Conditions: Thrombosis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 21
Healthy volunteers: yes

Brief summary:
The purpose of this study is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of xisomab 3G3 in healthy adult subjects.

Detailed description:

Arms:
arm 1: Participants will receive a single intravenous dose of 0.1 mg/kg xisomab 3G3. arm 2: Participants will receive a single intravenous dose of 0.5 mg/kg xisomab 3G3. arm 3: Participants will receive a single intravenous dose of 2.0 mg/kg xisomab 3G3. arm 4: Participants will receive a single intravenous dose of 5.0 mg/kg xisomab 3G3. arm 5: Participants will receive a single intravenous dose of placebo.

Interventions: intervention 1: xisomab 3G3- Dose 1 intervention 2: xisomab 3G3-Dose 2 intervention 3: xisomab 3G3-Dose 3 intervention 4: xisomab 3G3- Dose 4 intervention 5: Placebo
Intervention descriptions: intervention 1: Participants will receive a single intravenous dose of 0.1 mg/kg xisomab 3G3. intervention 2: Participants will receive a single intravenous dose of 0.5 mg/kg xisomab 3G3. intervention 3: Participants will receive a single intravenous dose of 2.0 mg/kg xisomab 3G3. intervention 4: Participants will receive a single intravenous dose of 5.0 mg/kg xisomab 3G3. intervention 5: Participants will receive a single intravenous dose of placebo.

Protocol document:
Prot_000.pdf: 
 
Page 1 
CA19214 (3G3-15-01)_Amend 3 Final Protocol_06Nov2017 
 
 
 
 
 
 
 
 
 
 
 
Celerion Project No.: CA19214 
 
Sponsor Project No.: 3G3-15-01 
 
US PIND No.: 127850 
 
 
A Phase 1, Single Ascending Dose, Randomized, Double-Blind, Placebo-Controlled 
Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics 
of Xisomab 3G3 in Healthy Adult Subjects 
 
 
 
 
 
 
 
 
 
GCP Statement 
This study is to be performed in full compliance with the protocol, Good Clinical Practices 
(GCP), and applicable regulatory requirements. All required study documentation will be 
archived as required by regulatory authorities. 
Confidentiality Statement 
This document is confidential. It contains proprietary information of Aronora, Inc. and/or 
Celerion. Any viewing or disclosure of such information that is not authorized in writing by 
Aronora, Inc. and/or Celerion is strictly prohibited. Such information may be used solely for 
the purpose of reviewing or performing this study. 
 
 


xisomab 3G3 
SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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CA19214 (3G3-15-01)_Amend 3 Final Protocol_06Nov2017 
1. 
PROTOCOL REVISION HISTORY 
DATE/NAME 
DESCRIPTION 
06Nov2017 
by Caroline Engel 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Amendment 3, Final Protocol 
I. 
At the Sponsor request, exploratory analysis will be 
performed on leftover pharmacokinetic plasma samples. 
Hence the following sentence was added to Section 5 
Synopsis under Pharmacokinetic Sample Collection and 
Section 11.2.1 Blood Sampling and Processing: 
“Additional analysis for exploratory purposes, including but 
not limited to factor XIa activity, will be performed on 
leftover plasma samples at the Sponsor’s discretion.” 
II. 
In addition, the serum chemistry tests scheduled 8 hours 
postdose will not be performed following an 8-hour fast as 
subjects will receive their lunch approximately 4 hours before. 
Therefore the following sections were updated (added 
wording in bold): 
1. Section 6 Study Event Flow Chart (footnote h): 
“Samples for serum chemistry will be obtained following 
a fast of at least 8 hours (except for the 8-hour time 
point), however, in case of dropouts or rechecks, subjects 
may not have fasted for 8 hours before the serum 
chemistry sample is taken.” 
2. The first sentence in the last paragraph of Section 10.2.3.2 
Meal Schedule: 
“Subjects will be required to fast for at least 8 hours 
before the clinical laboratory tests at screening and before 
the clinical laboratory tests at other scheduled times 
(except for the 8-hour time point).” 
3. Section 11.1.5 Clinical Laboratory Tests (footnote *): 
“Serum chemistry tests will be performed after at least an 
8-hour fast (except for the 8-hour time point); however, 
in case of dropouts or rechecks, subjects may not have 
fasted for 8 hours before the serum chemistry sample is 
taken” 
III. 
Severity grading scales to be used for adverse events (AEs) 
reporting will be based on detailed toxicity scales provided 
in the FDA Guidance for Industry: Toxicity Grading Scale 
for Healthy Adult and Adolescent Volunteers Enrolled in 
Preventive Vaccine Clinical Trials. Hence the table listing 
the general definition for rating severity of the AE 


xisomab 3G3 
SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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CA19214 (3G3-15-01)_Amend 3 Final Protocol_06Nov2017 
DATE/NAME 
DESCRIPTION 
06Nov2017 
by Caroline Engel 
(Continued) 
 
generated from the FDA toxicity grading scale provided in 
Section 11.1.9.3 Reporting will be applied only for AEs not 
identified in the guidance. Therefore the section 11.1.9.3 
Reporting was updated as follow (added text in bold): 
“Severity of AE: 
Severity rating used during the study will be based on 
the the toxicity grading scale tables present in the FDA 
(Center for Biologics Evaluation and Research) toxicity 
grading scale for healthy volunteers 4-point severity 
scale (Grade 1, 2, 3 and 4).3 
The following definitions for rating severity will be used for 
AEs not identified in the guidance: (…)” 
IV. 
Formatting changes and typographical errors were corrected 
throughout the protocol.  
10May2017 
by Caroline Engel 
Amendment 2, Final Protocol 
1. At the Sponsor request a PT/INR sample was added on Day 4 of 
the study. Therefore, the following changes were made to 
reflect this addition: 
• Section 6 Study Event Flow Chart was updated to add an 
“X” on Day 4 for Coagulation (PT/INR) row. 
• To prevent confusion, the footnote “i” was removed from 
all the “X” between Day 2 and Day 29 in the Coagulation 
(PT/INR) row and added to “Coagulation (PT/INR)” in the 
Study Procedures column.  
• Table 2 was updated. The number of samples was updated 
to “at least 5” under Number of Time Points column and 
On-study coagulation (PT/INR only) row. 
2. Celerion recently moved from the standard 4.5mL tube for 
coagulation to a new 3.5mL tube. Therefore Table 2 was 
updated accordingly to reflect that change. The total blood 
volume has decreased from 318.5 mL to 300.5 mL. 
3. Formating changes were made throughout the protocol. 
02May2017 
by Caroline Engel 
 
 
02May2017 
Amendment 1, Final Protocol 
Based on FDA recommendations, the following changes were 
made to the protocol: 
 


xisomab 3G3 
SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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CA19214 (3G3-15-01)_Amend 3 Final Protocol_06Nov2017 
DATE/NAME 
DESCRIPTION 
by Caroline Engel 
(Continued) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
02May2017 
1. All subjects, regardless of their aPTT results, will be monitored 
until Day 29. Therefore, if aPTT value reaches ±10% of the 
baseline value or within the normal range by Day 29, the 
subject will return to the clinical research unit (CRU) for the FU 
visit on Day 36. If aPTT value does not reach ± 10% of the 
baseline value or within the normal range by Day 29, sampling 
will continue every 7 days (± 2 days) until the ± 10% of 
baseline value or the normal range is reached. Subjects will 
return for the FU visit (i.e., follow-up procedures and AE 
evaluation) 7 days (± 2 days) after aPTT value reaches ±10% of 
the baseline value or within the normal range. The protocol was 
updated throughout to reflect this change. 
2. The dosing interval between the sentinel group and the 
remaining subjects was revised to at least 7 days in Cohort 1. 
The remaining subjects in Cohort 1 and all subjects in 
Cohorts 2-4 will be dosed at an interval of 24 hours between 
subjects. The protocol was updated throughout to reflect this 
change. 
3. Section 10.2.3.3 was revised to clarify that the designated times 
for aPTT assessments are listed in the study events flow chart. 
4. Subjects with normal renal and liver function, and normal 
coagulation parameters will be enrolled in this study. Therefore 
the following inclusion criteria were added to Section 10.3.2 
Inclusion Criteria and Appendix 1 was added to list Celerion 
standards for normal limits of the listed laboratory tests: 
• Aspartate aminotransferase (AST), alanine aminotransferase 
(ALT), alkaline phosphatase (ALP), lactate dehydrogenase 
(LDH), blood urea nitrogen (BUN), creatinine must be 
between the lower limit of normal (LLN; or up to 15% 
below LLN as not indicative of hepatic or renal disease in 
healthy subjects) and the upper limit of normal, inclusive, as 
indicated in Appendix 1 at screening and check-in. 
• aPTT, PT/INR, and platelets, must be within the limits of 
normal, inclusive, as indicated in Appendix 1 at screening 
and check-in. 
• Bleeding time must be between 2 to 8 minutes, inclusive, at 
check-in. 
5. Up to 28 days of safety data will be used and reviewed for dose 
escalation decision instead of 7 days. As well, Section 10.4.1.4 
Dose Escalation and Stopping Rules was updated to clarify that 


xisomab 3G3 
SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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CA19214 (3G3-15-01)_Amend 3 Final Protocol_06Nov2017 
DATE/NAME 
DESCRIPTION 
by Caroline Engel 
(Continued) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
02May2017 
all data from all subjects will be used and reviewed for dose 
escalation decision and a minimum of 4 subjects must complete 
the study (up to Day 29) before proceeding to the next higher 
dosing cohort. The second paragraph of Section 10.4.1.4 Dose 
Escalation and Stopping Rules was updated as follows (deleted 
text presented in strikethrough; added text presented in bold): 
“The SRC will review all pertinent blinded safety/tolerability 
data (e.g., physical examinations, ECGs, vital signs, clinical 
laboratory tests, and AEs) using all available data collected 
from all subjects dosed to at least Day 8 for a minimum of 4 
out of 5 subjects from in the current cohort and from all 
subjects from previous cohorts to base dose escalation 
decision. At least 4 out of 5 subjects from the current cohort 
must complete scheduled safety procedures up to Day 29 
prior to the decision to open proceed to the next higher dosing 
cohort” 
6. All SAEs, regardless of presumed relatedness to study drug, 
will be considered for dose escalation decisions, except those 
that are clearly and incontrovertibly due to extraneous causes. 
Therefore rules #3a in Section 10.4.1.4 Dose Escalation and 
Stopping Rules was updated as follows (deleted text presented 
in strikethrough; added text presented in bold): 
“At least 1 subject has a SAE or visit to the emergency room 
deemed to be study drug related regardless of relatedness to 
the study drug, except SAEs that are clearly and 
incontrovertibly due to extraneous causes.” 
In addition, the following changes were made: 
7. Clinical laboratory tests were added 8 hour after dosing. 
Section 6 Study Event Flow Chart and Table 2 (in Section 11.4 
Blood Volume for Study Assessments) were updated 
accordingly.  
8. Section 8.4.2 Dose Selection was updated to add the following 
information (deleted text presented in strikethrough; added text 
presented in bold):  
“(…) Using the regulatory guidance for estimating a safe 
starting dose in humans, the maximum recommended starting 
dose (MRSD) based on the NOAEL from the toxicology studies 
with a default safety correction factor of 10 applied was 
determined to be 5 mg/kg. The PAD determined by the non-
GLP in vivo efficacy studies in baboons was 1 mg/kg and is, 


xisomab 3G3 
SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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CA19214 (3G3-15-01)_Amend 3 Final Protocol_06Nov2017 
DATE/NAME 
DESCRIPTION 
by Caroline Engel 
(Continued) 
therefore, 5-fold lower than the MRSD based on the 
NOAEL. Dividing the PAD by a safety factor of 10 would 
provide a very conservative starting dose of 0.1 mg/kg. The 
MRSD based on the pharmacologically active dose from in vivo 
efficacy studies in baboons with a correction factor of 10 was 
determined to be 0.1 mg/kg. (…)” 
9. In Section 14 Reference, reference #5 was removed since it is 
not referred to in the protocol. 
10. Typographical and gramatical errors were corrected throughout 
the protocol. 
11. Formating changes were made throughout the protocol. 
03Mar2017 
by Caroline Engel 
Final Protocol for FDA submission 
 


xisomab 3G3 
SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
Page 7 
CA19214 (3G3-15-01)_Amend 3 Final Protocol_06Nov2017 
2. PRINCIPAL INVESTIGATOR AND SPONSOR – SIGNATORIES 
 
A Phase 1, Single Ascending Dose, Randomized, Double-Blind, Placebo-Controlled 
Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics 
of Xisomab 3G3 in Healthy Adult Subjects 
 
 
SPONSOR: 
Aronora, Inc.  
4640 SW Macadam Avenue, Ste 200A  
Portland, Oregon 97239, USA  
Tel.: +1 503 964-0250  
 
SPONSOR’S  
REPRESENTATIVE: 
Christina Lorentz, PhD 
Senior Scientist 
4640 SW Macadam Avenue, Ste 200A  
Portland, Oregon 97239, USA 
Tel.: +1 503 964-0250 
E-mail: christina.lorentz@aronorabio.com 
 
 
 
 
 
Signature 
 Date 
CELERION PRINCIPAL INVESTIGATOR 
AND CLINICAL SITE: 
 
Danielle Armas, MD 
2420 West Baseline Road 
Tempe, Arizona 85283, USA 
Tel.: +1 602 437-0097 ext. 67597 
Fax: +1 602 437-3386 
E-mail: danielle.armas@celerion.com 
 
 
 
 
Signature 
 Date 
 
 
 


xisomab 3G3 
SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
Page 8 
CA19214 (3G3-15-01)_Amend 3 Final Protocol_06Nov2017 
3. ADDITIONAL KEY CONTACTS FOR THE STUDY 
Sponsor Contact for Serious Adverse Events 
Andras Gruber, MD 
President and CEO  
4640 SW Macadam Avenue, Ste 200A  
Portland, Oregon 97239, USA  
Tel.: +1 503 530-6842 
Fax: +1 503 389-7330 
E-mail: andras.gruber@aronorabio.com 
Mobile: +1 503 442-1213 
 
Celerion Protocol Author 
Caroline Engel, BSc. 
Senior Scientist II 
Celerion 
100 Alexis-Nihon Boulevard, Suite 360 
Montreal, Quebec H4M 2N8, Canada 
Tel.: +1 514 744-8738 
Fax: +1 514 744-8700 
E-mail: caroline.engel@celerion.com 
 
Certified Clinical Laboratory for Safety and 
Pharmacodynamic Samples 
Celerion 
2420 West Baseline Road 
Tempe, Arizona 85283, USA 
Contact: Ed Gritzfeld 
Tel.: +1 602 437-0097 ext. 67172 
Fax: +1 602 437-3386 
 
Bioanalytical Laboratory and 
Immunogenicity Testing 
Celerion 
624 Peach Street  
Lincoln, Nebraska 68502, USA 
Tel.: +1 402 476-2811 
Fax: +1 402 939-0428 
 
Pharmacokinetic and Statistical Analyses  
Celerion 
100 Alexis-Nihon Boulevard, Suite 360 
Montreal, Quebec H4M 2N8, Canada 
Tel.: +1 514 744-9090 
Fax: +1 514 744-8700 
and/or 
Celerion  
621 Rose Street 
Lincoln, Nebraska 68502, USA 
Tel.: +1 402 476-2811 
Fax: +1 402 476-7598 


xisomab 3G3 
SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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CA19214 (3G3-15-01)_Amend 3 Final Protocol_06Nov2017 
4. TABLE OF CONTENTS 
1. PROTOCOL REVISION HISTORY ............................................................................2 
2. PRINCIPAL INVESTIGATOR AND SPONSOR – SIGNATORIES ..........................7 
3. ADDITIONAL KEY CONTACTS FOR THE STUDY ...............................................8 
4. TABLE OF CONTENTS ...............................................................................................9 
5. SYNOPSIS ...................................................................................................................12 
6. STUDY EVENTS FLOW CHART .............................................................................17 
7. ABBREVIATIONS .....................................................................................................19 
8. BACKGROUND AND RATIONALE ........................................................................22 
8.1 
Introduction ........................................................................................................22 
8.2 
Background ........................................................................................................22 
8.3 
Nonclinical Studies ............................................................................................23 
8.3.1 Pharmacology .........................................................................................23 
8.3.2 Pharmacokinetics ...................................................................................23 
8.3.3 Toxicology .............................................................................................24 
8.4 
Rationale .............................................................................................................25 
8.4.1 Purpose of the Study ..............................................................................25 
8.4.2 Dose Selection ........................................................................................25 
8.5 
Risk/Benefit ........................................................................................................26 
9. STUDY OBJECTIVES AND ENDPOINTS ...............................................................27 
9.1 
Study Objectives ................................................................................................27 
9.2 
Study Endpoints .................................................................................................27 
10. INVESTIGATIONAL PLAN ......................................................................................28 
10.1 Overall Study Design and Plan ..........................................................................28 
10.1.1 Confinement, Return Visits, and Follow-Up .........................................28 
10.1.2 Study Duration .......................................................................................29 
10.2 Study Conduct ....................................................................................................29 
10.2.1 Screening ................................................................................................29 
10.2.2 Check-in Procedures (Day -1) ................................................................29 
10.2.3 Treatment Period (Day 1 to Day 29) ......................................................30 
10.2.3.1 Single-dose Administration (Day 1) and Study Procedures 
(Days 1 to 29) ........................................................................30 
10.2.3.2 Meal Schedule .......................................................................30 
10.2.3.3 Day 29 Study Procedures ......................................................30 
10.2.4 Follow-up Visit ......................................................................................31 
10.2.5 Scheduled End of Study .........................................................................31 
10.3 Selection of Study Population ............................................................................31 
10.3.1 Number of Subjects ................................................................................31 
10.3.2 Inclusion Criteria ....................................................................................32 


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SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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10.3.3 Exclusion Criteria ...................................................................................33 
10.3.4 Early Termination of Subjects from the Study .......................................35 
10.3.5 Study Restrictions ..................................................................................36 
10.3.5.1 Prohibitions and Concomitant Therapy .................................36 
10.3.5.2 Activity ..................................................................................36 
10.4 Treatments ..........................................................................................................37 
10.4.1 Treatments Administered .......................................................................37 
10.4.1.1 Drug Administration ..............................................................37 
10.4.1.2 Planned Dose Levels .............................................................37 
10.4.1.3 Additional Dose Levels .........................................................38 
10.4.1.4 Dose Escalation and Stopping Rules .....................................38 
10.4.2 Identity of Investigational Products .......................................................39 
10.4.3 Method of Assigning Subjects to Treatment Groups .............................39 
10.4.4 Blinding ..................................................................................................39 
10.4.4.1 Maintenance of Randomization .............................................40 
10.4.4.2 Procedures for Breaking the Blind Prior to Study 
Completion ............................................................................40 
10.4.4.3 Interim Analysis ....................................................................40 
10.4.4.4 Revealing of Randomization .................................................41 
10.4.5 Treatment Compliance ...........................................................................41 
11. STUDY PROCEDURES .............................................................................................42 
11.1 Safety Assessments ............................................................................................42 
11.1.1 Body Height and Weight ........................................................................42 
11.1.2 Physical Examination .............................................................................42 
11.1.3 Vital Signs ..............................................................................................42 
11.1.4 Electrocardiogram Monitoring ...............................................................43 
11.1.5 Clinical Laboratory Tests .......................................................................44 
11.1.6 Check-In Questionnaire ..........................................................................45 
11.1.7 Injection Site Reaction Assessment .......................................................45 
11.1.8 Immunogenicity Assessment ..................................................................45 
11.1.9 Adverse Events .......................................................................................46 
11.1.9.1 Adverse Event Definition ......................................................46 
11.1.9.2 Monitoring .............................................................................46 
11.1.9.3 Reporting ...............................................................................46 
11.1.9.4 Serious Adverse Events .........................................................48 
11.2 Pharmacokinetic Assessments ............................................................................48 
11.2.1 Blood Sampling and Processing .............................................................48 
11.2.2 Analytical Method ..................................................................................49 
11.3 Pharmacodynamic Assessments .........................................................................49 
11.4 Blood Volume for Study Assessments ...............................................................50 


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SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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12. DATA ANALYSIS ......................................................................................................51 
12.1 Statistical Analysis .............................................................................................51 
12.1.1 Sample Size Calculation .........................................................................51 
12.1.2 Subjects to Analyze ................................................................................51 
12.1.3 Safety Analysis .......................................................................................51 
12.1.4 Pharmacokinetic Analysis ......................................................................52 
12.1.4.1 Pharmacokinetic Parameters .................................................52 
12.1.5 Statistical Methods for Pharmacokinetic Analyses ................................54 
12.1.6 Pharmacodynamic Assessments .............................................................54 
12.1.7 Assessment of Efficacy ..........................................................................54 
13. STUDY ADMINISTRATION.....................................................................................55 
13.1 Ethics ..................................................................................................................55 
13.1.1 Institutional Review Board .....................................................................55 
13.1.2 Ethical Conduct of the Study .................................................................55 
13.1.3 Subject Information and Consent ...........................................................55 
13.2 Termination of the Study ....................................................................................55 
13.3 Data Quality Assurance ......................................................................................55 
13.4 Direct Access to Source Data/Documents .........................................................56 
13.5 Study Supplies ....................................................................................................56 
13.6 Data Handling and Record Keeping ...................................................................56 
13.7 Report Format ....................................................................................................57 
13.8 Protocol Amendments ........................................................................................57 
13.9 Publication Policy ..............................................................................................57 
14. REFERENCES ............................................................................................................58 
 
 
LIST OF TABLES 
 
Table 1: 
Product Descriptions ..................................................................................39 
Table 2: 
Blood Volume during the Study ................................................................50 
 
 
 
LIST OF APPENDICES 
 
Appendix 1 
Clinical Laboratory Reference Ranges ......................................................59 
 
 


xisomab 3G3 
SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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CA19214 (3G3-15-01)_Amend 3 Final Protocol_06Nov2017 
5. SYNOPSIS 
Compound 
xisomab 3G3 (anti-FXI monoclonal antibody, IgG4) 
Active Ingredient: xisomab 3G3 (∼15 mg/mL) 
Excipients: 8% sucrose, 10 mM histidine, 30 mM arginine HCl, 
10 mM methionine, 80 ppm polysorbate 80 
Clinical Indication 
Prevention and treatment of venous thrombosis and 
thromboembolism 
Study Phase and 
Type 
Phase 1, single ascending dose (SAD), first-in-human study 
Study Objectives 
The primary objective of the study is to assess the safety and 
tolerability of single intravenous (IV) doses of xisomab 3G3 when 
administered to healthy adult subjects. 
The secondary objectives of the study are as follows: 
1. To assess the pharmacokinetics (PK) of single IV doses of 
xisomab 3G3 when administered to healthy adult subjects. 
2. To assess the pharmacodynamics (PD) of single IV doses of 
xisomab 3G3 when administered to healthy adult subjects. The 
activated partial thromboplastin time (aPTT) will be used as a 
surrogate PD marker. 
Study Design 
This is a randomized, double-blind, placebo-controlled, SAD study 
conducted at one study center in the United States (US). 
Four (4) cohorts of either 6 subjects (Cohort 1 [4 active and 
2 placebo]) or 5 subjects (Cohorts 2, 3, and 4 [4 active and 
1 placebo]) are planned for evaluation. In each cohort, subjects will 
receive a single IV infusion of xisomab 3G3 or placebo. Subjects 
will participate in only one cohort. 
Safety (e.g., physical examinations, vital signs, electrocardiograms 
(ECGs), 
clinical 
laboratory 
tests, 
injection 
site 
reaction, 
immunogenicity, and adverse events [AEs]) will be assessed 
throughout the study; serial blood samples and urine samples will be 
collected for these assessments. 
Blood samples will also be collected for the PK (free xisomab 3G3) 
and PD (aPTT) assessments of xisomab 3G3 at scheduled time points 
as listed in the Study Events Flow Chart (Section 6) for at least 
672 hours postdose. Following the 672-hour time point, sample 
collection for PK and PD assessments will continue every 7 days 


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SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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(± 2 days) until aPTT values return within ±10% of the baseline 
value or the normal range.  
Anti-drug antibodies (ADA) sample collection will be performed on 
Days 15 and 29 for all subjects. If aPTT values remain elevated past 
Day 29, an additional ADA sample collection will occur at the 
follow-up (FU) visit. 
Dose escalation to the next dose level (i.e., next cohort) will not take 
place until the Safety Review Committee (SRC) has determined that 
adequate safety and tolerability of xisomab 3G3 from the current and 
previous cohorts has been demonstrated to permit proceeding to the 
next cohort.  
Interim PK and PD analyses may be performed to reconsider the 
sampling time points as the study progresses and to guide the 
dose-escalation decision.  
Subjects for whom aPTT value reaches ±10% of the baseline value 
or within the normal range by Day 29, will return to the clinical 
research unit (CRU) for the FU visit on Day 36 to perform scheduled 
follow-up procedures and to determine if any AE has occurred since 
the last study visit.  
Subjects for whom aPTT did not reach ±10% of the baseline value 
or within the normal range on Day 29, will return every 7 days 
(±2 days) until aPTT reach ±10% of the baseline value or within the 
normal range and for the FU visit (i.e., follow-up procedures and AE 
evaluation) 7 days (±2 days) after it was reached. If aPTT values 
remain elevated past Day 29, an additional ADA sample collection 
will occur at the FU visit. 
Subjects who terminate the study early will be asked to continue 
aPTT monitoring as scheduled in the Study Events Flow Chart 
(Section 6) until it reaches ±10% of the baseline value or within the 
normal range. They will return to the CRU approximately 7 days 
(±2 days) after aPTT reaches ±10% of the baseline value or within 
normal range for the FU visit to perform scheduled follow-up 
procedures, and to determine if any AE has occurred since the last 
study visit. They will also be asked to return on Days 15 and 29 to 
collect the ADA samples. 
Study Population 
Subjects will be healthy male subjects and healthy female subjects 
of non-childbearing potential. 
Number of 
Subjects 
The study is planned to enroll up to 21 subjects in 4 cohorts. The first 
cohort will enroll 6 subjects; 4 subjects randomized to receive the 
active drug and 2 subjects to receive the placebo. The remaining 3 
cohorts will enroll 5 subjects; 4 subjects randomized to receive the 


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SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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CA19214 (3G3-15-01)_Amend 3 Final Protocol_06Nov2017 
active drug and 1 subject to receive the placebo. In each cohort, at 
least 30% of the subjects must be of a race/ethnicity minority group. 
An attempt will be made to include at least 2 females per cohort. 
Two sentinel subjects will be dosed (one placebo, one active) in 
Cohort 1 and data will be collected through Day 8. The next subject 
in the cohort will be dosed after evaluation of the sentinel subjects’ 
Day 8 safety data. Each subject following these sentinel subjects will 
be dosed with an interval of 24-hour between subjects.  
Subjects in Cohorts 2, 3, and 4 will be dosed at an interval of 
24 hours between subjects. 
Additional subjects (N = 5 subjects per cohort; 4 active and 
1 placebo) may be enrolled if it is deemed appropriate by the SRC to 
repeat a dose level or to study an interim dose level (lower than those 
planned) in a new cohort of subjects.  
Duration of 
Participation for 
Subjects 
The total planned duration of subject participation is up to 63 days 
from screening to follow-up, if aPTT values return within ±10% of 
the baseline value or the normal range by Day 29. This participation 
period could be prolonged if aPTT values did not reach ±10% of the 
baseline value or within the normal range by Day 29. 
Study Products 
Xisomab 3G3 will be supplied as sterile powder for injection via the 
IV route, upon reconstitution. 
Matching placebo will be supplied as sterile powder for injection via 
IV route, upon reconstitution. 
An unblinded pharmacist will be responsible for providing 
xisomab 3G3 or placebo to the blinded study personnel for IV 
infusion. 
Planned Dose 
Levels 
On Day 1, subjects in each cohort will receive a single hand pushed 
IV infusion of xisomab 3G3 or placebo on one occasion. 
Planned doses will be as follows: 
Cohort 1: 0.1 mg/kg xisomab 3G3 or matching placebo 
Cohort 2: 0.5 mg/kg xisomab 3G3 or matching placebo 
Cohort 3: 2 mg/kg xisomab 3G3 or matching placebo 
Cohort 4: 5 mg/kg xisomab 3G3 or matching placebo 
Dosing will not exceed 5 mg/kg without a protocol amendment. 


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Safety 
Assessments 
Safety will be monitored through physical examinations, vital signs, 
ECGs, clinical laboratory tests (including, but not limited to, 
hematology, serum chemistry profile, coagulation, and urinalysis), 
injection site reaction, immunogenicity, and AEs. 
Safety Analysis 
The following analyses will be performed; however no formal 
inferential statistics will be done on safety assessments. 
The placebo subjects from all cohorts will be pooled into a single 
placebo group for all summaries and presentations. 
Descriptive statistics will be calculated for quantitative safety data 
and frequency counts will be compiled for classification of 
qualitative safety data. 
Adverse Events: 
AEs will be coded using the most current version of Medical 
Dictionary for Regulatory Activities® (MedDRA®) available at 
Celerion. 
A by-subject AE data listing, including verbatim term, preferred 
term, treatment, severity, and relationship to drug, will be provided. 
The number of subjects experiencing treatment-emergent adverse 
events (TEAEs) and number of TEAEs will be summarized by 
treatment using frequency counts. 
Injection site reaction will be assessed. 
Medical History and Physical Examination: 
Medical history will be listed by subject. 
Changes in physical examinations will be described in the text of the 
final report. 
Clinical Laboratory Results, Electrocardiograms, and Vital 
Signs Measurements: 
All clinical laboratory results, 12-lead ECGs, vital signs 
measurements, and their change from baseline, will be summarized 
by treatment and time point of collection. 
A shift table describing out-of-normal range shifts will be provided 
for clinical laboratory results. 
Concomitant Medications: 
Concomitant medications will be listed by treatment.  
Immunogenicity: 
ADA detection will be reported and summarized descriptively. 


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Pharmacokinetic 
Sample Collection 
Serial blood samples will be collected prior to and following the dose 
on Day 1 to determine the concentration of free xisomab 3G3 in 
plasma as indicated in the Study Events Flow Chart (Section 6). 
Additional analysis for exploratory purposes, including but not 
limited to factor XIa activity, will be performed on leftover plasma 
samples at the Sponsor’s discretion. 
The sampling schedule may be modified based on the results from 
previous cohorts. 
Note: the sample times for PK collection are in relation to the start 
of infusion. 
Pharmacokinetic 
Parameters and 
Analysis 
The following non-compartmental PK parameters will be calculated 
for free xisomab 3G3 in plasma, as appropriate: 
AUC0-t, AUC0-inf, AUC%extrap, Cmax, Tmax, Kel, T½, MRT, CL, and Vss.  
Additional PK parameters may be calculated if deemed appropriate. 
PK parameters will be summarized by treatment using descriptive 
statistics. 
Pharmacodynamic 
Assessment 
Serial blood samples will be collected prior to and following the dose 
on Day 1 for aPTT as indicated in the Study Events Flow Chart 
(Section 6).  
Pharmacodynamic 
Analysis 
aPTT values will be listed and presented graphically. PD parameters 
may be calculated if deemed appropriate. 


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CA19214 (3G3-15-01)_Amend 3 Final Protocol_06Nov2017 
6. STUDY EVENTS FLOW CHART 
Study Procedures a 
Screening b 
Study Days 
FU c 
Days → 
-1 
1 
2 
4 
6 
8 
10 
15 
22 
29 
Hours → 
C-I d 
0 
0.083 0.25 
0.5 
1 
3 
8 
24 
72 
120 
168 
216 
336 
504 
672 
Administrative Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Safety Evaluations 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Full Physical Examination e 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviated Physical Examination 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
 
 
X f 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-Lead Electrocardiogram 
X 
 
X g 
 
X 
 
 
 
 
 
 
 
X  
 
 
 
X f 
X 
Vital Signs (HR, BP, RR, and T) 
X 
 
X g 
 
X 
 
 
 
 
 
 
 
X  
 
 
 
X f 
X 
Hem, Serum Chem h, and UA  
X 
X 
 
 
 
 
 
 
X 
X 
 
 
X  
 
 
 
X f 
X 
Coagulation (PT/INR) i 
X 
X 
 
 
 
 
X 
 
 
X 
X 
 
X 
 
 
 
X f  
X 
Coagulation (aPTT) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Bleeding Time j 
 
X 
X k 
 
 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
Serum Pregnancy Test (females only) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Serum FSH (postmenopausal females only) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Alcohol/Drug Screen 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV/Hepatitis Screen 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse Events Monitoring 
 
X 
X 
Concomitant Medication Monitoring 
X 
X 
 
Study Drug Administration / PK / PD / 
Immunogenicity 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xisomab 3G3/Placebo Administration 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood for free xisomab 3G3 PK l 
 
 
X k 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Blood for xisomab 3G3 PD (aPTT) l 
 
 
X k 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Blood for Immunogenicity 
 
 
X k 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
X m 


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Study Procedures a 
Screening b 
Study Days 
FU c 
Days → 
-1 
1 
2 
4 
6 
8 
10 
15 
22 
29 
Hours → 
C-I d 
0 
0.083 0.25 
0.5 
1 
3 
8 
24 
72 
120 
168 
216 
336 
504 
672 
Other Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Injection Site Reaction 
 
 
X k 
 
 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
Confinement in the CRU i 
 
X 
 
 
 
 
 
 
 
 
Visit and Return Visits  i 
X 
 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
a: 
For details on Procedures, refer to Section 11. 
b:  Within 28 days prior to the study drug administration. 
c: 
Subjects for whom aPTT value reaches ± 10% of the baseline value or within the normal range by Day 29, will return to the CRU for the FU visit on Day 36 to perform 
scheduled follow-up procedures, and to determine if any AE has occurred since the last study visit. 
Subjects for whom aPTT did not reach ± 10% of the baseline value or within the normal range on Day 29, will return every 7 days (±2 days) until aPTT reach ±10% of the 
baseline value or within the normal range and for the FU visit (i.e., follow-up procedures and AE evaluation) 7 days (± 2 days) after it was reached. 
Subjects who terminate the study early will be asked to continue aPTT monitoring as scheduled until it reaches ± 10% of the baseline value or within the normal range. They 
will return to the CRU approximately 7 days (± 2 days) after aPTT reaches ± 10% of the baseline value or within normal range for the FU visit to perform scheduled follow-
up procedures, and to determine if any AE has occurred since the last study visit. They will also be asked to return on Days 15 and 29 to collect the ADA samples. 
d: 
Subjects will be admitted to the CRU on Day -1, at the time indicated by the CRU. 
e: 
Symptom-driven physical examination may be performed at other times, at the PI’s or designee discretion. 
f: 
To be performed on Day 29 or at early termination. 
g: 
To be performed within 24 hours prior to dosing. 
h: 
Samples for serum chemistry will be obtained following a fast of at least 8 hours (except for the 8-hour time point), however, in case of dropouts or rechecks, subjects may 
not have fasted for 8 hours before the serum chemistry sample is taken. 
i: 
If PT/INR values are ≤ 3.5 and judged not clinically significant by the PI or designee, the subject will be released from the CRU. Subject will need to return to the CRU at 
least 2 days after discharge to confirm these values. 
j: 
Bleeding time will be performed on both subject’s arm at each scheduled time point. 
k: 
To be performed prior to dosing. 
l: 
aPTT and free xisomab 3G3 blood samples will be collected for at least 672 hours and until aPTT values return within ± 10% of baseline value or the normal range. If by Day 
29, aPTT has not returned to baseline or normal range, sampling will continue every 7 days (± 2 days) until the ± 10% of baseline value or the normal range was reached or, 
as per PI discretion, a maximum of ~500 mL of blood was collected from the subject. Subjects who terminate the study early will return every 7 days (± 2 days) for aPTT 
monitoring until aPTT values return within ± 10% of baseline value or the normal range. 
m: An additional ADA sample will be collected at the FU visit only in the event that the FU visit occurs after Day 36. 
 
Abbreviations: ADA = anti-drug antibodies, aPTT = Activated partial thromboplastin time, BP = Blood pressure, C-I = Check-in, Chem = Chemistry, CRU = Clinical research 
unit, FSH = Follicle-stimulating hormone, FU = Follow-up, Hem = Hematology, HIV = Human immunodeficiency virus, HR = Heart rate, INR = International normalized ratio, 
PD = Pharmacodynamic, PI = Principal Investigator, PK = Pharmacokinetics, PT = Prothrombin time, RR = Respiratory rate, T = Temperature, UA = Urinalysis. 


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Celerion Project No.: CA19214 
US PIND No.: 127850 
 
Page 19 
CA19214 (3G3-15-01)_Amend 3 Final Protocol_06Nov2017 
7. ABBREVIATIONS 
ADA 
Anti-drug antibodies 
AE 
Adverse event 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
aPTT 
Activated partial thromboplastin time 
AST 
Aspartate aminotransferase 
AUC 
Area under the concentration-time curve 
AUC%extrap 
Percent of AUC0-inf extrapolated  
AUC0-inf 
Area under the concentration-time curve, from time 0 extrapolated 
to infinity 
AUC0-t 
Area under the concentration-time curve, from time 0 to the last 
observed non-zero concentration (t) 
BMI 
Body mass index 
BP 
Blood pressure 
bpm 
Beats per minute 
BUN 
Blood urea nitrogen 
°C 
Degrees Celsius 
CFR 
Code of Federal Regulations 
Chem 
Chemistry 
CL 
Apparent total plasma clearance 
cm 
Centimeter 
Cmax 
Maximum observed concentration  
CRF 
Case report form 
CRU 
Clinical Research Unit 
dL 
Deciliter 
ECG 
Electrocardiogram 
FDA 
Unites States Foods and Drug Administration 
FIX 
Factor IX 
FSH 
Follicle-stimulating hormone 
FU 
Follow-up  


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FXI 
Factor XI 
FXIa 
Activated factor XI 
FXII 
Factor XII 
FXIIa 
Activated factor XII 
g 
Gram 
GCP 
Good clinical practice 
GLP 
Good laboratory practice 
h 
Hour 
HBsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C virus 
HIV 
Human immunodeficiency virus 
HR 
Heart rate 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
IL 
Interleukin 
IND 
Investigational New Drug 
INR 
International normalized ratio 
IRB 
Institutional Review Board 
IV 
Intravenous 
Kel 
Apparent terminal elimination rate constant 
kg 
Kilogram 
L 
Liter 
LDH 
Lactate dehydrogenase 
LLN 
Lower limit of normal 
μg 
Microgram 
m2 
Meters squared 
MABEL 
Minimum anticipated biological effect level 
MedDRA® 
Medical Dictionary for Regulatory Activities® 
mg 
Milligram 
mL 
Milliliter 


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mmHg 
Millimeter of mercury 
MRSD 
Maximum recommended starting dose 
MRT 
Mean residence time 
msec 
Millisecond 
MTD 
Maximum tolerated dose 
No. 
Number 
NOAEL 
No observed adverse effect level 
oz 
Ounce 
PBMC 
Peripheral blood mononuclear cells 
PD 
Pharmacodynamics 
PI 
Principal Investigator 
PK 
Pharmacokinetics 
PT 
Prothrombin time 
QA 
Quality assurance 
QTcF 
Friderica’s correction 
SAD 
Single ascending dose 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SOP 
Standard operating procedure 
SRC 
Safety review committee 
T½ 
Apparent terminal elimination half-life 
TEAE 
Treatment-emergent adverse event 
Tmax 
Time to reach maximum observed concentration 
UA 
Urinalysis 
US 
Unites States of America 
USA 
United States of America 
Vd 
Apparent volume of distribution 
Vss 
Total apparent volume of distribution following single IV dose 
 


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8. BACKGROUND AND RATIONALE 
8.1 
Introduction 
This study is being conducted as the first in a series of studies for the clinical development of 
xisomab 3G3. The trial will be conducted in compliance with the protocol, Good Clinical 
Practice (GCP), and applicable regulatory requirements. The subject population will be 
comprised of healthy adult male and/or female subjects. 
A brief overview of available information regarding xisomab 3G3 follows below. Details can 
be found in the xisomab 3G3 Investigator’s Brochure (IB). 1 
8.2 
Background 
Xisomab 3G3 is a novel, injectable, therapeutic monoclonal antibody that inhibits activation 
of the contact (intrinsic) pathway of coagulation and is intended to address the problem of 
dose limiting bleeding side effects of current antithrombotic agents. Xisomab 3G3 was 
developed by Aronora, Inc. and the current formulation is intended for IV administration. 
The proposed indications for xisomab 3G3 include prevention or treatment of thrombotic and 
thromboembolic diseases, such as venous thrombosis and thromboembolism. 
Aronora, Inc. has conducted a comprehensive nonclinical pharmacology and toxicology 
program in support of clinical development of xisomab 3G3. Experimental evidence suggests 
that contact pathway activation promotes thrombosis, but it has no known role in normal 
hemostasis. Contact pathway activation is initiated by auto-activation of coagulation Factor 
XII (FXII) on negatively charged surfaces. Activated FXII (FXIIa) then activates coagulation 
Factor XI (FXI), which then activates coagulation Factor IX (FIX) and ultimately leads to 
generation of the procoagulant enzyme thrombin from prothrombin. The therapeutic 
monoclonal antibody xisomab 3G3 binds the apple 2 domain of FXI and therefore interferes 
with the activation of FXI by FXIIa. Importantly, this interaction selectively prevents 
activation of FXI by FXIIa without interfering with the vasoregulatory activities of FXIIa or 
the hemostatic feedback activation of FXI by thrombin, or other mechanisms, nor does it 
interfere with the catalytic activity of activated FXI (FXIa) on its hemostatic substrates. 
Because FXIIa does not contribute to the hemostasis of mammalian species, and activation of 
FXI by FXIIa is a pathological event that appears to promote thrombosis in experimental 
animals, inhibition of FXI activation by FXIIa using xisomab 3G3 is expected to be a safe 
and effective antithrombotic intervention in humans who are at risk or have developed 
thrombosis. 
The goal of xisomab 3G3 treatment is to achieve safe anticoagulation for several days with a 
single dose. A single dose of xisomab 3G3 demonstrated potent and sustained antithrombotic 
effects in both mice and nonhuman primate models, and showed no toxicity at and above 
saturating doses in nonclinical Good laboratory Practice (GLP) toxicity studies in rats and 
cynomolgus monkeys. Saturation of binding to the molecular target and the maximum FXI 
inhibitory effect is achieved at a relatively low dose of xisomab 3G3 because FXI circulates 
at a low plasma concentration (3 to 10 mg/L), and the antibody has high affinity toward FXI. 
The effect of increasing the dose above the saturating level results in prolongation of 


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anticoagulation in a dose-dependent manner. Since there has been no observed toxicity 
associated with a dose more than 50-fold over the predicted effective target dose in humans 
as determined by GLP toxicity studies in both rats and nonhuman primates, the therapeutic 
index is expected to be very high. 
8.3 
Nonclinical Studies 
8.3.1 Pharmacology 
Inhibition of the contact pathway of coagulation by xisomab 3G3 or its murine precursor, 
xisomab 14E11, is antithrombotic as demonstrated by both in vitro and in vivo aPTT 
prolongation and in several experimental animal models of thrombosis, including a mouse 
model of FeCl3-induced arterial thrombosis (Study No. AB023.4), a mouse model of sepsis 
(Study No. AB022.4), and a well-established model of thrombosis in baboons (Study 
No. AB023.5). Importantly, while treatment with xisomab 3G3 or 14E11 attenuated 
thrombosis in these experimental models of thrombosis, no demonstrable effect on 
hemostasis was observed. These data suggest that in contrast to currently marketed 
antithrombotics that target elements of the coagulation cascade important for both thrombosis 
and hemostasis, xisomab 3G3 is designed to selectively inhibit thrombosis without increasing 
risk of bleeding side effects. 
8.3.2 Pharmacokinetics 
Pharmacokinetics were evaluated in a non-GLP study in baboons (Papio Anubis) in which 
1 mg/kg of xisomab 3G3 was administered by IV injection and free xisomab 3G3 plasma 
concentration was measured over time. Non-compartmental analysis of the xisomab 3G3 
plasma concentration versus time curve revealed the maximal plasma concentrations 
normalized to dose (Cmax/Dose) was 19.66 ± 0.56 L/kg, the area under the concentration time 
curve from time 0 to the last time point measured post-dose normalized to dose 
(AUC0-xh/Dose) was 1594 ± 82 kg x h/L, and the apparent volume of distribution (Vd) was 
0.050 ± 0.0012 L/kg. Group mean terminal elimination half-lives (T½) ranged from 45 to 
75 hours and the mean residence time (MRT) ranged from 88 to 110 hours in baboons after a 
1 mg/kg IV injection.  
In addition, toxicokinetics were evaluated as part of the pivotal toxicity studies in 
cynomolgus monkey and Sprague Dawley rats. In both studies, IV doses of 0, 2, 10, and 
50 mg/kg of xisomab 3G3 were administered by IV bolus injection. All animals except 
controls showed systemic exposure to xisomab 3G3 following single IV dose. IV infusions of 
xisomab 3G3 in cynomolgus monkeys resulted in peak free xisomab 3G3 plasma 
concentrations at the first or second time point evaluated, approximately 0.5 - 3 hours 
following administration. Maximum concentrations remained generally sustained and 
therefore the terminal elimination phase was not well characterized for most profiles. In the 
absence of the recovery data for the main study animals, the terminal elimination phase could 
only be estimated with confidence for one male who received 10 mg/kg, with T½, CL and Vd 
of 31.9 hours, 0.513 mL/h/kg, and 23.6 mL/kg, respectively. Inclusion of the recovery 
animals (n = 2/sex/group) for all dose levels allowed for better characterization of the 
terminal elimination phase, however, it could only be estimated for six out of twelve 


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recovery animals. Consequently, individual T½ were longer and ranged from 61.4 to 248 
hours. Individual CL and Vd were estimated between 0.142 and 0.535 mL/h/kg and 34.0 and 
57.8 mL/kg, respectively. 
IV infusions of xisomab 3G3 in rats resulted in peak xisomab 3G3 plasma concentrations at 
the first or second time point evaluated, approximately 0.5 - 3 hours following 
administration. The terminal elimination phase was only characterized for the males and 
females at the 50 mg/kg dose level, as the terminal elimination phase for the 2 and 10 mg/kg 
dose levels was not reported due to either a coefficient of determination less than 0.800 or the 
extrapolation of the AUC to infinity represented more than 20% of the total area. The T½ for 
the males and females at the 50 mg/kg dose level was 155 hours and 185 hours respectively. 
The average volume of distribution (Vd) was 45.2 mL/kg and 45.3 mL/kg for the males 
respectively and the clearance (CL) was 0.202 and 0170 mL/h/kg for the males and females 
respectively. 
8.3.3 Toxicology 
The safety and toxicity profile of xisomab 3G3 was evaluated in two, GLP, single dose acute, 
toxicity studies in Sprague Dawley rats and cynomolgus monkeys. In both studies, a single 
dose of xisomab 3G3 was administered intravenously at doses of 0, 2, 10 and 50 mg/kg and 
animals were evaluated for 3 days (main group) and 28 days (recovery group) after dosing. 
Xisomab 3G3 was well tolerated in both species and no xisomab 3G3-related AEs were 
observed. An expected aPTT prolongation was observed in all groups dosed with xisomab 
3G3, and the duration of effect was dose dependent. In the cynomolgus monkey study, there 
was no difference in aPTT prolongation between males and females. The prolonged aPTT 
was first observed 30 minutes after dosing (the first time point evaluated) and persisted until 
336 hours postdose (Day 15) at 2 mg/kg and 672 hours postdose (Day 29) at 10 and 50 
mg/kg. Similarly, in the Sprague Dawley rats study, prolonged aPTT was first observed at 
30 minutes post-dose (the first time point evaluated) and was generally of similar magnitude 
across the dose groups and genders; the duration of the effect increased with increasing dose. 
The No Observed Adverse Effect Levels (NOAEL) for both studies was determined to be 50 
mg/kg. In addition to the toxicity studies, a GLP tissue cross reactivity study was performed 
in a panel of human tissue to assess potential cross-reactivity of xisomab 3G3. No xisomab 
3G3-related staining was observed in any of the human tissue samples (36 tissue types from 
3 normal healthy donors). Cytokine release assays performed in peripheral blood 
mononuclear cells (PBMCs) from 10 healthy donors revealed that xisomab 3G3, presented in 
three different stimulation formats, did not stimulate the release of interleukin (IL)-2, IL-4, 
IL-6, IL-10, tumor necrosis factor alpha or interferon gamma from PBMCs of any of the 
donors. 


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8.4 
Rationale 
8.4.1 Purpose of the Study 
This clinical trial will be a SAD study of xisomab 3G3 administered as an IV infusion. When 
developing new drugs for clinical indications, it is necessary to collect data on the safety, 
tolerability, and PK in order to support further development of the compound as a useful 
clinical candidate. This study will establish safety and tolerability profiles for xisomab 3G3 
and will allow identifications of recommended dose levels and dose intervals in Phase 2 and 
subsequent studies. 
8.4.2 Dose Selection 
Xisomab 3G3 appeared well tolerated in a panel of standard animal toxicology studies. Since 
this is the initial study in humans, the initial dose of xisomab 3G3 has been justified 
conservatively according to the US Food and Drug Administration (FDA) guidance 
document “Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for 
Therapeutics in Adult Healthy Volunteers”. 2  
The proposed clinical starting dose of 0.1 mg/kg was estimated based on the NOAEL 
determined by the toxicity studies, the pharmacologically active dose (PAD) from the non-
GLP in vivo efficacy studies in baboons, in vitro aPTT studies in pooled human plasma, and 
an understanding of the mechanism of action of xisomab 3G3 and its target, FXI. As 
recommended by the Guidance, 2 scaling based on body weight rather than body surface area 
will be used because the NOAEL determined in both the rat and nonhuman primate GLP 
toxicity studies occur at the same mg/kg dose and xisomab 3G3 is a monoclonal antibody to 
be administered intravascularly whose molecular weight is greater than 100,000 Daltons. 2 
On the basis of no adverse effects noted in the toxicity studies, the NOAEL was determined 
to be 50 mg/kg in both species. Using the regulatory guidance for estimating a safe starting 
dose in humans, the maximum recommended starting dose (MRSD) based on the NOAEL 
from the toxicology studies with a default safety factor of 10 applied was determined to be 
5 mg/kg. The PAD determined by the non-GLP in vivo efficacy studies in baboons was 1 
mg/kg and is, therefore, 5-fold lower than the MRSD based on the NOAEL. Dividing the 
PAD by a safety factor of 10 would provide a very conservative starting dose of 0.1 mg/kg. 
The selection of 0.1 mg/kg for the first in human starting dose is further supported when 
using the minimum anticipated biological effect level (MABEL) to select a starting dose. 
Using in vitro aPTT data from pooled human plasma in which the EC10 was calculated to be 
the equivalent of 0.11 mg/kg and knowledge of the xisomab 3G3 mechanism of action, the 
MABEL is estimated to be approximately 0.1 mg/kg. This dose is anticipated to produce a 
minimal biological effect in most human subjects. 
The expected maximum level of anticoagulation is estimated to be achieved at or below a 
dose of 1 mg/kg based on the effect of xisomab 3G3 or its murine precursor, xisomab 14E11, 
on the contact pathway of coagulation as demonstrated by both in vitro and in vivo aPTT 
prolongation in pooled human plasma (Study No. AB023.1) and in several experimental 
animal models of thrombosis, including a mouse model of FeCl3-induced arterial thrombosis 
(Study No. AB023.4), a mouse model of sepsis (Study No. AB022.4), and a well-established 


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model of thrombosis in baboons (Study No. AB023.5). 
The doses will be escalated until a dose of 5 mg/kg is reached, in order to provide a broad 
range of doses available for the subsequent studies patients with thrombotic disease and 
maintain a safety margin of 10-fold below the NOAEL determined in both pivotal GLP 
toxicity studies.  
Therefore, the present first-in-human dose escalation study will initiate single doses at 
0.1 mg/kg and may escalate doses up to 5 mg/kg depending on the safety and dose tolerance 
parameters observed at each dose level during the study. Dosing will not exceed 5 mg/kg 
without a protocol amendment. 
8.5 
Risk/Benefit 
The safety monitoring practices employed by this protocol (e.g., physical examination, vital 
signs, 12-lead ECG, hematology, serum chemistry, urinalysis, coagulation, injection site 
reaction monitoring, and AE questioning) are adequate to protect the subjects’ safety and 
should detect all expected TEAEs. 
As there is a potential to develop an immune response to a biologic agent, immunogenicity 
will be assessed in this study.  
The approximate volume of blood planned for collection from each subject over the course of 
the study (see Section 11.4), presents no undue risk to the subjects nor does the possibility of 
collection (for wasting to ensure clean sample) of additional blood in the event an indwelling 
cannula is utilized and the possibility of additional blood for recheck of safety labs if deemed 
necessary by the PI or designee. 
There will be no direct health benefit for trial participants from receipt of study drug. An 
indirect health benefit to the healthy subjects enrolled in this trial is the free medical tests 
received at screening and during the study. 
 
 


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9. STUDY OBJECTIVES AND ENDPOINTS 
9.1 
Study Objectives 
The primary objective of the study is to assess the safety and tolerability of single IV doses 
of xisomab 3G3 when administered to healthy adult subjects. 
The secondary objectives of the study are as follows: 
1. To assess the PK of single IV doses of xisomab 3G3 when administered to healthy adult 
subjects. 
2. To assess the PD of single IV doses of xisomab 3G3 when administered to healthy adult 
subjects. The aPTT will be used as a surrogate PD marker. 
9.2 
Study Endpoints 
The primary endpoints of the study will be the number and severity of TEAEs following 
single doses of xisomab 3G3 and placebo. 
The secondary endpoints are as follows: 
1. The following PK parameters of free xisomab 3G3 in plasma following single IV dose, 
will be calculated, as appropriate: AUC0-t, AUC0-inf, AUC%extrap, Cmax, Tmax, Kel, T½, 
MRT, CL, and Vss. 
2. aPTT values will be listed and presented graphically. PD parameters for aPTT following 
single IV doses of xisomab 3G3 may be calculated if deemed appropriate. 
 
 


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10. INVESTIGATIONAL PLAN 
10.1 Overall Study Design and Plan  
This is a randomized, double-blind, placebo-controlled, SAD study conducted at one study 
center in the US. 
Four (4) cohorts of either 6 subjects (Cohort 1 [4 active and 2 placebo]) or 5 subjects 
(Cohorts 2, 3, and 4 [4 active and 1 placebo]) are planned for evaluation. In each cohort, 
subjects will receive a single IV infusion of xisomab 3G3 or placebo. Subjects will 
participate in only one cohort. 
Safety (e.g., physical examinations, vital signs, ECGs, clinical laboratory tests, injection site 
reaction, immunogenicity, and AEs) will be assessed throughout the study; serial blood 
samples and urine samples will be collected for these assessments. 
Blood samples will also be collected for the PK (free xisomab 3G3) and PD (aPTT) 
assessments of xisomab 3G3 at scheduled time points as listed in the Study Events Flow 
Chart (Section 6) for at least 672 hours postdose. Following the 672-hour time point, sample 
collection for PK and PD assessments will continue every 7 days (± 2 days) until aPTT 
values return within ±10% of the baseline value or the normal range.  
ADA sample collection will be performed on Days 15 and 29 for all subjects. If aPTT values 
remain elevated past Day 29, an additional ADA sample collection will occur at the FU visit. 
Dose escalation to the next dose level (i.e., next cohort) will not take place until the SRC has 
determined that adequate safety and tolerability of xisomab 3G3 from the current and 
previous cohorts has been demonstrated to permit proceeding to the next cohort.  
Interim PK and PD analyses may be performed to reconsider the sampling time points as the 
study progresses and to guide the dose-escalation decision.  
See the planned dose escalations in Section 10.4.1.2. 
10.1.1 Confinement, Return Visits, and Follow-Up 
Subjects will be housed on Day -1, at the time indicated by the CRU, until after the 24-hour 
blood draw and/or study procedures. Subjects will only be discharged if the prothrombin time 
(PT)/international normalized ratio (INR) values are ≤ 3.5 and judged not clinically 
significant by the PI or designee. Subject will need to return to the CRU at least 2 days after 
discharge to confirm the PT/INR values. 
Subjects will return for study procedures as indicated in the Study Events Flow Chart 
(Section 6). At all times, a subject may be required to remain at the CRU for longer at the 
discretion of the PI or designee. 
Subjects for whom aPTT value reaches ±10% of the baseline value or within the normal 
range by Day 29, will return to the CRU for the FU visit on Day 36 to perform scheduled 


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follow-up procedures and to determine if any AE has occurred since the last study visit. 
Subjects for whom aPTT did not reach ±10% of the baseline value or within the normal 
range on Day 29, will return every 7 days (±2 days) until aPTT reach ±10% of the baseline 
value or within the normal range and for the FU visit (i.e., follow-up procedures and AE 
evaluation) 7 days (±2 days) after it was reached. If aPTT values remain elevated past Day 
29, an additional ADA sample collection will occur at the FU visit. 
Subjects who terminate the study early will be asked to continue aPTT monitoring as 
scheduled in the Study Events Flow Chart (Section 6) until it reaches ±10% of the baseline 
value or within the normal range. They will return to the CRU approximately 7 days 
(±2 days) after aPTT reaches ± 10% of the baseline value or within normal range for the FU 
visit to perform scheduled follow-up procedures and to determine if any AE has occurred 
since the last study visit. They will also be asked to return on Days 15 and 29 to collect the 
ADA samples. 
10.1.2 Study Duration 
The total planned duration of subject participation is up to 63 days from screening to follow-
up, if aPTT value returns within ±10% of the baseline value or the normal range by Day 29. 
This participation period could be prolonged if aPTT values did not reach ±10% of the 
baseline value or within the normal range by Day 29. 
10.2 Study Conduct 
Please see the Study Events Flow Chart for a summary of the schedule of study participation 
and procedures in Section 6. 
10.2.1 Screening 
Screening will begin within 28 days prior to dosing. Informed consent will be obtained at 
screening (see Section 13.1.3). Subjects will have to meet all eligibility criteria before being 
enrolled in the study (see Section 10.3). Subjects will be informed of the study restrictions 
(see Section 10.3.5). 
The following will be recorded at screening: medical history and demographic data, 
including name, sex, age, race, ethnicity, body weight (kg), height (cm), body mass index 
(BMI) (kg/m2), and history of alcohol and tobacco use. 
Screening procedures are listed in the Study Events Flow Chart Section 6. 
10.2.2 Check-in Procedures (Day -1) 
At check-in (Day -1), subjects will return to the CRU, and those subjects who satisfy all of 
the inclusion criteria and none of the exclusion criteria will qualify and be eligible for 
randomization. A check-in questionnaire will be reviewed for each subject to ensure that 
subjects remain eligible for the study since screening. Questions will focus on inclusion and 
exclusion criteria and on study restrictions. 
Check-in procedures are listed in the Study Events Flow Chart (see Section 6). 


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10.2.3 Treatment Period (Day 1 to Day 29) 
10.2.3.1 Single-dose Administration (Day 1) and Study Procedures (Days 1 to 29) 
On the morning of Day 1, predose evaluations will be obtained. 
Subjects will receive a single IV infusion dose of the assigned formulation (xisomab 3G3 or 
placebo) on the morning of Day 1. See Section 10.4.1 and Section 10.4.3. 
Safety and tolerability will be monitored throughout the treatment period as listed in the 
Study Events Flow Chart (see Section 6). 
Blood samples for PK and PD assessments (see Section 11.2.1 and Section 11.3) will be 
collected at the time points listed in the Study Events Flow Chart (see Section 6), for at least 
672 hours postdose. Following the 672-hour time point, sample collection for PK and PD 
assessments will continue every 7 days (± 2 days) until aPTT values return within ±10% of 
the baseline value or the normal range, as indicated in in the Study Events Flow Chart (see 
Section 6). ADA sample collection will be performed on Days 15 and 29 for all subjects. 
10.2.3.2 Meal Schedule 
Water will be allowed ad libitum at all times. Other fluids may be given as part of meals and 
snacks but will be restricted at all other times throughout the confinement period. 
At the CRU, standard meals and snacks will be provided at appropriate times. When confined 
in the CRU, subjects will be required to fast from all food and drink except water between 
meals and snacks. 
Each meal and/or snack served at the CRU will be standardized and will be similar in caloric 
content and composition. The same menu and meal schedule will be administered uniformly 
for all subjects for all cohorts. 
Subjects will be required to fast for at least 8 hours before the clinical laboratory tests at 
screening and before the clinical laboratory tests at other scheduled times (except for the 
8-hour time point). However, in case of dropouts or rechecks, subjects may not have fasted 
for 8 hours before the serum chemistry sample is taken. 
10.2.3.3 Day 29 Study Procedures 
Before leaving the CRU facility on Day 29, all subjects will undergo all study procedures 
listed on Day 29 in the Study Events Flow Chart (see Section 6). In the event that aPTT 
values did not return within ±10% of the baseline value or the normal range, sampling will 
continue every 7 days (±2 days) , as indicated in in the Study Events Flow Chart (see 
Section 6), until ±10% of the baseline value or the normal range is reached.  


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10.2.4 Follow-up Visit 
Subjects for whom aPTT value reaches ±10% of the baseline value or within the normal 
range by Day 29 will return to the CRU for the FU visit on Day 36 to perform scheduled 
follow-up procedures and to determine if any AE has occurred since the last study visit. 
Subjects for whom aPTT did not reach ±10% of the baseline value or within the normal 
range on Day 29, will return every 7 days (±2 days) until aPTT reach ±10% of the baseline 
value or within the normal range and for the FU visit (i.e., follow-up procedures and AE 
evaluation) 7 days (±2 days) after it was reached. If aPTT values remain elevated past 
Day 29, an additional ADA sample collection will occur at the FU visit. 
Subjects who terminate the study early will be asked to continue aPTT monitoring as 
scheduled in the Study Events Flow Chart (Section 6) until it reaches ±10% of the baseline 
value or within the normal range. They will return to the CRU approximately 7 days 
(±2 days) after aPTT reaches ±10% of the baseline value or within normal range for the FU 
visit to perform scheduled follow-up procedures, and to determine if any AE has occurred 
since the last study visit. They will also be asked to return on Days 15 and 29 to collect the 
ADA samples. 
The follow-up procedures are listed in the Study Events Flow Chart (see Section 6). 
10.2.5 Scheduled End of Study 
The end of the study is scheduled after completion of the evaluations in the 4 cohorts or after 
dose-limiting clinical safety endpoints have been reached to preclude further increases of 
dose.  
10.3 Selection of Study Population 
10.3.1 Number of Subjects 
The study is planned to enroll up to 21 subjects in 4 cohorts. The first cohort will enroll 
6 subjects; 4 subjects randomized to receive the active drug and 2 subjects to receive the 
placebo. The remaining 3 cohorts will enroll 5 subjects; 4 subjects randomized to receive the 
active drug and 1 subject to receive the placebo per the randomization. In each cohort, at 
least 30% of the subjects must be of a race/ethnicity minority group. An attempt will be made 
to include at least 2 females per cohort.  
Two sentinel subjects will be dosed (one placebo, one active) in Cohort 1 and data will be 
collected through Day 8 as described in the Study Events Flow Chart (Section 6). The next 
subject in the cohort will be dosed after evaluation of the sentinel subjects’ Day 8 safety data. 
Each subject following these sentinel subjects will be dosed with an interval of 24-hour 
between subjects 
Subjects in Cohorts 2, 3, and 4 will be dosed at an interval of 24 hours between subjects. 
Additional subjects (N = 5 subjects per cohort; 4 active and 1 placebo) may be enrolled if it is 
deemed appropriate by the SRC to repeat a dose level or to study an interim dose level (lower 
than those planned) in a new cohort of subjects. 


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10.3.2 Inclusion Criteria 
Subjects must fulfill all of the following inclusion criteria to be eligible for participation in 
the study, unless otherwise specified: 
1. Healthy adult male and/or female (non-childbearing potential only), 18 to 48 years of 
age, inclusive, at screening. 
2. Continuous non-smoker who has not used nicotine-containing products for at least 
3 months prior to dosing and throughout the study. 
3. Body mass index (BMI) ≥ 19 and ≤ 29.0 (kg/m2) and weight between 50 and 125 kg 
(inclusive) at screening.  
4. Medically healthy with no clinically significant medical history, physical examination, 
laboratory profiles, vital signs or ECGs, as deemed by the PI or designee. 
5. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase 
(ALP), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), creatinine must be 
between the lower limit of normal (LLN; or up to 15% below LLN as not indicative of 
hepatic or renal disease in healthy subjects) and the upper limit of normal, inclusive, as 
indicated in Appendix 1 at screening and check-in. 
6. aPTT, PT/INR, and platelets, must be within the limits of normal, inclusive, as indicated 
in Appendix 1 at screening and check-in. 
7. Bleeding time must be between 2 to 8 minutes, inclusive, at check-in. 
8. For a female of non-childbearing potential: must have undergone one of the following 
sterilization procedures at least 6 months prior to dosing: 
• hysteroscopic sterilization; 
• bilateral tubal ligation or bilateral salpingectomy; 
• hysterectomy; 
• bilateral oophorectomy; 
or be postmenopausal with amenorrhea for at least 1 year prior to dosing and 
follicle-stimulating hormone (FSH) serum levels consistent with postmenopausal status 
as per PI or designee judgment. 
9. A non-vasectomized male subject whose sexual partner is sterile or was advised to use 
one of the following during the course of the study (or prior to study as specified) and for 
90 days following dosing:  
• Abstain from sexual intercourse; 


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• An intrauterine device with spermicide; 
• A physical barrier method (e.g., male or female condom, contraceptive sponge, 
diaphragm, cervical cap) with spermicide; 
• An intravaginal system (e.g., NuvaRing®) for at least 3 months prior to dosing; 
• An oral, implantable, transdermal, or injectable hormonal contraceptive for at least 3 
months prior to dosing. 
No restrictions are required for a vasectomized male provided his vasectomy has been 
performed 4 months or more prior to dosing. A male who has been vasectomized less 
than 4 months prior to dosing must follow the same restrictions as a non-vasectomized 
male. 
10. If male, must agree to not donate sperm from dosing until 90 days after dosing. 
11. Understands the study procedures in the informed consent form (ICF), and be willing and 
able to comply with the protocol. 
10.3.3 Exclusion Criteria 
Subjects will be excluded from the study if there is evidence of any of the following criteria 
at screening or check-in, as appropriate.  
1. Subject is mentally or legally incapacitated or has significant emotional problems at the 
time of the screening visit or expected during the conduct of the study. 
2. History or presence of clinically significant medical or psychiatric condition or disease in 
the opinion of the PI or designee. 
3. History of any illness that, in the opinion of the PI or designee, might confound the 
results of the study or poses an additional risk to the subject by their participation in the 
study. 
4. History or presence of drug abuse within the last 2 years prior to dosing. 
5. History of alcoholism within the last 2 years prior to dosing or a current history of 
imbibing 3 or more units of alcohol per day (1 unit is equivalent to 150 mL of wine or 
360 mL of beer or 45 mL of 45% alcohol). 
6. History or presence of hypersensitivity or idiosyncratic reaction to the study drug, any 
ingredients of the study drug, or related compounds. 
7. History of a clinically significant allergy of any kind including a history of allergic or 
hypersensitivity reactions to any drugs. 


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8. History or presence of: 
• Bleeding disorder(s) and/or at risk of bleeding, including relevant familial history; 
• Clinically significant anemia, in the opinion of the PI or designee; 
• Thromboembolic disease; 
• Bleeding in the gastrointestinal tract or central nervous system. 
9. Allergy to rodents. 
10. Had a minor surgery or major physical injury less than 4 weeks or major surgery less than 
12 weeks prior to screening. 
11. Was hospitalized within 2 months of dosing, unless deemed acceptable by the PI or 
designee. 
12. Female subjects of childbearing potential. 
13. Female subjects who are pregnant or lactating.  
14. Positive urine drug or alcohol results at screening or check-in.  
15. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B 
surface antigen (HBsAg), or hepatitis C antibodies (HCV). 
16. Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at 
screening. 
17. Seated heart rate is lower than 40 bpm or higher than 100 bpm at screening. 
18. QTcF interval is >450 msec (males) or >460 msec (females) or has ECG findings deemed 
abnormal with clinical significance by the PI or designee at screening. 
19. Hemoglobin value of less than 11.5 g/dL for females and 13.0 g/dL for males, at 
screening or check-in. 
20. Unable to refrain from or anticipates the use of: 
• Any prescription medications, non-prescription medications, herbal remedies, or 
vitamin supplements beginning approximately 14 days prior to dosing and throughout 
the study. Acetaminophen (up to 2 g per 24 hour period) may be permitted during the 
study and will be documented. 
• Any anticoagulants (i.e., warfarin, Low Molecular Weight Heparin), coagulants, anti-
platelet (e.g., clopidogrel), nonsteroidal anti-inflammatory drugs and/or 


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acetylsalicylic acid beginning approximately 28 days prior to dosing and throughout 
the study. Appropriate sources will be consulted by the PI or designee to confirm lack 
of PK/PD interaction with study drug.  
• Any investigational drugs or biologics beginning approximately 30 days prior to 
dosing and throughout the study. 
• Any biologics developed from chinese hamster ovary cell cultures in their life time. 
21. Has been on a diet incompatible with the on-study diet, in the opinion of the PI or 
designee, within the 28 days prior to dosing and throughout the study. 
22. Donation of blood or significant blood loss within 56 days prior to dosing. 
23. Plasma donation within 7 days prior to dosing. 
24. Strenuous exercise/physical activity which could cause muscle aches or injury, including 
contact sports at any time from 72 hours before dosing until completion of the study. 
25. Participation in another clinical study within 30 days prior to dosing. The 30-day window 
will be derived from the date of the last blood collection or dosing, whichever is later, in 
the previous study to Day 1 of the current study. 
26. Presence of any scars, or tattoos which may obscure the injection site, as deemed by PI or 
designee. 
27. Any condition or circumstance, in the opinion of the PI or designee, which may make the 
subject unlikely to complete the study or comply with study procedures and 
requirements, or may pose a risk to the subject's safety. 
10.3.4 Early Termination of Subjects from the Study 
Subject participation in this trial may be discontinued for any of the following reasons: 
1. Occurrence of any medical condition or circumstance that exposes the subject to 
substantial risk and/or does not allow the subject to adhere to the requirements of the 
protocol. 
2. Any SAE, clinically significant AE, severe laboratory abnormality, intercurrent illness, or 
other medical condition that indicates to the PI that continued participation is not in the 
best interest of the subject. 
3. Subject's decision to withdraw. 
4. Requirement of prohibited concomitant medication. 
5. Subject failure to comply with protocol requirements or study related procedures. 


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6. Termination of the study by the Sponsor, FDA, Celerion, SRC, or other regulatory 
authorities. 
The clinical report will include reason(s) for subject withdrawals as well as details relevant to 
the subject withdrawal. If a subject is withdrawn from the trial prior to study completion, the 
subject will undergo all procedures scheduled for early termination as the situation allows 
(see Section 10.2.3.3). Any subject withdrawn due to an AE (whether serious or non-serious) 
or clinically significant abnormal laboratory test values will be evaluated by the PI or a 
monitoring physician and will be treated and/or followed up until the symptoms or values 
return to normal or acceptable levels, as judged by the PI or designee. 
Subjects withdrawn may be replaced at the Sponsor’s discretion. 
10.3.5 Study Restrictions 
10.3.5.1 Prohibitions and Concomitant Therapy 
Consumption of foods and beverages containing the following substances will be prohibited 
as indicated: 
• Xanthines/caffeine: 48 hours before dosing and throughout the period of sample 
collection (small amounts of caffeine derived from normal foodstuffs e.g., 250 mL/8 
oz. decaffeinated coffee or other decaffeinated beverage, per day, with the exception 
of espresso; 45 g/1.5 oz chocolate bar, per day, would not be considered a deviation 
to this restriction) 
• Alcohol: 48 hours before dosing and throughout the period of sample collection; 
Concomitant therapies will be prohibited as listed in the exclusion criteria in Section 10.3.3. 
During the study, acetaminophen (up to 2 g per 24 hours) may be administered at the 
discretion of the PI or designee.  
If deviations occur, the PI or designee will decide on a case-by-case basis whether the subject 
may continue participation in the study based on the time the study medication was 
administered and its pharmacology. 
All medications taken by subjects during the course of the study will be recorded. 
10.3.5.2 Activity 
Subjects will remain ambulatory or seated upright for the first 4 hours following study 
medication administration, except when they are supine or semi-reclined for study 
procedures. However, should AEs occur at any time, subjects may be placed in an 
appropriate position or will be permitted to lie down on their side.  
Subjects will be instructed to refrain from strenuous exercise/physical activity which could 
cause muscle aches or injury, including contact sports at any time from 72 hours before to 
dosing until completion of the study. 


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10.4 Treatments 
10.4.1 Treatments Administered 
A separate dosing manual will detail the drug preparation and treatment administration to be 
followed for this study. 
10.4.1.1 Drug Administration 
Xisomab 3G3 will be supplied as sterile powder for injection via the IV route, upon 
reconstitution. 
Matching placebo will be supplied as sterile powder for injection via IV route, upon 
reconstitution. 
An unblinded pharmacist will be responsible for providing xisomab 3G3 or placebo to the 
blinded study personnel for administration as per the randomization scheme. All doses will 
be administered by a hand pushed IV infusion into a peripheral vein. The time of infusion for 
each dose level is outlined below: 
Dose Level 
Manual Push time 
Cohort 1: 0.1 mg/kg 
~1 minute 
Cohort 2: 0.5 mg/kg 
~2 minutes 
Cohort 3: 2 mg/kg 
~3 minutes 
Cohort 4: 5 mg/kg 
~5 minutes 
Dosing will be done while subjects are supine in bed. 
The subject weight recorded at check-in will be used to calculate the study drug dose. 
The time at which the infusion is started and stopped must be recorded.  
Should the need arise to change the infusion rate (i.e., due to an AE), changes to the infusion 
rate and the times at which those changes are made will be documented.  
Hour 0 will correspond to the start of the infusion. 
10.4.1.2 Planned Dose Levels 
The planned dose levels are as follows: 
Cohort 1: 0.1 mg/kg xisomab 3G3 or matching placebo 
Cohort 2: 0.5 mg/kg xisomab 3G3 or matching placebo 
Cohort 3: 2 mg/kg xisomab 3G3 or matching placebo 
Cohort 4: 5 mg/kg xisomab 3G3 or matching placebo 


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Two sentinel subjects will be dosed (one placebo, one active) in Cohort 1 and data will be 
collected through Day 8 as described in the Study Events Flow Chart (Section 6). The next 
subject in the cohort will be dosed after evaluation of the sentinel subjects’ Day 8 safety data. 
Each subject following these sentinel subjects will be dosed with an interval of 24-hour 
between subjects. 
In Cohorts 2, 3, and 4, subjects will be dosed at an interval of 24 hours between subjects. 
10.4.1.3 Additional Dose Levels 
Additional subjects (N = 5 subjects per cohort; 4 active and 1 placebo) may be enrolled if it is 
deemed appropriate by the SRC to repeat a dose level or to study an interim dose level (lower 
than those planned) in a new cohort of subjects. 
The IRB should be immediately notified of this revised approach. 
10.4.1.4 Dose Escalation and Stopping Rules 
A decision to proceed to the next higher dose administration will be made by SRC comprised 
of, but not limited to, the medical monitor, PI, and Sponsor Representative. 
The SRC will review all pertinent blinded safety/tolerability data (e.g., physical 
examinations, ECGs, vital signs, clinical laboratory tests, and AEs) using all available data 
through Study Day 29 collected from all subjects dosed in the current cohort and from all 
subjects from previous cohorts to base dose escalation decision. At least 4 out of 5 subjects 
from the current cohort must complete scheduled safety procedures up to Day 29 prior to the 
decision to proceed to the next higher dosing cohort. 
The safety data evaluation conducted by the SRC will be documented with the timing, 
recommendations, and decisions made by the SRC. 
The maximum tolerated dose (MTD) will be considered as the last dose level before the dose 
level at which dose escalation is discontinued. 
The SRC will make one of the following determinations: 
1. To continue with the study as planned. 
2. To continue with the study and add additional safety evaluations. 
3. To stop the study or to continue with the study by adjusting to an intermediate dose 
between the current dose and the previous lower dose, if : 
a. At least 1 subject has a SAE or visit to the emergency room regardless of relatedness 
to the study drug, except SAEs that are clearly and incontrovertibly due to extraneous 
causes (see Section 11.1.9.4).  
b. At least 25% of subjects in a cohort experience a grade ≥ 2 AE. 


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Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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Cohorts will be staggered to allow sufficient time for adequate review of safety and 
tolerability from the prior cohort.  
PK data from a cohort may be used to guide the dose-escalation decision. 
When applicable, a written statement fully documenting the reasons for study termination 
will be provided to the IRB. 
10.4.2 Identity of Investigational Products 
Investigational materials will be provided by the Sponsor as in Table 1. 
Table 1: 
Product Descriptions 
Product 
Description 
Test 
Lyophilized xisomab 3G3 (∼15 mg/mL) sterile powder for 
injection in formulation buffer (8% sucrose, 10 mM 
histidine, 30 mM arginine HCl, 10 mM methionine, 80 ppm 
polysorbate 80, pH ~ 5.4). 
Placebo 
Lyophilized formulation buffer (8% sucrose, 10 mM 
histidine, 30 mM arginine HCl, 10 mM methionine, 80 ppm 
polysorbate 80, pH ~ 5.4). 
10.4.3 Method of Assigning Subjects to Treatment Groups 
Each subject will be assigned a unique identification number upon screening. Subjects who 
complete the study screening assessments and meet all the eligibility criteria will be assigned 
a unique randomization identification number prior to dosing, different from the screening 
number, and will receive the corresponding product according to a randomization scheme 
generated at Celerion.  
Subjects will be randomized to receive either xisomab 3G3 or placebo, maintaining a 4:2 
ratio in Cohort 1 and a 4:1 ratio in Cohorts 2, 3, and 4. Subjects in the first enrollment cohort 
will be numbered 1001 – 1006; subjects in the second enrollment cohort will be numbered 
2001 – 2005, etc. 
If replacement subjects are used, the replacement subject number will be 100 more than the 
original (e.g., Subject No. 1101 will replace Subject No. 1001).  
10.4.4 Blinding 
This is a double-blind, placebo-controlled study. 
PI and clinical staff are blinded to the treatment; however safety review of clinical 
laboratories including aPTT will be done real-time. These results may have potential to show 
pharmacologic effect, but treatment will not be unblinded unless needed for safety reasons. 


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Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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10.4.4.1 Maintenance of Randomization 
A computerized randomization scheme will be created by a Celerion statistician and shall be 
considered blinded as per the following: the randomization is available only to the clinic 
pharmacy staff that is preparing the drug and is not involved in any other aspect of the study 
including administration of the drug. It will not be made available to the Sponsor, subjects, or 
members of the staff responsible for the monitoring and evaluation of safety assessments. 
10.4.4.2 Procedures for Breaking the Blind Prior to Study Completion 
One set of sealed envelopes containing the randomization code will be supplied to the PI or 
designee at the start of the study. 
Breaking of the blind is expressly forbidden except in the event of a medical emergency 
where the identity of the drug must be known in order to properly treat the subject, or in the 
event of a safety interim analysis at the request of the sponsor (see Section 10.4.4.3).  
In the event of a medical emergency, it is requested that the PI or designee make every effort 
to contact the Study Monitor or designee prior to breaking the blind. If breaking the blind is 
required because of a medical emergency, the treatment identity would be revealed by the PI 
or designee, for that subject only. In the event that the emergency is one, in which it appears 
that the other subjects may be at imminent risk, the blind may be broken for all subjects 
dosed at that dose level. The unblinding will be properly documented in the study file. 
In all cases where the code is broken, the PI or designee should record the date and reason for 
code breaking. 
At the end of the study, envelopes will be retained or destroyed according to site procedures 
unless specified otherwise by the Sponsor. 
10.4.4.3 Interim Analysis 
Safety: 
All available blinded safety data will be reviewed by the SRC prior to dose escalation.  
At the Sponsor’s request, unblinded safety tables, figures, and data listings may be presented 
to the sponsor’s medical expert and head of regulatory for the purposes of planning the next 
initial Phase 2 studies prior to database lock. These interim analyses will be performed on 
data that will be edit-checked and monitored. 
A safety programmer and a biostatistician at Celerion who are not involved with the present 
study will be unblinded to prepare unblinded safety tables, figures, and data listings. All the 
personnel related to the present study will remain blinded. 


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SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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Pharmacokinetics:  
Preliminary PK analysis may be performed to evaluate the sampling time points as the study 
progresses and to guide the dose escalation decision. In such a case, interim PK analysis will 
not use the actual subject numbers in order to avoid breaking the blind. 
Pharmacodynamics: 
Preliminary PD analysis may be performed to evaluate the sampling time points as the study 
progresses and to guide the dose escalation decision. In such a case, interim PD analysis will 
not use the actual subject numbers in order to avoid breaking the blind. 
10.4.4.4 Revealing of Randomization 
In the absence of a medical emergency, the blinded randomization for this study will not be 
revealed until all data are entered in the database, edits checks are performed, queries closed, 
case report forms (CRFs) signed by the PI, and the database is officially locked.  
10.4.5 Treatment Compliance  
Drug administration will be performed by a qualified designee (e.g., nurse). Before and after 
IV infusion, the qualified designee will visually inspect the syringe to ensure that the subject 
has received the entire dose. In the case of an incomplete dosing (e.g., large droplet of study 
medication on the surface of the skin) as deemed by the PI and/or Sponsor, the subject may 
be withdrawn. 
 


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SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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11. STUDY PROCEDURES 
11.1 Safety Assessments 
The Study Events Flow Chart (Section 6) summarizes the clinical procedures to be 
performed at each visit. Individual clinical procedures are described in detail below. 
Additional evaluations/testing may be deemed necessary by the PI or designee and/or the 
Sponsor for reasons related to subject safety. 
For this study, the primary assessment is the safety and tolerability. Safety will be determined 
by evaluating physical examinations, vital signs, ECGs, clinical laboratory parameters, 
including but not limited to, hematology, serum chemistry profile, coagulation, urinalysis, 
injection site reaction, immunogenicity, and AEs as outlined in the Study Events Flow Chart 
(Section 6).  
Any nonscheduled procedures required for urgent evaluation of safety concerns take 
precedence over all routine scheduled procedures. 
11.1.1 Body Height and Weight 
Body height (centimeters) and body weight (kilograms) will be measured as outlined in the 
Study Events Flow Chart (Section 6). BMI will be calculated at screening. 
11.1.2 Physical Examination 
Full and abbreviated physical examinations will be performed as per Study Events Flow 
Chart (Section 6).  
Full physical examinations will include, at a minimum, assessment of the following systems: 
skin, head, ears, eyes, nose and throat, respiratory system, cardiovascular system, 
gastrointestinal system, neurological condition, blood and lymphatic systems, and the 
musculoskeletal system. 
Abbreviated physical examinations will include at the minimum, examination of respiratory, 
cardiovascular, and gastrointestinal systems, with the option for further examination of 
additional systems as necessary based on reported symptoms/AEs. 
Symptom-driven physical examination may be performed at other times, if deemed necessary 
by the PI or designee.  
Medical history will be recorded at screening.  
11.1.3 Vital Signs 
Single measurements of body temperature, respiratory rate, blood pressure, and heart rate 
will be measured as outlined in the Study Events Flow Chart (Section 6). Additional vital 
signs may be taken at any other times, if deemed necessary by the PI or designee. 
Vital sign measurements will be performed with subjects in a seated position, except when 
they are supine or semi-reclined because of study procedures and/or AEs (e.g., nausea, 


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SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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dizziness) or if deemed necessary by the PI or designee. 
Vital signs will be measured within 24 hours prior to dosing for the predose time point. 
When scheduled postdose, vital signs will be performed within approximately 10 minutes of 
the scheduled time point.  
11.1.4 Electrocardiogram Monitoring 
Single 12-lead ECGs will be performed as outlined in the Study Events Flow Chart 
(Section 6). Additional ECGs may be taken at any other times, if deemed necessary by the PI 
or designee. 
ECGs will be performed with subjects in a supine position. All ECG tracings will be 
reviewed by the PI or designee. 
ECGs will be measured within 24 hours prior to dosing for the predose time point. When 
scheduled postdose, ECGs will be performed within approximately 20 minutes of the 
scheduled time point. 


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SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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11.1.5 Clinical Laboratory Tests 
All tests listed below will be performed as per Study Events Flow Chart (Section 6). In 
addition, laboratory safety tests may be performed at various unscheduled time points, if 
deemed necessary by the PI or designee. 
Hematology 
 
Serum Chemistry* 
• Hemoglobin 
• Hematocrit  
• Total and differential 
leukocyte count 
• Red blood cell count 
• Platelet count 
 
Coagulation 
• PT/INR 
• aPTT 
 
 
• BUN 
• Bilirubin (total and direct) 
• ALP 
• AST 
• ALT 
• LDH 
• Albumin 
• Sodium 
• Potassium 
• Chloride 
• Glucose (fasting) 
• Creatinine** 
Urinalysis 
 
Additional Tests 
• pH 
• Specific gravity 
• Protein*** 
• Glucose 
• Ketones 
• Bilirubin 
• Blood*** 
• Nitrite*** 
• Urobilinogen 
• Leukocyte esterase*** 
 
• HIV test 
• HBsAg 
• HCV 
• Urine drug screen 
Ø Opiate  
Ø Amphetamines  
Ø Cocaine 
Ø Cannabinoids 
• Urine alcohol screen 
• Bleeding time 
• Serum pregnancy test  
(for females only) 
• FSH (for postmenopausal females 
only) 
 
* 
Serum chemistry tests will be performed after at least an 8-hour fast (except for the 8-hour 
time point); however, in case of dropouts or rechecks, subjects may not have fasted for 8 hours 
before the serum chemistry sample is taken. 
** At screening, creatinine clearance will be calculated using the Cockcroft-Gault formula. 
*** If urinalysis is positive for protein, blood, nitrite and/or leukocyte esterase, a microscopic 
examination (for red blood cells, white blood cells, bacteria, casts, and epithelial cells) will be 
performed. 


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SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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11.1.6 Check-In Questionnaire 
A check-in questionnaire will be reviewed for each subject to ensure that they remain eligible 
for the study. The questions will be based on the inclusion and exclusion criteria and study 
restrictions. 
11.1.7 
Injection Site Reaction Assessment 
The monitoring of AEs will pay special attention to potential injection site reactions. 
Therefore, inspection of the injection site and surrounding area will be performed. Any 
abnormal findings will be reported as AEs. Injection site reactions will be evaluated as 
outlined in the Study Events Flow Chart (Section 6). Prior to dosing, the injection site will be 
examined. When scheduled postdose, injection site examinations will be performed within 
approximately 20 minutes of the scheduled time point. Reactions will be rated according to 
the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent 
Volunteers Enrolled in Preventive Vaccine Clinical Trials 3 as follows: 
Local Reaction 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Pain 
Does not interfere 
with activity 
Repeated use of 
non-narcotic pain 
reliever > 24 hours 
or interferes with 
activity 
Any use of narcotic 
pain reliever or 
prevents daily 
activity 
Tenderness 
Mild discomfort to 
touch 
Discomfort with 
movement 
Significant 
discomfort at rest 
Erythema/Redness* 
2.5 – 5 cm 
5.1 – 10 cm 
> 10 cm 
Induration/Swelling** 
2.5 – 5 cm and 
does not interfere 
with activity 
5.1 – 10 cm or 
interferes with 
activity 
> 10 cm or prevents 
daily activity 
* In addition to grading the measured local reaction at the greatest single diameter, the 
measurement should be recorded as a continuous variable. 
** Induration/swelling should be evaluated and graded using the functional scale as well as 
the actual measurement. 
11.1.8 
Immunogenicity Assessment 
Blood samples for immunogenicity assessment will be performed from the PK blood 
collection tubes as per Study Events Flow Chart (Section 6). 
Instruction for blood sampling, collection, and processing will be provided separately. 


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SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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11.1.9 
Adverse Events 
11.1.9.1 Adverse Event Definition 
An AE means any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug related. 
A suspected adverse reaction means any AE for which there is a reasonable possibility that 
the drug caused the AE. Reasonable possibility means there is evidence to suggest a causal 
relationship between the drug and the AE.  
An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not related to the medicinal (investigational) product. 4 
Prolonged aPTT is an expected pharmacological effect of xisomab 3G3 and will, therefore, 
not be considered an AE. 
11.1.9.2 Monitoring 
Subjects will be monitored throughout confinement for adverse reactions to the study drug 
and/or procedures. Subjects will be asked how they are feeling once per day during 
confinement and at each return/follow-up visit.  
AEs (whether serious or non-serious) and clinically significant abnormal laboratory test 
value(s) will be evaluated by the PI or designee and treated and/or followed up until the 
symptoms or value(s) return to normal, or acceptable levels, as judged by the PI or designee. 
Treatment of SAEs will be performed by a licensed medical provider, either at Celerion or at 
a nearby hospital emergency room. Where appropriate, medical test(s) and/or examination(s) 
will be performed to document resolution of event(s). Outcome may be classified as 
resolved, improved, unchanged, worse, fatal, or unknown (lost to follow up). 
11.1.9.3 Reporting 
All AEs that occurred during this clinical trial will be recorded. AEs will be coded using the 
most current MedDRA® available at Celerion. 
The PI or designee will review each event and assess its relationship to drug treatment 
(likely, probably, possibly, unlikely or unrelated). Each sign or symptom reported will be 
graded on the FDA (Center for Biologics Evaluation and Research) toxicity grading scale for 
healthy volunteers 4-point severity scale (Grade 1, 2, 3 and 4).3 The date and time of onset, 
time relationship to drug dosing, duration, and outcome of each event will be noted.  


xisomab 3G3 
SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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Relationship of AE: 
The relationship of each AE to the study drug will be assessed using the following 
definitions: 
Unrelated 
§ The adverse event must clearly be caused by the participants 
clinical state, or the study procedure/conditions 
§ Definitely not related to drug 
§ Temporal sequence of an adverse event onset relative to 
administration of drug not reasonable 
§ Another obvious cause of an adverse event 
Unlikely 
§ Time sequence is unreasonable 
§ There is another more likely cause for an adverse event 
Possibly 
§ Corresponds to what is known about the drug 
§ Time sequence is reasonable 
§ Could have been due to another equally, likely cause 
Probably 
§ Is a known effect of the drug 
§ Time sequence from taking drug is reasonable 
§ Ceases on stopping the drug 
§ Cannot be reasonably explained by the known characteristics of 
the participants clinical state 
Likely 
§ Is a known effect of the drug (e.g. listed in IB) 
§ Time sequence from taking drug is reasonable 
§ Event stops upon stopping drug, event returns upon restarting 
drug 
Note: Prolonged aPTT is an expected pharmacological effect of 
xisomab 3G3 and will, therefore, not be considered an AE. 
Severity of AE: 
Severity rating used during the study will be based on the the toxicity grading scale tables 
present in the FDA (Center for Biologics Evaluation and Research) toxicity grading scale for 
healthy volunteers 4-point severity scale (Grade 1, 2, 3 and 4).3 
The following definitions for rating severity will be used for AEs not identified in the 
guidance: 
Mild (Grade 1) 
The AE does not interfere with daily activity 
Moderate (Grade 2) 
The AE interferes with daily activity, but no medical 
intervention is required 


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Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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Severe (Grade 3) 
The AE prevents daily activity and requires medical 
intervention 
Potentially Life-threatening 
(Grade 4) 
Emergency room visit or hospitalization is required 
11.1.9.4 Serious Adverse Events 
If any AEs are serious, as defined by the FDA Code of Federal Regulations (CFR), Chapter 
21, special procedures will be followed. All SAEs will be reported to the Sponsor via fax or 
e-mail within one working day of becoming aware of the event, whether or not the serious 
events are deemed drug-related. All serious event reporting will adhere to 21 CFR 312.32 for 
Investigational New Drugs (IND) and to the Guidance for Industry and Investigators: Safety 
Reporting Requirements for INDs and BA/BE, dated December 2012. 4 The IRB will be 
notified of the Alert Reports as per FDA regulations. 
A SAE is any AE or suspected adverse reaction that in the view of either the PI (or designee) 
or Sponsor, results in any of the following outcomes: Death, a life-threatening adverse event, 
inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant 
incapacity or substantial disruption of the ability to conduct normal life functions, or a 
congenital anomaly/birth defect. Important medical events that may not result in death, be 
life-threatening, or require hospitalization may be considered serious when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in the above definition. 
Examples of such medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias or convulsions that do not 
result in inpatient hospitalization, or the development of drug dependency or drug abuse.  
Life-threatening is defined as an AE or suspected adverse reaction that in the view of the PI 
(or designee) or Sponsor, its occurrence places the patient or 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. 
Unexpected is defined as an AE or suspected adverse reaction that is not listed in the IB or is 
not listed at the specificity or severity that has been observed; or is not consistent with the 
risk information described in the general investigational plan or elsewhere in the current 
application, as amended. 
If a SAE occurs to a subject on this study, contact the Sponsor personnel listed in Section 3. 
11.2 Pharmacokinetic Assessments 
11.2.1 Blood Sampling and Processing 
For all subjects, blood samples for the determination of free xisomab 3G3 will be collected in 
sodium citrate blood collection tubes at scheduled time points as delineated in the Study 
Events Flow Chart (Section 6). 


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SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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The sample times for PK collection are in relation to the start of infusion. 
Instruction for blood sampling, collection, and processing will be provided separately. 
Following completion of the samples analysis, leftover plasma samples will be shipped to the 
Sponsor, as per their instructions provided seperately. Additional analysis for exploratory 
purposes, including but not limited to actor XIa activity, will be performed on leftover 
plasma samples at the Sponsor’s discretion. 
11.2.2 Analytical Method 
Plasma sample analysis will be performed using validated bioanalytical methods. 
11.3 Pharmacodynamic Assessments 
For all subjects, blood samples for the determination of aPTT will be collected in blood 
collection tubes containing sodium citrate (3.2%) at scheduled time points as delineated in 
the Study Events Flow Chart (Section 6). 


xisomab 3G3 
SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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11.4 Blood Volume for Study Assessments 
Table 2: 
Blood Volume during the Study 
Sample Type 
Number of 
Time Points 
Approximate 
Volume per Time 
Point * (mL) 
Approximate Sample 
Volume Over Course 
of Study (mL) 
Screening laboratory safety tests (including 
hematology, serum chemistry, serology, and 
coagulation), FSH (for postmenopausal 
female subjects only) and serum pregnancy 
(for female subjects only). 
1 
16 
16 
On-study hematology 
at least6† 
4 
24 or more 
On-study serum chemistry (this includes 
serum pregnancy for female subjects only 
when scheduled at the same time) 
at least 6† 
8.5 
51 or more 
On-study coagulation (PT/INR only) 
at least 5† 
** 
** 
On-study coagulation (PT/INR and safety 
aPTT) 
2 
3.5 
7 
Blood for PK (free xisomab 3G3)† 
at least 15† 
10 
150 or more 
Blood for PD (aPTT)† 
at least 15† 
3.5 
52.5 or more 
Blood for Immunogenicity 
at least 3 
†† 
†† 
Total Blood Volume (mL)→ 
300.5 or more †,††† 
* 
Represents the largest collection tube that may be used for this (a smaller tube may be used). 
** 
PT/INR samples will be taken from aPTT samples, either the safety coagulation sample or the PD samples. 
Additional PT/INR will be taken at least 2 days after discharge to confirm the PT/INR discharge value of ≤ 3.5; If 
this sample does not correspond with a safety coagulation sample or the PD samples (aPTT), an extra 3.5 mL of 
blood will be collected. 
† 
PK and PD samples will be collected for a minimum of 28 days postdose (Day 29). If by Day 29 aPTT values have 
not returned within ± 10% of the baseline value or the normal range, sampling will continue every 7 days (± 2 days) 
for PK, PD, and, as per PI discretion, safety clinical laboratories test until the ± 10% of baseline value or to the 
normal range is reached or a maximum of ~500 mL of blood is collected from the subject. Subjects who terminate 
the study early will also be asked to return every 7 days (± 2 days) for aPTT monitoring until aPTT values return 
within ± 10% of baseline value or the normal range. 
†† 
Sample for immunogenicity will be taken from the PK sample tube. If this sample does not correspond with a PK 
sample, an extra 10 mL of blood sample will be collected. 
††† 
If additional safety, PK, or PD analysis is necessary or if larger collection tubes are required to obtain sufficient 
plasma/serum for analysis, additional blood may be obtained (up to a maximum of ~500 mL; this volume could be 
exceeded only with agreement of the PI on a case-by-case basis). 
 


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Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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12. DATA ANALYSIS 
Data will be handled and processed according to Celerion Standard Operating Procedures 
(SOPs), which are written based on the principles of GCP. 
12.1 Statistical Analysis 
Detailed methodology for summary and statistical analyses of the data collected in this trial 
will be documented in a Statistical Analysis Plan (SAP). The SAP will be prepared by 
Celerion and agreed upon with the Sponsor. This document may modify the plans outlined in 
the protocol; however, any major modifications of the primary endpoints definition and/or its 
analysis will also be reflected in a protocol amendment. Additional statistical analyses other 
than those described in this section may be performed if deemed appropriate and included in 
the SAP.  
12.1.1 Sample Size Calculation 
The sample size chosen for this study was selected without statistical considerations. It has 
been determined adequate to meet the study objectives. Cohorts of up to 6 (4:2 ratio of active 
study drug:placebo) and 5 subjects (4:1 ratio of active study drug:placebo) are sufficient to 
characterize the single-dose safety, tolerability, PK, and PD profile.  
12.1.2 Subjects to Analyze 
Safety population: All subjects who received the study drug (active or placebo) will be 
included in the safety summary. 
PK population: All subjects receiving the active drug and having any measurable plasma 
concentration of study drug will be included in the PK data set. All subjects who comply 
sufficiently with the protocol and display an evaluable PK profile (e.g., exposure to 
treatment, availability of measurements and absence of major protocol violations) will be 
included in the statistical analyses. 
PD population: All subjects receiving the study drug (active or placebo) and having any 
measurable PD data will be included in the PD data set.  
12.1.3 Safety Analysis 
The following analyses will be performed; however no formal inferential statistics will be 
done on safety assessments. 
The placebo subjects from all cohorts will be pooled into a single placebo group for all 
summaries and presentations. 
Descriptive statistics will be calculated for quantitative safety data and frequency counts will 
be compiled for classification of qualitative safety data. 


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Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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Adverse Events: 
AEs will be coded using the most current version of MedDRA® available at Celerion.  
A by-subject AE data listing, including verbatim term, preferred term, treatment, severity, 
and relationship to drug, will be provided. 
The number of subjects experiencing TEAEs and number of TEAEs will be summarized by 
treatment using frequency counts. 
Injection site reaction will be assessed. 
Medical History and Physical Examination: 
Medical history will be listed by subject. 
Changes in physical examinations will be described in the text of the final report. 
Clinical Laboratory Results, Electrocardiograms, and Vital Signs Measurements: 
All clinical laboratory results, 12-lead ECGs, vital signs measurements, and their change 
from baseline, will be summarized by treatment and time point of collection. 
A shift table describing out-of-normal range shifts will be provided for clinical laboratory 
results. 
Concomitant Medications: 
Concomitant medications will be listed by treatment. 
Immunogenicity: 
ADA detection will be reported and summarized descriptively. 
12.1.4 Pharmacokinetic Analysis 
12.1.4.1 Pharmacokinetic Parameters 
The following PK parameters will be computed, as appropriate, for plasma free xisomab 3G3 
from the individual plasma concentrations using a noncompartmental approach. 
AUC0-t: 
 
The area under the plasma concentration-time curve, from time 0 
to the last measurable non-zero concentration, as calculated by the 
linear trapezoidal method. 
AUC0-inf: 
The area under the plasma concentration-time curve from time 0 
extrapolated to infinity. AUC0-inf is calculated as the sum of AUC0-t 
plus the ratio of the last measurable plasma concentration to the 
elimination rate constant. 


xisomab 3G3 
SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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AUC%extrap: 
Percent of AUC0-inf extrapolated, represented as 
(1 - AUC0-t/AUC0-inf)*100. 
AUMC0-inf:* 
Area under the moment curve from time 0 to the last measurable 
concentration, = AUMC0-t + [(tlast x Ct)/ Kel]+ Ct/(Kel)2 
Cmax: 
Maximum observed concentration. 
Tmax: 
Time to reach Cmax. If the maximum value occurs at more than one 
time point, Tmax is defined as the first time point with this value. 
Kel: 
Apparent first-order terminal elimination rate constant calculated 
from a semi-log plot of the plasma concentration versus time 
curve. The parameter will be calculated by linear least-squares 
regression analysis using the maximum number of points in the 
terminal log-linear phase (e.g., three or more non-zero plasma 
concentrations). 
T½: 
Apparent first-order terminal elimination half-life will be 
calculated as 0.693/ Kel. 
CL: 
Apparent total plasma clearance calculated as [Dose/AUC0-inf]. 
MRT:* 
Mean residence time = AUMC0-inf/AUC0-inf (for IV infusion) 
Vss: 
Total apparent volume of distribution following single IV dose 
administration calculated as Vss = MRT x CL. 
* 
AUMC0-inf and MRT values will be used for Vss calculation but will not be listed in 
the PK tables. 
Additional PK parameters may be computed if deemed appropriate. 
No PK parameters will be calculated for subjects with 2 or fewer consecutive time points 
with detectable concentrations. 
No value for Kel, T½, AUC0-inf, AUC%extrap, CL, and Vss, as appropriate, will be reported for 
cases that do not exhibit a terminal log-linear phase in the concentration versus time profile. 
Individual and mean plasma concentration time curves (both linear and log-linear) will be 
included in the final report. 


xisomab 3G3 
SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
Page 54 
CA19214 (3G3-15-01)_Amend 3 Final Protocol_06Nov2017 
12.1.5 Statistical Methods for Pharmacokinetic Analyses 
Values will be calculated for the plasma concentrations and the PK parameters listed in 
Section 12.1.4.1 using appropriate summary statistics to be fully outlined in the SAP.  
Figures will be created to display mean and individual free xisomab 3G3 concentration-time 
curves.  
Additional analyses may be performed as deemed necessary upon review of the data. 
12.1.6 Pharmacodynamic Assessments 
aPTT values will be listed and presented graphically. 
PD parameters may be calculated if deemed appropriate. 
12.1.7 Assessment of Efficacy 
Efficacy will not be assessed in this study. 
 
 


xisomab 3G3 
SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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13. STUDY ADMINISTRATION 
13.1 Ethics 
13.1.1 Institutional Review Board  
This protocol will be reviewed by the Chesapeake Research Review, Inc. IRB, and the study 
will not start until the IRB has approved the protocol or a modification thereof. The IRB is 
constituted and operates in accordance with the principles and requirements described in the 
US Code of Federal Regulations (21 CFR Part 56). The IRB is compliant to International 
Conference on Harmonisation (ICH) guidelines, and may be reached at: 
Chesapeake IRB 
6940 Columbia Gateway Drive, Suite 110 
Columbia, Maryland 21046, USA 
Tel.: +1 410 884-2900 
13.1.2 Ethical Conduct of the Study 
This research will be carried out in accordance with the protocol, US Code of Federal 
Regulations, 21 CFR Parts 50, 56, and 312, the ethical principles set forth in the Declaration 
of Helsinki, GCP, and the ICH harmonized tripartite guideline regarding GCP (E6 
Consolidated Guidance, April 1996). 
13.1.3 Subject Information and Consent 
The purpose of the study, the procedures to be carried out and the potential hazards will be 
described to the subjects in non-technical terms. Subjects will be required to read, sign and 
date an ICF summarizing the discussion at screening, and will be assured that they may 
withdraw from the study at any time without jeopardizing their medical care. 
Subjects will be given a copy of their signed ICF. 
13.2 Termination of the Study 
The Sponsor reserves the right to discontinue the study and Celerion reserves the right to 
terminate the study in the interest of subject welfare, at any time. 
13.3 Data Quality Assurance 
Standard operating procedures are available for all activities performed at Celerion relevant 
to the quality of this study. Designated personnel of Celerion will be responsible for 
implementing and maintaining quality assurance (QA) and quality control systems to ensure 
that the trial is conducted, and that data are generated, documented and reported in 
compliance with the study protocol, GCP and GLP requirements as well as applicable 
regulatory requirements and local laws, rules and regulations relating to the conduct of the 
clinical study. 


xisomab 3G3 
SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
Page 56 
CA19214 (3G3-15-01)_Amend 3 Final Protocol_06Nov2017 
The Clinical Study Report will be audited by the QA department and the QA audit certificate 
will be included in the study report. 
All clinical data will undergo a 100% quality control check prior to clinical database lock. 
Edit checks are then performed for appropriate databases as a validation routine using SAS® 
to check for missing data, data inconsistencies, data ranges etc. Corrections are made prior to 
statistical database lock. 
13.4 Direct Access to Source Data/Documents 
The PI must maintain, at all times, the primary records (i.e., source documents) of each 
subject’s data. Examples of source documents are laboratory reports, drug inventory, study 
drug label records, and CRFs that are used as the source. 
Celerion will ensure that the sponsor, IRB and inspection by domestic and foreign regulatory 
authorities will have direct access to all trial-related sites, source data/documents, and reports 
for the purpose of monitoring, auditing (ICH[E6] 5.1.2 & 6.10) and inspection. In the event 
that other trial-related monitoring should be done by other parties, they will be required to 
sign a confidentiality agreement prior to any monitoring and auditing. 
13.5 Study Supplies 
The Sponsor will supply sufficient quantities study drug and matching placebo to allow 
completion of this study. The lot numbers, manufacture dates, and expiration dates (if 
available) of the drugs supplied will be recorded in the final report. 
The investigational product(s) will be shipped to a designee at the study site and must be 
stored in a pharmacy or locked and secured in a storage facility with controlled temperature. 
Humidity in the room will be monitored. The room is accessible only to those individuals 
authorized by the PI. 
Records will be made of the receipt and dispensing of the study drugs supplied. At the 
conclusion of the study, any unused study drugs (including placebo) as well as original 
containers (even if empty), will be retained by Celerion, returned to the Sponsor or designee, 
or destroyed, as per Sponsor instructions. If no supplies remain, this fact will be documented 
in the pharmacy product accountability records. 
13.6 Data Handling and Record Keeping 
Celerion standard CRFs will be used. CRFs are printed directly from the ClinQuick® 
database. Each CRF is reviewed and signed off by the PI. 
ClinQuick® is a fully integrated, study management and data capture system designed and 
built by Celerion for use in Phase 1 clinical research centers. ClinQuick® will be used for all 
data that can be captured electronically via barcode or electronic acquisition (e.g., vital signs, 
meal times, blood draw times, etc.). Electronic changes will be traceable through computer 
capture. 
Other data (e.g., medical history, inclusion/exclusion criteria, etc.) will be entered into 
ClinQuick® by remote data entry or via double data entry by 2 different associates using an 
automated verification system within ClinQuick®. AEs and concomitant medications will be 


xisomab 3G3 
SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
Page 57 
CA19214 (3G3-15-01)_Amend 3 Final Protocol_06Nov2017 
entered into ClinQuick® by single data entry. 
Visual and computerized methods of data validation will be applied in order to ensure 
accurate, consistent, and reliable data for the subsequent statistical analysis. 
These procedures aim to detect out-of-range values, contradictory data, abnormal evolutions 
over time, and possible undetected protocol violations (eligibility criteria, time and 
medication compliance, etc.). 
All raw data generated in connection with this study, together with the original copy of the 
final report, will be retained by Celerion until at least 5 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or at least 5 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. It is the responsibility of the Sponsor to 
inform the PI/Institution as to when these documents no longer need to be retained. 
13.7 Report Format 
According to the ICH Harmonized Tripartite Guideline (Organization of the Common 
Technical Document for the Registration of Pharmaceuticals for Human Use M4 and the ICH 
M2 Expert Working Group), the final report will be written according to the ICH E3 Guideline 
(Structure and Content of Clinical Study Reports). 
13.8 Protocol Amendments 
Any amendments to the study protocol that seem to be appropriate as the study progresses 
will be discussed between Sponsor and the PI or designee. All revisions and/or amendments 
to the protocol in writing must be approved by the Sponsor, the PI or designee, and the IRB 
before implementation. 
13.9 Publication Policy 
All unpublished information given to Celerion by the Sponsor shall not be published or 
disclosed to a third party without the prior written consent of the Sponsor. 
The data generated by this study are considered confidential information and the property of 
the Sponsor. This confidential information may be published only in collaboration with 
participating personnel from the Sponsor or upon Sponsor’s written consent to publish the 
article. 
 


xisomab 3G3 
SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
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CA19214 (3G3-15-01)_Amend 3 Final Protocol_06Nov2017 
14. REFERENCES 
1. Xisomab 3G3. Aronora, Inc. Investigator Brochure. Version Number 1; 01 Jan 2017. 
2. FDA Guidance for Industry: Estimating the maximum safe starting dose in initial clinical 
trials for therapeutics in adult healthy volunteers. July 2005. Available online: 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInfor 
mation/Guidances/ucm078932.pdf 
3. FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent 
Volunteers Enrolled in Preventive Vaccine Clinical Trials. September 2007. Available 
online: http://www.fda.gov/downloads/BiologicsBloodVaccines 
/GuidanceComplianceRegulatoryInformation/Guidances/Vaccines/ucm091977.pdf 
4. FDA Guidance for Industry and Investigators: Safety Reporting Requirements for INDs 
and BA/BE, dated December 2012. Available online at: 
http://www.fda.gov/downloads/Drugs/.../Guidances/UCM227351.pdf 


xisomab 3G3 
SAD Study Protocol 
Aronora, Inc. 
Sponsor Project No.: 3G3-15-01 
Celerion Project No.: CA19214 
US PIND No.: 127850 
 
Page 59 
CA19214 (3G3-15-01)_Amend 3 Final Protocol_06Nov2017 
Appendix 1 
Clinical Laboratory Reference Ranges 
 
Name of Laboratory: 
Celerion 
 
Adress: 
2420 West Baseline Road 
Tempe, Arizona 85283, 
USA 
 
 
 
 
Laboratory Test 
Adult Reference Range* 
(Male and Female) 
 
 
 
Hematology 
 
 
 
 
 
Platelet Count 
162-399 Thou/μL 
Both 
 
 
 
Coagulation 
 
 
 
 
 
PT/INR 
0.9-1.1 
Both 
aPTT 
23-32 seconds 
Both 
Bleeding Time** 
2.0-8.0 minutes 
Both 
 
 
 
Serum Chemistry 
 
 
 
 
 
ALP 
47-132 U/L 
Male 
 
41-129 U/L 
Female 
ALT 
10-60 U/L 
Both 
AST 
14-47 U/L 
Both 
LDH 
125-248 U/L 
Both 
BUN 
7.0-21.0 mg/dL 
Male 
 
6.0-20.0 mg/dL 
Female 
Creatinine  
0.67-1.22 mg/dL 
Male 
 
0.44-0.93 mg/dL 
Female 
 
 
 
* Based on Celerion Screening Population 
** Using Simplate method 

SAP_001.pdf: 
 
Statistical Analysis Plan 
 
 
 
 
A Phase 1, Single Ascending Dose, Randomized, Double-Blind, Placebo-Controlled Study to 
Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of 
Xisomab 3G3 in Healthy Adult Subjects 
 
 
 
 
 
 
Protocol No: 3G3-15-01 
Final Protocol Date: 03 March 2017 
Amendment One Date: 02 May 2017 
Amendment Two Date: 10 May 2017 
Compound Name: xisomab 3G3 
 
 
 
 
Celerion Project CA19214 
Final Version 1.0 
Date: 25 August 2017 
 
 
 
Aronora, Inc. 
4640 SW Macadam Avenue, Ste 200A 
Portland, Oregon 97239, USA 
 
 
 
 
 
 
Celerion 
621 Rose Street, Lincoln, Nebraska 68502, USA 
100 Alexis-Nihon Boulevard, Suite 360, Montreal, QC, H4M 2N8, Canada 
Date: 
 
 
 
 
 
 
 


 
Statistical Analysis Plan Signature Page 
 
Compound Name: xisomab 3G3 
Protocol: 3G3-15-01 
Study Title: A Phase 1, Single Ascending Dose, Randomized, Double-Blind, Placebo-
Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and 
Pharmacodynamics of Xisomab 3G3 in Healthy Adult Subjects 
Issue Date: 
 07 August 2017 
                  
Signature:_____________________________________ 
Date:__25 Aug 2017___ 
Karly Williams, MS 
SAS Data Analyst, Data Management and Biometrics 
Celerion, Lincoln, Nebraska, USA 
Signature:_____________________________________ 
Date:__25 Aug 2017_  _  
Tamara Cuddy, MS 
Director Biostatistics 
Celerion, Lincoln, Nebraska, USA 
Signature:_____________________________________ 
Date:__ 25 Aug 2017___ 
Jennifer Lu, PhD 
Pharmacokinetic Scientist I, Clinical Pharmacology and Pharmacometrics, 
Data Management and Biometrics 
Celerion, Montreal, Quebec, Canada 
Signature:_____________________________________ 
Date:__ 28 Aug 2017___ 
Christina Lorentz, PhD 
Senior Scientist 
Aronora, Inc. 
Portland, Oregon 97239, USA 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 3 of 81 
 
 
 
Table of Contents 
1. INTRODUCTION ............................................................................................................5 
2. OBJECTIVES AND ENDPOINTS ..................................................................................5 
2.1 
Objectives ..................................................................................................................5 
2.2 
Endpoints ...................................................................................................................5 
3. STUDY DESIGN .............................................................................................................6 
4. ANALYSIS POPULATIONS ..........................................................................................7 
4.1 
Analysis Populations .................................................................................................7 
4.2 
Preliminary Data and Interim Analysis .....................................................................8 
5. TREATMENT DESCRIPTIONS .....................................................................................9 
6. PHARMACOKINETIC ANALYSIS .................................................................................. 10 
6.1 
Measurements and Collection Schedule ..................................................................10 
6.2 
Bioanalytical Method ..............................................................................................10 
6.3 
Investigational Product and PK Analyte Information..............................................10 
6.3.1 Xisomab 3G3 ...............................................................................................10 
6.4 
Pharmacokinetic Concentrations .............................................................................10 
6.5 
Noncompartmental Pharmacokinetic Analysis and Parameter Calculation.............11 
6.5.1 Plasma Pharmacokinetic Parameters ...........................................................11 
6.6 
Data Summarization and Presentation .....................................................................13 
7. PHARMACODYNAMIC ANALYSIS ............................................................................... 14 
7.1 
Measurement and Collection Schedule ...................................................................14 
7.2 
Biomarker Method ..................................................................................................14 
7.3 
Activated Partial Thromboplastin Time ..................................................................14 
7.4 
Activated Partial Thromboplastin Time Values ......................................................14 
7.5 
Data Summarization and Presentation .....................................................................14 
8. SAFETY .........................................................................................................................15 
8.1 
Subject Discontinuation...........................................................................................15 
8.2 
Demographics ..........................................................................................................16 
8.3 
Adverse Events and Injection Site Reaction............................................................16 
8.4 
Clinical Laboratory Tests (Coagulation, Serum Chemistry, Hematology, 
Urinalysis) ...............................................................................................................17 
8.5 
Vital Signs ...............................................................................................................18 
8.6 
Electrocardiogram ...................................................................................................18 
8.7 
Concomitant Medications ........................................................................................18 
8.8 
Physical Examination ..............................................................................................18 
8.9 
Medical History .......................................................................................................19 
8.10 Immunogenicity.......................................................................................................19 
9. SUMMARY OF CHANGES FROM PROTOCOL-PLANNED ANALYSIS .................19 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 4 of 81 
 
 
10. SUMMARY TABLES AND FIGURES ...........................................................................20 
10.1 In-text Summary Tables and Figures.......................................................................20 
10.2 Section 14 Summary Tables and Figures ................................................................20 
10.3 Section 16 Data Listings ..........................................................................................24 
11. TABLE AND FIGURE SHELLS ........................................................................................... 27 
11.1 In-text Summary Tables Shells ...............................................................................28 
11.2 Figures Shells ..........................................................................................................32 
11.3 Section 14 Summary Tables Shells .........................................................................36 
12. LISTING SHELLS ...........................................................................................................57 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 5 of 81 
 
 
 
 
1. INTRODUCTION 
 
The following statistical analysis plan (SAP) provides the framework for the 
summarization of the data from this study. The SAP may change due to unforeseen 
circumstances. Any changes made from the planned analysis within protocol, after 
the unblinding, or locking of the database will be documented in the clinical study 
report (CSR). The section referred to as Table Shells within this SAP describes the 
traceability of the tables, figures, and listings (TFLs) back to the data. Note that the 
header for this page will be the one used for the main body of the CSR. 
 
Any additional exploratory analyses not addressed within this statistical analysis plan 
(SAP) and/or driven by the data, or requested by the Aronora Inc., will be considered 
out of scope and must be described in the CSR. 
 
2. OBJECTIVES AND ENDPOINTS 
 
2.1 
Objectives 
 
The primary objective of the study is to assess the safety and tolerability of single 
intravenous (IV) doses of xisomab 3G3 when administered to healthy adult subjects. 
 
The secondary objectives of the study are as follows: 
 
• To assess the pharmacokinetics (PK) of single IV doses of xisomab 3G3 when 
administered to healthy adult subjects. 
 
• To assess the pharmacodynamics (PD) of single IV doses of xisomab 3G3 when 
administered to healthy adult subjects. The activated partial thromboplastin time 
(aPTT) will be used as a surrogate PD marker. 
 
2.2 
Endpoints 
 
The primary endpoints of the study will be the number and severity of treatment- 
emergent adverse events (TEAEs) following single doses of xisomab 3G3 and 
placebo. Other safety endpoints include clinical laboratories, vital signs, 
electrocardiograms, physical examinations, and immunogenicity. 
 
• The following PK parameters of free xisomab 3G3 in plasma following single IV 
dose, will be calculated, as appropriate: AUC0-t, AUC0-inf, AUC%extrap, Cmax, 
Tmax, Kel, T½, MRT, CL, and Vss. 
 
• aPTT values will be listed with descriptive statistics and presented graphically. 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 6 of 81 
 
 
 
3. STUDY DESIGN 
 
This is a randomized, double-blind, placebo-controlled, SAD study conducted at one 
study center in the US. 
 
Four (4) cohorts of either 6 subjects (Cohort 1 [4 active and 2 placebo]) or 5 subjects 
(Cohorts 2, 3, and 4 [4 active and 1 placebo]) are planned for evaluation. In each 
cohort, subjects will be randomized to receive a single IV infusion of xisomab 3G3 or 
placebo. In each cohort, at least 30% of the subjects were to be of a race/ethnicity 
minority group. An attempt will be made to include at least 2 females per cohort. 
Subjects will participate in only one cohort. 
 
Two (2) sentinel subjects will be dosed (one placebo, one active) in Cohort 1 and data 
will be collected through Day 8. The next subject in the cohort will be dosed after 
evaluation of the sentinel subjects’ Day 8 safety data. Each subject following these 
sentinel subjects will be dosed with an interval of 24-hours between subjects. 
Subjects in Cohorts 2, 3, and 4 will be dosed at an interval of 24 hours between 
subjects. 
 
Screening of subjects will occur within 28 days prior to dosing. 
 
Subjects will receive a single IV infusion dose of the assigned formulation (xisomab 
3G3 or placebo) on the morning of Day 1. 
 
Subjects will be housed on Day -1, at the time indicated by the Clinical Research Unit 
(CRU), until after the 24-hour blood draw and/or study procedures. Subjects will only 
be discharged if the prothrombin time (PT)/international normalized ratio (INR) 
values are ≤ 3.5 and judged not clinically significant by the PI or designee. Subjects 
will need to return to the CRU at least 2 days after discharge to confirm the PT/INR 
values. 
 
Blood samples will also be collected for the PK (free xisomab 3G3) and PD (aPTT) 
assessments of xisomab 3G3 at scheduled time points for at least 672 hours postdose. 
The planned time points are at predose, and at 0.083, 0.25, 0.5, 1, 3, 8, 24, 72, 120, 
168, 216, 336, 504, and 672 hours after xisomab 3G3 start of infusion. Following the 
672-hour time point, sample collection for PK and PD assessments will continue 
every 7 days (±2 days) until aPTT values return within ±10% of the baseline value or 
the normal range. 
 
Safety and tolerability will be monitored throughout the study by repeated clinical 
and laboratory evaluations. 
 
Subjects for whom aPTT value reaches ± 10% of the baseline value or within the 
normal range by Day 29 will return to the CRU for the follow-up visit on Day 36 to 
perform scheduled follow-up procedures and to determine if any adverse event has 
occurred since the last study visit. 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 7 of 81 
 
 
 
Subjects for whom aPTT did not reach ±10% of the baseline value or within the 
normal range on Day 29, will return every 7 days (±2 days) until aPTT reaches ±10% 
of the baseline value or within the normal range and for the follow-up visit. 
 
Subjects who terminate the study early will be asked to continue aPTT monitoring 
until it reaches ±10% of the baseline value or within the normal range. They will 
return to the CRU approximately 7 days (±2 days) after aPTT reaches ± 10% of the 
baseline value or within normal range for the follow up (FU) visit to perform 
scheduled follow-up procedures and to determine if any AE has occurred since the 
last study visit. They will also be asked to return on Days 15 and 29 to collect the 
anti-drug antibody (ADA) samples. 
 
ADA sample collection will be performed on Days 15 and 29 for all subjects. If aPTT 
values remain elevated past Day 29, an additional ADA sample collection will occur 
at the follow-up visit. 
 
Dose escalation to the next dose level (i.e., next cohort) will not take place until the 
safety review committee (SRC) has determined that adequate safety and tolerability 
of xisomab 3G3 from the current and previous cohorts has been demonstrated to 
permit proceeding to the next cohort. 
 
The total planned duration of subject participation is up to 63 days from screening to 
follow-up, if aPTT value returns within ± 10% of the baseline value or the normal 
range by Day 29. This participation could be prolonged if aPTT values did not reach 
± 10% of the baseline value or within the normal range by Day 29. 
 
4. ANALYSIS POPULATIONS 
 
4.1 
Analysis Populations 
Safety Population 
The safety population will include all subjects who received at least one dose of study 
drug (active or placebo). 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 8 of 81 
 
 
 
Pharmacokinetic Population 
 
The PK population will include data from all subjects who received at least one dose 
of active study drug and completed at least one PK blood draw resulting in at least 
one quantifiable plasma concentration. Samples from all subjects will be assayed 
even if the subjects do not complete the study. All subjects who comply sufficiently 
with the protocol and display an evaluable PK profile (e.g., exposure to treatment, 
availability of measurements and absence of major protocol violations) will be 
included in the PK parameter summary and statistical analyses. 
Pharmacodynamic Population 
 
The PD population will include all subjects who received the study drug (active or 
placebo) and have at least one predose and one postdose quantifiable PD biomarker 
value. All subjects who comply sufficiently with the protocol and display an 
evaluable PD profile will be used for summary statistics. 
 
4.2 
Preliminary Data and Interim Analysis 
 
Please note that Celerion Data Management and Biometrics has not participated in 
providing any of these following outputs. At this point Celerion has not been 
contracted to complete any interim safety, PK, and PD analyses, if required to do so 
an additional interim analysis plan would be required. 
 
Safety: 
 
All available blinded safety data will be reviewed by the SRC prior to dose 
escalation. 
 
The protocol states that at the Sponsor’s request unblinded safety tables, figures, and 
data listings may be presented to the sponsor’s medical expert and head of regulatory 
for the purposes of planning the next initial Phase 2 studies prior to database lock. 
 
PK: 
 
The protocol states that preliminary PK analysis may be performed to evaluate the 
sampling time points as the study progresses and to guide the dose escalation 
decision. 
 
PD: 
 
The protocol states that preliminary PD analysis may be performed to evaluate the 
sampling time points as the study progresses and to guide the dose escalation 
decision. 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 9 of 81 
 
 
 
5. TREATMENT DESCRIPTIONS 
 
Planned doses for each cohort of the study are as follows: 
 
Cohort 1: 
4 subjects, 0.1 mg/kg xisomab 3G3, and 2 subjects, matching placebo 
 
Cohort 2 
4 subjects, 0.5 mg/kg xisomab 3G3, and 1 subject, matching placebo 
 
Cohort 3: 
4 subjects, 2 mg/kg xisomab 3G3, and 1 subject, matching placebo 
 
Cohort 4: 
4 subjects, 5 mg/kg xisomab 3G3, and 1 subject, matching placebo 
 
The subject weight recorded at check-in will be used to calculate the study drug dose. 
Treatments will be described as follows: 
Cohort 
Treatment 
Short Description 
(used in text) 
Long Description (used in Tables 
Figures and Listings) 
 
Cohorts 1-4 Treatment P 
Pooled Placebo 
Single IV Infusion of Placebo 
(Pooled) 
 
Cohort 1 
Treatment A 0.1 mg/kg xisomab 
3G3 
Single IV Infusion of 0.1 mg/kg 
xisomab 3G3 
 
Cohort 2 
Treatment B 0.5 mg/kg xisomab 
3G3 
Single IV Infusion of 0.5 mg/kg 
xisomab 3G3 
 
Cohort 3 
Treatment C 2 mg/kg xisomab 
3G3 
Single IV Infusion of 2 mg/kg 
xisomab 3G3 
 
Cohort 4 
Treatment D 5 mg/kg xisomab 
3G3 
Single IV Infusion of 5 mg/kg 
xisomab 3G3 
 
Additional subjects (N = 5 subjects per cohort; 4 active and 1 placebo) may be 
enrolled if it is deemed appropriate by the SRC to repeat a dose level or to study an 
interim dose level (lower than those planned) in a new cohort of subjects. If cohorts 
are reassigned to different dose levels, treatment descriptions will be updated in the 
TFLs and CSR accordingly. 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 10 of 81 
 
 
 
6. PHARMACOKINETIC ANALYSIS 
 
6.1 
Measurements and Collection Schedule 
 
For all subjects, blood samples for the determination of xisomab 3G3 will be 
collected at predose, and at 0.083, 0.25, 0.5, 1, 3, 8, 24, 72, 120, 168, 216, 336, 504, 
and 672 hours after xisomab 3G3 start of infusion. Following the 672-hour time 
point, sample collection for PK assessment will continue every 7 days (± 2 days) until 
aPTT values return within ± 10% of the baseline value or the normal range. 
 
All concentration data will be included in the calculation of the individual PK 
parameters, the individual concentration-time plots (based on actual sample times), 
and in the mean concentration-time plots (based on nominal sample times). However, 
if there are any significant deviations from nominal sample times, some concentration 
data may be excluded from mean concentration-time plots and/or additional 
concentration-time plots of the mean data may be provided. All deviations and 
excluded data will be provided and discussed in the CSR. 
 
6.2 
Bioanalytical Method 
 
Plasma concentrations of xisomab 3G3 will be determined using enzyme-linked 
immunosorbent assay (ELISA) validated with respect to accuracy, precision, 
linearity, sensitivity, and specificity at Celerion, Lincoln, Nebraska. The analytical 
range (lower limit of quantitation [LLOQ] – upper limit of quantitation [ULOQ]) for 
xisomab 3G3 is expected to be 50 – 5000 ng/mL. 
 
6.3 
Investigational Product and PK Analyte Information 
 
6.3.1 Xisomab 3G3 
 
Xisomab 3G3 is a novel, injectable, therapeutic monoclonal antibody (IgG4, S241P 
hinge-modified) that prevents activation of the contact (intrinsic) pathway of 
coagulation and is intended to address the problem of dose limiting bleeding side 
effects of current antithrombotic agents. Xisomab 3G3 was developed by Aronora, 
Inc. and is intended for IV administration. The proposed indication for xisomab 3G3 
is as a therapeutic treatment of venous thromboembolism. The goal of xisomab 3G3 
treatment is to achieve safe anticoagulation for several days with a single dose. 
 
Xisomab 3G3 is provided as sterile powder for injection via the IV route, upon 
reconstitution. 
 
6.4 
Pharmacokinetic Concentrations 
 
Plasma concentrations of xisomab 3G3 as determined at the collection times and per 
the bioanalytical method described in Section 6.1 and Section 6.2, respectively, will 
be used for the calculation of the plasma xisomab 3G3 PK parameters. 


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Statistical Analysis Plan, 25 August 2017 
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6.5 
Noncompartmental Pharmacokinetic Analysis and Parameter Calculation 
 
6.5.1 Plasma Pharmacokinetic Parameters 
 
The appropriate noncompartmental PK parameters will be calculated from the plasma 
xisomab 3G3 concentration-time data using Phoenix® WinNonlin® Version 6.3 or 
higher. Actual sample times will be used in the calculations of the PK parameters. 
The calculation of the actual time for xisomab 3G3 will be in respect to the start of 
infusion time of xisomab 3G3 on Day 1. All PK parameters included in the protocol 
are listed in Table 6.1 below, and are defined as appropriate for study design. 
 
Table 6.1.  Noncompartmental Pharmacokinetic Parameters to be Calculated 
 
Parameter 
Label to be 
Used in the 
Text, Tables 
and Figures 
Definition 
Method of 
Determination 
AUC0-t 
AUC0-t 
Area under the concentration-time 
curve from time 0 to the time of the 
last measurable non-zero 
concentration 
Calculated using the 
Linear Trapezoidal with 
Linear Interpolation 
Method 
AUC0-inf 
AUC0-inf 
Area under the concentration-time 
curve from time 0 extrapolated to 
infinity 
AUC0-inf = AUC0-t + 
(Clast/kel) 
where Clast is the last 
observed/measured 
concentration 
AUC%extrap 
AUC%extrap 
Percent of AUC0-inf extrapolated 
AUC%extrap = 
(1 - AUC0-t/AUC0- 
inf)*100 
AUMC0-inf * 
AUMC0-inf 
Area under the moment curve from 
time 0 extrapolated to infinity 
AUMC0-inf = AUMC0-t 
+ [(tlast x Clast)/ Kel]+ 
[Clast/(Kel)2] 
Cmax 
Cmax 
The maximum observed concentration 
Taken directly from 
bioanalytical data 
Tmax 
Tmax 
The time to reach Cmax. If the 
maximum value occurs at more than 
one time point, Tmax is defined as the 
first time point with this value 
Taken from clinical 
database as the 
difference in the start 
time of the infusion and 
the time of the blood 
draw which is associated 
with the Cmax. 
Kel 
Kel 
Apparent first-order terminal 
elimination rate constant calculated 
from a semi-log plot of the plasma 
concentration versus time curve 
The parameter will be 
calculated by linear 
least-squares regression 
analysis using the 
maximum number of 
points in the terminal 
log-linear phase (e.g., 
three or more non-zero 
plasma concentrations). 


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Statistical Analysis Plan, 25 August 2017 
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Parameter 
Label to be 
Used in the 
Text, Tables 
and Figures 
Definition 
Method of 
Determination 
T1/2 
T1/2 
Apparent first-order terminal 
elimination half-life 
Calculated as: 0.693/ Kel 
CL 
CL 
The apparent total plasma clearance 
after IV administration 
Calculated as: 
Dose/(AUC0-inf) 
MRT * 
MRT 
Mean residence time of unchanged 
drug in the systemic circulation when 
the drug concentrations are 
extrapolated to infinity 
Calculated as: 
(AUMC0-inf/AUC0-inf ) 
– (TI/2) 
Where TI is the duration 
of infusion 
Vss 
Vss 
Total apparent volume of distribution 
following single IV dose 
administration 
Calculated as: 
MRT x CL 
* AUMC0-inf and MRT values will be used for Vss calculation but will not be listed in the PK tables. 
* Note for the programmer: Parameters which are calculated for use in the calculation of a separate 
parameter but that are not summarized in the PK tables (i.e., AUMC0-inf and MRT) will be included 
in the study data tabulation model (SDTM) PP(Pharmacokinetic Parameters) domain, but not included 
in the analysis data model (ADaM) ADPP (Pharmacokinetic Parameters Analysis) domain. 
 
PK parameters will not be calculated for subjects with less than 3 consecutive 
postdose time points with quantifiable concentrations. Subjects for whom there are 
insufficient data to calculate the PK parameters will be included in the concentration 
tables only and excluded from the statistical analysis. 
 
For the calculation of the PK parameters, plasma concentrations below the limit of 
quantitation (BLQ) prior to the first quantifiable concentration will be set to 0 and 
plasma concentrations BLQ after the first quantifiable concentration will be treated as 
missing. 
 
The Kel will be determined using linear regressions composed of least 3 data points. 
The Kel will not be assigned if 1) the terminal elimination phase is not apparent, 2) if 
Tmax is one of the 3 last data points, or 3) if the R2 value is less than 0.8. In cases 
where the Kel interval is not assigned, the values of AUC0-inf, AUC%extrap, 
AUMC0-inf, T1/2, CL, MRT, and Vss are considered not calculable and will not be 
reported. Wherever the resulting T1/2 is more than half as long as the sampling 
interval, the Kel values and associated parameters (AUC0-inf, AUC%extrap, 
AUMC0-inf, T1/2, CL, MRT, and Vss) may not be presented as judged appropriate 
and in accordance with Celerion SOPs. 


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Statistical Analysis Plan, 25 August 2017 
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6.6 
Data Summarization and Presentation 
 
All plasma xisomab 3G3 PK concentrations and/or PK parameters descriptive 
statistics will be generated using SAS® version 9.3 or higher. A concentration table 
will be presented for pooled placebo samples without descriptive statistics. 
 
The plasma concentrations of xisomab 3G3 will be listed and summarized by 
treatment and time points for all subjects in the PK Population. Plasma concentrations 
of xisomab 3G3 will be presented with the same level of precision as received from 
the bioanalytical laboratory. Summary statistics, including sample size (n), arithmetic 
mean (Mean), standard deviation (SD), coefficient of variation (CV%), standard error 
of the mean (SEM), minimum, median, and maximum will be calculated for all 
nominal concentration time points. Excluded subjects will be included in the 
concentration listings, but will be excluded from the summary statistics and noted as 
such in the tables. All BLQ values will be presented as “BLQ” in the concentration 
listings and footnoted accordingly. 
 
Mean and individual concentration-time profiles will be presented on linear and semi- 
log scales. Linear mean plots will be presented with and without SD. 
 
Plasma xisomab 3G3 PK parameters will be listed and summarized by treatment for 
all subjects in the PK Population. Pharmacokinetic parameters will be reported to 3 
significant figures for individual parameters, with the exception of T1/2 and Tmax, 
which will be presented with 2 decimal places. Summary statistics (n, Mean, SD, 
CV%, SEM, minimum, median, maximum, geometric mean [Geom Mean] and 
geometric CV% [Geom CV%]) will be calculated for plasma xisomab 3G3 PK 
parameters. Excluded subjects will be listed in the PK parameter tables, but will be 
excluded from the summary statistics and noted as such in the tables. 
 
The level of precision for each concentration and PK parameter statistic will be 
presented as follows: 
 
• minimum/maximum: in same precision as in the bioanalytical data for 
concentrations and same precision for PK parameters presentation 
• Mean/median/Geom Mean: in one more level of precision than 
minimum/maximum 
• SD/SEM: in one more level of precision than Mean/median/Geom Mean 
• n will be presented as an integer 
• CV% and Geom CV% will be presented to the nearest tenth 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
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7. 
PHARMACODYNAMIC ANALYSIS 
 
7.1 
Measurement and Collection Schedule 
 
For all subjects, blood samples for the assessment of aPTT will be collected at 
predose, and at 0.083, 0.25, 0.5, 1, 3, 8, 24, 72, 120, 168, 216, 336, 504, and 672 
hours after xisomab 3G3 start of infusion. Following the 672-hour time point, sample 
collection for PD assessment will continue every 7 days (± 2 days) until aPTT values 
return within ± 10% of the baseline value or the normal range. 
 
7.2 
Biomarker Method 
 
aPTT will be determined using a light scattering method. This method is a Food and 
Drug Administration (FDA) approved kit for diagnostic testing and has been 
validated with respect to accuracy and precision at Celerion, Tempe, Arizona in 
accordance with the College of American Pathologists (CAP) and the Clinical 
Laboratory Improvement Amendments (CLIA) requirements for coagulation testing. 
The reference range for aPTT coagulation time is 23 – 32 seconds. 
 
7.3 
Activated Partial Thromboplastin Time 
 
Inhibition of the blood coagulation contact pathway by xisomab 3G3 or its murine 
precursor, xisomab 14E11, is anticoagulant, as demonstrated by both in vitro and in 
vivo activated partial thromboplastin time (aPTT) prolongation. 
 
7.4 
Activated Partial Thromboplastin Time Values 
 
aPTT values as determined at the collection times and per the biomarker method 
described in Section 7.1 and Section 7.2, respectively, will be used for the calculation 
of change from baseline. 
 
7.5 
Data Summarization and Presentation 
 
aPTT values will be extracted from the clinical laboratory database and descriptive 
statistics will be generated using SAS® version 9.3 or higher. A table will be 
presented for the aPTT change from baseline with descriptive statistics. Change from 
baseline will be calculated by subtracting the predose aPTT value from the postdose 
aPTT value at each time point. The mean change from baseline will be calculated 
using the individual change from baseline values. If change from baseline results in a 
negative value, this value will be set to ‘0’ for the calculation of the summary 
statistics. 
 
aPTT values will be listed and summarized by treatment and time points for all 
subjects in the PD Population. aPTT values will be presented with the same level of 
precision as received from the clinical laboratory database. Summary statistics, 
including n, Mean, SD, CV%, SEM, minimum, median, and maximum will be 


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xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
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calculated for all nominal values time points. Excluded subjects will be included in 
the aPPT values tables, but will be excluded from the summary statistics and noted as 
such in the tables. 
 
Mean and individual aPTT values-time and change from baseline-time profiles will 
be presented on linear scale. Linear mean plots will be presented with and without 
SD. 
 
The level of precision for the aPPT values summary statistic will be presented as 
follows: 
 
• minimum/maximum: in same precision as in the clinical laboratory database 
• Mean/median: in one more level of precision than minimum/maximum 
• SD/SEM: in one more level of precision than Mean/median 
• n will be presented as an integer 
• CV% will be presented to the nearest tenth 
 
8. SAFETY 
 
No inferential statistics will be performed on safety data. 
 
All case report form (CRF) data will be listed by subject and chronologically by 
assessment time points. This will include rechecks, unscheduled assessments, and 
early termination. 
 
Applicable continuous variables will be summarized using n, arithmetic mean, SD, 
minimum, median, and maximum. Data from subjects who received the placebo 
treatment will be pooled across cohorts. 
 
The level of precision will be presented as follows: minimum/maximum in the same 
precision as in the database, mean/median in one more precision level than 
minimum/maximum, SD in one more precision level than mean/median, and n will be 
presented as an integer. 
 
Where individual data points are missing because of dropouts or other reasons, the 
data will be summarized based on reduced denominators. 
 
8.1 
Subject Discontinuation 
 
Subjects will be summarized by number of subjects dosed, completed, and 
discontinued the study with discontinuation reasons by treatment (pooled placebo and 
xisomab 3G3 dose levels), pooled active, and overall. Any screen failure data will be 
listed. 


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Statistical Analysis Plan, 25 August 2017 
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8.2 
Demographics 
 
Descriptive statistics will be calculated for continuous variables (age, weight, height, 
and body mass index) by treatment (pooled placebo and xisomab 3G3 dose levels), 
pooled active, and overall. Age will be derived from date of birth to date of first 
dosing and reported as an integer. Any screen failure data will be listed. 
 
Frequency counts will be provided for categorical variables (race, ethnicity, and sex) 
by treatment (pooled placebo and xisomab 3G3 dose levels) and overall. 
 
8.3 
Adverse Events and Injection Site Reaction 
 
All adverse events (AEs) occurring during this clinical trial will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA®), Version 20.0. 
All AEs captured in the database will be listed in by-subject data listings including 
verbatim term, coded term, treatment, severity, relationship to study drug, and action; 
however, only treatment-emergent AEs (TEAEs) will be summarized. 
 
A TEAE is defined as an AE that is starting or worsening at the start time of study 
drug administration or after. Each TEAE will be attributed to a treatment based on the 
onset date and time of the AE. 
 
If an AE increases in severity, that AE will be given a resolution date and time and a 
new record will be initiated with the new severity. If the severity of an AE remains 
the same or decreases, the AE will be kept open through to resolution. 
 
If the onset time of an AE is missing and the onset date is the same as the treatment 
dosing date or after the treatment dosing date, then the AE will be considered 
treatment emergent. If the onset date of an AE is missing, then the AE will be 
considered treatment emergent. 
 
TEAEs will be tabulated by System Organ Class (SOC) and Preferred Term. 
Summary tables will include number of subjects reporting the AE and as percent of 
number of subjects dosed by treatment (pool placebo and xisomab 3G3 dose levels) 
and pooled active (xisomab 3G3 doses pooled). The number of AEs will be tabulated 
in a similar manner. Tables which tabulate the number of TEAEs by severity and 
relationship to study treatment will also be included. 
 
Injection site reaction will be assessed and any abnormal finding will be reported as 
an adverse event. 
 
Serious adverse events (SAEs), if present, will also be listed. Applicable narratives 
will be included in the CSR. 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 17 of 81 
 
 
 
8.4 
Clinical Laboratory Tests (Coagulation, Serum Chemistry, Hematology, 
Urinalysis) 
 
Clinical laboratory tests for serum chemistry, hematology, and urinalysis will be 
performed at Screen, Check-in (Day -1), Hour 8 postdose on Day 1, Day 2, Day 8, 
Day 29, and Follow-up (Day 36) or prior to early termination. Bleeding time, which is 
contained in the hematology panel was performed at Check-in (Day -1), Predose, 
Hour 1 postdose on Day 1, and Day 2. Clinical laboratory tests for coagulation will be 
performed at Screen, Check-in (Day -1), and Follow-up (Day 36) or prior to early 
termination, with additional assessments at Hour 1 postdose on Day 1, Day 2, Day 4, 
Day 8, and Day 29 for PT and INR. 
 
Out-of-normal range flags will be recorded as follows: high (H) and low (L) for 
numerical results and did-not-match (*) for categorical results. If a value fails the 
reference range, it will automatically be compared to a computer clinically significant 
(CS) range. If the value falls within the computer CS range, it will be noted as “N” 
for not clinically significant. If the value fails (i.e., fall outside of the CS range) the 
computer CS range, it will be flagged with a “Y” which prompts the PI to determine 
how the out-of-range value should be followed using 4 Investigator flags: "N", not 
clinically significant, "R", requesting a recheck, "^", checking at the next scheduled 
visit, or "Y", clinically significant. To distinguish the PI flag from the computer CS 
range flags, the PI flags of “N” and “Y” will be presented as “-“ and “+”, 
respectively, in the data listing. Additionally, a derived flag based on a search of the 
PI comments for a comment of “CS” or “Clinically Significant” will be used. The 
derived flag will be populated with “+” if the positive clinically significant 
determination is found in the comments for cases when the PI flag is populated with a 
“^” or a “R”. 
 
Out-of-range values and corresponding recheck results will be listed. Results that are 
indicated as CS by the PI (either in the PI flag or in PI comments) will be listed in a 
table. 
 
Bleeding time will be listed with the hematology results and will be included in the 
hematology out-of-range table but will be summarized with the coagulation results. 
 
All coagulation results for PD endpoint aPTT will be listed with the clinical 
laboratory results and included in the out-of-range table, but for the time points 
outlined in Section 7.1 summaries will not be included in the clinical laboratory 
summary tables. 
 
For all numeric laboratory values, descriptive statistics will be presented for each 
laboratory test by assessment time point and treatment (pooled placebo and xisomab 
3G3 dose levels). Change from baseline will be summarized in a similar manner. 
Baseline is defined as the result closest and prior to dose which may include 
unscheduled or recheck results. This will typically be the result collected on Day -1. 


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Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
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Postdose unscheduled events or rechecks will not be included in summaries. Similarly 
early termination results will not be included in summaries. 
 
For each laboratory test, a shift table will be developed to compare the frequency of 
the results at baseline (above normal, normal, or below normal) with the respective 
postdose results. For urinalysis tests, the categories are normal and outside normal. 
 
8.5 
Vital Signs 
 
Vital signs (heart rate, blood pressure, respiration rate, and temperature) will be 
performed at Screen, predose, Hour .25 postdose on Day 1, as well as Day 8, Day 29, 
and Follow-up (Day 36) or prior to early termination. 
 
Descriptive statistics will be presented for each vital sign measurement by assessment 
time point and treatment (pooled placebo and xisomab 3G3 dose levels). Change 
from baseline will be summarized in a similar manner. Baseline is defined as the 
result closest and prior to dose which may include unscheduled or recheck results. 
This will typically be the result collected predose on Day 1. Postdose unscheduled 
events or rechecks will not be included in summaries. Similarly early termination 
results will not be included in summaries. 
 
8.6 
Electrocardiogram 
 
Single 12-Lead Electrocardiograms will be performed at Screen, predose, Hour .25 
postdose on Day 1, as well as Day 8, Day 29, and Follow-up (Day 36) or prior to 
early termination. ECG parameters include heart rate, PR, QRS, QT, QTcF (QT 
corrected for heart rate using Fridericia’s correction), and overall interpretation. 
 
Descriptive statistics will be presented for each ECG parameter by assessment time 
point and treatment (pooled placebo and xisomab 3G3 dose levels). Change from 
baseline will be summarized in a similar manner. Baseline is defined as the result 
closest and prior to dose which may include unscheduled or recheck results. This will 
typically be the result collected predose on Day 1. Postdose unscheduled events or 
rechecks will not be included in summaries. Similarly early termination results will 
not be included in summaries. 
 
8.7 
Concomitant Medications 
 
All concomitant medications recorded during the study will be coded with the WHO 
Dictionary Version 01MAR2017 and listed. 
 
8.8 
Physical Examination 
 
Full physical examinations will be performed at Screen and Check-in (Day -1), and 
abbreviated physical examinations will be performed at Hour 1 postdose on Day 1, 
Day 2, Day 29, and Follow-up (Day 36) or prior to early termination. Symptom- 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 19 of 81 
 
 
 
driven physical examinations may be performed at other times, at the PI’s or 
designee’s discretion. All data found in the CRF will be listed. Any changes in 
physical examinations will be captured and summarized with the adverse events and 
described in the text of the report. 
 
8.9 
Medical History 
 
All medical and surgical history will be will be coded using the Medical Dictionary 
for Regulatory Activities (MedDRA®), Version 20.0 and listed. 
8.10 
Immunogenicity 
 
Blood samples will be collected from each subject for ADA detection at predose, 
Day 15, Day 29, and at the Follow-up visit only in the event that the Follow-up visit 
occurs after Day 36. Immunogenicity testing will be done at Celerion, Lincoln, 
Nebraska. 
 
A qualitative screening assay will be performed on all samples and results reported as 
positive or negative for ADA detection. If the screening assay is positive, a 
qualitative confirmatory assay will be performed on the sample to confirm that the 
antibodies are specific to xisomab 3G3, with results reported as positive or negative. 
Confirmed positive samples for ADA will be reassayed, at a series of 2-fold dilutions 
prior to analysis. The greatest dilution that results in a mean response greater than the 
assay cut point will be reported as the titer for that sample. 
 
On the other hand, if the screening result is negative, confirmatory and titer assays 
will not be performed. In the case where the confirmatory result is negative, but the 
screening result was positive, the titer assay will not be performed. 
 
Results from the qualitative screening and confirmatory ADA detections will be listed 
as positive or negative. For samples with a positive confirmatory assay, a titer value 
will be presented with the same level of precision as received from the bioanalytical 
laboratory. 
 
Frequency counts of positive and negative ADA detection will be presented by 
collection time, assay type (screening or confirmatory) and treatment (pooled placebo 
and xisomab 3G3 dose levels). 
 
9. SUMMARY OF CHANGES FROM PROTOCOL-PLANNED ANALYSIS 
 
Per the protocol, immunogenicity data will be summarized descriptively. ADA 
detection is categorical data and thus descriptive summaries cannot be calculated. 
Frequency counts of positive and negative ADA detection will be presented instead. 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
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10. SUMMARY TABLES AND FIGURES 
 
Summary tables and figures are numbered following the International Conference on 
Harmonization (ICH) structure but may be renumbered as appropriate during the 
compilation of the tables and figures for the CSR. Note that all PK, PD, and Safety 
summary tables and figures will be generated using SAS® Version 9.3 or higher. 
10.1 
In-text Summary Tables and Figures 
 
The following is a list of table and figure titles that will be included in the text of the 
CSR. Tables and figures will be numbered appropriately during compilation of the 
CSR. 
 
Section 10: 
 
Table 10-1 
Disposition Summary 
Section 11: 
Table 11-1 
Demographic Summary 
 
Table 11-2 
Summary of Plasma Xisomab 3G3 Pharmacokinetics Following a 
Single IV Infusion of 0.1, 0.5, 2, and 5 mg/kg Xisomab 3G3 
 
Figure 11-1 
Arithmetic Mean Plasma Xisomab 3G3 Concentration -Time Profiles 
Following a Single IV Infusion of 0.1, 0.5, 2, and 5 mg/kg Xisomab 
3G3 (Linear Scale) 
 
Figure 11-2 
Arithmetic Mean aPPT Values Versus Time Following a Single IV 
Infusion of 0.1, 0.5, 2, and 5 mg/kg Xisomab 3G3 and Pooled Placebo 
(Linear Scale) 
 
Figure 11-3 
Arithmetic Mean aPPT Change From Baseline Versus Time Following 
a Single IV Infusion of 0.1, 0.5, 2, and 5 mg/kg Xisomab 3G3 and 
Pooled Placebo (Linear Scale) 
 
Section 12: 
 
Table 12-1 
Adverse Event Frequency by Treatment - Number of Subjects 
Reporting the Event (% of Subjects Dosed) 
 
10.2 
Section 14 Summary Tables and Figures 
 
The following is a list of table and figure titles that will be included in Section 14 of 
the report. Table and figure titles may be renumbered as appropriate during the 
compilation of the report. 


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Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
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14.1 
Demographic Data Summary Tables 
 
Table 14.1.1 Summary of Disposition (Safety Population) 
Table 14.1.2 Demographic Summary (Safety Population) 
14.2 
Pharmacokinetic and Pharmacodynamic Data Summary Tables and 
Figures 
 
14.2.1 Plasma Pharmacokinetic Xisomab 3G3 Tables 
 
Table 14.2.1.1 Plasma Xisomab 3G3 Concentrations (ng/mL) Following a 
Single IV Infusion of 0.1 mg/kg Xisomab 3G3 (Treatment A) 
(Pharmacokinetic Population) 
Table 14.2.1.2 Plasma Xisomab 3G3 Concentrations (ng/mL) Following a 
Single IV Infusion of 0.5 mg/kg Xisomab 3G3 (Treatment B) 
(Pharmacokinetic Population) 
Table 14.2.1.3 Plasma Xisomab 3G3 Concentrations (ng/mL) Following a 
Single IV Infusion of 2 mg/kg Xisomab 3G3 (Treatment C) 
(Pharmacokinetic Population) 
Table 14.2.1.4 Plasma Xisomab 3G3 Concentrations (ng/mL) Following a 
Single IV Infusion of 5 mg/kg Xisomab 3G3 (Treatment D) 
(Pharmacokinetic Population) 
Table 14.2.1.5 Plasma Xisomab 3G3 Concentrations (ng/mL) Following a 
Single IV Infusion of Placebo (Pooled) (Treatment P) 
Table 14.2.1.6 Plasma Xisomab 3G3 Pharmacokinetic Parameters 
Following a Single IV Infusion of 0.1 mg/kg Xisomab 3G3 
(Treatment A) (Pharmacokinetic Population) 
Table 14.2.1.7 Plasma Xisomab 3G3 Pharmacokinetic Parameters 
Following a Single IV Infusion of 0.5 mg/kg Xisomab 3G3 
(Treatment B) (Pharmacokinetic Population) 
Table 14.2.1.8 Plasma Xisomab 3G3 Pharmacokinetic Parameters 
Following a Single IV Infusion of 2 mg/kg Xisomab 3G3 
(Treatment C) (Pharmacokinetic Population) 
Table 14.2.1.9 Plasma Xisomab 3G3 Pharmacokinetic Parameters 
Following a Single IV Infusion of 5 mg/kg Xisomab 3G3 
(Treatment D) (Pharmacokinetic Population) 
Table 14.2.1.10  Intervals (Hours) Used for Determination of Plasma Xisomab 
3G3 Kel Values (Pharmacokinetic Population) 
14.2.2 Plasma Pharmacokinetic Xisomab 3G3 Figures 
 
Figure 14.2.2.1  Mean (SD) Plasma Xisomab 3G3 Concentration Versus Time 
Profiles Following a Single IV Infusion of 0.1, 0.5, 2, and 5 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 22 of 81 
 
 
 
mg/kg Xisomab 3G3 (Linear Scale) (Pharmacokinetic 
Population) 
Figure 14.2.2.2  Mean Plasma Xisomab 3G3 Concentration Versus Time 
Profiles Following a Single IV Infusion of 0.1, 0.5, 2, and 5 
mg/kg Xisomab 3G3 (Linear Scale) (Pharmacokinetic 
Population) 
Figure 14.2.2.3  Mean Plasma Xisomab 3G3 Concentration Versus Time 
Profiles Following a Single IV Infusion of 0.1, 0.5, 2, and 5 
mg/kg Xisomab 3G3 (Semi-Log Scale) (Pharmacokinetic 
Population) 
 
14.2.3 Plasma Pharmacodynamic aPTT Table 
 
Table 14.2.3.1 Mean aPTT Values (sec) and Mean Change from Baseline 
aPTT Values (sec) Following a Single IV Infusion of 0.1, 
0.5, 2.0, and 5 mg/kg Xisomab 3G3 and Placebo 
(Pharmacodynamic Population) 
 
 
14.2.4 Plasma Pharmacodynamic aPTT Figures 
 
Figure 14.2.4.1  Arithmetic Mean (SD) aPTT Values Versus Time Following 
a Single IV Infusion of 0.1, 0.5, 2, and 5 mg/kg Xisomab 
3G3 and Placebo (Linear Scale) (Pharmacodynamic 
Population) 
Figure 14.2.4.2  Arithmetic Mean aPTT Values Versus Time Following a 
Single IV Infusion of 0.1, 0.5, 2, and 5 mg/kg Xisomab 3G3 
and Placebo (Linear Scale) (Pharmacodynamic Population) 
Figure 14.2.4.3  Mean (SD) Change From Baseline of aPTT Values Versus 
Time Following a Single IV Infusion of 0.1, 0.5, 2, and 5 
mg/kg Xisomab 3G3 and Placebo (Linear Scale) 
(Pharmacodynamic Population) 
Figure 14.2.4.4  Mean Change From Baseline of aPTT Values Versus Time 
Following a Single IV Infusion of 0.1, 0.5, 2, and 5 mg/kg 
Xisomab 3G3 and Placebo (Linear Scale) (Pharmacodynamic 
Population) 
 
14.3 
Safety Data Summary Tables 
 
14.3.1 
Displays of Adverse Events 
 
Table 14.3.1.1 Treatment-Emergent Adverse Event Frequency by Treatment 
– Number of Subjects Reporting the Event (% of Subject 
Dosed) (Safety Population) 


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Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 23 of 81 
 
 
 
Table 14.3.1.2 Treatment-Emergent Adverse Event Frequency by Treatment 
– Number of Adverse Events (% of Total Adverse Events) 
(Safety Population) 
Table 14.3.1.3 Treatment-Emergent Adverse Event Frequency by 
Treatment, Severity, and Relationship to Drug – Number of 
Adverse Events (Safety Population) 
 
14.3.2 
Listings of Deaths, other Serious and Significant Adverse Events 
 
Table 14.3.2.1 Serious Adverse Events (Safety Population) <if no serious 
adverse event occurred, a statement ‘No serious adverse 
event was reported’> 
 
14.3.3 
Narratives of Deaths, other Serious and Certain other 
Significant Adverse Events 
 
14.3.4 
Abnormal Laboratory Value Listing (each patient) 
 
Table 14.3.4.1 Out-of-Range Values and Recheck Results – Serum 
Chemistry (Safety Population) 
Table 14.3.4.2 Out-of-Range Values and Recheck Results – Hematology 
(Safety Population) 
Table 14.3.4.3 Out-of-Range Values and Recheck Results – Urinalysis 
(Safety Population) 
Table 14.3.4.4 Out-of-Range Values and Recheck Results – Coagulation 
(Safety Population) 
Table 14.3.4.5 Clinically Significant Values and Corresponding Results 
(Safety Population) 
14.3.5 
Displays of Other Laboratory, Vital Signs, Electrocardiogram, 
Physical Examination, and Other Safety Data 
 
Table 14.3.5.1 Clinical Laboratory Summary – Serum Chemistry (Safety 
Population) 
Table 14.3.5.2 Clinical Laboratory Change From Baseline – Serum 
Chemistry (Safety Population) 
Table 14.3.5.3 Clinical Laboratory Shift From Baseline – Serum Chemistry 
(Safety Population) 
Table 14.3.5.4 Clinical Laboratory Summary – Hematology (Safety 
Population) 
Table 14.3.5.5 Clinical Laboratory Change From Baseline – Hematology 
(Safety Population) 
Table 14.3.5.6 Clinical Laboratory Shift From Baseline – Hematology 
(Safety Population) 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 24 of 81 
 
 
 
Table 14.3.5.7 Clinical Laboratory Summary – Urinalysis (Safety 
Population) 
Table 14.3.5.8 Clinical Laboratory Change From Baseline – Urinalysis 
(Safety Population) 
Table 14.3.5.9 Clinical Laboratory Shift From Baseline – Urinalysis (Safety 
Population) 
Table 14.3.5.10  Clinical Laboratory Summary – Coagulation & Bleeding 
Time (Safety Population) 
Table 14.3.5.11  Clinical Laboratory Change From Baseline – Coagulation & 
Bleeding Time (Safety Population) 
Table 14.3.5.12  Clinical Laboratory Shift From Baseline – Coagulation & 
Bleeding Time (Safety Population) 
Table 14.3.5.13  Vital Sign Summary (Safety Population) 
Table 14.3.5.14  Vital Sign Change From Baseline (Safety Population) 
Table 14.3.5.15 12-Lead Electrocardiogram Summary (Safety Population) 
Table 14.3.5.16 12-Lead Electrocardiogram Change From Baseline (Safety 
Population) 
 
Table 14.3.5.17 ADA Detection Summary by Collection Time and Treatment 
(Safety Population) 
 
10.3 
Section 16 Data Listings 
 
Note: Hepatitis and HIV results that are provided by the clinical laboratory will not be 
presented in subject data listings and will not be included in any database transfer. 
 
Data listings are numbered following the ICH structure but may be renumbered as 
appropriate during the compilation of the TFLs for the CSR. The following is a list of 
appendix numbers and titles that will be included as data listings: 
 
16.1 
Study Information 
 
Appendix 16.1.9 
Statistical Methods 
 
Appendix 16.1.10.1 
Clinical Laboratory Reference Ranges 
 
16.2 
Subject Data Listings 
 
16.2.1 
Subject Discontinuation 
 
Appendix 16.2.1 
Subject Disposition (Safety Population) 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 25 of 81 
 
 
 
16.2.2 
Protocol Deviations 
 
Appendix 16.2.2 
Protocol Deviations 
 
16.2.3 
Subjects Excluded from Pharmacokinetic/Pharmacodynamic 
Analysis 
 
Appendix 16.2.3.1 
Subjects Excluded from Pharmacokinetic Analysis 
Appendix 16.2.3.2 
Subjects Excluded from Pharmacodynamic Analysis 
Note: Appendices 16.2.2, 16.2.3.1, and 16.2.3.2 are generated in MS Word for 
inclusion in the study report. 
 
16.2.4 
Demographic Data 
 
Appendix 16.2.4.1 
Demographics (Safety Population) 
Appendix 16.2.4.2 
Physical Examination (Safety Population) 
Appendix 16.2.4.3 
Medical History (Safety Population) 
Appendix 16.2.4.4 
Substance Use (Safety Population) 
 
16.2.5 
Compliance and/or Drug Concentration Data 
 
Appendix 16.2.5.1.1   Inclusion Criteria 
Appendix 16.2.5.1.2   Exclusion Criteria 
Appendix 16.2.5.2 
Subject Eligibility (Safety Population) 
Appendix 16.2.5.3 
Check-in Criteria and Return Responses (Safety 
Population) 
Appendix 16.2.5.4.1   Test Compound Description (Safety Population) 
Appendix 16.2.5.4.2   Test Compound Administration Times (Safety 
Population) 
Appendix 16.2.5.5 
Blood Draw Times (Safety Population) 
Appendix 16.2.5.6 
Meal Times (Safety Population) 
Appendix 16.2.5.7 
Prior and Concomitant Medications (Safety Population) 
 
16.2.6 
Individual Pharmacokinetic/Pharmacodynamic Response Data 
 
Appendix 16.2.6.1 
Individual Plasma Xisomab 3G3 Concentrations Versus 
Time Profiles Following a Single IV Infusion of <X> 
mg/kg Xisomab 3G3 (Linear and Semi-Log Scale) for 
<Subject #> 
 
Appendix 16.2.6.2 
Individual aPTT Values (sec) Following a Single IV 
Infusion of <X> mg/kg Xisomab 3G3 <or Placebo> 


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Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 26 of 81 
 
 
 
Appendix 16.2.6.3 
Individual aPTT Values Versus Time Profiles 
Following a Single IV Infusion of <X> mg/kg Xisomab 
3G3 <or Placebo> (Linear) for <Subject #> 
 
Appendix 16.2.6.4 
Individual Change from Baseline aPTT Values (sec) 
Following a Single IV Infusion of <X> mg/kg Xisomab 
3G3 <or Placebo> 
 
Appendix 16.2.6.5 
Individual Change From Baseline aPTT Values Versus 
Time Profiles Following a Single IV Infusion of <X> 
mg/kg Xisomab 3G3 <or Placebo> (Linear) for 
<Subject #> 
 
16.2.7 
Adverse Events Listings 
 
Appendix 16.2.7.1.1   Adverse Events (I of II) (Safety Population) 
Appendix 16.2.7.1.2   Adverse Events (II of II) (Safety Population) 
Appendix 16.2.7.2 
Adverse Event Non-Drug Therapy (Safety Population) 
Appendix 16.2.7.3 
Adverse Event Preferred Term Classification (Safety 
Population) 
 
16.2.8 
Listings of Individual Laboratory Measurements and Other 
Safety Observations 
 
Appendix 16.2.8.1.1   Clinical Laboratory Report - Serum Chemistry (Safety 
Population) 
Appendix 16.2.8.1.2   Clinical Laboratory Report - Hematology (Safety 
Population) 
Appendix 16.2.8.1.3   Clinical Laboratory Report - Urinalysis (Safety 
Population) 
Appendix 16.2.8.1.4   Clinical Laboratory Report - Coagulation (Safety 
Population) 
Appendix 16.2.8.1.5   Clinical Laboratory Report - Urine Drug Screening 
(Safety Population) 
Appendix 16.2.8.1.6   Clinical Laboratory Report - Comments (Safety 
Population) 
Appendix 16.2.8.2 
Vital Signs (Safety Population) 
Appendix 16.2.8.3 
12-Lead Electrocardiogram (Safety Population) 
Appendix 16.2.8.4 
Immunogenicity Response Results (Safety Population) 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 27 of 81 
 
 
 
11. TABLE AND FIGURE SHELLS 
 
The following table shells provide a framework for the display of data from this 
study. The shells may change due to unforeseen circumstances. These shells may not 
be reflective of every aspect of this study, but are intended to show the general layout 
of the tables that will be presented and included in the final report. Unless otherwise 
noted, all tables will be presented in Times New Roman font size 8. These tables will 
be generated off of the Celerion ADaM Version 2.1 data structure. 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
 
 
 
 
11.1 
In-text Summary Tables Shells 
 
In-text Table 10-1 will be in the following format: 
 
Table 10-1 
Disposition Summary 
 
 
Treatment 
Disposition 
A 
B 
C 
D 
Pooled Placebo 
Pooled Active 
Overall 
Dosed 
X (100%) 
X (100%) 
X (100%) 
X (100%) 
X (100%) 
X (100%) 
X (100%) 
Completed 
X (X%) 
X (X%) 
X (X%) 
X (X%) 
X (X%) 
X (X%) 
X (X%) 
Discontinued Early 
X (X%) 
X (X%) 
X (X%) 
X (X%) 
X (X%) 
X (X%)  
X (X%)  
<Reason> 
X (X%) 
X (X%) 
X (X%) 
X (X%) 
X (X%) 
X (X%) 
X (X%) 
Treatment A: Single IV Infusion of 0.1 mg/kg xisomab 3G3 
Treatment B: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
Treatment C: Single IV Infusion of 2 mg/kg xisomab 3G3 
Treatment D: Single IV Infusion of 5 mg/kg xisomab 3G3 
Source: Table 14.1.1 
Program:  /CAXXXXX/sas_prg/stsas/intext/t_disp.sas 08OCT2015  16:36 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
 
 
 
In-text Table 11-1 will be in the following format: 
 
Table 11-1 
Demographic Summary 
 
 
Treatment 
Trait 
Category/Statistics 
A 
B 
C 
D 
Pooled Placebo 
Pooled Active 
Overall 
Sex 
Male 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
Female 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Race 
Asian 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
Black or African American 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
White 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Ethnicity 
Not Hispanic or Latino 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
Hispanic or Latino 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Age (yrs) 
n 
X 
X 
X 
X 
X 
X 
X 
 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Weight (kg) 
n 
X 
X 
X 
X 
X 
X 
X 
 
Mean 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
SD 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
 
Minimum 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
Median 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
Maximum 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Height (cm) 
n 
X 
X 
X 
X 
X 
X 
X 
 
Mean 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
 
SD 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
 
Minimum 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
 
Median 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
 
Maximum 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
BMI (kg/m²) 
n 
X 
X 
X 
X 
X 
X 
X 
 
Mean 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
 
SD 
X.XXXX 
X.XXXX 
X.XXXX 
X.XXXX 
X.XXXX 
X.XXXX 
X.XXXX 
 
Minimum 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
Median 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
 
Maximum 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Treatment A: Single IV Infusion of 0.1 mg/kg xisomab 3G3 
Treatment B: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
Treatment C: Single IV Infusion of 2 mg/kg xisomab 3G3 
Treatment D: Single IV Infusion of 5 mg/kg xisomab 3G3 
BMI = Body mass index 
Age is calculated at the time of dosing and reported as an integer. 
Source: Table 14.1.2 
Program:  /CAXXXXX/sas_prg/stsas/intext/t_dem.sas 08OCT2015  16:36 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
 
 
 
In-text Table 11-2 will be in the following format: 
 
 
Table 11-2: Summary of Plasma Xisomab 3G3 Pharmacokinetics Following a Single IV 
Infusion of 0.1, 0.5, 2, and 5 mg/kg Xisomab 3G3 
 
 
Pharmacokinetic 
Parameters 
Single IV Infusion of 0.1 mg/kg xisomab 3G3 
Single IV Infusion of 0.5 mg/kg xisomab 3G3 
Param1 (units) 
XXX.X (XX.X) [n=xx] 
XXX.X (XX.X) [n=xx] 
Param2 (units) 
XXX.X (XX.X) [n=xx] 
XXX.X (XX.X) [n=xx] 
Param3 (units) 
XXX.X (XX.X) [n=xx] 
XXX.X (XX.X) [n=xx] 
Param4 (units) 
XXX.X (XX.X) [n=xx] 
XXX.X (XX.X) [n=xx] 
Treatment A: Single IV Infusion of 0.1 mg/kg xisomab 3G3 
Treatment B: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
Treatment C: Single IV Infusion of 2 mg/kg xisomab 3G3 
Treatment D: Single IV Infusion of 5 mg/kg xisomab 3G3 
AUCs and Cmax values are presented as geometric mean and geometric CV%. 
Tmax values are presented as median (min, max). 
Other parameters are presented as arithmetic mean (± SD). 
Source: Tables 14.2.1.6 through 14.2.1.9 
 
 
 
Notes for Generating the Actual Table: 
Presentation of Data: 
• 
The following PK parameters will be presented in the following order and with following 
units: AUC0-t <ng*hr/mL>, AUC0-inf <ng*hr/mL>, AUC%extrap <%>, Cmax <ng/mL>, Tmax <hr>, 
Kel <1/hr>, T1/2 <hr>, CL <L/hr>, Vss <L> 
• 
n will be presented as an integer (with no decimal); 
• 
Summary statistics will be presented with same precision as defined in post-text shells 
• 
Internal template ITPar1 
Celerion Note: Per study design needs, the following changes are made to this table relative to 
Celerion’s standard shell: addition of a third and fourth column for Treatment C and D, 
respectively 
 
 
Program: /CAXXXXX/sas_prg/pksas/intext-pk-tables.sas 
DDMMMYYYY HH:MM 
Program: /CAXXXXX/sas_prg/pksas/adam_intext_pkparam.sas DDMMMYYYY HH:MM 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
 
 
 
In-text Table 12-1 will be in the following format: 
 
Table 12-1 
Adverse Event Frequency by Treatment – Number of Subjects Reporting 
the Event (% of Subjects Dosed) 
 
Treatment 
TE Adverse Events* 
A 
B 
C 
D 
Pooled Placebo 
Pooled Active 
Number of Subjects Dosed 
X (100%) 
X (100%) 
X (100%) 
X (100%) 
X (100%) 
X (100%) 
Number of Subjects With TE Adverse Events 
X (XX%)   
X (XX%)   
X (XX%)   
X (XX%)   
X (XX%)   
X (XX%)   
Number of Subjects Without TE Adverse Events 
X (XX%)   
X (XX%)   
X (XX%)   
X (XX%)   
X (XX%)   
X (XX%)   
General disorders and administration site conditions 
X (XX%)   
X (XX%)   
X (XX%)   
X (XX%)   
X (XX%)   
X (XX%)   
Vessel puncture site pain 
X (XX%)   
X (XX%)   
X (XX%)   
X (XX%)   
X (XX%)   
X (XX%)   
Vessel puncture site reaction 
X (XX%)   
X (XX%)   
X (XX%)   
X (XX%)   
X (XX%)   
X (XX%)   
Treatment A: Single IV Infusion of 0.1 mg/kg xisomab 3G3 
Treatment B: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
Treatment C: Single IV Infusion of 2 mg/kg xisomab 3G3 
Treatment D: Single IV Infusion of 5 mg/kg xisomab 3G3 
*Adverse events are classified according to MedDRA® Version 20.0 
TE = Treatment-emergent 
Although a subject may have had 2 or more clinical adverse experiences, the subject is counted only once within a category. The same subject may appear in 
different categories. 
Source: Table 14.3.1.1 
Program:  /CAXXXXX/sas_prg/stsas/intext/t_ae.sas 08OCT2015  16:36 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
 
 
 
11.2 
Figures Shells 
 
In-text Figures 11-1 through 11-3, post-text Figures 14.2.2.1 through 14.2.2.3, post-text 
Figures 14.2.4.1 through 14.2.4.4, and Individual Listings in 16.2.6.3 and 16.2.6.5 will be in 
the following format: 
 
Figure 11-1 Arithmetic Mean Plasma Xisomab 3G3 Concentration-Time Profiles 
Following a Single IV Infusion of 0.1, 0.5, 2, and 5 mg/kg Xisomab 3G3 
(Linear Scale) 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
 
 
 
Notes for Generating the Actual Mean Figure: 
•    Figures 11-1, 14.2.2.1 through 14.2.2.3 
o y-axis: Plasma Xisomab 3G3 Concentration (ng/mL) 
o X-axis: Hours From Start of Infusion 
•    Figures 11-2, 14.2.4.1 through 14.2.4.2, 16.2.6.3 
o y-axis: Arithmetic Mean aPTT (sec) 
o X-axis: Hours From Start of Infusion 
•    Figures 11-3, 14.2.4.3 through 14.2.4.4, 16.2.6.5 
o y-axis: aPTT Mean Change from Baseline (sec) 
o X-axis: Hours From Start of Infusion 
• Source tables 
o 
Figure 11-1: 14.2.1.1 through 14.2.1.4 
o 
Figure 11-2: 14.2.3.1 
o 
Figure 11-3: 14.2.3.1 
Figure Legend: 
Treatment A: Single IV Infusion of 0.1 mg/kg xisomab 3G3 
Treatment B: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
Treatment C: Single IV Infusion of 2 mg/kg xisomab 3G3 
Treatment D: Single IV Infusion of 5 mg/kg xisomab 3G3 
Treatment P: Single IV Infusion of Placebo (Pooled) 
 
 
Program: /CAXXXXX/sas_prg/pksas/meangraph.sas 
DDMMMYYYY HH:MM 
Program: /CAXXXXX/sas_prg/pksas/adam_meangraph.sas 
 
DDMMMYYYY HH:MM 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
 
 
 
Figures in Appendix 16.2.6.1 will be in the following format: 
 
Appendix 16.2.6.1 Individual Plasma Xisomab 3G3 Concentrations Versus Time Profiles 
Following a Single IV Infusion of 0.1, 0.5, 2, and 5 mg/kg Xisomab 3G3 (Linear and Semi- 
Log Scale) for Subject X 
 
 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
 
 
 
Notes for Generating the Actual Individual Figure: 
 
• Appendix 16.2.6.1 
o y-axis: Plasma Xisomab 3G3 Concentration (ng/mL) 
o X-axis: Hours From Start of Infusion 
 
Figure Legend: 
 
Treatment A: Single IV Infusion of 0.1 mg/kg xisomab 3G3 
Treatment B: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
Treatment C: Single IV Infusion of 2 mg/kg xisomab 3G3 
Treatment D: Single IV Infusion of 5 mg/kg xisomab 3G3 
Treatment P: Single IV Infusion of Placebo (Pooled) 
 
 
Program: /CAXXXXX/sas_prg/pksas/indgraph-all.sas 
DDMMMYYYY HH:MM 
Program: /CAXXXXX/sas_prg/pksas/adam_indgraph.sas 
 
DDMMMYYYY HH:MM 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 36 of 81 
 
 
 
11.3 
Section 14 Summary Tables Shells 
 
 
 
Table 14.1.1 Summary of Disposition (Safety Population) 
Part 1 of X 
 
Treatment 
-------------------------------------------------------- 
Disposition 
A 
B 
C 
D Pooled Placebo Pooled Active 
Overall 
------------------------------------------------------------------------------------------------------ 
 
Dosed 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Completed 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Discontinued Early 
X 
X 
X 
X 
X 
X 
X 
<Reason> 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
 
Program: /AAXXXXX/ECR/sas_prg/stsas/tab prog_name.sas DDMMMYYYY HH:MM 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 37 of 81 
 
 
 
 
Table 14.1.2 Demographic Summary (Safety Population) 
Page 1 of X 
 
Treatment 
---------------------------------------------------------- 
Trait 
A 
B 
C 
D 
Pooled Placebo Pooled Active Overall 
---------------------------------------------------------------------------------------------------------------------- 
 
Sex 
Male 
Female 
X 
X 
(XX.X%) 
(XX.X%) 
X 
X 
(XX.X%) 
(XX.X%) 
X 
X 
(XX.X%) 
(XX.X%) 
X 
X 
(XX.X%) 
(XX.X%) 
X 
X 
(XX.X%) 
(XX.X%) 
X 
X 
(XX.X%) 
(XX.X%) 
X 
X 
(XX.X%) 
(XX.X%) 
Race 
American Indian 
X (XX.X%) X (XX.X%) 
X (XX.X%) X (XX.X%) X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Asian 
X (XX.X%) X (XX.X%) 
X (XX.X%) X (XX.X%) X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Black 
X (XX.X%) X (XX.X%) 
X (XX.X%) X (XX.X%) X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Ethnicity 
Hispanic or Latino 
X (XX.X%) X (XX.X%) 
X (XX.X%) X (XX.X%) X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Not Hispanic or Latino X (XX.X%) X (XX.X%) 
X (XX.X%) X (XX.X%) X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Age* (yrs) 
n 
X 
X 
X 
X 
X 
X 
X 
Mean 
X.X 
X.X 
X.X 
X.X 
X.X 
X.X 
X.X 
SD 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
X.X 
X.X 
X.X 
X.X 
X.X 
X.X 
X.X 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Weight (kg) n 
X 
X 
X 
X 
X 
X 
X 
Mean 
X.X 
X.X 
X.X 
X.X 
X.X 
X.X 
X.X 
SD 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
X.X 
X.X 
X.X 
X.X 
X.X 
X.X 
X.X 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Programmer Note: Add Height (cm) and Body Mass Index (kg/m2) to the following page 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
*Age is calculated at the time of dosing and reported as an 
integer. Program:
 
/AAXXXXX/ECR/sas_prg/stsas/tab programname.sas DDMMMYYYY HH:MM 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 38 of 81 
 
 
 
Tables 14.2.1.1 through 14.2.1.5 and Appendix 16.2.6.2 and 16.2.6.4 will be in the following format: 
 
 
Table 14.2.1.1 Plasma Xisomab 3G3 Concentrations (ng/mL) Following a Single IV Infusion of 0.1 mg/kg Xisomab 3G3 (Treatment A) 
(Pharmacokinetic Population) 
 
 
Subject --------------------------------- Sample Times (hr) -------------------------------- 
Number Predose 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
------------------------------------------------------------------------------------------------------- 
------------------------------------------------------------------------------------------------------- 
 
n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
CV% 
. 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
SEM 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
------------------------------------------------------------------------------------------------------- 
For the calculation of summary statistics, values that are below the limit of quantitation (BLQ) of 50 ng/mL are treated as 0 
before the first quantifiable concentration and as missing elsewhere. 
. = Value missing or not reportable. 
 
 
X 
BLQ 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
X 
BLQ 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
X 
BLQ 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 39 of 81 
 
 
 
Notes for Generating the Actual Table: 
 
• 
Please use CPConc1 template 
• 
Per study design needs, the following changes are made to this table relative to Celerion standard: columns <Treatment Sequence> and 
<Study Period> will be removed. 
• 
Concentrations will be presented to the same precision as in the bio data. 
• 
aPTT values will be presented to the same precision as in the clinical laboratory data. 
• 
Summary statistics presentation with respect to the precision of the bio data or clinical laboratory data: n = integer; Mean and 
Median +1; SD and SEM +2, Min and Max +0, CV% to 1 decimal 
• 
PK and PD Time points are: predose and 0.083, 0.25, 0.5, 1, 3, 8, 24, 72, 120, 168, 216, 336, 504, and 672 hours postdose (additional 
time points might be added depending on the conduct of the study) 
 
 
 
Program: 
/CAXXXXX/sas_prg/pksas/pk-conc-tables.sas 
DDMMMYYYY 
HH:MM 
Program: 
/CAXXXXX/sas_prg/pksas/pk-conc-tables-sig.sas 
DDMMMYYYY 
HH:MM 
Program: /CAXXXXX/sas_prg/pksas/adam_conc.sas        DDMMMYYYY HH:MM 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 40 of 81 
 
 
 
 
Tables 14.2.1.6 through 14.2.1.9 will be in the following format: 
 
 
Table 14.2.1.6 Plasma Xisomab 3G3 Pharmacokinetic Parameters Following a Single IV Infusion of 0.1 mg/kg Xisomab 3G3 (Treatment A) 
(Pharmacokinetic Population) 
 
 
 
------------------------------------ Parameters --------------------------- 
 
Subject 
param1 
param2 
param3 
param4 
param5 
param6 
Number 
(units) 
(units) 
(units) 
(units) 
(units) 
(units) 
-------------------------------------------------------------------------------------------------- 
 
X 
XXX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
X 
XX.X 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
X 
XXX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
X 
XX.X 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
X 
XX.X 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
X 
X.XX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
X 
XXX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
-------------------------------------------------------------------------------------------------- 
 
n 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XXX.X 
X.XXX 
XXX.X 
XXX.X 
XX.XX 
X.XXXX 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
CV% 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
SEM 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Minimum 
XX.X 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
Median 
XX.XX 
X.XXX 
XXX.X 
XXX.X 
XX.XX 
X.XXXX 
Maximum 
XXX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
Geom Mean 
XXX.X 
X.XXX 
XXX.X 
XXX.X 
XX.XX 
X.XXXX 
Geom CV% 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
-------------------------------------------------------------------------------------------------- 
. = Value missing or not reportable. 
 
 
 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 41 of 81 
 
 
 
Notes for Generating the Actual Table: 
 
• 
Please use CPPar1 template 
• 
Per study design needs, the following changes are made to this table relative to Celerion standard: columns <Treatment Sequence> and 
<Study Period> will be removed. 
• 
PK Parameters will be presented in the following order and with following units: AUC0-t <ng*hr/mL>, AUC0-inf <ng*hr/mL>, AUC%extrap 
<%>, Cmax <ng/mL>, Tmax <hr>, Kel <1/hr>, T1/2 <hr>, CL <L/hr>, Vss <L> 
• 
n will be presented as an integer (with no decimal); 
• 
Exposure parameters (i.e. AUCs, Cmax, Vss, CL) will be presented with, at maximum, the precision of the bio data, and, at minimum, 3 
significant figures (to be determined by the PKist once bio data are received). 
o 
Summary statistics will be presented with respect to the precision of the bio data: Mean, Median, and Geom Mean = +1; SD and 
SEM = +2, Min and Max = +0. 
• 
Time parameters (i.e. Tmax, T1/2) will be presented with 2 decimals. 
o 
Summary statistics will be presented with respect to the number of decimals: Mean, Median, and Geom Mean = +1; SD and SEM = 
+2, Min and Max = +0. 
• 
Values for rate constants (i.e. Kel) will be presented with 3 significant figures. 
o 
Summary statistics for Kel will be presented as: Mean, Median, and Geom Mean = +1; SD and SEM = +2, Min and Max = +0. 
• 
CV% and Geom CV% for all parameters will be presented with 1 decimal 
 
 
 
Program: /CAXXXXX/sas_prg/pksas/pk-tables.sas 
DDMMMYYYY HH:MM 
Program: /CAXXXXX/sas_prg/pksas/adam_pkparam.sas 
DDMMMYYYY HH:MM 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 42 of 81 
 
 
 
Table 14.2.1.10 will be in the following format: 
 
Table 14.2.1.10 Intervals (Hours) Used for Determination of Plasma Xisomab 3G3 Kel Values (Pharmacokinetic Population) 
 
 
Subject Treatment 
---------- 
<Treatment A> 
------- 
---------- <Treatment B> ---------- 
Number 
Sequence 
Interval 
R2 
n 
Interval 
R2 
n 
------------------------------------------------------------------------------------------------------------------------- 
 
X 
XX 
XX.X - XX.X 
X.XXX 
X 
XX.X - XX.X 
X.XXX 
X 
X 
XX 
XX.X - XX.X 
X.XXX 
X 
XX.X - XX.X 
X.XXX 
X 
X 
XX 
XX.X - XX.X 
X.XXX 
X 
XX.X - XX.X 
X.XXX 
X 
X 
XX 
XX.X - XX.X 
X.XXX 
X 
XX.X - XX.X 
X.XXX 
X 
X 
XX 
XX.X - XX.X 
X.XXX 
X 
XX.X - XX.X 
X.XXX 
X 
X 
XX 
XX.X - XX.X 
X.XXX 
X 
XX.X - XX.X 
X.XXX 
X 
------------------------------------------------------------------------------------------------------------------------- 
Treatment A: Single IV Infusion of 0.1 mg/kg xisomab 3G3 
Treatment B: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
Treatment C: Single IV Infusion of 2 mg/kg xisomab 3G3 
Treatment D: Single IV Infusion of 5 mg/kg xisomab 3G3 
R2 = Coefficient of determination 
n = Number of points used in Kel calculation 
. = Kel value not reportable. 
 
 
 
Notes for Generating the Actual Table: 
 
• 
Please use CPKel1 template 
• 
Per study design, the “Treatment Sequence” column will be replaced with ‘Treatment’ and the data will be presented vertically 
instead of horizontally. 
• 
Interval start and stop times will be presented to 1 decimal or 3 significant figures minimum 
• 
R2 will be presented to 3 decimals 
• 
n will be presented as an integer 
 
Program: /CAXXXXX/sas_prg/pksas/kel-tables-xover.sas 
DDMMMYYYY HH:MM 
Program: /CAXXXXX/sas_prg/pksas/adam_kel.sas 
DDMMMYYYY HH:MM 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 43 of 81 
 
 
 
Table 14.2.3.1 will be presented in the following format: 
 
Table 14.2.3.1 Mean aPTT Values (sec) and Mean Change from Baseline aPTT Values (sec) Following a Single IV Infusion of 0.1, 0.5, 2.0, and 
5 mg/kg Xisomab 3G3 and Placebo (Pharmacodynamic Population) 
 
Mean aPTT Values 
Mean Change From Day 1 Predose 
------------------------------------- 
------------------------------------- 
Measurement 
Day 
Hour 
Statistic 
P 
A 
B 
C 
P 
A 
B 
C 
--------------------------------------------------------------------------------------------------------------------------------- 
 
aPTT Values (sec) 
1 
0 
N 
Mean 
SD 
Median 
Minimum 
Maximum 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
1 
0.083 N 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Mean 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
SD 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Median 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Minimum 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Maximum 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
1 
0.25 N 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Mean 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
SD 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Median 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Minimum 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Maximum 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
 
1 
0.5 
N 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Mean 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
SD 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Median 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Minimum 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Maximum 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
 
Notes for Generating the Actual Table: 
 
• 
Per study design, an additional column for treatment D will be added 
• 
aPTT values will be presented with the same level of precision as received from the clinical laboratory database 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 44 of 81 
 
 
 
• 
Summary statistics presentation with respect to the precision of the clinical laboratory data: n = integer; Mean and Median +1; 
SD and SEM +2, Min and Max +0, CV% to 1 decimal 
• 
PD Time points are: predose and 0.083, 0.25, 0.5, 1, 3, 8, 24, 72, 120, 168, 216, 336, 504, and 672 hours postdose (additional 
time points might be added depending on the conduct of the study) 
 
Add the following to the footnote: 
 
Treatment A: Single IV Infusion of 0.1 mg/kg xisomab 3G3 
Treatment B: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
Treatment C: Single IV Infusion of 2 mg/kg xisomab 3G3 
Treatment D: Single IV Infusion of 5 mg/kg xisomab 3G3 
Treatment P: Single IV Infusion of Placebo (Pooled) 
 
Program: /AAXXXXX/ECR/sas prg/stsas/tab tab-programname.sas DDMMMYYYY HH:MM 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 45 of 81 
 
 
 
 
Table 14.3.1.1 Treatment-Emergent Adverse Event Frequency by Treatment – 
Number of Subjects Reporting the Event (% of Subjects Dosed) (Safety 
Population) 
Page 1 of X 
 
Treatment 
--------------------------------------------------------- 
A 
B 
C 
D 
Pooled Placebo Pooled 
Adverse Event* 
Active 
-------------------------------------------------------------------------------------------------------------------
- Number of Subjects Dosed 
XX (XXX%) XX (XXX%) XX (XXX%) XX (XXX%) 
XX (XXX%) 
XX (XXX%) 
Number of Subjects With TEAEs 
 X ( X%)  X ( XX%)  X ( X%) X ( XX%) 
 X ( XX%) 
X ( XX%) 
Number of Subjects Without TEAEs 
XX ( XX%) XX ( XX%) XX ( XX%) XX ( XX%) 
XX ( XX%) 
XX ( XX%) 
-------------------------------------------------------------------------------------------------------------------- 
 
Eye disorders 
Vision blurred 
Gastrointestinal disorders 
Dyspepsia 
Nausea 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Musculoskeletal and connective tissue disorders 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Back pain 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Muscle cramps 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Musculoskeletal pain 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Nervous system disorders 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Headache NOS 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Reproductive system and breast disorders 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Vaginal discharge 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Respiratory, thoracic and mediastinal disorders 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Epistaxis 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Skin and subcutaneous tissue disorders 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Sweating increased 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
*Adverse events are classified according to MedDRA Version 20.0. TEAEs = Treatment-emergent adverse 
events Program: 
/AAXXXXX/ECR/sas_prg/stsas/tab progrname.sas
 
DDMMMYYYY 
HH:MM 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 46 of 81 
 
 
 
 
Table 14.3.1.2 Treatment-Emergent Adverse Event Frequency by Treatment – 
Number of Adverse Events (% of Total Adverse Events) (Safety Population) 
Page 1 of X 
 
Treatment 
--------------------------------------------------------- 
Adverse Event* 
A 
B 
C 
D 
Pooled Placebo Pooled 
Active 
------------------------------------------------------------------------------------------------------------------
- Number of TEAEs 
XX (XXX%) XX (XXX%) XX (XXX%) XX (XXX%) 
XX (XXX%) 
XX (XXX%) 
-------------------------------------------------------------------------------------------------------------------- 
 
Eye disorders 
Vision blurred 
Gastrointestinal disorders 
Dyspepsia 
Nausea 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Musculoskeletal and connective tissue disorders 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Back pain 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Muscle cramps 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Musculoskeletal pain 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Nervous system disorders 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Headache NOS 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Reproductive system and breast disorder 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Vaginal discharge 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Respiratory, thoracic and mediastinal disorders 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Epistaxis 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Skin and subcutaneous tissue disorders 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
Sweating increased 
X ( X%) 
X ( X%) 
X ( X%) X ( X%) 
X ( X%) 
X ( X%) 
 
 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
*Adverse events are classified according to MedDRA Version 20.0. TEAEs = Treatment-emergent adverse 
events Program: 
/AAXXXXX/ECR/sas_prg/stsas/tab programname.sas
 
DDMMMYYYY 
HH:MM 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 47 of 81 
 
 
 
Page 1 of X 
Table 14.3.1.3 Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - 
Number of Adverse Events (Safety Population) 
 
Number of 
Severity/Intensity 
Subjects Number---------------------------------- 
Relationship to Study Drug 
Treat- With 
of 
Mild 
Moderate Severe 
 PLT^ 
------------------------------------------- 
Adverse Event* 
ment 
TEAEs 
TEAEs (Grd 1) (Grd 2) (Grd 3) (Grd 4) Unrelated Unlikely Possibly Probably Likely 
----------------------------------------------------------------------------------------------------------------------- 
 
Abdominal pain 
A 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Constipation 
C 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dry throat 
B 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dysmenorrhoea 
B 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dyspepsia 
D 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Headache 
A 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
B 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pooled X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Active 
Myalgia 
P 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Nasal congestion 
B 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Skin laceration 
B 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
----------------------------------------------------------------------------------------------------------------------- 
 
Treatment A 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Treatment B 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Treatment C 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Treatment D 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pooled Placebo 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pooled Active 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
----------------------------------------------------------------------------------------------------------------------- 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment P: < > 
*Adverse events are classified according to MedDRA Version 20.0. TEAEs = Treatment-emergent adverse events 
^PLT = Potentially Life-threatening; Grd = Grade 
 
Program: /AAXXXXX/ECR/sas_prg/stsas/tab programname.sas DDMMMYYYY HH:MM 
 
Page 1 of X 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 48 of 81 
 
 
 
 
Table 14.3.2.1 Serious Adverse Events (Safety Population) 
Page 1 of X 
 
----------------------------------------------------------------------------------------------------------------------- 
Will match 16.2.7 
 
Or contain statement as follows: 
 
“There were no serious adverse events recorded during the study.” 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: /AAXXXXX/ECR/sas_prg/stsas/programname.sas DDMMMYYYY HH:MM 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 49 of 81 
 
 
 
Tables 14.3.4.1 to 14.3.4.4 will have the following format: 
 
 
Table 14.3.4.1 Out-of-Range Values and Recheck Results - Serum Chemistry (Safety Population) 
Page 1 of X 
 
Parameter1 Parameter2 Parameter3 Parameter4 Parameter5 
Subject Age#/ 
Study 
Treat- 
 
 
 
 
<Range> 
<Range> 
<Range> 
 <Range> 
 <Range> 
Cohort Number Sex 
Period 
ment 
Day Hour 
Date 
Time 
(Unit) 
(Unit) 
(Unit) 
(Unit) 
(Unit) 
------------------------------------------------------------------------------------------------------------------------------------------- 
 
X 
X 
XX/X 
Screen 
DDMMMYYYY HH:MM:SS 
XX HN 
XX HN 
1 
X 
-X -XX.XX 
DDMMMYYYY HH:MM:SS 
XX LY^ 
XX LN 
XX LYR+ 
 
 
 
 
 
 
Programmer notes: Replace Parameter1, 2 etc. with actual lab tests in the study. Sort unscheduled assessment and early 
termination chronologically with other scheduled assessments and rechecks. Recheck should be sorted with the scheduled 
time point the recheck is for. 
 
Programmer notes: Clinically significant lab values generally will be captured as AEs, some of which the PI may indicate in Appendix 16.2.8.1.6 lab 
comments (as per GPG.03.0028 sections 2.9 and 2.10). Derive an additional CS flag for PI flag (+) based on positive comments (i.e. CS/Clinically 
Significant). Present this derived 4th column in all tables, and list only subjects/tests which are PI-determined clinically significant lab values in 
Table 14.3.4.5. 
 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment P: < > 
#Age is calculated from the date of first dosing. F = Female, M = Male 
H = Above reference range, L = Below reference range 
Computer: N = Not clinically significant, Y = Clinically significant 
PI Interpretation: - = Not clinically significant, R = Recheck requested, ^ = Will be retested later, + = Clinically significant 
Program: /CAXXXXX/sas_prg/stsas/tab_PROGRAMNAME.sas DDMMMYYYY HH:MM 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 50 of 81 
 
 
 
Table 14.3.4.5 Clinically Significant Values and Corresponding Results (Safety Population) 
Subject Age#/ Study 
Page 1 of X 
Cohort Number Sex 
Period Treatment Day 
Hour 
Date 
Time 
Department 
Test 
Result 
Reference Range 
Unit 
----------------------------------------------------------------------------------------------------------------------------------------- 
 
X 
X XX/X 
1 
X 
-X -XX.XX DDMONYYYY HH:MM:SS Serum Chemistry Cholesterol 
XXX 
XX – XX 
mg/dL 
X 
XX.XX DDMONYYYY HH:MM:SS Serum Chemistry Cholesterol 
XXX HYR+ 
XX – XX 
mg/dL 
X 
XX.XX DDMONYYYY HH:MM:SS Serum Chemistry Cholesterol 
XXX HYR+ 
XX – XX 
mg/dL 
 
 
 
 
 
 
 
 
 
 
 
 
Programmer notes: All time points for a subject/test with at least one value deemed as CS by the PI will be presented in this table. 
If no event meets this criteria then include a statement as follows: 
“There were no clinical laboratory results documented as clinically significant by the PI.” 
 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment P: < > 
#Age is calculated from the date of first dosing. F = Female, M = Male 
H = Above reference range, L = Below reference range 
Computer: N = Not clinically significant, Y = Clinically significant 
PI Interpretation: - = Not clinically significant, R = Recheck requested, ^ = Will be retested later, + = Clinically significant 
Program: /CAXXXXX/ECR/sas_prg/stsas/tab programname.sas DDMMMYYYY 
HH:MM 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 51 of 81 
 
 
 
Tables 14.3.5.4 (hematology), 14.3.5.7 (urinalysis), and 14.3.5.10 (coagulation & bleeding time) will resemble 14.3.5.1. 
Table 14.3.5.1 Clinical Laboratory Summary - Serum Chemistry (Safety Population) 
 
Page 1 of X 
 
Treatment 
Reference 
--------------------------------------------------- 
Laboratory Test (units) Range 
Time Point 
Statistic 
A 
B 
C 
D 
Pooled Placebo 
----------------------------------------------------------------------------------------------------------------- 
 
Testname (unit) 
< - ># 
Screen 
n 
X 
X 
X 
X 
X 
Mean 
X.X* 
X.X 
X.X 
X.X 
X.X 
SD 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
Median 
X.X 
X.X 
X.X 
X.X 
X.X 
Maximum 
XX 
XX 
XX 
XX 
XX 
 
Baseline 
n 
X 
X 
X 
X 
X 
Mean 
XX.XX 
XX.XX 
XX.XX* 
XX.XX 
XX.XX 
SD 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
Minimum 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Median 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Maximum 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Programmer note: Time points are Screen, Baseline, Day 1 Hour 8, Day 2, Day 8, Day 29, and Follow-up. Coagulation time 
points are Screen, Baseline, Day 1 Hour 1, Day 2, Day 4, Day 8, Day 29, and Follow-up. aPTT samples for PD time points 
are not presented here. Bleeding time is presented with coagulation with time points Check-in, Baseline, Day 1 Hour 1, 
and Day 2. 
Programmer note: Treatment means at specific time points will be flagged (with a *) if they are above or below the 
reference range. This only applies to the clinical laboratory treatment results (i.e., not the change from baseline 
or any other endpoints). 
Programmer note: The following footnote only presented on Coagulation summary tables 
Summaries for aPTT associated with PD time points can be found in Table 
14.X.X.X. 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Baseline is the last predose measurement. 
# = Lowest of the lower ranges and highest of the higher ranges are used. Refer to Appendix 16.1.10.1 for the 
breakdown. 
*Outside reference range 
Program: /CAXXXXX/ECR/sas_prg/stsas/tab programname.sas DDMMMYYYY HH:MM 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 52 of 81 
 
 
 
Tables 14.3.5.5 (hematology), 14.3.5.8 (urinalysis), and 14.3.5.11 (coagulation & bleeding time) will resemble 14.3.5.2. 
 
 
Table 14.3.5.2 Clinical Laboratory Change From Baseline - Serum Chemistry (Safety Population) 
Page 1 of X 
 
Treatment 
--------------------------------------------------- 
Laboratory Test (units) Time Point 
Statistic 
A 
B 
C 
D 
Pooled Placebo 
------------------------------------------------------------------------------------------------------- 
 
Testname (unit) 
Day 1 Hour 8 
n 
X 
X 
X 
X 
X 
Mean 
X.X 
X.X 
X.X 
X.X 
X.X 
SD 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
Median 
X.X 
X.X 
X.X 
X.X 
X.X 
Maximum 
XX 
XX 
XX 
XX 
XX 
 
Day 2 
n 
X 
X 
X 
X 
X 
Mean 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
SD 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
Minimum 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Median 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Maximum 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
Programmer note: Time points are Day 1 Hour 8, Day 2, Day 8, Day 29, and Follow-up. Coagulation time points are Day 1 
Hour 1, Day 2, Day 4, Day 8, Day 29, and Follow-up. aPTT samples for PD time points are not presented here. Bleeding 
time is presented with coagulation with time points Day 1 Hour 1 and Day 2. 
Programmer note: The following footnote only presented on Coagulation summary tables 
Change from baseline summaries for aPTT associated with PD time points can be found Table 14.X.X.X. 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Baseline is the last predose measurement. 
 
Program: /CAXXXXX/ECR/sas_prg/stsas/tab programname.sas DDMMMYYYY HH:MM 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 53 of 81 
 
 
 
Tables 14.3.5.6 (hematology), 14.3.5.9 (urinalysis), and 14.3.5.12 (coagulation & bleeding time) will resemble 14.3.5.3 
Page 1 of X 
Table 14.3.5.3 Clinical Laboratory Shift From Baseline - Serum Chemistry (Safety Population) 
 
Baseline L 
Baseline N 
Baseline H 
------------------ ----------------- ----------------- 
Postdose 
Postdose 
Postdose 
------------------ ----------------- ---------------- 
Laboratory Test (units) 
Treatment Time Point 
L 
N 
H 
L 
N 
H 
L 
N 
H 
-------------------------------------------------------------------------------------------------------- 
Testname (unit) 
 
 
Follow-up 
X 
XX 
X 
X 
XX 
X 
X 
XX 
X 
 
Testname (unit) 
 
 
Follow-up 
X 
XX 
X 
X 
XX 
X 
X 
XX 
X 
 
 
Programmer note: Time points are Day 1 Hour 8, Day 2, Day 8, Day 29, and Follow-up. Coagulation time points are Day 1 
Hour 1, Day 2, Day 4, Day 8, Day 29, and Follow-up. aPTT samples for PD time points are not presented here. Bleeding 
time is presented with coagulation with time points Day 1 Hour 1 and Day 2. 
Programmer note: For urinalysis, the following footnote is used since the categories of N and O will be used instead of 
L, N, and H 
Note: N = Within reference range, O = Outside reference range 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
N = Within reference range, L = Below reference range, H = Above reference range 
Baseline is the last predose measurement. 
 
Program: /CAXXXXX/ECR/sas_prg/stsas/tab prograname.sas DDMMMYYYY HH:MM 
X 
Day 1 Hour 8 X 
XX 
X 
X 
XX 
X 
X 
XX 
X 
Day 2 
X 
XX 
X 
X 
XX 
X 
X 
XX 
X 
Day 8 
X 
XX 
X 
X 
XX 
X 
X 
XX 
X 
Day 29 
X 
XX 
X 
X 
XX 
X 
X 
XX 
X 
X 
Day 1 Hour 8 X 
XX 
X 
X 
XX 
X 
X 
XX 
X 
Day 2 
X 
XX 
X 
X 
XX 
X 
X 
XX 
X 
Day 8 
X 
XX 
X 
X 
XX 
X 
X 
XX 
X 
Day 29 
X 
XX 
X 
X 
XX 
X 
X 
XX 
X 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 54 of 81 
 
 
 
Change From Baseline Table 14.3.5.14 will resemble 14.3.5.13 
 
 
Table 14.3.5.13 Vital Sign Summary (Safety Population) 
Page 1 of X 
 
Treatment 
--------------------------------------------------------- 
Vital Sign (units) 
Time Point 
Statistic 
A 
B 
C 
D 
Pooled Placebo 
------------------------------------------------------------------------------------------------------------------- 
 
Testname (unit) 
Screen 
n 
Mean 
SD 
Minimum 
Median 
Maximum 
X 
X.X 
X.XX 
XX 
X.X 
XX 
X 
X.X 
X.XX 
XX 
X.X 
XX 
X 
X.X 
X.XX 
XX 
X.X 
XX 
X 
X.X 
X.XX 
XX 
X.X 
XX 
X 
X.X 
X.XX 
XX 
X.X 
XX 
Baseline 
n 
X 
X 
X 
X 
X 
Mean 
X.X 
X.X 
X.X 
X.X 
X.X 
SD 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
Median 
X.X 
X.X 
X.X 
X.X 
X.X 
Maximum 
XX 
XX 
XX 
XX 
XX 
Day 1 Hour 0.25 n 
X 
X 
X 
X 
X 
Mean 
X.X 
X.X 
X.X 
X.X 
X.X 
SD 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
Median 
X.X 
X.X 
X.X 
X.X 
X.X 
Maximum 
XX 
XX 
XX 
XX 
XX 
Programmer note: Time points are Screen, Baseline, Day 1 Hour 0.25, Day 8, Day 29, and Follow-up. 
 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Baseline is the last predose measurement. 
 
Program: /CAXXXXX/ECR/sas_prg/stsas/tab programname.sas DDMMMYYYY HH:MM 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 55 of 81 
 
 
 
Change From Baseline Table 14.3.5.16 will resemble 14.3.5.15 
Table 14.3.5.15 12-Lead Electrocardiogram Summary (Safety Population) 
 
Page 1 of X 
 
Treatment 
--------------------------------------------------------- 
Measurement (units) 
Time Point 
Statistic 
A 
B 
C 
D 
Pooled Placebo 
------------------------------------------------------------------------------------------------------------------- 
 
Testname (unit) 
Screen 
n 
Mean 
SD 
Minimum 
Median 
Maximum 
X 
X.X 
X.XX 
XX 
X.X 
XX 
X 
X.X 
X.XX 
XX 
X.X 
XX 
X 
X.X 
X.XX 
XX 
X.X 
XX 
X 
X.X 
X.XX 
XX 
X.X 
XX 
X 
X.X 
X.XX 
XX 
X.X 
XX 
Baseline 
n 
X 
X 
X 
X 
X 
Mean 
X.X 
X.X 
X.X 
X.X 
X.X 
SD 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
Median 
X.X 
X.X 
X.X 
X.X 
X.X 
Maximum 
XX 
XX 
XX 
XX 
XX 
Day 1 Hour 0.25 n 
X 
X 
X 
X 
X 
Mean 
X.X 
X.X 
X.X 
X.X 
X.X 
SD 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
Median 
X.X 
X.X 
X.X 
X.X 
X.X 
Maximum 
XX 
XX 
XX 
XX 
XX 
Programmer note: Time points are Screen, Baseline, Day 1 Hour 0.25, Day 8, Day 29, and Follow-up. 
 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Baseline is the last predose measurement. 
 
Program: /CAXXXXX/ECR/sas_prg/stsas/tab programname.sas DDMMMYYYY HH:MM 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 56 of 81 
 
 
 
 
Table 14.3.5.17 ADA Detection Summary by Collection Time and Treatment (Safety Population) 
 
Treatment 
---------------------------------------------------------
- 
Time Point Assay Type 
Result 
A 
B 
C 
D 
Pooled Placebo 
----------------------------------------------------------------------------------------------
- 
Page 1 of X 
 
Predose 
Screening 
Confirmatory 
Negative 
Positive 
Negative 
Positive 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Day 15 
Screening 
Negative 
X 
X 
X 
X 
X 
Positive 
X 
X 
X 
X 
X 
Confirmatory Negative 
X 
X 
X 
X 
X 
Positive 
X 
X 
X 
X 
X 
Day 29 
Screening 
Negative 
X 
X 
X 
X 
X 
Positive 
X 
X 
X 
X 
X 
Confirmatory Negative 
X 
X 
X 
X 
X 
Positive 
X 
X 
X 
X 
X 
Follow-up 
Screening 
Negative 
X 
X 
X 
X 
X 
Positive 
X 
X 
X 
X 
X 
Confirmatory Negative 
X 
X 
X 
X 
X 
Positive 
X 
X 
X 
X 
X 
Overall* 
Screening 
Negative 
X 
X 
X 
X 
X 
Positive 
X 
X 
X 
X 
X 
Confirmatory Negative 
X 
X 
X 
X 
X 
Positive 
X 
X 
X 
X 
X 
 
 
 
Note: Follow-up ADA detection sample only collected if Follow-up visit occurred after Day 36. 
*For overall counts, if the response of a subject is positive at least once, the subject will be counted as positive; otherwise, 
the subject will be considered negative. 
 
Program: /CAXXXXX/ECR/sas_prg/stsas/tab programname.sas DDMMMYYYY 
HH:MM 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
 
 
 
12. LISTING SHELLS 
 
The following listing shells provide a framework for the display of data from this 
study. The shells may change due to unforeseen circumstances. These shells may not 
be reflective of every aspect of this study, but are intended to show the general layout 
of the listings that will be presented and included in the final report. These listings 
will be generated off of the Celerion SDTM Version 3.2 data structure. All listings 
will be presented in Courier New size font 9. Subject listings will be provided in 
subject order within cohort order. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Statistical Analysis Plan, 25 August 2017 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 58 of 81 
 
 
 
 
Appendix 16.1.10.1 Clinical Laboratory Reference Ranges 
Page 1 of X 
Laboratory Group 
Test Name 
Sex 
Age Category Reference Range 
Unit 
---------------------------------------------------------------------------------------------------------------------- 
 
Serum Chemistry 
Test name 
XXX 
XX - XX 
XX – XX 
units 
Test name 
XXX 
XX - XX 
XX – XX 
units 
Test name 
XXX 
XX - XX 
XX – XX 
units 
Test name 
XXX 
XX - XX 
XX – XX 
units 
Test name 
XXX 
XX - XX 
XX – XX 
units 
Test name 
XXX 
XX - XX 
XX – XX 
units 
Test name 
XXX 
XX - XX 
XX – XX 
units 
Hematology 
Test name 
XXX 
XX - XX 
XX – XX 
units 
Test name 
XXX 
XX - XX 
XX – XX 
units 
Test name 
XXX 
XX - XX 
XX – XX 
units 
Test name 
XXX 
XX - XX 
XX – XX 
units 
Test name 
XXX 
XX - XX 
XX – XX 
units 
Test name 
XXX 
XX - XX 
XX – XX 
units 
Test name 
XXX 
XX - XX 
XX – XX 
units 
 
 
 
 
 
 
 
 
 
 
 
<Similar for all remaining laboratory groups and test names, note that age category will only be presented when different normal ranges 
exist> 
 
Program: /CAXXXXX/sas_prg/stsas/standardlis/cdash_lis_lno.sas 27NOV2015 18:34 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 59 of 81 
 
 
 
 
Appendix 16.2.1 Subject Disposition (Safety Population) 
Page 1 of X 
 
Subject 
Study 
Cohort Number 
Treatment Period 
Date 
Completed 
Study? 
Primary Discontinuation Reason 
----------------------------------------------------------------------------------------- 
X 
1 
X 
Post 
DDMONYYYY 
YES 
2 
X 
Post 
DDMONYYYY 
YES 
3 
X 
Post 
DDMONYYYY 
NO 
Adverse Event 
 
 
 
 
 
 
 
 
 
 
 
 
Programmer Note: Add any potential screen failure subjects to the end of this listing 
 
 
 
 
Note: Treatment A: Single IV Infusion of 0.1 mg/kg xisomab 3G3 
Treatment B: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
Treatment C: Single IV Infusion of 2 mg/kg xisomab 3G3 
Treatment D: Single IV Infusion of 5 mg/kg xisomab 3G3 
Treatment P: Single IV Infusion of Placebo 
 
Program: /CAXXXXX/sas_prg/stsas/standardlis/cdash_lis_dis.sas 27NOV2015 18:35 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 60 of 81 
 
 
 
 
Appendix 16.2.4.1 Demographics (Safety Population) 
Page 1 of X 
 
Body Mass Informed 
Subject 
Date Of 
Age* 
Height 
Weight 
Index 
Consent 
Cohort Number 
Birth 
(yrs) 
Sex 
Race 
Ethnicity 
(cm) 
(kg) 
(kg/m²) 
Date 
---------------------------------------------------------------------------------------------------------------------------------------- 
X 
1 
DDMONYYYY 
47 
Male 
< > 
Not Hispanic or Latino 
XXX 
XX.X 
XX.XX 
DDMONYYYY 
2 
<similar to above. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmer Note: Add any potential screen failure subjects to the end of this listing 
 
 
 
 
 
Note: *Age is calculated at the time of dosing and reported as an integer. 
Program: /CAXXXXX/sas_prg/stsas/standardlis/cdash_lis_dem.sas 27NOV2015 18:35 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 61 of 81 
 
 
 
 
 
 
Subject Study 
 
Appendix 16.2.4.2 Physical Examination (Safety Population) 
Page 1 of X 
Cohort 
Number 
Period  Treatment 
Day Hour 
Date 
Question 
Result Description or Comment 
------------------------------------------------------------------------------------------------------------------------ 
X 
1 
Screen 
DDMONYYYY Was PE performed? (Yes/No) YES 
 
1 
X 
-1 -19.25 DDMONYYYY 
1 
1.25 DDMONYYYY 
Was PE performed? (Yes/No) 
Was PE performed? (Yes/No) 
NO 
NO 
2 
Screen 
1 
X 
DDMONYYYY 
-1 -19.25 DDMONYYYY 
1 
1.25 DDMONYYYY 
Was PE performed? (Yes/No) 
Was PE performed? (Yes/No) 
Was PE performed? (Yes/No) 
YES 
NO 
NO 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment P: < > 
 
Program: /CAXXXXX/sas_prg/stsas/standardlis/cdash_lis_phy_best_practice.sas 27NOV2015 18:35 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 62 of 81 
 
 
 
 
 
Appendix 16.2.4.3 Medical History (Safety Population) 
Date 
Subject 
Any 
System Organ Class/ 
------------------- 
 
Page 1 of X 
Cohort 
Number  History? System Reviewed 
Preferred Term* 
Category Start 
End 
Ongoing? Condition or Event 
--------------------------------------------------------------------------------------------------------------------------------- 
X 
1 
No 
 
2 
Yes 
XXXXXXXXXXXXX 
XXXXXXXXX/XXXXXXXX 
Medical  YYYY 
YES 
< > 
 
<Note date can be YYYY, MONYYYY, or DDMONYYYY based on individual subject data.> 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: *Medical history events are classified according to MedDRA Version 20.0. 
Program: /CAXXXXX/sas_prg/stsas/standardlis/cdash_lis_mh.sas 27NOV2015 18:35 


Aronora, Inc. 
xisomab 3G3, 3G3-15-01 
Celerion, Clinical Study Report No. CA19214 
Statistical Analysis Plan, 25 August 2017 
Page 63 of 81 
 
 
 
 
Appendix 16.2.4.4 Substance Use (Safety Population) 
Subject 
Study 
 
Description 
Start 
End 
Cohort 
Number 
Period 
Substance 
 of Use 
Date 
Date 
----------------------------------------------------------------------------------------- 
X 
1 
Screen 
Tobacco Use 
NON-SMOKER 
03DEC1967 06OCT2016 
0-4 CIGARETTES WEEK 
06OCT2016 
2 
Screen 
Tobacco Use 
NON-SMOKER 
DDMONYYYY 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Page 1 of X 


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Appendix 16.2.5.1.1 Inclusion Criteria 
Page 1 of X 
 
1. Healthy adult male and/ or female (non-childbearing potential only), 18 to 48 years of age, inclusive, at screening. 
2. < > 
3. < > 
4. < > 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Statistical Analysis Plan, 25 August 2017 
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Appendix 16.2.5.1.2 Exclusion Criteria 
Page 1 of X 
 
1. Subject is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected 
during the conduct of the study. 
2. < > 
3. < > 
4. < > 
5. < > 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: /CAXXXXX/sas_prg/stsas/standardlis/cdash_lis_exc.sas 27NOV2015 18:35 


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Appendix 16.2.5.2 Subject Eligibility (Safety Population) 
Page 1 of X 
 
Subject Study 
Did subject meet 
Cohort 
Number 
Period 
all eligibility criteria? 
Specify 
----------------------------------------------------------------------------- 
X 
1 
Screen 
YES 
2 
Screen 
NO 
<This column prints only 
if data are present.> 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Statistical Analysis Plan, 25 August 2017 
Page 67 of 81 
 
 
 
 
Appendix 16.2.5.3 Check-in Criteria and Return Responses (Safety Population) 
Check-in Criteria 
Subject Study 
----------------- 
Cohort 
Number 
Period  Day 
Hour  Date 
Time 
1 
2 
Specify 
--------------------------------------------------------------------------------------------------- 
Page 1 of X 
 
X 
1 
1 
-1 -22.50 DDMONYYYY MM:HH 
NO 
NA 
4 
71.50 DDMONYYYY MM:HH 
YES 
YES 
<This column prints only 
6 119.50 DDMONYYYY MM:HH 
NO 
NA 
if data are present> 
8 167.50 DDMONYYYY MM:HH 
NO 
NA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Check-in Criteria 1 = Did the Subject report any study restriction violations since the last study visit? 
2 = IF YES TO ANY QUESTION, WAS SUBJECT APPROVED FOR STUDY? 
NA = Not Applicable 
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Appendix 16.2.5.4.1 Test Compound Description (Safety Population) 
Compound 
Interval 
Form 
Route 
Page 1 of X 
------------------------------------------------------------------------------------------------------- 
< > 
XX.XX TO XX.XX 
SOLUTION 
INJECTION IV BOLUS/PUSH 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Statistical Analysis Plan, 25 August 2017 
Page 69 of 81 
 
 
 
 
Appendix 16.2.5.4.2 Test Compound Administration Times (Safety Population) 
Time 
Subject Study 
----------------- 
Page 1 of X 
Cohort 
Number  Period Treatment  Day  Interval 
Date 
Start 
Stop 
Compound 
Dosage 
Comments 
------------------------------------------------------------------------------------------------------------------------------------------ 
X 
1 
1 
X 
1 XX.XX TO XX.XX DDMONYYYY 
HH:MM:SS HH:MM:SS XXXXXXX 
< > 
<This column prints only 
if data are present.> 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment P: < > 
 
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Statistical Analysis Plan, 25 August 2017 
Page 70 of 81 
 
 
 
 
Appendix 16.2.5.5 Blood Draw Times (Safety Population) 
Subject Study 
Actual 
Cohort 
Number 
Period  Treatment 
Day 
Hour 
Date 
Time 
Vacutainer ID  Bioassay  Comments 
Page 1 of X 
------------------------------------------------------------------------------------------------------------------------------------- 
X 
1 
1 
X 
1 
-0.50 DDMONYYYY HH:MM:SS XXXXXXXXXXX 
XXXXXXX 
<This column prints only 
0.08 DDMONYYYY HH:MM:SS XXXXXXXXXXX 
XXXXXXX 
if data are present.> 
<similar for all other time points and subjects> 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment P: < > 
 
Program: /CAXXXXX/sas_prg/stsas/standardlis/cdash_lis_bld.sas 27NOV2015 18:35 


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Statistical Analysis Plan, 25 August 2017 
Page 71 of 81 
 
 
 
 
Appendix 16.2.5.6 Meal Times (Safety Population) 
Start 
Subject Study 
------------------ 
Stop 
Cohort 
Number 
Period  Treatment  Day 
Hour 
Event 
Date 
Time 
Time 
Comments 
Page 1 of X 
----------------------------------------------------------------------------------------------------------------------- 
 
X 
1 
1 
X 
-1 -19.50 
LUNCH 
DDMONYYYY HH:MM:SS HH:MM:SS 
-15.00 
DINNER 
DDMONYYYY  HH:MM:SS HH:MM:SS 
-11.00 
SNACK 
DDMONYYYY  HH:MM:SS HH:MM:SS 
1 
1.50 
BREAKFAST DDMONYYYY HH:MM:SS HH:MM:SS DID NOT CONSUME 10% OF MEAL 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment P: < > 
 
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Statistical Analysis Plan, 25 August 2017 
Page 72 of 81 
 
 
 
 
Appendix 16.2.5.7 Prior and Concomitant Medications (Safety Population) 
Page 1 of X 
 
Prior 
Subject 
Any 
Treat- Medication 
 
 
Start 
Start 
Stop 
Stop 
to 
Cohort Number Medications? ment (WHO DD*) 
Dosage 
Route 
Date 
Time 
Date 
Time Frequency Indication Continuing? Study? 
------------------------------------------------------------------------------------------------------------------------------------------ 
 
X 
1 
NO 
None 
2 
NO 
None 
3 
YES 
 
X 
CETIRIZINE 
(CETIRIZINE) 
PARACETAMOL 
(PARACETAMOL) 
X MG 
X MG 
XXXXXXXXX DDMONYYYY UNK 
XXXXXXXXX DDMONYYYY HH:MM 
DDMONYYYY HH:MM XXXXXXX 
DDMONYYYY HH:MM XXXXXXXX 
XXXXXXX 
XXXXXXXX 
NO 
XX 
Yes 
 
 
 
 
 
 
 
 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment P: < > 
*Concomitant medications are coded with WHO Dictionary Version 01MAR217. 
UNK = Unknown, WHO DD = World Health Organization Drug 
 
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Appendix 16.2.7.1.1 Adverse Events (I of II) (Safety Population) 
Time From 
Page 1 of X 
Subject 
---------- --------------- --------------- ---------- 
Cohort Number 
Treatment TE? Adverse Event 
Preferred Term* 
(DD:HH:MM) 
Date 
Time 
Date 
Time (DD:HH:MM) 
-------------------------------------------------------------------------------------------------------------------------------------- 
X 
1 
None 
2 
None 
3 
No 
XXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXX 
XX:XX:XX  DDMONYYYY HH:MM DDMONYYYY HH:MM  DD:HH:MM 
XXXXXXXXXXXXXXXXX 
XXXXXXXXXXXX 
X 
Yes XXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXX 
<similar to above> 
 
 
 
 
 
 
 
 
 
 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment P: < > 
*Adverse events are classified according to MedDRA Version 20.0. 
TE = Treatment-emergent 
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Statistical Analysis Plan, 25 August 2017 
Page 74 of 81 
 
 
Appendix 16.2.7.1.2 Adverse Events (II of II) (Safety Population) 
Page 1 of X 
 
Subject 
--------------- 
Severity/ 
Relationship 
Cohort Number 
Treatment Adverse Event 
Date 
Time Frequency 
Intensity Serious Outcome 
to Study Drug Action 
---------------------------------------------------------------------------------------------------------------------------------- 
X 
1 
None 
2 
None 
3 
XXXXXXXXXXXXXXXXXXXXX 
DDMONYYYY XX:XX Cont. 
Mild 
NS 
Resolved 
Unrelated 
None 
X 
XXXXXXXXXXXXXXXXXXXXX 
DDMONYYYY XX:XX <similar to above> 
 
 
 
 
 
 
 
 
Programmer Note: Shorten Frequency and Serious headers to Freq^ and Ser*, respectively and add ‘Freq^ represents Frequency:’ and ‘Ser* 
represents Serious:’ before their respective decodes in the footnotes as necessary. 
 
 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment P: < > 
NS = Not Serious 
SE = Single Episode, Inter. = Intermittent, Cont. = Continuous 
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Statistical Analysis Plan, 25 August 2017 
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Appendix 16.2.7.2 Adverse Event – Non Drug Therapy (Safety Population) 
Onset 
Therapy 
Subject 
--------------- ------------------------------------ 
Cohort Number 
Treatment Adverse Event 
Date 
Time Date 
Time Description 
------------------------------------------------------------------------------------------------------------- 
X 
6 
X 
< > 
DDMONYYYY HH:MM DDMONYYYY HH:MM TRENDELENBURG 
POSITION 
Page 1 of X 
 
 
 
 
 
 
 
 
 
 
 
 
Programmer Note: If there are no non drug therapies the listing will contain the statement “There were no non drug therapies 
administered during the study.” 
 
 
 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment P: < > 
 
Program: /CAXXXXX/sas_prg/stsas/lis_dev/cdash_lis_ae3.sas 02DEC2015 
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Appendix 16.2.7.3 Adverse Event Preferred Term Classification (Safety Population) 
Page 1 of X 
 
Onset 
Subject 
--------------- 
Cohort Number 
Treatment Adverse Event 
Preferred Term* 
System Organ Class 
Date 
Time 
-------------------------------------------------------------------------------------------------------------------------------------------- 
 
X 
1 
None 
2 
None 
3 
X 
XXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXXX 
DDMONYYYY 
DDMONYYYY 
HH:MM 
HH:MM 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment P: < > 
*Adverse events are classified according to MedDRA Version 20.0. 
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Appendices 16.2.8.1.1 to 16.2.8.1.5 will have the following format: 
Appendix 16.2.8.1.1 Clinical Laboratory Report - Serum Chemistry (Safety Population) 
 
Page 1 of X 
 
Subject Age#/ Study 
Treat- 
Parameter1 
<Range> 
Parameter2 
<Range> 
Parameter3 
<Range> 
Parameter4 
<Range> 
Cohort Number Sex 
Period 
ment Day Hour 
Date 
Time 
(Unit) 
(Unit) 
(Unit) 
(Unit) 
-------------------------------------------------------------------------------------------------------------------------------- 
X 
1 
XX/M 
Screen 
1 
Recheck 
X 
DDMONYYYY HH:MM:SS 
XXX 
-1 -22.50 DDMONYYYY HH:MM:SS 
XXX HYR 
DDMONYYYY HH:MM:SS 
XXX 
X.X 
X.X 
X.X 
X.X 
X.X 
X.X 
XXX HN 
XXX HYR+ 
XXX 
<similar to above for all subjects/time points> 
 
 
 
 
 
 
Programmer Notes: Replace Parameter1, 2 etc. with actual lab tests in the study. Sort unscheduled assessment and early termination chronologically with 
other scheduled assessments and rechecks. Recheck should be sorted with the scheduled time point the recheck is for. 
 
Programmer Notes: Clinically significant lab values generally will be captured as AEs, some of which the PI may indicate in Appendix 16.2.8.1.1.6 lab 
comments (as per GPG.03.0028 sections 2.9 and 2.10). Derive an additional flag for PI flag (+) based on positive CS/Clinically Significant comments. 
Present this derived 4th column in all tables, and list only PI-determined out-of-range clinically significant lab values in Table 14.3.4.5. 
 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment P: < > 
#Age is calculated from the date of first dosing. F = Female, M = Male 
H = Above reference range, L = Below reference range 
Computer: N = Not clinically significant, Y = Clinically significant 
PI Interpretation: - = Not clinically significant, R = Recheck requested, ^ = Will be retested later, + = Clinically significant 
 
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Statistical Analysis Plan, 25 August 2017 
Page 78 of 81 
 
 
 
 
 
 
Subject Study 
 
 
Appendix 16.2.8.1.6 Clinical Laboratory Report – Comments (Safety Population) 
 
Page 1 of X 
Cohort Number Period Treatment Day 
Hour 
Date 
Department 
Test 
Result 
Unit 
Comment 
----------------------------------------------------------------------------------------------------------------------------------------- 
X 
2 
1 
X 
X 
X.XX DDMONYYYY Serum Chemistry 
Chloride 
XXX 
mg/dL 
NOT SIGNIFICANT IN CONTEXT 
OF STUDY 
3 Screen 
DDMONYYYY Serum Chemistry 
Direct Bilirubin 
X.X 
mg/dL 
LESS THAN 0.1 MG/DL 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmer Note: Footnote NCS = Not clinically significant, CS = Clinically significant, WNL = Within normal limits, etc. as needed 
 
 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment P: < > 
 
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Statistical Analysis Plan, 25 August 2017 
Page 79 of 81 
 
 
 
 
Appendix 16.2.8.2 Vital Signs (Safety Population) 
Blood Pressure 
(mmHg) 
Respir- Temper- 
Page 1 of X 
Subject Study 
------------------------ Pulse ation 
ature 
Weight 
Cohort Number 
Period 
Treatment Day Hour 
Date 
Time 
Test Systolic/Diastolic (bpm) (rpm) 
(°C) 
(kg) 
Comment 
------------------------------------------------------------------------------------------------------------------------------------------ 
X 
1 
Screen 
DDMONYYYY HH:MM:SS 
 
 
 
 
 
XX.X 
<This 
column SIT1 
XXX/ XX 
XX 
XX 
XX.X 
 
 
prints only 
R 
HH:MM:SS 
SIT1 
XXX/ XX 
XX 
XX 
XX.X 
if data are 
R 
HH:MM:SS 
SIT1 
XXX/ XX 
XX 
XX 
XX.X 
present.> 
1 
X 
-1 -21.00 DDMONYYYY HH:MM:SS 
SIT1 
XXX/ XX 
XX 
XX 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment P: < > 
SIT1 = 1-minute sitting, R = Recheck value 
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Statistical Analysis Plan, 25 August 2017 
Page 80 of 81 
 
 
 
 
Appendix 16.2.8.3 12-Lead Electrocardiogram (Safety Population) 
Heart 
Subject Study 
Rate 
PR 
QRS 
QT 
QTcF* 
Page 1 of X 
Cohort Number Period Treatment Day 
Hour Date 
Time 
Result (bpm) (msec) (msec) (msec) (msec) 
Comments 
----------------------------------------------------------------------------------------------------------------------------------------- 
X 
1 Screen 
DDMONYYYY HH:MM:SS ANCS 
XX 
XXX 
XX 
XXX 
XXX 
EARLY REPOLARIZATION; LEFT 
AXIS DEVIATION 
 
1 
X 
-1 -18.50 DDMONYYYY HH:MM:SS ANCS 
XX 
XXX 
XX 
XXX 
XXX 
LEFT AXIS DEVIATION 
1 
0.17 DDMONYYYY HH:MM:SS < > 
XX 
XXX 
XX 
XXX 
XXX 
SINUS BRADYCARDIA 
8 167.75 DDMONYYYY HH:MM:SS < > 
XX 
XXX 
XX 
XXX 
XXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment P: < > 
ANCS = Abnormal, not clinically significant 
QTcF* = QT corrected for heart rate using Fridericia's correction. 
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Page 81 of 81 
 
 
 
 
Appendix 16.2.8.4 Immunogenicity Response Results (Safety Population) 
Page 1 of X 
 
Subject 
Study 
Screening 
Confirmatory 
Cohort Number 
Period Treatment Day 
Hour 
Date 
Time 
Result 
Result 
Titer Value* Comments 
-------------------------------------------------------------------------------------------------------------------------------- 
X        1   1         X     1  -0.50  DDMONYYYY  HH:MM:SS  Negative 
<This column 
15  336.00 
DDMONYYYY 
HH:MM:SS 
Negative 
prints only 
29  672.00 
DDMONYYYY 
HH:MM:SS 
Positive 
Positive 
XX 
if data are 
present.> 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment P: < > 
*If the screening result is negative, confirmatory and titer assays will not be performed. If confirmatory result is negative, but 
the screening was positive, the titer assay will not be performed. 
 
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