for NEOD001 Safety Population and OLE Safety 
Population. 
Baseline in all efficacy analyses refers to PRONTO Baseline and OLE Baseline, unless 
otherwise specified. 
8.1. 
Adjustments for Covariates 
For analyses of change from baseline, restricted maximum likelihood (REML) based mixed-
effect model for repeated measures (MMRM) or analysis of covariance (ANCOVA) models will 
be used and the corresponding baseline value will be used as a covariate in the model. 
8.2. 
Handling of Dropouts or Missing Data  
For the SF-36v2, missing data conventions for partially completed questionnaires are specified in 
Section 2.3.2.2. 
The following methods will be implemented to address missing data for relevant efficacy 
endpoint analyses. 
8.2.1. 
Time to All-Cause Mortality 
Subjects with no data after randomization will be censored on Day 1 (first day of study drug 
dosing).  


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8.2.2. 
Responder Endpoints 
For analyses of best response, a subject missing response status will be considered as a non-
responder for 2-category response (response, non-response), or progressed for a 3-category 
response (response, stable, progression). 
For analysis for response at each visit, analyses will use “observed cases,” where subjects who 
do not provide an assessment at the specified time point for the defining of response will not be 
included. That is, for the percentage of responders, the subject will not be included in the 
numerator or the denominator.  
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. 
8.6. 
NT-proBNP (Cardiac) Endpoint Analyses 
8.6.1. 
Best Response from Baseline 
Best response will be derived from Baseline. All visits after the first infusion of study drug will 
be included. The number and percentage, with associated two-sided exact (Clopper-Pearson) 
95% CIs, of subjects in each category of best response (response, nonresponse) will be 
presented. Refer to Section 8 for details about course of the study and relative first infusion of 
study drug for each set of analyses. 
Cardiac response as 3 categories (response, stable, and progression) will be presented in the same 
manner described above. 
8.6.2. 
Response at Each Visit 
Response from baseline at each visit will be analyzed in the same manner described Section 
8.6.1.  
8.6.3. 
NT-proBNP Endpoint:  Change from Baseline 
Change from baseline will be analyzed using a REML based MMRM model including a fixed 
effect for categorical time point and with the baseline value included as a covariate. The 
unstructured covariance model will be used. If the computational algorithm fails to converge, the 
following structures will be executed:  heterogeneous Toeplitz, Toeplitz, heterogeneous First-
Order Autoregressive [AR(1)], AR(1), heterogeneous compound symmetry (HCS), and 
compound symmetry (CS). The covariance structure converging to the best fit, as determined by 
Akaike’s information criterion (AIC), will be used. The Kenward and Roger method will be used 
to calculate the denominator degrees of freedom for the test of fixed effects. All visits will be 


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included in the model. Estimates of least-square (LS) means, standard errors (StdErr), and 95% 
CIs will be presented at each visit.  
Descriptive statistics for NT-proBNP, change from baseline, and percent change from baseline 
will be presented by visit.  
8.7. 
Quality of Life Endpoint: SF-36V2 
PCS score, change from baseline, and percentage change from baseline will be analyzed in the 
same manner described in Section 8.6.3. 
8.8. 
Functional Endpoint: 6WMT Distance 
Subjects will be ranked at each visit ordered from worst to best, based on the completed distance.  
No imputations for missing data will be made. 
Descriptive statistics for 6MWT distance, change from baseline, and percent change from 
baseline will be presented by visit. The change from baseline at each visit in 6MWT distance 
will be analyzed using a rank ANCOVA model including the ranked baseline value as a 
covariate. Estimates of least-square (LS) means, standard errors (StdErr), and 95% CIs will be 
presented by at each visit.  
Only valid assessments 6MWT distance will be included in analysis. Reasons for results being 
invalid will be presented in a listing and will be finalized prior to database lock. Reasons for 
results being invalid may include:   
• Incorrect course length 
• Use of unapproved course 
• Unapproved administrator of test 
• A site staff member has stopped the stopwatch either inadvertently or incorrectly 
before the 6 minutes are complete and the subject is still able to walk 
Descriptive statistics for observed value, change from baseline, and percent change from baseline 
will also be presented by visit. 
8.9. 
Renal Endpoint Analyses 
The following endpoints will be evaluated in the Renal Evaluable Population. 
8.9.1. 
Best Renal Response from Baseline 
Best renal response will be analyzed in the same manner described Section 8.6.1.  
8.9.2. 
Renal Response at Each Visit 
Renal response at each visit will be analyzed in the same manner described Section 8.6.1 .  
8.9.3. 
Creatinine, Proteinuria and eGFR:  Change from Baseline 
Change from baseline in creatinine, proteinuria and eGFR will be analyzed in the same manner 
described in Section 8.6.3. 


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8.10. 
Peripheral Neuropathy Endpoint: Change from Baseline in NIS-LL 
Total Score 
Change from baseline in NIS-LL will be evaluated in the Peripheral Neuropathy Evaluable 
Population, in the same manner described in Section 8.6.3. 
8.11. 
All-Cause Mortality (Overall Survival) 
Overall survival, time to all-cause mortality, will be calculated in days as the date of death minus 
the date of first NEOD001 infusion plus 1. Subjects will be censored at their last assessment 
known to be alive prior to LSLV. Refer to Section 8 for details about course of the study and 
relative first infusion of study drug for each set of analysis. 
Kaplan-Meier (KM) estimates of the distribution of the time-to-event will be tabulated. The 
tabulation will include the KM estimate of the medians, 25th and 75th quartiles, and 
corresponding 95% CIs, if estimable. The number and percent of subjects censored and with 
events will be presented.  
8.12. 
Other Efficacy Data 
Below efficacy data will be presented in by-subject data listings for the OLE Safety Population. 
• Visual Analog Scale – Pain Intensity (VASPI) 
• Kansas City Cardiomyopathy Questionnaire (KCCQ) 
• Eastern Cooperative Oncology Group (ECOG) performance 
• Free light chains (sFLCs), serum and 24-hour urine protein electrophoresis (PEP), 
and serum and urine immunofixation electrophoresis (IFE)  
• Severity of disease-related symptoms including any changes from baseline  
• Pharmacokinetics (PK)  
 
 
 


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9. 
SAFETY ANALYSES 
All recorded safety endpoint data will be presented in by-subject data listings for the OLE Safety 
Population. TEAE summaries will be presented for All Treated Subjects. Extent of exposure will 
be summarized for NEOD001 Safety Population and OLE Safety Population.  
No inferential comparison of safety endpoints will be performed.  
9.1. 
Extent of Exposure 
The total patient exposure years (PEY) for each subject is defined as the time interval between 
the first dose and the last dose, inclusive, of study drug based on the subject’s study drug 
administration information. One PEY is the equivalent of 1 subject exposed to study drug for 
1 year. Two subjects who are exposed to study drug for half a year together contribute one PEY. 
The total PEY is the sum of the person exposure years of each subject in that treatment group. 
Duration of exposure is defined in days as the date of the last infusion of study drug – the date of 
the first infusion of study drug + 1. 
 Study drug exposure summaries will include: 
• The number of subjects exposed to NEOD001, the total PEY, and duration of 
exposure will be summarized using descriptive statistics. 
• 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.  The number of infusions received will be 
summarized using descriptive statistics. In addition, cumulative number of subjects 
receiving infusions at each visit will be presented. 
All recorded and derived exposure data will be presented in a by-subject data listing. 
9.2. 
Use of 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 
Anatomical Therapeutic Chemical (ATC) class and Preferred Name using the WHO Drug 
Dictionary, B2 Enhanced December 2015. 
Premedication data will be presented in a by-subject data listing. 
9.3. 
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).  
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 


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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.  
To assess the long-term treatment effects overall and relative to shorter term treatment, TEAE 
incidence will be summarized separately by the original parent study (NEOD001-201) and OLE 
study (NEOD001-OLE251) as shown in Table 6. TEAEs collected during original parent study 
will be summarized by actual treatment subjects received. TEAEs that start on or after the first 
dose of OLE study will be summarized by treatment group subjects received in parent study. 
Overall summary will also be presented for NEOD001-OLE251.   
Table 6: 
Treatment Group Schema  
NEOD001-201  
NEOD001-OLE251 
NEOD001  
(N=xx) 
Placebo 
 (N=xx) 
NEOD001-201 
NEOD001  
(N=xx) 
NEOD001-201  
Placebo 
 (N=xx) 
Overall 
(N=xx) 
Each AE summary will be presented according to Table 6 for All Treated Subjects. Summaries 
that are displayed by SOC and PT will be ordered by descending order of NEOD001-OLE251 
overall incidence of SOC and PT within each SOC.  
• An overall summary of AE incidences will be presented, including the number and 
percent of subjects with at least one of: 
o Any TEAE 
o TEAE by maximum CTCAE Grade 
o CTCAE Grade ≥3 TEAE 
o Serious TEAE 
o Fatal TEAEs (outcome=“Fatal” or severity=CTCAE Grade 5) 
o Treatment-related TEAE 
o Treatment-related serious TEAE 
o Treatment-related TEAE of CTCAE ≥Grade 3 
o TEAE leading to infusion interruption  
o TEAE leading to dose reduction  
o TEAE leading to dose being held 
o TEAE leading to prolongation of infusion time (>2.5 hours) 
o Infusion associated TEAE as determined by the Investigator 
o TEAE leading to study drug withdrawal  
• Subject incidence of TEAEs by MedDRA SOC and PT 
• Subject incidence of serious TEAEs by MedDRA SOC and PT  
The following listings will be presented by subject for OLE Safety Population: 


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• All AEs 
• SAEs (this is a subset of the AEs where serious is marked as “Yes”) 
• AEs leading to Study Drug Withdrawal (this is a subset of the AEs where Action Taken 
with Study Treatment is checked as “Drug Discontinued”) 
• AEs leading to death (this is a subset of the AEs where outcome is indicated as “Fatal” or 
the CTCAE grade is 5) 
9.4. 
Clinical Laboratory Evaluations 
Laboratory parameters include serum chemistry, hematology and coagulation.  
All clinical laboratory data will be presented in by-subject data listings using standard 
international (SI) system of units. In addition, separate listings will be presented for any subject 
with a post-baseline CTCAE grade 3 or 4 laboratory value, or with a post-baseline value outside 
the normal range where CTCAE criteria cannot be applied to an analyte. 
The following normal ranges will be used where not provided in the central laboratory data: 
• INR Upper Limit of Normal (ULN) = 1.1 
• eGFR LLN = 90 mL/min/1.73m2 
9.4.1. 
Pregnancy Testing and Urinalysis Dipstick 
Pregnancy test results and urinalysis dipstick results will be provided in a by-subject data listing. 
9.5. 
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 provided in a by-subject data listing. 
9.6. 
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. 
9.7. 
Electrocardiograms 
ECGs measurements will be made in triplicate, 5 to 10 minutes apart and assessed by a central 
reader. ECG parameters include, 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]. 
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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9.8. 
Physical Examination 
Physical examination findings entered on the eCRF will be listed. 
9.9. 
Immunogenicity  
Immunogenicity of NEOD001 will be assessed by anti-NEOD001 antibody levels. Serum anti-
NEOD001 antibody levels will be listed.  


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10. 
CHANGES TO PROTOCOL PLANNED ANALYSES 
Due to the discontinuation of the NEOD001 program, the following changes were made to any 
protocol planned analyses: 
1. All safety analyses were removed except AE overview, TEAEs and SAEs. 
2. The below efficacy analyses were removed:  
• Change from baseline in troponin T  
• Change from baseline in the Short Form-36 Health Survey version 2 (SF-36v2) 
Mental Component Score (MCS) and the 8 subscales  
• Progression-free survival  
• For renal-evaluable subjects:  
 Time to eGFR:  
 Time to any worsening in CKD Stage  
 Time to 40% reduction in eGFR  
 Time to doubling of creatinine  
• For peripheral neuropathy-evaluable subjects:  
 Peripheral neuropathy best response  
 Peripheral neuropathy response   
 For subjects with painful peripheral neuropathy in Study NEOD001-201 (i.e., 
baseline Visual Analog Scale – Pain Intensity [VASPI] score >0) change from 
baseline in the VASPI score  
• For hepatic-evaluable subjects:  
 Hepatic response  
 Hepatic best response from baseline  
 Frequency and duration of hospitalizations over the course of the study  
• Change from baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) 
subscores and overall summary score  
• Time to progression for each organ (cardiac/NT-proBNP, renal, peripheral 
neuropathy, hepatic) separately and to any organ progression  
• Eastern Cooperative Oncology Group (ECOG) Performance Status and New York 
Heart Association (NYHA) Class at each visit including any changes from baseline  
• Change from baseline in serum free light chains (sFLCs), serum and 24-hour urine 
protein electrophoresis (PEP), and serum and urine immunofixation electrophoresis 
(IFE)  
• Severity of disease-related symptoms including any changes from baseline  


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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. 
Coelho T, Maia LF, Martins da Silva A, et al. Tafamidis for transthyretin familial amyloid 
polyneuropathy:  a randomized, controlled trial. Neurology. 2012;79(8):785-92. 
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. 
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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12. 
APPENDICES 


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APPENDIX 1. HEMATOLOGIC RESPONSE AND PROGRESSION 
CRITERIA 
Response Subcategory 
Response Criteria 
Complete Response (CR) 
Normalization of free light chain levels and ratio, negative 
serum and urine immunofixation 
Very Good Partial Response (VGPR)* 
Reduction in the dFLC to <40 mg/L (<4.0 mg/dL) 
Partial Response (PR)* 
A greater than 50% reduction in the dFLC 
No Response (NR) 
Less than a PR 
Progression 
From CR:  any detectable monoclonal protein or abnormal 
free light chain ratio (light chain must double) 
From PR, 50% increase in serum M protein to > 0.5 g/dL 
or 50% increase in urine M protein to > 200 mg/day (a 
visible peak must be present) or free light chain increase of 
50% to > 10 mg/dL (100 mg/L) 
Abbreviations:  dFLC = difference between involved and uninvolved free light chains. 
*Only applicable for subjects who had dFLC > 50 mg/L (5 mg/dL) prior to treatment. 
Source:  Comenzo 2012. 
 


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APPENDIX 2. ORGAN RESPONSE AND PROGRESSION CRITERIA 
Organ 
Response 
Progression 
Heart/Cardiaca,b 
NT-proBNP response (>30% and >300 ng/L 
decrease in subjects with baseline NT-
proBNP ≥650 ng/L)  
OR 
NYHA class response (≥2 class decrease in 
subjects with baseline NYHA class III or IV)b 
NT-proBNP progression (>30% 
and >300 ng/L increase)c 
Renald  
≥30% decrease in proteinuria or drop of 
proteinuria below 0.5 g/24 hours in the 
absence of renal progression 
≥25% decrease in eGFR 
Peripheral 
Nervee 
NIS-LL increase from baseline of <2 points 
NIS-LL increase from baseline of 
≥2 points 
Abbreviations:  ALP = alkaline phosphatase; eGFR = estimated glomerular filtration rate; NIS-LL = Neuropathy Impairment 
Score–Lower Limbs; NT-proBNP = N-terminal pro brain natriuretic peptide; NYHA = New York Heart Association.  
a 
Modified from Table 2 in Comenzo 2012.  
b  
NYHA class not considered for primary efficacy endpoint analyses.  
c 
Subjects with progressively worsening renal function cannot be scored for NT-proBNP progression.  
d 
Palladini 2014. 
e 
Coelho 2012. 
 


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APPENDIX 3. 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 4. 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 5. NEUROPATHY IMPAIRMENT SCALE – LOWER LIMBS 
 


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APPENDIX 6. VISUAL ANALOG SCALE – PAIN INTENSITY (VASPI) 
 


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APPENDIX 7. SF-36V2 HEALTH SURVEY 
 


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APPENDIX 8. KANSAS CITY CARDIOMYOPATHY QUESTIONNAIRE 
(KCCQ) 
 


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APPENDIX 9. LABORATORY TESTS 
Serum Chemistry: 
ALP (E)a 
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 
Creatine kinase  
Uric acid 
Estimated glomerular filtration rate (E)e 
Estimated creatinine clearance 
Cystatin C 
Hematology: 
Hemoglobin (E) 
Hematocrit 
RBC 
WBC 
Neutrophils (absolute [E], %) 
Lymphocytes (absolute, %) 
Monocytes (absolute, %) 
Eosinophils (absolute, %) 
Basophils (absolute, %) 
Platelet count (E) 
Otherb: 
Serum anti-NEOD001 antibodiesc 
Serum NEOD001 concentration 
Serum FLCsd 
24-hr urine protein excretion & total volume 
Serum & 24-hr urine PEP 
Serum & urine IFE 
Inflammatory Biomarkersb: 
IL-6 
IL-8 
TNF-alpha 
INF-gamma 
Complements C3, C4, and CH50 
CRP 
SAA (A-SAA) 
Tryptase 
Urinalysis - Dipstick: 
Color & clarity 
Specific gravity 
pH 
Protein 
Glucose  
Ketones 
Bilirubin 
Urobilinogen 
Blood 
Nitrite 
Leukocyte esterase 
Microscopic 
Urinalysis - Quantitative 
Analysis/Renal 
Biomarkersf: 
Urine albumin/creatinine 
ratio 
Urine NGAL 
Urine RBP  
Cardiac Biomarkers: 
Troponin T 
NT-proBNP  
Coagulation: 
PT/INR 
PTT 
Additional indices - see Appendix 11 
Women of childbearing potential only: 
Serum beta hCG pregnancy tests (E) 


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Abbreviations:  ALP = alkaline phosphatase; ALT = alanine aminotransferase; A-SAA = acute phase serum 
amyloid A; AST = aspartate aminotransferase; BUN = blood urea nitrogen; CRP = C-reactive protein; (E) = 
may be used for eligibility; FLCs = free light chains; GGT = gamma-glutamyl transpeptidase; hCG = human 
chorionic gonadotropin; IFE = immunofixation electrophoresis; IL = interleukin; INF = interferon; 
LDH = lactate dehydrogenase; NGAL = neutrophil gelatinase-associated lipocalin; NT-proBNP = N-terminal 
pro-brain natriuretic peptide; PEP = protein electrophoresis; PT/INR = prothrombin time/international 
normalized ratio; PTT = partial thromboplastin time; RBC = red blood cell; RBP = retinol-binding protein; 
SAA = serum amyloid A; TNF = tumor necrosis factor; WBC = white blood cell. 
a 
Including isozymes for subjects with ALP >5 × upper limit of normal.  
b 
See details in protocol Section 5.4.2 regarding collection of samples in cases of suspected systemic infusion-
related/hypersensitivity reactions. 
c 
Any sample found to be confirmed positive for anti-NEOD001 antibodies may be further evaluated by a 
neutralizing antibody assay. 
d 
Including dFLC (difference between involved and uninvolved FLCs) and FLC ratio. 
e 
GFR = 141 × min (Scr /κ, 1)α × max(Scr /κ, 1)-1.209 × 0.993Age × 1.018 [if female] × 1.159 [if black] where:  
Scr = serum creatinine in mg/dL; κ = 0.7 for females, 0.9 for males; α = -0.329 for females, -0.411 for males; 
min = the minimum of Scr /κ or 1; max = the maximum of Scr /κ or 1. 
f 
It is important that the sample be taken before exercising and at approximately the same time for each 
collection; therefore, the first morning void is recommended. Urine samples to be collected and frozen for 
potential future analysis. 


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APPENDIX 10. COAGULATION INDICES 
For each coagulation time point in Table 1 , citrated plasma samples will be frozen for potential 
analysis of coagulation indices at a later date; 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 11. RENAL STAGE 
Renal Staging 
Test 
Value 
Score 
Proteinuria [Total Protein] 
≤5 g/24 hours 
0 
 
>5 g/24 hours 
1 
eGFR 
≥50 mL/min/1.73 m2 
0 
<50 mL/min/1.73 m2 
1 
Total Score 
0 = Renal Stage I 
1 = Renal Stage II 
2 = Renal Stage III 
eGFR = estimated glomerular filtration rate. 
RCSource: Palladini 2014.