Clinical trial NCT03612856
Conditions: End Stage Renal Disease Thrombosis
Keywords: Hemodialysis
Sponsor: Aronora, Inc.
Start date: 2018-10-29; Completion date: 2019-07-06
Enrollment: 27 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study evaluates the safety and efficacy of AB023 (xisomab 3G3) in patients with end stage renal disease on chronic hemodialysis. Two dose levels will be evaluated in two cohorts. Within each cohort the patients will be randomized to receive either AB023 (xisomab 3G3) or placebo (at a ratio of 2:1 active: placebo).

Detailed description:

Arms: arm 1: Participants will receive a single dose of 0.25 mg/kg xisomab 3G3. arm 2: Participants will receive a single dose of 0.5 mg/kg xisomab 3G3. arm 3: Participants will receive a single dose of placebo.
Interventions: intervention 1: AB023- Dose 1 intervention 2: AB023-Dose 2 intervention 3: placebo
Intervention descriptions: intervention 1: Participants will receive a single dose of 0.25 mg/kg AB023. intervention 2: Participants will receive a single dose of 0.5 mg/kg AB023. intervention 3: Participants will receive a single dose of placebo.

Protocol documents:
ICF_002.pdf: 
 
 
June 20, 2018 
 
Principal Investigator: Thomas C. Marbury, M.D. 
Sponsor: Aronora, Inc. 
Protocol Number: 3G3-18-02 
Study Title: “A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and 
Efficacy/Potency of a Single Dose of Xisomab 3G3, Administered at the Beginning of a Regular 
Hemodialysis Procedure, in Patients with End-Stage Renal Disease on Chronic Hemodialysis” 
 
Dear Dr. Marbury: 
 
A convened IRB meeting of IntegReview was held on the above-referenced date. The following full board 
action was taken on initial review of the above-referenced study: 
 
Approved: 
Principal Investigator 
Investigative site(s) as submitted with initial submission documents 
Protocol dated 25May2018; Amendment 1 dated 14June2018 
Informed Consent, English language, dated June 20, 2018, (refer to IntegReview modifications as 
reflected on the following document containing revision marks) 
 
The Board reviewed the Investigator’s Brochure, Version 2.0 dated 24May2018, for the study drug(s), as  
appropriate. 
 
IMPORTANT 
• 
The following changes in approved research may not be implemented until you have received 
approval from IntegReview except where necessary to eliminate apparent immediate hazards 
to the human subjects: 
➢ Protocol Amendments 
➢ Change in the Principal Investigator and/or Sub-investigators (only if the Sub- 
investigators will be performing study-related procedures that the PI is not qualified 
through expertise to perform) 
➢ Change in the address at the study site or the addition of a study site(s) 
• 
Only Informed Consent documents containing IntegReview’s approval stamp may  be utilized: 
➢ There must be procedures in place to guarantee that consent has been voluntarily obtained 
and properly documented. 
➢ For participants that do not speak English, the informed consent document must be in a 
language understandable to them; Non-English speaking subjects may not be enrolled until 
the foreign language Informed Consent Document(s) has been approved by IntegReview. 
➢ Only IntegReview staff may initiate modifications to Informed Consent documents. The 
Informed Consent document for your site will be maintained in our computer files, and 
IntegReview will make all revisions following IRB approval. 
 
 
 
 
3815 S. Capital of Texas Hwy, Suite 320, Austin, TX 78704 
Tel. 512.326.3001 Local Fax. 512.697.0085 http://www.integreview.com 
 
IRB Registration Numbers: IRB00008463, IRB00003657, IRB00004920, IRB00001035, IRB00006075 


Thomas C. Marbury, M.D. 
Aronora, Inc., Protocol Number 3G3-18-02 
Page 2 
 
 
➢ Any modifications made to informed consents without prior IRB approval will be 
considered non-compliance and subject to, but not limited to, full board review, FDA 
review, suspension and/or termination of IRB approval. 
• 
Only recruiting materials containing IntegReview’s approval stamp may be utilized. All 
audio/video recording(s) must be submitted for IRB approval prior to broadcast. 
• 
Revision requests should be submitted on IntegReview’s forms, which are available in 
IRBManager. 
• 
Visit our website at www.integreview.com for information on research regulations, reporting 
requirements, Investigator and research personnel training, etc. 
 
IntegReview approval for this study expires June 19, 2019. 
 
In order to obtain extended IRB approval, IntegReview must receive your form for continuing review two 
weeks prior to the IRB expiration date. Appropriate forms will be forwarded to you approximately four 
weeks prior to the approval expiration date. Should the study end before you receive notification, submit a 
Closure Notification form. 
 
REPORTING REQUIREMENTS 
 
To ensure compliance with the applicable federal regulations as well as International Conference on 
Harmonisation (ICH), E6: Good Clinical Practice: Consolidated Guideline, and/or IntegReview’s 
requirements, notification of the following are required for review/approval: 
 
• 
Report immediately: 
➢ Changes in research that were initiated without IRB review and approval to eliminate 
apparent immediate hazards to the human subjects to ensure the continued safety and welfare 
of subjects 
➢ Modifications to previously approved documents 
➢ Receipt of investigator/site 483, Determination letter or Warning letter 
➢ If your license is suspended, revoked, placed on probation or restricted in any state or country 
➢ Safety information that may help to provide additional protections for subject’s safety and 
well-being, throughout the course of the study and after study completion. 
➢ Communication of results from a research study to subjects when those results directly affect 
their safety or medical care 
➢ Reports of pregnancy 
➢ Data Monitoring Committee (DMC/DSMB) Reports 
• 
Report within 10 calendar days of discovery: 
➢ Revisions to the Investigator's Brochure, as applicable 
➢ Revisions to the report of prior investigations, as applicable 
➢ Non-compliance – Failure by an investigator and/or sponsor to follow IntegReview’s 
requirements, applicable regulations or to protect human  research subjects, including but not 
limited to the principles of the Belmont Report 
➢ Serious non-compliance issues - non-compliance as defined as above and as determined to be 
serious in a way that adversely affects the rights and welfare of human subjects following 
the investigation and review by the IRB 
➢ Continuing non-compliance issues – A pattern of repeated non-compliance or serious non- 
compliance as determined by the IRB 
➢ Significant deviations – Significant deviations are those that deviate from the approved 
protocol, informed consent process and affect or potentially affect the safety of subjects. 
IntegReview does not consider protocol deviations to be different from protocol violations. 
➢ Unanticipated adverse device effects, as applicable 


Thomas C. Marbury, M.D. 
Aronora, Inc., Protocol Number 3G3-18-02 
Page 3 
 
 
➢ Unanticipated problems should be reported regardless of whether they occur during the study, 
after the study completion, or after participant withdrawal or completion. Unanticipated 
problems involving risks to human subjects or others that are (1) unexpected (in terms of 
nature, severity, or frequency) given (a) the research procedures that are described in the 
protocol-related documents, such as the IRB-approved research protocol and informed 
consent document; and (b) the characteristics of the subject population being studied; (2) 
related or possibly related to participation in the research (possibly related means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures in the research); and (3) suggests that the research places subjects or others at a 
greater risk of harm (including physical, psychological, economic, or social harm) than was 
previously known or recognized. Examples of problems or events that may meet the 
definition of unanticipated problems involving risk to subjects or others may include, but are 
not limited to the following: 
• 
Imminent threat of a reportable event that has not yet occurred 
• 
Information indicating a change to the risk/benefit ratio of the research 
• 
Death 
• 
Breach of confidentiality, including lost or stolen study documents/data 
• 
Report within 30 days of acquisition or discovery 
➢ New or additional conflicts of interests 
• 
Submit prior to publication/distribution: 
➢ Any modification(s) to the previously approved Informed Consent document 
➢ New and/or modifications to previously approved recruiting/miscellaneous materials to be 
seen or heard by subjects 
• 
Submit two weeks prior to IntegReview approval expiration date: 
➢ Continuing review documents 
• 
Submit upon completion of the study: 
➢ Notification of study closure 
 
At its discretion, IntegReview IRB reserves the right to visit the study site. 
 
IntegReview IRB is organized and operates in accordance with the applicable federal regulations, and ICH 
Guidelines for Good Clinical Practices, E6.  In addition, Standard Operating Procedures have been created   to 
ensure compliance with these regulations and guidelines. 
 
If you have any questions regarding these procedures or if you wish to appeal the decision of the Board, you 
may address your comments to the IntegReview Chair. Your comments will be reviewed and discussed at the 
next convened meeting. 
 
Failure to comply with the Code of Federal Regulations or the requirements or determinations of 
IntegReview IRB can result in suspension or termination of IntegReview approval. 
 
Sincerely, 
Angelica Martinez, CCRP 
IRB Coordinator, Co-chair 


 
 
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APPROVED BY 
INTEGREVIEW IRB 
JUNE 20, 2018 
INFORMED CONSENT DOCUMENT 
AGREEMENT TO BE IN A RESEARCH STUDY 
 
NAME OF SPONSOR COMPANY: 
Aronora, Inc. 
 
PROTOCOL NUMBER AND TITLE OF STUDY: 
3G3-18-02: “A Phase 2, Randomized, Double- 
Blind, Placebo-Controlled Study of the Safety 
and Efficacy/Potency of a Single Dose of 
Xisomab 3G3, Administered at the Beginning of 
a Regular Hemodialysis Procedure, in Patients 
with End-Stage Renal Disease on Chronic 
Hemodialysis ” 
 
NAME OF PERSON IN CHARGE OF THE 
RESEARCH STUDY (STUDY DOCTOR/ 
INVESTIGATOR): 
Thomas C. Marbury, M.D. 
 
TELEPHONE NUMBER(S), DAYTIME 
AND AFTER HOURS: 
(407) 240-7878 
 
INTRODUCTION 
 
You are being asked to participate in the above-named research study. Before agreeing to participate in this 
research study, it is important that you read and understand this informed consent document and ask any 
questions that you may have. This document describes, in detail, the following: 
 
• 
purpose of the study; 
• 
contact information if you have any questions; 
• 
information about the study drugs used in the study; 
• 
requirements for participating in the study; 
• 
procedures to be completed during the study; 
• 
benefits and alternatives to you as a study participant; 
• 
potential risks and discomforts you may experience as a result of participating in this study; 
• 
precautions you must take during the study; 
• 
your right to withdraw from the study at any time; 
• 
compensation you will receive for your time and travel. 
 
Please take the time to read the following information carefully and discuss it with others. If this form 
contains any words that you do not understand, please ask the site medical team or staff to explain them to 
you. 
 
If you have decided that you want to take part, you will be asked to sign the informed consent form. You 
will get a copy of the signed form. Your decision to take part in this study is voluntary. That means you are 
free to decide to join this study or not join this study, and refusal to join will not affect your medical care. 
You are also free to stop study drug dosing and study-related activities at any time and without any reason. 
 
The pharmaceutical company sponsoring this study is Aronora, Inc. Orlando Clinical Research Center is 
being paid by Aronora, Inc. to conduct this study. 


Protocol number: 3G3-18-02 
Informed Consent 
Thomas C. Marbury, M.D. 
Page 2 of 20 
APPROVED BY 
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JUNE 20, 2018 
 
 
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You must be honest with the study doctor about your health history or it may not be safe for you to be in this 
study. 
 
In this document, you may see the terms “medication” and “treatment”; these are terms used in research 
studies as mentioned above, this does not mean that you will be receiving medical treatment for any 
condition. These terms apply to the investigational study drug and parts of the study where you will be 
receiving this investigational product. 
 
PURPOSE OF THE STUDY 
 
Aronora, Inc. is sponsoring this study of an investigational drug called xisomab 3G3. The National Institute 
of Heart Lung Blood (NIHLB), part of the National Institutes of Health (NIH), is funding the study. 
Investigational means that the drug being tested is not approved by the United States Food and Drug 
Administration (FDA) for general use in the United States, but may be tested in research studies such as 
this one. 
 
Xisomab 3G3 is being developed for the prevention of treatment of thrombotic and thromboembolic 
diseases, such as venous thrombosis and thromboembolism. 
 
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the 
circulatory system. 
 
The purpose of this study is to evaluate the safety and tolerability of a single dose of xisomab 3G3 when 
injected through a port into the arterial dialysis line immediately after the start of a hemodialysis treatment. 
 
Up to 24 men and women, ages 18 to 80 will be enrolled in the study at 2 centers in the United States. 
 
The study will last about 7 weeks and will involve a screening period, a 14 day/13 night stay at the study 
site and 3 follow up visits. 
 
STUDY DRUG DOSING 
 
This is a randomized, double-blind, placebo-controlled study. Randomized means the study treatment you 
take will be chosen by chance (like flipping a coin). 
 
Double-blind means that you and your study doctor will not know what study drug you are taking. 
The placebo is a substance that looks like a drug, but has no drug in it. 
Be aware that sometimes this form refers to both xisomab 3G3 and placebo as “study drug”. 
 
You and the study doctor will not choose which group you will participate in; however, this information 
can be obtained if needed in an emergency. The study drug you will receive will be assigned by chance, 
like the flip of a coin. 


Protocol number: 3G3-18-02 
Informed Consent 
Thomas C. Marbury, M.D. 
Page 3 of 20 
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If you agree to join this study and qualify, you will be assigned to 1 of 2 dosing groups as follow: 
 
• 
Group 1: Infusion dose of 0.25 mg/kg xisomab 3G3 or placebo 
• 
Group 2: Infusion dose of 0.5 mg/kg xisomab 3G3 or placebo 
 
The amount of study drug/placebo you receive will depend on how much you weigh. There are 2 different 
doses: 0.25 and 0.5 milligrams of study drug for each kilogram of weight. A kilogram equals about 2.2 lbs. 
So, for example, if you weighed 70 kilograms (154 pounds), and you received (0.5mg/kg) your dose would 
be 0.5 times 70, which means you would receive 35 milligrams of study drug/placebo. 
 
The study drug/placebo will be given to you on Day 1. The study drug/placebo will be injected through a 
port into the arterial dialysis line immediately after the start of a hemodialysis treatment. 
 
SCREENING VISIT 
 
Before any study procedures being performed, you will be asked to sign this informed consent. Before the 
study starts, you will be asked to do some procedures to find out if you qualify to be in the study. This 
process is called “Screening.” 
 
• 
You will be asked about your health, how you are feeling, your use of alcohol and tobacco products 
as well as your medical history. 
• 
Your demographics will be collected (such as age, sex, race, ethnicity, date of birth). 
• 
A full physical exam will be done. 
• 
Your height, weight, body temperature, breathing rate and blood pressure and heart rate will be 
measured. 
• 
You will be asked about any medications. (over the counter, prescription, herbal supplements or 
vitamins) 
• 
You will have an electrocardiogram (ECG) to measure the electrical activity of your heart. You may 
be asked to remove your blouse or shirt for the ECG. 
• 
Blood and urine will be collected for laboratory testing. (must be fasting for a minimum of 4 hours 
before clinical lab tests) 
• 
You will have a test for alcohol and drugs of abuse. 
• 
You will have a blood test for hepatitis B and C (an infection of the liver) and HIV. State law requires 
that positive test results for hepatitis/HIV be reported to a local health agency. You will be asked to 
sign a separate HIV consent. 
o The results of these tests are expected to stay confidential. There is a chance that a breach in 
confidentiality could happen; this means that people that were not originally supposed to have 
this information could see these results. For example, it is possible for a court of law to get 
health or study records without your permission. Please speak to the study staff or your personal 
doctor, if you want to know more about what it could mean to you if somebody outside of this 
research study has access to this information. 
• 
If you are female, you will have a pregnancy test. Females who might be postmenopausal will have a 
blood test done to confirm that they are post-menopausal. If you are a female capable of becoming 
pregnant, you will not be eligible to participate in this study. 
 
After all screening tests have been done, if you are determined to be eligible to continue in the study, you 
will return to the clinic to check-in and start the evaluation period (7 days before dosing). 


Protocol number: 3G3-18-02 
Informed Consent 
Thomas C. Marbury, M.D. 
Page 4 of 20 
APPROVED BY 
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STUDY PROCEDURES 
 
Please note the exact schedule for the procedures described in this consent form are subject to change. 
Some procedures may not be performed, and some may be added or moved to other study days. 
 
DAY -8 (Check-In) / EVALUATION PERIOD (DAY -8 THROUGH DAY -1) 
 
You will come to the research clinic to begin the evaluation/confinement period. During the evaluation 
period (Day -8 through Day -1) you will have hemodialysis treatment according to your dialysis schedule. 
 
Day -8: 
The following procedures will be done: 
 
• 
Your medical and medication history will be reviewed and updated if needed. Tell the staff about any 
prescription drugs, over-the counter medicines, herbal and vitamin supplements you are taking. This is 
very important. 
• 
A physical exam will be done 
• 
Your weight will be measured. 
• 
Electrocardiograms (ECG) will be done. 
• 
Your vital signs including blood pressure, heart rate, temperature and breathing rate will be measured. 
• 
Blood and urine will be collected for laboratory testing. 
• 
You will have a test for drugs of abuse and alcohol. 
• 
If you are female, you will have a pregnancy test. 
 
Day -7, Day -5, Day -3/ Hemodialysis day 
The following procedures will be done: 
 
• 
Your weight will be measured. 
• 
Blood samples will be collected before and after hemodialysis for laboratory testing. 
• 
Your vital signs including blood pressure, heart rate, temperature and breathing rate will be measured. 
• 
You will be asked about any medications you might have taken or negative side effects that you 
might have experienced. 
• 
Dialysate samples will be collected. Fluid which passes through the dialyzer will be collected. Dialysate 
sample will be taken for future analysis (e.g., assessment of urea or drug in the dialysate). Samples will 
be stored for up to 5 years). 
• 
Fistula or graft for dialysis access will be assessed for bleeding and any abnormality (bleeding and 
visual assessment). 
 
Day -6, Day -4, Day -2, and Day -1: 
The following procedures will be done: 
 
• 
You will be asked about any medications you might have taken or negative side effects that you 
might have experienced. 
• 
Your weight will be measured. 
 
By the end of the evaluation period the study doctor will determine if you are eligible to continue into the 
study. If you will not be able to continue in the study, the study doctor will explain why. 


Protocol number: 3G3-18-02 
Informed Consent 
Thomas C. Marbury, M.D. 
Page 5 of 20 
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JUNE 20, 2018 
 
 
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The sponsor and study doctor reserve the right to make the final decision on subject selection for 
participation into the study. This may occur as late as just before dosing. Each subject will need to meet 
study requirements again at check-in. 
 
DAY 1 (DOSING DAY) / HEMODIALYSIS DAY 
 
While you are in the clinic, you will have the following tests done: 
 
• 
You will be asked about any medications you might have taken or negative side effects that you 
might have experienced. 
• 
Your vital signs, including body temperature, blood pressure, heart rate and breathing rate will be 
measured multiple times before and after receiving the study drug/ placebo. 
• 
ECG will be done. 
• 
Your weight will be measured. 
• 
Blood and urine samples will be collected for laboratory testing before and after hemodialysis. 
• 
A physical exam will be done. 
• 
After an overnight fast of at least 4 hours, the study staff will give you the study drug. Refer to 
section “STUDY DRUG DOSING”. 
• 
Blood will be collected to find out the amount of study drug /placebo in your body. A sample will be 
obtained before you receive the study drug, then at up to 11 times after receiving the study drug. 
• 
A blood sample will be collected for immunogenicity analysis (to found out your immune response). 
• 
Dialysate samples will be collected. 
• 
Bleeding and visual assessments will be completed. 
 
DAY 2 AND DAY 4 
 
The following procedures will be done: 
 
• 
You will be asked about any medications you might have taken or negative side effects that you 
might have experienced. 
• 
Blood samples will be collected to find out the amount of study drug /placebo present in your body. 
• 
Blood sample will be collected for laboratory testing. 
• 
Your weight will be measured. 
 
DAY 3 AND DAY 5 / HEMODIALYSIS DAY 
 
The following procedures will be done: 
 
• 
You will be asked about any medications you might have taken or negative side effects that you 
might have experienced 
• 
Your weight will be measured. 
• 
Your vital signs, including body temperature, blood pressure, heart rate and breathing rate will be 
measured. 
• 
Blood samples will be collected for laboratory testing. 
• 
Bleeding and visual assessments will be completed. 


Protocol number: 3G3-18-02 
Informed Consent 
Thomas C. Marbury, M.D. 
Page 6 of 20 
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JUNE 20, 2018 
 
 
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DAY 6 (DISCHARGE): 
 
Discharge procedures will be completed on Day 6 
 
• 
You will be asked about any medications you might have taken or negative side effects that you 
might have experienced. 
• 
Your vital signs, including body temperature, blood pressure, heart rate and breathing rate will be 
measured. 
• 
ECG will be done. 
• 
A physical exam will be completed. 
• 
Blood and urine samples will be collected for laboratory testing. 
• 
Blood will be collected to find out the amount of study drug /placebo present in your body. 
 
You will be discharged from the clinic after all the Day 6 procedures have been completed. You will be 
required to return to the clinic for a follow up visit on Days 8, 10 and 12 (Hemodialysis day) 
 
During the study, you will be monitored closely for possible side effects. You will be asked about any 
symptoms or illnesses that you may experience. Additional physical exams may be performed at the 
discretion of the study doctor. You should report any changes in your physical or mental condition, or any 
side effects that you may have during the study. In addition, you will be asked to inform the investigator 
and/or study staff of any medications, procedures or therapies you are taking while you are participating in 
this study. 
 
DAY 8 AND DAY 10/ HEMODIALYSIS DAY / FOLLOW UP VISIT 
 
The following procedures will be done: 
 
• 
You will be asked about any medications you might have taken or negative side effects that you 
might have experienced 
• 
Your weight will be measured. 
• 
Your vital signs, including body temperature, blood pressure, heart rate and breathing rate will be 
measured. 
• 
Blood samples will be collected for laboratory testing. 
• 
Bleeding and visual assessments will be completed. 
 
DAY 12 / HEMODIALYSIS DAY /FOLLOW UP VISIT PROCEDURES 
 
You will be required to return to the clinic on Day 12 for a follow up visit. Anyone who receives study 
drug/placebo will be asked to return for this visit. 
 
• 
Your vital signs, including body temperature, blood pressure, heart rate and breathing rate will be 
measured. 
• 
ECG will be done. 
• 
A physical exam will be completed. 
• 
Your weight will be measured. 
• 
Blood and urine samples will be collected for laboratory testing. 
• 
Blood will be collected to find out the amount of study drug /placebo present in your body. 


Protocol number: 3G3-18-02 
Informed Consent 
Thomas C. Marbury, M.D. 
Page 7 of 20 
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JUNE 20, 2018 
 
 
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• 
A pregnancy test for all females will be performed. 
• 
You will be asked how you are feeling and about whether you have taken any medications since your 
last visit. 
• 
Bleeding and visual assessments will be completed. 
• 
A blood sample will be collected for immunogenicity analysis response. 
• 
Dialysate samples will be collected. 
 
Your participation in the study will be completed when all the study procedures and the review of the 
medical and safety evaluations have been done. You may require longer observation in the clinic or 
additional laboratory testing based on the effects of the medication or the results of the laboratory tests. 
 
BLOOD SAMPLE COLLECTION 
 
Blood samples may be drawn from an intravenous catheter (a tube that is left in your arm). The catheter 
will be inspected, maintained and may be changed, if necessary. If the use of the catheter is not possible, 
the blood samples will be taken by individual needle-sticks from a vein in your arm. 
 
The total amount of blood drawn is up to 436 mL (a little less than 2 cup). For comparison, the standard 
blood donation is about 480 mL (about half liter, or two U.S. cups). 
 
This total volume does not include discarded blood from pre-draws used to remove fluid from flushed 
catheters which is approximately 0.5 mL per blood draw. Additional blood samples may be drawn during 
the study if the study doctor considers it necessary for monitoring your health. It is possible that more than 
one attempt to obtain a blood sample may be necessary. 
 
SUBJECT RESPONSIBILITIES 
 
As a participant in this study, you have certain responsibilities to help ensure your safety. These 
responsibilities are listed below: 
 
• 
Provide truthful information about your health history. 
• 
Complete all required visits. 
• 
Participate in all study-related procedures as required by the study. 
• 
Follow the restrictions listed in the section below. 
• 
Use contraception as described later in this document. 
• 
Report all changes in your health, side effects, and medical problems immediately to the site medical 
team, even if you do not think they are related to the study. 
• 
Inform the site medical team or staff if you decide to discontinue your participation. If you decide to 
drop out of the study after receiving any study medication, you will be required to complete at least one 
follow-up visit. 
 
RESTRICTIONS 
 
For your own safety, it is important that you follow without exception the Clinical Research Center In- 
House Guidelines. Violations of these In-House Guidelines may make it necessary to remove you from the 
study. If you are taken out of this study because you are unable to follow the In-House Guidelines, you may 
not be asked to take part in other studies done at this research clinic. 


Protocol number: 3G3-18-02 
Informed Consent 
Thomas C. Marbury, M.D. 
Page 8 of 20 
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JUNE 20, 2018 
 
 
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During your stay in the Research Center, you must follow the study rules about tobacco, alcohol, or any 
unauthorized drugs. 
 
• 
Smoking is not permitted at any time in the building. Subjects are prohibited from smoking during 
study confinement. 
• 
Food and beverages will be provided during your stay at the research center except when fasting is 
required. You will be served standard meals and snacks according to a strict daily diet and according 
to the study procedures. You may not bring your own food or beverages. 
• 
You must not take certain medicines before and during the study. The study staff will discuss this with 
you. Please tell the study staff about all of the medications, drugs, and supplements you are taking. This 
includes any prescription or over-the-counter medications. If you have any questions about any 
medication, please ask the study staff before taking it. 
• 
You must not have received a study drug or participated in another clinical trial within 30 days before 
Day – 8 of admission. 
• 
Beverages or foods containing caffeine and/ or, xanthine (coffee, tea, cola, chocolate, etc.) are not 
allowed 48 hours before receiving the study drug and throughout the period of sample collection. 
• 
You must not drink any alcohol (beer, wine, liquor) starting 48 hours before receiving the study drug 
and throughout the period of blood sample collection. 
• 
You must not engage in strenuous exercise 48 hours before Day -8 and while participating in this study. 
 
It is very important that you follow all the rules, restrictions, and instructions given by the staff. If you do 
not follow the restrictions or follow the guidance of the study staff, there can be a risk to your health and/or 
false study results. 
 
VOLUNTEERING TO BE IN THE STUDY AND WITHDRAWAL OF YOUR CONSENT TO 
PARTICIPATE IN THIS STUDY 
 
The study doctor, the sponsor company, IntegReview, or the FDA may take you out of the study without 
your permission, at any time, for the following reasons: 
 
• 
If you do not follow the study doctor’s instructions 
• 
If we find out you should not be in the study 
• 
If the research study is stopped 
• 
If participation in the research study becomes harmful to your health 
 
It is your choice if you want to be in the research study. No one can force you to be in the research study. 
You may decide to stop your study participation which may include stopping any further assessments or 
contact by the study staff. This is considered a withdrawal of your consent from participation in this study. 
 
It is important that you inform your study doctor of your decision to withdraw your consent by providing 
written notice to the study doctor. If you leave the study, no more information about you will be collected 
for this study. However, the sponsor will continue to retain and use all research results and any biological 
samples that have already been collected for the study evaluation (as per local regulations). 
 
You can discuss further regular medical care with the study doctor. The choice to withdraw from research 
study will not affect your medical care. 


Protocol number: 3G3-18-02 
Informed Consent 
Thomas C. Marbury, M.D. 
Page 9 of 20 
APPROVED BY 
INTEGREVIEW IRB 
JUNE 20, 2018 
 
 
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If you drop out or are removed from the research study after having taken the study drug, you may be asked 
to come back to the clinic for a follow-up visit. At this visit you will have discharge procedures performed 
and blood tests to ensure that there are no changes to your current health status. You will be asked about 
any changes in your health or in the medications you are taking. 
 
POSSIBLE RISKS AND SIDE EFFECTS 
 
If you do not understand what any of these side effects mean, please ask the study doctor or study staff to 
explain these terms to you. 
 
The most common side effects in a 21 normal healthy volunteer study include injection site skin reaction, 
cough, increased diastolic blood pressure, and upper respiratory tract infection. 
 
Because the study drug is investigational, there may be side effects that we do not yet know about. There 
may be rare and unknown side effects. Some of these may be life threatening. 
 
The study drug (xisomab 3G3) is being developed to treat or prevent blood clots and, therefore, taking the 
study drug may increase your risk for bleeding or bruising. While the study drug has been developed 
specifically with the intent to reduce blood clotting inside blood vessels without increasing the risk of 
bleeding, risks of side effects in humans cannot be established without testing the effects of the study drug 
in human subjects. 
 
The study drug is a therapeutic antibody and there are risks associated with taking this type of drug which 
include allergic reactions, such as rash, swelling, hives, difficulty breathing, blood pressure changes, among 
others. A severe and life threatening allergic reaction can occur. 
 
Throughout the duration of the study, you will not receive heparin during your hemodialysis sessions. This 
may put you at a higher risk of developing clotting within the dialyzer cartridge during hemodialysis sessions. 
Because the study drug (xisomab 3G3) is being developed to treat or prevent blood clots, you may be less 
likely to develop blood clots during hemodialysis after receiving the study drug. However, if you are randomly 
selected to receive placebo you will undergo nine consecutive hemodialysis sessions without heparin 
anticoagulation, which may put you at a higher risk of developing a clotting within the dialyzer during 
hemodialysis. 
 
You must tell the study doctor or study staff about all side effects that you have. If you are not honest about 
your side effects, you may harm yourself by staying in this study. 
 
Until you know how the drug(s) will affect you, you should use caution by avoiding stairs, not driving a 
car or working with machinery. 
 
ADDITIONAL RISKS OR DISCOMFORTS 
 
Blood Draws: 
 
The risks of taking blood may include fainting, pain, nerve damage, redness, bleeding and/or bruising. 
Rarely, there may be a small blood clot or infection at the site of the needle puncture. If you feel faint tell 
the study staff right away. 


Protocol number: 3G3-18-02 
Informed Consent 
Thomas C. Marbury, M.D. 
Page 10 of 20 
APPROVED BY 
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JUNE 20, 2018 
 
 
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Two indwelling, intravenous catheters may be inserted in one arm to collect blood samples. An indwelling 
catheter is a special needle device designed to be placed in a vein, and then to remain in the vein for a period 
of time. This could cause: infection, pain, redness, bruising, nerve damage, local swelling due to IV fluid 
(saline/ heparin flush that will be used to keep the indwelling catheter open) accidentally entering the tissue 
rather than the vein, blood clots, which may cause inflammation, swelling and pain. It is possible that the 
catheter will stop working and may have to be replaced in a different vein. 
 
Blood Pressure: 
 
The blood pressure cuff may also cause discomfort or bruising to the upper arm. 
Electrocardiogram (ECG): 
The ECG test is a recording of the electrical activity of your heart. The sticky pads used may be cold when 
applied and sometimes cause some discomfort such as redness or itching. If the hair under the patches needs 
to be shaved, irritation from shaving also could occur. You may experience some skin irritation from the 
electrode adhesive or develop contact dermatitis (a skin condition caused by contact between skin and some 
substance) which may appear as lighter as or darker than the surrounding skin for possibly an extended 
period of time. 
 
Digital Photos 
 
In the event of any physical abnormal finding, digital photos will be taken of the areas. The photos will be 
taken in a manner so that there is no way you could be identified in the pictures. 
 
Your image may be sent electronically to the sponsor. The photographs or electronic images will be labeled 
with your study number and not your name. People working for the Sponsor, the FDA, and IRB will have 
access to your photographs if they have a valid reason for seeing them. Valid reasons include but are not 
limited to, monitoring or auditing the study, to assess the skin condition or to determine the cause of the 
skin condition. When the study is over, your photograph or electronic image will be stored with the study 
files indefinitely. Your picture will not be used for teaching purposes and will not be published in any 
medical journal. You may be asked to have additional tests to assess the condition. The Study Doctor will 
discuss this with you before any other tests are done. You are giving the site  permission to take photos of 
the area indicated by signing this consent form. 
 
BIRTH CONTROL, DANGERS OF PREGNANCY AND BREASTFEEDING 
 
The effects of the study drug on an unborn child are not known. Only females who are not able to get 
pregnant are allowed to be enrolled in this research study. 
 
Females who are not able to get pregnant are defined as being permanently sterile (due to hysterectomy 
[removal of uterus], bilateral salpingectomy [removal of both ovaries and fallopian tubes], bilateral 
oophorectomy [removal of ovaries], or confirmed tubal occlusion more than 6 months before the first dose 
of study drug) or postmenopausal (defined as at least 12 months without a period without an alternative 
medical cause). If you think that you have become pregnant during the study, it is important that you inform 
the study doctor immediately. 


Protocol number: 3G3-18-02 
Informed Consent 
Thomas C. Marbury, M.D. 
Page 11 of 20 
APPROVED BY 
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JUNE 20, 2018 
 
 
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Male subjects must either be sterile (vasectomy with history of a negative sperm count following the 
procedure); practice total abstinence from sexual intercourse as the preferred lifestyle (periodic abstinence 
is not acceptable); use a male condom with any sexual activity; or agree to use a birth control method (such 
as one of the methods identified above for female subjects) from the time of Screening until 90 days after 
the last dose of study drug. Male subjects must agree not to donate sperm for a period of 90 days after the 
last dose of study drug. 
 
Even if you use birth control during the study, there is a chance your partner could become pregnant. A 
pregnancy test is not always right, especially in the early stages of pregnancy. If your partner becomes 
pregnant, you must inform the study doctor immediately. The study doctor may request to track the 
pregnancy and report the outcome to the Sponsor. 
 
Unknown Risks 
 
There may be additional risks that are currently unknown and unanticipated related to taking the study 
drug. There may be rare and unknown side effects. Some of these may be life threatening. 
 
You might have side effects or discomforts that are not listed in this form. Some side effects may not be 
known yet. New ones could happen to you. If new risks associated with the dosing of study drug are 
identified during the study, you will be told about them. 
 
SAFEGUARDS 
 
You must tell the study doctor about all of your past and present experiences with pain relievers, diseases, 
addictions, drinking habits, and allergies of which you are aware, and all drugs and medications which you 
are presently taking including vitamins and any herbal supplements. 
 
POSSIBLE BENEFITS OF THE STUDY 
 
You will not receive any direct benefit from participating in this study. This study may help physicians 
and scientists learn things about the study drug that will help others. 
 
ALTERNATIVES TO PARTICIPATING IN THE STUDY 
 
Your alternative is to not take part in the study. 
 
CONFIDENTIALITY 
 
Information about you and your participation in the study will be kept confidential according to  applicable 
privacy laws and any policies of your study doctor and the sponsor. Your original study records may contain 
your name, address, health information and other personal data (“Personally Identifiable Information”). 
These study records will be kept by your study doctor as required by applicable law and the sponsor. These 
records may be held forever. 


Protocol number: 3G3-18-02 
Informed Consent 
Thomas C. Marbury, M.D. 
Page 12 of 20 
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JUNE 20, 2018 
 
 
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USE OF YOUR STUDY RECORDS 
 
The study results may be looked at to make sure the study is being done correctly. The sponsor may work 
with other companies and government agencies for reasons related to the study. In order for this to take 
place, these companies and government agencies will have access to the original records or the data 
contained in the records and may copy some of the information, which may contain your Personally 
Identifiable Information. These companies and government agencies include: 
 
• 
Regulatory authorities including in other countries, such as the FDA 
• 
Other government agencies 
• 
IntegReview IRB 
• 
Contracted Monitors/Auditors and other individuals or companies used by the sponsor to help with 
the study 
• 
Affiliated companies of the sponsor 
 
After the study doctor shares your records with the sponsor and others, the laws may no longer protect the 
privacy of your records. If all information that does or can identify you is removed from your records, the 
remaining information may be used or shared for other purposes. 
 
Your results will be coded with numbers and initials. Companies and government agencies (for example 
the FDA and IntegReview, the IRB for this research study) will not know your name unless it is necessary 
for purposes relevant to a study. The results of a study may be shown in publications or at meetings. You 
will not be identified by name. Under certain circumstances, some test results will be reported to health 
authorities as required by law. Note that once your test results or samples leave the US, they are not 
protected by the same laws in other countries. 
 
The sponsor and its affiliated companies may use and disclose your records and health information collected 
for this study to conduct additional clinical or data research studies or to develop proposals for new studies. 
The sponsor also may use the information about you in the study to improve the design and efficiency of 
future research studies. 
 
The Institutional Review Board (IRB), IntegReview, and accrediting agencies may inspect and copy your 
records, which may have your name on them. Therefore, total confidentiality cannot be guaranteed. If the 
study results are presented at meetings or printed in publications, your name will not be used. 
 
If a medical emergency happens, your study results may be given to emergency medical staff. If you decide 
to stop being in a study, the information already gathered will still be kept in the study database. 
 
A description of this clinical trial will be available on http://www.clinicaltrials.gov as required by U.S. Law. 
This Web site will not include information that can identify you. At most, the Web site will include a 
summary of the results. You can search this Web site at any time. 
 
NEW INFORMATION 
 
You will be informed, in writing, of any new or important findings that are learned during this study that 
might influence your choice to start or remain in the study. You may be asked to sign an updated consent 
form. 


Protocol number: 3G3-18-02 
Informed Consent 
Thomas C. Marbury, M.D. 
Page 13 of 20 
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JUNE 20, 2018 
 
 
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ADDITIONAL COSTS 
 
There will be no cost to you for participating in this research study. 
 
PAYMENT FOR PARTICIPATION IN THIS STUDY 
 
You will be compensated for your time and travel. If your research study participation is ended because of 
a positive drug screen, you will not get any compensation. 
 
If after being enrolled in the research study, your participation in the study is ended for any other reason 
besides a positive drug screen, you will receive compensation based on the visits and/or days that you have 
completed. You will not receive payment for partially completed days/visits. Payment is outlined below. 
 
Completion of Screening: $50.00 
Completion of Day -8: 
$125.00 
Completion of Day -7 : 
$200.00 
Completion of Day -6 : 
$250.00 
Completion of Day -5 : 
$250.00 
Completion of Day -4 : 
$250.00 
Completion of Day -3 : 
$250.00 
Completion of Day -2 : 
$250.00 
Completion of Day -1 : 
$250.00 
Completion of Day 1: 
$250.00 
Completion of Day 2: 
$250.00 
Completion of Day 3: 
$250.00 
Completion of Day 4: 
$250.00 
Completion of Day 5: 
$250.00 
Completion of Day 6: 
$125.00 
Completion of Day 8: 
$125.00 
Completion of Day 10: $125.00 
Completion of Day 12:        $125.00 
Total: $3625.00 
 
Schedule of payments: 
 
• 
1st payment of $ 2000.00 within 7 days of Day 6 completion 
• 
2nd payment of $ 1625.00 within 7 days of Day 12 completion 
 
If you choose to leave or are withdrawn from the study for any reason, you will receive payment within 7 
days of your last study visit. 
 
If you are requested to complete any unscheduled visits due to a side effect or safety follow up, you will 
receive $50.00 each additional visit for your time and travel. 
 
In addition, you will be asked to read and sign a document entitled “Site Guidelines” which outlines 
penalties for certain violations of the rules for when you are staying at the clinic. 
 
In agreeing to take part in this study, you will be acting as an independent contractor, not as an employee 
of Orlando Clinical Research Center. Payments made to you for taking part in this study will be reported to 
the IRS as income, as required by law. No taxes are deducted from your check. You are responsible for 
reporting this compensation on state and federal tax returns and for the payment of any taxes that are due 
on this compensation. You will be required to provide your Social Security number or tax identification 
number to Orlando Clinical Research Center. If you get more than $600.00 in one calendar year from 
Orlando Clinical Research Center, you will get a 1099 tax form the following January. 


Protocol number: 3G3-18-02 
Informed Consent 
Thomas C. Marbury, M.D. 
Page 14 of 20 
APPROVED BY 
INTEGREVIEW IRB 
JUNE 20, 2018 
 
 
IN CASE OF STUDY RELATED INJURY 
 
It is important that you follow carefully all the instructions given by the study doctor and his/her staff 
regarding this study. 
 
If you become ill or are physically injured as a result of participation in this study, please contact the study 
doctor right away and you will be treated or referred for treatment. 
 
The sponsor Aronora, Inc., will pay the costs of this treatment to the extent that such treatment is not paid 
by your medical insurance or by third party or governmental programs. For this to happen, the injury, in the 
opinion of the study doctor and the sponsor must be confirmed to have been a direct result of your 
participation in this study in accordance with the study directions. No other financial compensation will be 
offered by the sponsor. No long-term medical care or financial compensation for research-related injuries 
will be provided by the NIH or the Federal Government. If you would like further information about 
compensation for research-related injuries, please ask the study doctor. 
 
Please be aware that some insurance plans may not pay for research-related injuries. You should contact 
your insurance company for more information. 
 
LEGAL RIGHTS 
 
You will not lose any of your legal rights to which you are otherwise entitled by signing this consent form. 
 
CONTACT INFORMATION 
 
If you have any questions, concerns, or complaints during this study, or if you think you may have 
experienced a research-related injury, you should contact the study doctor or study staff: 
 
Thomas C. Marbury, M.D. 
(407) 240-7878, 24-hours a day 
 
If you are unable to reach anyone at the number(s) listed above and you require immediate (life 
threatening) medical attention, please go to the nearest emergency room. 
 
If you do not want to talk to the study doctor or study staff, if you have concerns or complaints about the 
research, or to ask questions about your rights as a study subject you may contact IntegReview. 
IntegReview’s policy indicates that all concerns/complaints are to be submitted in writing for review at a 
convened IRB meeting to: 
 
Mailing Address: 
OR 
Email Address: 
Chairperson 
IntegReview IRB 
3815 S. Capital Of Texas Highway 
Suite 320 
Austin, Texas 78704 
integreview@integreview.com 
 
 
 
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Protocol number: 3G3-18-02 
Informed Consent 
Thomas C. Marbury, M.D. 
Page 15 of 20 
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JUNE 20, 2018 
 
 
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If you are unable to provide your concerns/complaints in writing or if this is an emergency situation 
regarding subject safety, contact our office at: 
 
512-326-3001 or 
toll free at 1-877-562-1589 
between 8 a.m. and 5 p.m. Central Time 
 
IntegReview has approved the information in this consent form and has given approval for the study doctor 
to do the study. This does not mean IntegReview has approved your being in the study. You must consider 
the information in this consent form for yourself and decide if you want to be in this study. 
 
CONFIDENTIALITY AND AUTHORIZATION TO COLLECT, USE AND DISCLOSE 
PERSONAL MEDICAL INFORMATION 
 
A federal regulation called the “Health Insurance Portability and Accountability Act” (HIPAA) describes 
how protected health information (PHI) may be used, disclosed (shared), and made accessible to you. This 
privacy rule is designed to protect the confidentiality of PHI. Please read this form carefully as it describes 
your rights regarding the use or disclosure of your PHI under this authorization. 
 
You are being asked to allow the use of your PHI because this study may be performed only by collecting 
and using this information. Your study records will be kept confidential as described in this form. Unless 
required by law, your name will not be disclosed outside the research clinic. Your name will be available 
only to the following people or agencies: the study doctor and staff; and authorized representatives of the 
study doctor; the sponsor and its affiliates and people or companies working for or with the sponsor, ethics 
committees (IRB), health authority inspectors, such as the US Food & Drug Administration; NIHLB and 
their contractors, study monitors and auditors; Emergency medical personnel and Authorized Clinical 
Research Organization representatives. The above mentioned individuals will use the personal information 
collected as part of this study, including your medical records (“Study Information”) to check that the study 
is conducted correctly and to ensure the accuracy of the Study Information. These people are all obligated 
to maintain confidentiality by the nature of their work, or are bound by confidentiality agreements. If 
required, the Study Doctor may contact your personal physician to collect additional medical information 
and your past medical history. 
 
The sponsor and the groups above will use your health information: 
 
• 
to complete this research 
• 
to evaluate the results of the study 
• 
to check that the study is being done properly 
• 
to obtain marketing approval for new products resulting from this research 
• 
The sponsor and its affiliated companies may also use and disclose your de-identified records and health 
information collected for this study to conduct additional clinical or data research studies or to develop 
proposals for new studies or to improve the design and efficiency of future research studies. 
 
The study doctor may only share your Study Information with people whom you have permitted to see it. 
However, once your Study Information is shared as authorized, it may no longer be protected by Federal or 
state law and may be re-disclosed without your permission. 


Protocol number: 3G3-18-02 
Informed Consent 
Thomas C. Marbury, M.D. 
Page 16 of 20 
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JUNE 20, 2018 
 
 
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While participating in this study, the study doctor will replace your name with a special code that identifies 
you. This code, along with your study information, will be used by the study sponsor, and their 
representatives (the “Sponsor”), for the study purposes mentioned above and to help establish whether the 
study drug is safe and effective. The sponsor may share your coded information, as necessary, with other 
members of the Sponsor’s worldwide group of related companies, people and companies who work with 
the sponsor and who work within the scope of this consent ethics committees and regulatory agencies such 
as the US Food & Drug Administration, the national health authorities. 
 
In addition, if you withdraw from this study, you have the right to request of your study doctor that your 
blood samples be destroyed. If you request that your samples be destroyed, all data generated up to the time 
of the request will be used for the study, but no other additional data will be generated from your samples. 
The Sponsor is responsible for the destruction of remaining samples at the end of the storage period. 
 
The people, companies, and agencies listed above that have access to your information may be located in 
countries of the European Economic Area (EEA); the United States; and other countries around the world. 
You should be aware that some countries may not offer the same level of privacy protection as you are used 
to in the country where you live or where this study is conducted. However, the sponsor will keep any 
information it receives to the same standard of confidentiality as far as permitted by applicable local law. 
 
The study information will be kept confidential within the limits of the law and used only for this study as 
well as combined with other studies as applicable, for pooled analysis and interpretation needed for any 
regulatory submissions linked to this compound. If the results of this study are published or presented in a 
meeting, you will not be named and nobody will be able to tell that you were in the study from the 
publication or presentation. 
 
Your participation in this study is voluntary and you may cancel this consent at any time and without any 
reason and will not involve any penalty or loss of access to treatment or other benefits to which you are 
entitled. If you withdraw your permission, no new health information will be gathered unless you have a 
side effect related to the study. 
 
If you withdraw from the study but do not withdraw your Authorization, new health information may be 
collected until this study ends. This Authorization will not expire unless revoked. To revoke your 
Authorization, you must write to the study doctor, stating that you are revoking your Authorization to Use 
and Disclose Protected Health Information at: 
 
Thomas C. Marbury, M.D. 
Orlando Clinical Research Center 
5055 S. Orange Avenue 
Orlando, FL 32809 
 
The sponsor will continue to retain and use all research results that have already been collected for the study 
evaluation. All biological samples that have already been collected may be retained and analyzed at a later 
date (as per local regulations). 


Protocol number: 3G3-18-02 
Informed Consent 
Thomas C. Marbury, M.D. 
Page 17 of 20 
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JUNE 20, 2018 
 
 
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You have the right to review your Study Information and medical records and request changes to the Study 
Information if it is not correct. However, please note that during the study, access to Study Information may 
be limited if it weakens the integrity of the research. You may have access to the Study Information held 
by the Study Doctor at the end of the study. 
 
If you have any questions about the collection and use of information about you, or would like to exercise 
rights that you may have regarding this information, you should ask your Study Doctor. 
 
THE REASON FOR INSTITUTIONAL REVIEW BOARDS AND INFORMED CONSENT 
 
What is a consent form? 
The informed consent document contains information required by federal regulations. The informed 
consent document must be approved by an Institutional Review Board (IRB). 
 
What is an Institutional Review Board (IRB)? 
An Institutional Review Board (IRB) is a group of people that reviews research studies. The main goal of 
this review is to protect the rights and well-being of the human subjects participating in research studies. 
 
IntegReview, the IRB for this study 
IntegReview is an IRB whose board members provide IRB services across the United States, Japan, and 
Latin America. 
 
To meet requirements of the law, the IntegReview Boards currently include: 
 
• 
Doctors 
• 
Pharmacists 
• 
Nurses 
• 
Toxicologists (people who study the harmful effects of chemicals) 
• 
Other specialists 
• 
Others who do not have a background in science/medicine 


Protocol number: 3G3-18-02 
Informed Consent 
Thomas C. Marbury, M.D. 
Page 18 of 20 
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PRIMARY CARE PHYSICIAN NOTIFICATION 
 
If you agree, your primary care physician will be informed of your participation in the study. Indicate 
your choice by initialing only one (1) section below. 
 
 
Initials 
I do not have a primary care physician 
  
 
Initials 
I do not want my primary care physician notified 
  
 
Initials 
I would like my primary care physician notified and below is my physician’s contact 
information. 
Physician’s Name:   
 
Address:   
 
Phone No.:   
 


Protocol number: 3G3-18-02 
Informed Consent 
Thomas C. Marbury, M.D. 
Page 19 of 20 
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AGREEMENT TO BE IN THE STUDY 
 
This consent form contains important information to help you decide if you want to be in the study. If you 
have any questions that are not answered in this consent form, ask one of the study staff. 
 
Please answer YES or NO to the following questions: 
 
A. 
Is this document in a language you understand? 
B. 
Do you understand the information in this consent form? 
 
 
C. 
Have you been given enough time to ask questions and talk about the study? 
 
 
D. 
Have all of your questions been answered to your satisfaction? 
 
 
E. 
Do you think you received enough information about the study? 
 
 
F. 
Do you volunteer to be in this study of your own free will and without being 
pressured by the investigator or study staff? 
 
 
G. 
Do you know that you can leave the study at any time without giving 
a reason and without affecting your health care? 
 
 
H. 
Do you know that your health records from this study may be reviewed 
by the sponsor company and by government authorities? 
 
 
I. 
Do you know that you cannot be in another study while you are in this study? 
 
 
J. 
Do you authorize the use and disclosure of your medical information? 
 
 
 
IF YOU ANSWERED “NO” TO ANY OF THE ABOVE QUESTIONS, 
OR YOU ARE UNABLE TO ANSWER ANY OF THE ABOVE QUESTIONS, 
YOU SHOULD NOT SIGN THIS CONSENT FORM. 
 
 
Printed Name of Adult Study Subject 
 
 
Signature of Adult Study Subject 
Date 
 
 
Printed Name of Person Explaining Consent Form 
 
 
Signature of Person Explaining Consent Form 
Date 
 
You will be given a signed and dated copy of this informed consent to keep. 


Protocol number: 3G3-18-02 
Informed Consent 
Thomas C. Marbury, M.D. 
Page 20 of 20 
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CONSENT FOR SUBJECTS WHO ARE VISUALLY IMPAIRED 
 
The study subject has indicated that he/she is visually impaired. The consent document has been read to the 
subject by a member of the study staff, discussed with the subject by a member of the study staff, and the 
subject has been given an opportunity to ask questions of the study staff. 
 
 
Printed Name of Impartial Witness 
 
 
Signature of Impartial Witness* 
Date 
 
*Impartial Witness: A person, who is independent of the study, who cannot be unfairly influenced by people 
involved with the study, who attends the informed consent process if the subject cannot read, and who reads 
the informed consent and any other written information provided to the subject. 
 
You will receive a signed and dated copy of this consent form to keep. 


M Denotes regular Monday board members T Denotes regular Tuesday board members W Denotes regular Wednesday board members Th Denotes regular Thursday board members 
F Denotes regular Friday board members Other members are alternates All regular Board members can serve as alternates on other Boards as specified by their positions (e.g. Scientific for Scientific) 
Non-scientific members represent the general perspective of study participants 
Note: In addition to our regular members, we have access to specialists in therapeutic areas not represented on this roster. 
Page 1 of 5 
 
 
 
MEMBERSHIP ROSTER 
As of February 19, 2018 
 
Sponsor Name: Aronora, Inc. 
Protocol Number: 3G3-18-02 
Principal Investigator Name: Thomas C. Marbury, M.D. 
Meeting Date: June 20, 2018 
C Denotes consultants (non-voting) assisting in the review of the study when the knowledge and expertise in a particular therapeutic area is not available among the 
voting members 
A Denotes members abstaining from the vote 
Denotes (voting) members who were in attendance at the meeting and reviewed the study information 
 
 
NAME 
DEGREES/ 
CERTS. 
BOARD 
POSITION 
EXPERIENCE 
AFFILIATION 
WITH IRB 
ALTERNATE 
FOR 
 
M M. Alexander Kenaston, 
Chairman 
Ph.D., M.S. 
(Toxicology), 
R.N., CIP 
Scientific 
Toxicology Research Scientist, representative for 
first time in human studies, Pharmacology/ 
Toxicology, Licensed Registered Nurse; 
previously employed as Project Manager, CRA 
and CRC for CRO 
Non-affiliated 
Paid Consultant 
Scientific members 
 
M Jami Brackeen, Co-chair 
CST, CCRP 
Scientific 
IRB Coordinator, Co-chair, administrative 
support for IntegReview; former Quality Control 
Associate for IRB Regulatory Compliance; 
Certified Surgical Technologist 
Full time Employee 
Scientific members 
 
M Olga Obrda 
B.S. (Chemistry) 
Scientific 
BD Representative; previously employed as 
Project Management and Business Development 
for CRO 
Non-affiliated 
Paid Consultant 
Scientific members 


M Denotes regular Monday board members T Denotes regular Tuesday board members W Denotes regular Wednesday board members Th Denotes regular Thursday board members 
F Denotes regular Friday board members Other members are alternates All regular Board members can serve as alternates on other Boards as specified by their positions (e.g. Scientific for Scientific) 
Non-scientific members represent the general perspective of study participants 
Note: In addition to our regular members, we have access to specialists in therapeutic areas not represented on this roster. 
Page 2 of 5 
 
 
 
 
Sponsor Name: Aronora, Inc. 
Protocol Number: 3G3-18-02 
Principal Investigator Name: Thomas C. Marbury, M.D. 
Meeting Date: June 20, 2018 
 
 
NAME 
DEGREES/ 
CERTS. 
BOARD 
POSITION 
EXPERIENCE 
AFFILIATION 
WITH IRB 
ALTERNATE 
FOR 
 
M Bryson Michael Duhon 
Pharm.D., BCPS 
Scientific 
Clinical Assistant Professor UT College of 
Pharmacy; Adjoint Professor at UT Health 
Science Center (UTHSCSA) Department of 
Medicine 
Non-affiliated 
Paid Consultant 
Scientific members 
 
M Ashley Hutson 
Non- 
scientific 
Previously volunteered as research subject in 
clinical trials; homemaker 
Non-affiliated 
Paid Consultant 
Non-scientific 
members 
 
M Karen Haslund 
M.D. 
Scientific 
Licensed physician, Pediatrics 
Non-affiliated 
Paid Consultant 
Scientific members 
 
T Charles F. Ryan, Chairman 
Ph.D., M.S. 
Scientific 
Representative for first time in human studies; 
Pharmacology, Toxicology, Radiation Safety, 
Radioisotope, Nutritional/Food supplements and 
Medical Foods 
Non-affiliated 
Scientific members 
(Pharmacology & 
Paid Consultant 
Toxicology), 
R.Ph. 
 
T Tonya Reed, Co-chair 
Non- 
scientific 
IRB Coordinator, administrative support for 
IntegReview; previously employed as a Project 
Assistant for CRO 
Full time Employee 
Non-scientific 
members 
 
T Sara Bartos 
M.D. 
Scientific 
Licensed physician, Internal Medicine 
Non-affiliated 
Paid Consultant 
Scientific members 
 
T Marcy Goodfleisch 
B.S., M.A. (Liberal 
Studies); Mediator 
(Civil & Family 
Non- 
scientific 
Adjunct University Professor; Ethicist; Management 
& Communication Consultant. Former Clinic 
Administrator for nationally recognized HIV Clinic 
and large FQHC community health center. 
Non-affiliated 
Paid Consultant 
Non-scientific 
members 
Dispute Resolution); 
Graduate work in 
Communications 
and English 


M Denotes regular Monday board members T Denotes regular Tuesday board members W Denotes regular Wednesday board members Th Denotes regular Thursday board members 
F Denotes regular Friday board members Other members are alternates All regular Board members can serve as alternates on other Boards as specified by their positions (e.g. Scientific for Scientific) 
Non-scientific members represent the general perspective of study participants 
Note: In addition to our regular members, we have access to specialists in therapeutic areas not represented on this roster. 
Page 3 of 5 
 
 
 
 
NAME 
DEGREES/ 
CERTS. 
BOARD 
POSITION 
EXPERIENCE 
AFFILIATION 
WITH IRB 
ALTERNATE 
FOR 
 
T Michael D. Aldridge 
Ph.D. (Nursing 
Education), R.N., 
CNE 
Scientific 
Assistant Professor of Nursing; previously 
employed in various Nursing roles for pediatric 
intensive care unit, including Specialty Education 
Coordinator for pediatric ICU, previous experience 
as an IRB member 
Non-affiliated 
Paid Consultant 
Scientific members 
 
T Christine du Castel 
M.D. 
Scientific 
Medical Advisor; previously licensed to practice 
General Medicine in France 
Non-affiliated 
Paid Consultant 
Scientific members 
 
W Carolyn Hensler, 
Chairman 
B.S. (Physical 
Education) 
Scientific 
Quality Assurance and Quality Control 
Administrator for CRO; previously employed as a 
Clinical Research Monitor; and Project Manager 
Non-affiliated 
Paid Consultant 
Scientific members 
 
W Angelica Martinez, Co- 
Chair 
CCRP 
Non- 
scientific 
IRB Coordinator, administrative support for 
IntegReview 
Full time Employee 
Non-scientific 
members 
 
W Raymond Carr 
R.Ph. 
Scientific 
Staff Pharmacist 
Non-affiliated 
Paid Consultant 
Scientific members 
 
W Christopher P. Martin 
Pharm.D., M.S., 
BCPS 
Scientific 
Clinical Assistant Professor, Division of 
Pharmacotherapy UT; Clinical Pharmacy 
Coordinator; Assistant Professor University of 
Oklahoma Health Sciences Center, College of 
Pharmacy 
Non-affiliated 
Paid Consultant 
Scientific members 
 
W Robert A. Blum 
Pharm.D. 
Scientific 
Various experience as a principal investigator for 
research studies 
Non-affiliated 
Paid Consultant 
Scientific members 
 
W William K. Rawlinson 
M.D., FCCP, 
FAASM 
Scientific 
Licensed physician, Pulmonary, Critical Care and 
Internal Medicine 
Non-affiliated 
Paid Consultant 
Scientific member 
 
Th Frederick Kopec, 
Chairman 
J.D., B.A. 
(Philosophy) 
Non- 
scientific 
Licensed, Practice of Law, Ethicist 
Non-affiliated 
Paid Consultant 
Non-scientific 
members 


M Denotes regular Monday board members T Denotes regular Tuesday board members W Denotes regular Wednesday board members Th Denotes regular Thursday board members 
F Denotes regular Friday board members Other members are alternates All regular Board members can serve as alternates on other Boards as specified by their positions (e.g. Scientific for Scientific) 
Non-scientific members represent the general perspective of study participants 
Note: In addition to our regular members, we have access to specialists in therapeutic areas not represented on this roster. 
Page 4 of 5 
 
 
 
 
NAME 
DEGREES/ 
CERTS. 
BOARD 
POSITION 
EXPERIENCE 
AFFILIATION 
WITH IRB 
ALTERNATE 
FOR 
 
Th Bridget Briseno, Co-chair 
Non- 
scientific 
IRB Coordinator, administrative support for 
IntegReview 
Full time Employee 
Non-scientific 
members 
 
Th Michael Romain 
M.D. 
Scientific 
Licensed physician, Internal Medicine 
Non-affiliated 
Paid Consultant 
Scientific members 
 
Th Mary O’Connell 
Scientific 
Quality & Regulatory Affairs Manager; previously 
employed as Clinical Research Recruiter, Data 
Associate, Coordinator and QC Auditor for CRO, 
IRB Administrator, Emergency Medical Technician 
Paramedic 
Non-affiliated 
Paid Consultant 
Scientific members 
 
Th Matthew Pfeiffer 
Ph.D. 
(Pharmacology & 
Toxicology) 
Scientific 
Project Manager and CRA for CRO; Representative 
for first in human studies; clinical and research 
experience; Pharmacology, Toxicology, CNS, 
Infectious disease, Metabolic/Endocrine Disorders, 
Oncology 
Non-affiliated 
Paid Consultant 
Scientific members 
 
Th Susan Parker Ginnings 
R.Ph. 
Scientific 
Previously employed as Hospital Pharmacy 
Supervisor 
Non-affiliated 
Paid Consultant 
Scientific members 
 
F Mary Ruwart, Chairman 
Ph.D. 
(Biophysics); 
B.S. 
(Biochemistry) 
Scientific 
Research Scientist, Drug Delivery Systems, 
Diabetes, GI Diseases, Drug Metabolism 
Non-affiliated 
Paid Consultant 
Scientific members 
 
F Francine Lopez, Co-chair 
B.S., CCRP 
Non- 
scientific 
IRB Coordinator, administrative support for 
IntegReview 
Full time Employee 
Non-scientific 
members 
 
F Laurajo Ryan 
Pharm.D., MSc 
(Clinical 
Investigations), 
BCPS, CDE 
Scientific 
Clinical Associate Professor of Pharmacotherapy 
UT Austin, Department of Medicine UTHSCSA, 
Clinical Pharmacist Specialist South Texas Veterans 
Administration 
Non-affiliated 
Paid Consultant 
Scientific members 


M Denotes regular Monday board members T Denotes regular Tuesday board members W Denotes regular Wednesday board members Th Denotes regular Thursday board members 
F Denotes regular Friday board members Other members are alternates All regular Board members can serve as alternates on other Boards as specified by their positions (e.g. Scientific for Scientific) 
Non-scientific members represent the general perspective of study participants 
Note: In addition to our regular members, we have access to specialists in therapeutic areas not represented on this roster. 
Page 5 of 5 
 
 
 
 
NAME 
DEGREES/ 
CERTS. 
BOARD 
POSITION 
EXPERIENCE 
AFFILIATION 
WITH IRB 
ALTERNATE 
FOR 
 
F Dennis Brannon 
R.Ph., B.S. 
(Animal Science) 
Scientific 
Clinical Research Consultant, Director of Pharmacy; 
Executive Director Clinical Development; 
previously employed as Senior Project Manager and 
CRA for CRO 
Non-affiliated 
Paid Consultant 
Scientific members 
 
F Bennie C. Lopez 
MBA 
Non- 
scientific 
Representative for adult and juvenile prisoner 
population; Teacher with Austin ISD Alternative 
Learning Center; previously employed as 
Corrections Officer and retired military 
Non-affiliated 
Paid Consultant 
Non-scientific 
members 
 
F Patricia M. Houser 
M.D. 
Scientific 
Licensed physician; Family practice 
Non-affiliated 
Paid Consultant 
Scientific members 
 
Victoria Govea 
CCRP 
Non- 
scientific 
Management support for IntegReview; former IRB 
Coordinator, Co-chair for IntegReview 
Full time Employee 
Non-scientific 
members 
 
Lynn Goldman 
B.S. (Nutrition), 
MSHP 
(Healthcare 
Administration), 
RD, LD, CCRP 
Scientific 
Management support for IntegReview; former IRB 
Coordinator, Co-chair; previously employed as 
Research Coordinator, Health Care Administration 
and Education, Clinical Nutrition, Registered 
Dietician/Certified Pediatric Nutrition Specialist 
Full time Employee 
Scientific members 
 
Christina H. Walker 
M.D., B.S. 
Scientific 
Physician 
Non-affiliated 
Paid Consultant 
Scientific members 
 
Rosa S. Sandoval 
B.S. (Chemistry), 
CCRP 
Scientific 
IRB Operations Supervisor; Former Senior IRB 
Coordinator, Co-chair and administrative support for 
IntegReview; previously employed as Clinical 
Research 
Coordinator 
and 
Medical 
Research 
Assistant for University 
Full time Employee 
Scientific members 
 
Levi Machado 
CCRP 
Non- 
scientific 
IRB 
Training 
Administrator; 
former 
IRB 
Coordinator, 
Co-chair; 
previously 
provided 
administrative support for IntegReview 
Full time Employee 
Non-scientific 
members 
 

Prot_000.pdf: 
 
Page 1 
  
 
 
 
Clinical Protocol 
 
 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and 
Efficacy/Potency of a Single Dose of Xisomab 3G3, Administered at the Beginning of a 
Regular Hemodialysis Procedure, in Patients with End-Stage Renal Disease on Chronic 
Hemodialysis 
 
 
 
Celerion Project No.: CA23900  
 
 
Sponsor Project No.: 3G3-18-02 
 
 
US IND No.: 127850 
 
 
 
 
 
 
 
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. 
 


CONFIDENTIAL  
CA23900 (3G3-18-02), Final Protocol Amendment 1 14June2018 
 
Page 2 
1 
PROTOCOL REVISION HISTORY 
Date/Name 
Description 
14June2018 
by Natacha Benrimoh 
Final Protocol, Amendment 1 
Following review by the Institutional Review Board, this protocol 
is being amended to provide justification for the use of a 
placebo-control design. In addition, information on safety 
measures that will be undertaken by the Investigators should there 
be clotting in the extracorporeal circuit has been added. 
Thus, Section 8.4.1 Rationale for this Study and Study Design, 
Section 8.5 Risks and/or Benefits to Patients, and 
Section 11.3 Early Termination of Patients from the Study were 
updated. Section 13.3 Hemodialysis Procedure and Blood Clots in 
the Dialyzer Cartridge was created. 
In addition, the following changes were made: 
- 
Section 11.2 Exclusion criteria, criterion 2 was updated 
(changes in strikethrough and additions in bold): “With the 
exception of unfractionated heparin during HD, 
Cconcomitant or prior use of anticoagulant/antiplatelet agents 
(e.g., low molecular weight heparins, warfarin, apixaban, 
bivalirudin, ticagrelor, edoxaban, dabigatran, rivaroxaban, 
clopidogrel, prasugrel, ticlopidine, eptifibatide, tirofiban, 
dipyridamole, diclofenac, and all other NSAIDs) that may 
affect hemostasis for 2 weeks prior to check-in on Day -8 and 
throughout the study.” 
- 
Section 11.2 Exclusion criteria, criterion 3 was updated 
(changes in strikethrough and additions in bold): “Use of 
unfractionated heparin for HD sessions from check-in on 
Day -8 and throughout the study.” 
- 
Section 11.2 Exclusion criteria, criterion 9: The value for 
hemoglobin concentration at screening was increased from 
8.5 g/dL to 10 g/dL. The hemoglobin limit was increased to 
allow for the possibility of blood loss of up to 228 mL if there 
is a clot in the dialyzer circuit. Also, the 5 other clinical 
laboratory values had no specific timing on when these values 
were required; thus, “at screening” was added for these clinical 
laboratory tests. 
- 
Section 13.6 Dialysate Analysis; this section was added as 
samples of the dialysate will be taken for future analysis (e.g., 
assessment of urea or drug level in the dialysate). Samples will 
be stored for up to 5 years). 


CONFIDENTIAL  
CA23900 (3G3-18-02), Final Protocol Amendment 1 14June2018 
 
Page 3 
- 
Section 13.7.1 Blood Sampling and Processing, wording was 
added that leftover samples would be stored for up to 5 years. 
Updates in blood volume (i.e., correction in number of samples 
were made increasing the total blood volume by about 5 mL (from 
430 mL to 435.9 mL) 
Minor editorial, consistency, and formatting updates were made 
throughout the protocol. 
25May2018  
by Natacha Benrimoh 
Final Protocol  
 
 


CONFIDENTIAL  
CA23900 (3G3-18-02), Final Protocol Amendment 1 14June2018 
 
Page 4 
2 
PRINCIPAL INVESTIGATOR AND SPONSOR – SIGNATORIES 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and 
Efficacy/Potency of a Single Dose of Xisomab 3G3, Administered at the Beginning of a 
Regular Hemodialysis Procedure, in Patients with End-Stage Renal Disease on Chronic 
Hemodialysis 
 
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 
Tel.: +1 503 964-0250 
E-mail: christina.lorentz@aronorabio.com 
 
 
 
 
 
Signature 
 Date 
PRINCIPAL INVESTIGATORS AND CLINICAL SITES: 
 
 
 
 
 
 
Signature 
Printed Name:  
 Date 
 
 
 
 
Signature 
Printed Name:  
 Date 


CONFIDENTIAL  
CA23900 (3G3-18-02), Final Protocol Amendment 1 14June2018 
 
Page 5 
3 
ADDITIONAL KEY CONTACTS FOR THE STUDY 
Sponsor Contact for Serious Adverse Event 
Reporting 
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 
Mobile: +1 503 442-1213 
E-mail: andras.gruber@aronorabio.com 
 
Protocol Author 
Natacha Benrimoh, M.Sc.  
Associate Director 
Celerion 
100 Alexis-Nihon Boulevard, Suite 360 
Montreal, Quebec H4M 2N8, Canada 
Tel.: +1 514 744-8742 
Fax: +1 514 744-8700 
E-mail: natacha.benrimoh@celerion.com 
 
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: +1 402 939-0428 
 
 


CONFIDENTIAL  
CA23900 (3G3-18-02), Final Protocol Amendment 1 14June2018 
 
Page 6 
4 
TABLE OF CONTENTS 
1 PROTOCOL REVISION HISTORY ............................................................................. 2 
2 PRINCIPAL INVESTIGATOR AND SPONSOR – SIGNATORIES ......................... 4 
3 ADDITIONAL KEY CONTACTS FOR THE STUDY ................................................ 5 
4 TABLE OF CONTENTS ................................................................................................. 6 
5 SYNOPSIS ......................................................................................................................... 9 
6 STUDY EVENTS FLOW CHART ............................................................................... 12 
7 ABBREVIATIONS ......................................................................................................... 16 
8 INTRODUCTION........................................................................................................... 19 
8.1 
Background ............................................................................................................. 19 
8.2 
Nonclinical Studies ................................................................................................. 20 
8.2.1 
Pharmacology ........................................................................................... 20 
8.2.2 
Pharmacokinetics ...................................................................................... 20 
8.2.3 
Toxicology ................................................................................................ 21 
8.3 
Clinical Studies ....................................................................................................... 21 
8.3.1 
Safety Data ................................................................................................ 22 
8.3.2 
Pharmacokinetics and Pharmacodynamics Data ...................................... 22 
8.4 
Rationale .................................................................................................................. 25 
8.4.1 
Rationale for this Study and Study Design ............................................... 25 
8.4.2 
Rationale for the Dose Selection ............................................................... 26 
8.5 
Risks and/or Benefits to Patients ............................................................................. 27 
9 OBJECTIVES AND ENDPOINTS ............................................................................... 28 
9.1 
Objectives ................................................................................................................ 28 
9.2 
Endpoints ................................................................................................................. 28 
10 STUDY DESIGN ............................................................................................................. 29 
10.1 Overall Study Design and Plan ............................................................................... 29 
10.1.1 
Confinement and Follow-Up .................................................................... 30 
10.1.2 
End of Study Definition ............................................................................ 30 
11 STUDY POPULATION ................................................................................................. 31 
11.1 Inclusion Criteria ..................................................................................................... 31 
11.2 Exclusion Criteria .................................................................................................... 32 
11.3 Early Termination of Patients from the Study ........................................................ 34 
11.4 Study Restrictions ................................................................................................... 35 
11.4.1 
Prohibitions and Concomitant Medication ............................................... 35 
11.4.2 
Meals ......................................................................................................... 35 


CONFIDENTIAL  
CA23900 (3G3-18-02), Final Protocol Amendment 1 14June2018 
 
Page 7 
11.4.3 
Activity ..................................................................................................... 35 
12 TREATMENTS............................................................................................................... 36 
12.1 Treatments Administered ........................................................................................ 36 
12.2 Dose Modification ................................................................................................... 36 
12.3 Method of Assigning Patients to Treatment Groups ............................................... 37 
12.4 Blinding ................................................................................................................... 37 
12.4.1 
Maintenance of Randomization ................................................................ 37 
12.4.2 
Procedures for Breaking the Blind Prior to Study Completion ................ 37 
12.4.3 
Revealing of Randomization..................................................................... 38 
12.5 Treatment Compliance ............................................................................................ 38 
13 STUDY ASSESSMENTS AND PROCEDURES ......................................................... 39 
13.1 Screening ................................................................................................................. 39 
13.2 Safety and Tolerability Assessments ....................................................................... 39 
13.2.1 
Physical Examination................................................................................ 39 
13.2.2 
Vital Signs ................................................................................................. 40 
13.2.3 
ECG Monitoring ....................................................................................... 40 
13.2.4 
Body Weight ............................................................................................. 40 
13.2.5 
Vascular Access Site Reaction Assessment .............................................. 40 
13.2.6 
Bleeding of Access Site ............................................................................ 41 
13.2.7 
Clinical Laboratory Tests .......................................................................... 42 
13.2.8 
Adverse Events ......................................................................................... 43 
13.2.8.1 Adverse Event Definition ......................................................... 43 
13.2.8.2 Monitoring ............................................................................... 43 
13.2.8.3 Reporting .................................................................................. 43 
13.2.8.4 Serious Adverse Event ............................................................. 45 
13.3 Hemodialysis Procedure and Blood Clots in the Dialyzer Cartridge ...................... 45 
13.4 Immunogenicity Assessment ................................................................................... 46 
13.5 Pharmacodynamic Assessments .............................................................................. 46 
13.6 Dialysate Analysis ................................................................................................... 47 
13.7 Pharmacokinetic Assessments ................................................................................. 47 
13.7.1 
Blood Sampling and Processing ............................................................... 47 
13.7.2 
Plasma Pharmacokinetic Parameters ........................................................ 47 
13.7.3 
Analytical Method .................................................................................... 48 
13.8 Blood Volume Drawn for Study Assessments ........................................................ 49 
14 STATISTICAL CONSIDERATIONS .......................................................................... 50 
14.1 Sample Size Determination ..................................................................................... 50 
14.2 Population for Analyses .......................................................................................... 50 


CONFIDENTIAL  
CA23900 (3G3-18-02), Final Protocol Amendment 1 14June2018 
 
Page 8 
14.3 Statistical Analyses ................................................................................................. 50 
14.3.1 
Safety and Tolerability Analyses .............................................................. 50 
14.3.2 
Immunogenicity Analyses ........................................................................ 51 
14.3.3 
Pharmacodynamic Analyses ..................................................................... 51 
14.3.4 
Pharmacokinetic Analyses ........................................................................ 52 
15 STUDY ADMINISTRATION........................................................................................ 53 
15.1 Ethics ....................................................................................................................... 53 
15.1.1 
Institutional Review Board ....................................................................... 53 
15.1.2 
Ethical Conduct of the Study .................................................................... 53 
15.1.3 
Patient Information and Consent .............................................................. 53 
15.2 Termination of the Study ......................................................................................... 53 
15.3 Data Quality Assurance ........................................................................................... 53 
15.4 Direct Access to Source Data/Documents .............................................................. 54 
15.5 Drug Supplies, Packaging and Labeling ................................................................. 54 
15.6 Data Handling and Record Keeping ........................................................................ 54 
15.7 Report Format ......................................................................................................... 55 
15.8 Protocol Amendments ............................................................................................. 55 
15.9 Publication Policy ................................................................................................... 55 
16 REFERENCES ................................................................................................................ 56 
 
LIST OF FIGURES 
Figure 1: 
Mean Concentration Profile ........................................................................... 23 
Figure 2: 
Mean aPTT Profile Over Time ...................................................................... 24 
 
LIST OF TABLES 
Table 1: 
Key PK Parameters ........................................................................................ 23 
Table 2: 
Cohort and Treatment Randomization ........................................................... 29 
Table 3: 
Identity of Investigational Products ............................................................... 36 
Table 4: 
Blood Volume during the Study .................................................................... 49 
 


CONFIDENTIAL  
CA23900 (3G3-18-02), Final Protocol Amendment 1 14June2018 
 
Page 9 
5 
SYNOPSIS 
Compound: 
xisomab 3G3 (anti-factor [F] XI 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 or treatment of thrombotic and thromboembolic 
diseases 
Study Phase: 
Phase 2 
Study Objectives: 
The primary objective of this study is: 
• To assess the safety and tolerability of a single dose of 
xisomab 3G3 when injected through a port into the proximal 
(arterial) dialysis line immediately after initiation of a 
hemodialysis (HD) procedure in patients with end stage renal 
disease (ESRD). 
The secondary objectives of this study are: 
• To assess the pharmacodynamics (PD) of a single dose of 
xisomab 3G3 when injected through a port into the proximal 
(arterial) dialysis line immediately after initiation of a HD 
procedure in patients with ESRD. 
• To assess the efficacy of a single dose of xisomab 3G3 on HD 
efficiency when injected through a port into the proximal 
(arterial) dialysis line immediately after initiation of a HD 
procedure in patients with ESRD. 
• To assess the pharmacokinetics (PK) of a single dose of 
xisomab 3G3 when injected through a port into the proximal 
(arterial) dialysis line immediately after initiation of a HD 
procedure in patients with ESRD. 
Summary of Study 
Design: 
This is a phase 2, randomized, double-blind, placebo-controlled, 
single-dose study of xisomab 3G3 designed to evaluate the safety, 
efficacy/potency, and PK at 2 dose levels administered to patients 
with ESRD undergoing HD.  
Patients will be enrolled into Cohort 1 or Cohort 2; cohorts will be 
dosed sequentially. Within a cohort, patients will be randomized to 
active drug or placebo as summarized below: 


CONFIDENTIAL  
CA23900 (3G3-18-02), Final Protocol Amendment 1 14June2018 
 
Page 10 
Cohort 
Treatment 
Active:Placebo 
Cohort Size 
1 
Infusion dose of 0.25 mg/kg 
xisomab 3G3 or placebo 
2:1 
9-12 
2 
Infusion dose of 0.5 mg/kg 
xisomab 3G3 or placebo 
2:1 
9-12 
This study includes a screening period of 28 days prior to 
checking-in to the clinical research unit on Day -8.  From Day -7 
(one week prior to dosing on Day 1) through Day -1, all patients 
will undergo HD 3 times and will be assessed for all scheduled 
procedures and endpoints before and after each HD session as per 
the Study Events Flow Chart (Section 6).  
On Study Day 1, prior to dosing, patients will undergo baseline 
measurements followed by initiation of a regular HD procedure, 
consistently using only one type of dialyzer cartridge in each 
patients. Immediately after the start of blood perfusion, a single 
dose of xisomab 3G3 or matching placebo will be injected through 
a port into the flowing arterial blood in the proximal dialysis line. 
Patients will continue to undergo HD procedures and scheduled 
assessments from Day 1 through Day 12.   
Study assessments will include physical examinations, vital signs, 
electrocardiogram (ECGs), clinical laboratory tests, HD vascular 
access site (AV fistula or AV graft) reaction, antibody titer 
(immunogenicity), adverse events (AEs), PD blood sampling 
(coagulation parameters), and PK blood sampling to be performed 
throughout the study according to the Study Events Flow Chart 
(Section 6). On Days -7, -5, and -3 and Days 1, 3, 5, and 12, 
bleeding time from the HD vascular access sites on the AV fistula 
or AV graft (ladder or buttonhole technique) will be evaluated at 
the end of the HD session. The dialyzer cartridge will be rinsed and 
visually inspected at the end of the HD procedure and graded 
against a standardized visual assessment scale. After visual 
assessment, the used and rinsed dialyzer cartridge will be frozen 
and saved for later retained content (deposited blood-derived 
material) analysis. The number of dialyzer cartridges used for the 
HD session will be recorded.  
All patients who received the study drug or placebo (including 
patients who terminate the study early) will undergo follow-up 
procedures at the Clinical Research Unit (CRU) approximately 
12 days after dosing. 
Number of Patients: 
A total of up to 24 adult male and female patients will be enrolled; 
9-12 patients are planned for each cohort. 
In each cohort, an attempt will be made to enroll at least 50% of 
females and at least 30% of a race/ethnicity minority group. An 


CONFIDENTIAL  
CA23900 (3G3-18-02), Final Protocol Amendment 1 14June2018 
 
Page 11 
attempt will also be made to approximately match key 
characteristics, including sex, average age, and weight per cohort. 
Dosage, Dosage 
Form, Route, and 
Dose Regimen: 
On Day 1, patients in each cohort will receive a single dose of 
xisomab 3G3 or placebo injection into the proximal (arterial) 
dialysis line on one occasion. Cohort 1 will be conducted prior to 
initiation of Cohort 2. 
Planned doses will be as follows: 
Cohort 1: 0.25 mg/kg xisomab 3G3 or matching placebo 
Cohort 2: 0.5 mg/kg xisomab 3G3 or matching placebo 
Key Assessments: 
Safety  
Safety assessment will include physical examinations, vital signs, 
ECGs, clinical laboratory tests, vascular access site reaction, 
bleeding time, and AEs.  
Number/severity of AE will be tabulated and summary statistics for 
the 12-lead ECGs, vital signs, and clinical laboratory tests may be 
computed and provided, as deemed clinically appropriate.  
Pharmacodynamics: 
Efficacy/potency assessment will be measured as efficiency of the 
hemodialysis by assessing thrombus accumulation (ranked by 
visual inspection) in the dialyzer cartridge, protein accumulation in 
the HD filter, BUN and potassium blood levels, length of HD, 
measurement of urea removed by 3 hours of dialysis, and total 
dialysate urea (Kt/V and urea reduction ratio [URR)]. Coagulation 
tests will also be performed. 
Change from baseline will be summarized by treatment (2 active 
dose levels and pooled placebo) and per timepoints using 
descriptive statistics.  
Pharmacokinetics: 
The following PK parameters will be calculated for xisomab 3G3 in 
plasma, as appropriate: AUC0-t, AUC0-inf, AUC%extrap, Cmax, 
Tmax, Kel, t½, CL, and Vss. 
PK parameters will be summarized by dose level using descriptive 
statistics. 
Immunogenicity:  
Development of antibodies against the study drug will be evaluated 
by determining the anti-drug antibody (ADA) titer. 
 


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CA23900 (3G3-18-02), Final Protocol Amendment 1 14June 2018 
 
Page 12 
6 
STUDY EVENTS FLOW CHART 
Study Procedures a: 
Screening b: 
(Day -37 to 
Day -9) 
Study Days 
Evaluation Period 
Days → 
-8 
-7 
-6 
-5 
-4 
-3 
HD → 
 
HD d: 
 
HD d: 
 
HD d: 
Hours → 
C-I c: 
start 
end 
 
start 
end 
 
start 
end 
Administrative Procedures 
 
 
 
 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
X 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
Safety Evaluations  
 
 
 
 
 
 
 
 
 
 
Full Physical Examination e: 
X 
X 
 
 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X f: 
X g: 
X 
X f: 
X g: 
X 
X f: 
X g: 
12-Lead Safety ECG  
X 
X 
 
 
 
 
 
 
 
 
Vital Signs (HR, BP, RR, and T)  
X 
X 
X f: 
 
 
X f: 
 
 
X f: 
 
Bleeding of Access Site 
 
 
 
X g:  
 
 
X g: 
 
 
X g: 
Hem, Serum Chem h:, and UA i: 
X 
X 
 
 
 
 
 
 
 
 
Coagulation j:  
X 
 
X f: 
X g: 
 
X f: 
X g: 
 
X f: 
X g: 
Platelet Count s: 
 
 
X f: 
X g: 
 
X f: 
X g: 
 
X f: 
X g: 
Serum Pregnancy Test (♀only) 
X 
X 
 
 
 
 
 
 
 
 
Serum FSH (PMP ♀only)  
X 
 
 
 
 
 
 
 
 
 
Urine/Saliva Drug and Alcohol Screen 
X 
X 
 
 
 
 
 
 
 
 
HIV/Hepatitis Screen 
X 
 
 
 
 
 
 
 
 
 
AE Monitoring 
 
X 
ConMeds Monitoring 
X 
X 
Other Procedures 
 
 
 
 
 
 
 
 
 
 
Blood BUN and Potassium (for Kt/V and 
URR) s: 
 
 
X f: 
X g: 
 
X f: 
X g: 
 
X f: 
X g: 
Dialysate Analysis 
 
 
X k: 
X k: 
 
X k: 
X k: 
 
 
 
Visual Assessment and Processing of 
Dialyzer Membrane 
 
 
 
X l: 
 
 
X l: 
 
 
X l: 
Confinement in the CRU 
 
X 
Visit 
X 
 
 
 
 
 
 
 
 
 
 
 
 


CONFIDENTIAL 
CA23900 (3G3-18-02), Final Protocol Amendment 1 14June 2018 
 
Page 13 
 
 
Study Procedures a: 
Study Days 
PK/PD Period 
Days → 
1 
2 
3 
4 
5 
6 
HD → 
HD d: 
 
 
HD d: 
 
 
HD d: 
 
Hours → 0-0.016 0.167 0.5 
1 
2 
3 
4 
6 
8 
12 
16 
24 
48 
start 
end 
72 
96 
start 
end 
120 
Safety Evaluations  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviated Physical 
Examination e: 
X m: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X p: 
Weight 
X f: 
 
 
 
 
X g: 
 
 
 
 
 
X 
 
X f: 
X g: 
X 
 
X f: 
X g: 
X p: 
12-Lead Safety ECG 
X m: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X p: 
Vital Signs (HR, BP, RR and T) 
X m: 
 
 
X  
 
 
 
 
 
 
 
 
 
X f: 
 
 
 
X f: 
 
X p: 
Bleeding of Access Site 
 
 
 
 
 
X g: 
 
 
 
 
 
 
 
 
X g: 
 
 
 
X g: 
 
Hem, Serum Chem h:, and UA i: 
X m: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X p: 
Coagulation j: 
X f: 
 
 
 
 
X g: 
 
 
 
 
 
 
 
X f: 
X g: 
 
 
X f: 
X g: 
X p: 
Platelet Count s: 
X f: 
 
 
 
 
X g: 
 
 
 
 
 
 
 
X f: 
X g: 
 
 
X f: 
X g: 
 
AE Monitoring 
X 
ConMeds Monitoring 
X 
Study Drug Administration / 
PK/PD/Immunogenicity 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xisomab 3G3 Administration n: 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood for free xisomab 3G3 PK 
X o: 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X o: 
 
 
 
X o: 
 
 
X p: 
Blood for free xisomab 3G3 PD 
(aPTT) s: 
X o: 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X o: 
 
 
 
X o: 
 
 
X p: 
Blood for Immunogenicity 
X m: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood BUN and Potassium (for 
Kt/V and URR) s: 
X f: 
 
 
 
 
X g: 
 
 
 
 
 
 
 
X f: 
X g: 
 
 
X f: 
X g: 
 
Dialysate Analysis 
 
 
X k: 
 
 
X k: 
 
 
 
 
 
 
 
X k: 
X k: 
 
 
 
 
 
Visual Assessment and 
Processing of Dialyzer 
Membrane 
 
 
 
 
 
X l: 
 
 
 
 
 
 
 
 
X l: 
 
 
 
X l: 
 
Other Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vascular Access Site Reaction 
X m: 
 
 
 
 
X q: 
 
 
 
 
 
 
 
 
X q: 
 
 
 
X q: 
 
Confinement in the CRU 
X 
Return Visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


CONFIDENTIAL 
CA23900 (3G3-18-02), Final Protocol Amendment 1 14June 2018 
 
Page 14 
Study Procedures a: 
Study Days 
Follow-up Period 
Days → 
7 
8 
9 
10 
11 
12 
HD → 
 
HD d: 
 
HD d: 
 
HD d: 
 
Hours → 
 
start 
end 
 
start 
end 
 
start 
end 
 
Safety Evaluations  
 
 
 
 
 
 
 
 
 
 
Abbreviated Physical Examination  e: 
 
 
 
 
 
 
 
 
 
X r: 
Weight 
 
X f: 
X g: 
 
X f: 
X g: 
 
X f: 
X g: 
 
12-Lead Safety ECG  
 
 
 
 
 
 
 
 
 
X r: 
Vital Signs (HR, BP, RR, and T)  
 
X f: 
 
 
X f: 
 
 
X f: 
 
X r: 
Bleeding of Access Site 
 
 
 
 
 
 
 
 
X g: 
 
Hem, Serum Chem h:, and UA i: 
 
 
 
 
 
 
 
 
 
X r: 
Coagulation j: 
 
 
 
 
 
 
 
X f: 
X g: 
X r: 
Platelet Count s: 
 
 
 
 
 
 
 
X f: 
X g: 
 
Serum Pregnancy Test (♀only) 
 
 
 
 
 
 
 
 
 
X r: 
AE Monitoring 
X 
X 
ConMeds Monitoring 
X 
 
Study Drug Administration / 
PK/PD/Immunogenicity 
 
 
 
 
 
 
 
 
 
 
Blood for free xisomab 3G3 PK 
 
 
 
 
 
 
 
 
 
X r: 
Blood for free xisomab 3G3 PD (aPTT) s: 
 
X o: 
 
 
X o: 
 
 
 
 
 
Blood for Immunogenicity 
 
 
 
 
 
 
 
 
 
X r: 
Other Procedures 
 
 
 
 
 
 
 
 
 
 
Blood BUN and Potassium (for Kt/V and URR) 
 
 
 
 
 
 
 
X f: 
X g: 
 
Dialysate Analysis  
 
 
 
 
 
 
 
X k: 
X k: 
 
Visual Assessment and Processing of Dialyzer 
Membrane 
 
 
 
 
 
 
 
 
X l: 
 
Return Visits 
 
X 
 
X 
 
X 
 
 
 


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CA23900 (3G3-18-02), Final Protocol Amendment 1 14June 2018 
 
Page 15 
a: For details on Procedures, refer to Section 13 
b: Within 28 days prior to Day -8. 
c: Patients will be admitted to the CRU on Day -8, at the time indicated by the CRU and will remain confined up to Day 6 or prior early termination. 
d: Patients will undergo hemodialysis 3 times a week, on Day -7, Day -5, Day -3, and Day 1, Day 3, Day 5, Day 8, Day 10, and Day 12. For each patient, 
the hemodialysis will last at least 3 hours as per patient standard schedule which will be the same throughout the study. 
e: Symptom-driven physical examination may be performed at other times, at the PI’s or designee’s discretion. 
f: 
To be performed ~ 1 hour prior to the start of hemodialysis. 
g: To be performed at the end of hemodialysis.  
h: Samples for serum chemistry will be obtained following a fast of at least 4 hours, however, in case of dropouts or rechecks, patients may not have fasted 
for 4 hours prior to the serum chemistry sample is taken. 
i: 
For anuric patients, urinalysis may not be performed.  
j: 
Coagulation parameters (activated partial thromboplastin time [aPTT], prothrombin time [PT], and international normalized ratio [INR]). 
k: The dialysate sample will be taken at 30 minutes and at 3 hours after the start of hemodialysis. The dialysate will be freeze and sent to Aronora. 
l: 
To be performed when the dialyzer cartridge is removed and collected at the end of HD. 
m: To be performed prior to dosing. 
n: A single dose of xisomab 3G3 or matching placebo will be administered at Hour 0. The dose will be injected through a port into the flowing arterial 
blood in the proximal dialysis line according to the randomization schedule, immediately after the start of HD. 
o: When the PK or PD sample is on an HD day, the sample should be taken at least 1 hour prior the start of HD session. The actual time will be recorded. 
p: To be performed at discharge or early termination; the PK and aPTT should be taken at 120 hour postdose. 
q: The vascular access sites (AV fistula or AV graft puncture sites) are to be evaluated immediately after the end of HD and removal of the needles from 
the fistula or graft for bleeding cessation or other reactions. 
r: 
All patients who received the study drug or placebo (including patients who terminate the study early) will undergo follow-up procedures at the Clinical 
Research Unit (CRU) approximately 12 days after dosing, as they return for their last HD. Events performed on Day 12 can performed at end of HD if 
more appropriate. 
s: 
Platelet count, BUN and potassium, and aPTT value will be taken from the hematology, serum chemistry, and coagulation sample, respectively, when 
these are scheduled to be collected at the same time. Samples will not be taken twice at a same timepoint. 
Abbreviations: 
♀ = Females, 
AE = Adverse 
events, 
BUN = Blood 
urea 
nitrogen, 
BP = Blood 
pressure, 
C-I = Check-in, 
Chem = Chemistry, 
ConMeds = Concomitant medication, CRU = Clinical research unit, ECG = Electrocardiogram, FSH = Follicle-stimulating hormone, FU = Follow-up, 
Hem = Hematology, HD = Hemodialysis, HIV = Human immunodeficiency virus, HR = Heart rate, Kt/V = ratio of volume of fluid completely cleared of urea 
PD = Pharmacodynamic, PK = Pharmacokinetics, PMP = Postmenopausal, RR = Respiratory rate, T = Temperature, UA = Urinalysis URR = Urea reduction 
ratio. 
 


CONFIDENTIAL 
CA23900 (3G3-18-02), Final Protocol Amendment 1 14June 2018 
 
Page 16 
7 
ABBREVIATIONS 
AE 
Adverse event 
 
ALT 
Alanine aminotransferase 
 
aPTT 
Activated partial thromboplastin time 
 
AST 
Aspartate aminotransferase  
 
AUC%extrap 
Percent of AUC0-inf extrapolated  
 
AUC0-t 
Area under the concentration-time curve, from time 0 to the last observed 
non-zero concentration (t) 
 
AUC0-inf 
Area under the concentration-time curve, from time 0 extrapolated to 
infinity 
 
bpm 
Beats per minute 
 
BMI 
Body mass index 
 
°C 
Degrees Celsius 
 
CFR 
Code of Federal Regulations 
 
CI 
Confidence interval 
 
CL 
Apparent total plasma clearance after oral (extravascular) administration 
 
Cm 
Centimeter 
 
Cmax 
Maximum observed concentration  
 
CRF 
Case report form 
 
CRU 
Clinical Research Unit 
 
CS 
Clinical significant 
 
CV 
Coefficient of variation 
 
ECG 
Electrocardiogram 
 
ESRD 
End stage renal disease 
 
FDA 
Food and Drug Administration 
 
FIH 
First in Human 
 
FSH 
Follicle-stimulating hormone 
 
FXI 
Factor XI 
 
FXIa 
Activated FXI  
 
FXII 
Factor XII 
 
FXIIa 
Activated FXII 
 
G 
Gram 
 


CONFIDENTIAL 
CA23900 (3G3-18-02), Final Protocol Amendment 1 14June 2018 
 
Page 17 
GCP 
Good Clinical Practice 
 
GLP 
Good Laboratory Practice 
 
h 
Hour 
 
HBsAg 
Hepatitis B surface antigen 
 
hCG 
Human chorionic gonadotropin  
 
HCV 
Hepatitis C virus 
 
HD 
Hemodialysis 
 
HIV 
Human immunodeficiency virus 
 
IB 
Investigator’s Brochure 
 
ICF 
Informed Consent Form 
 
ICH 
International Council on Harmonisation 
 
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 
 
LS 
Least squares 
 
m2 
Meters squared 
 
MedDRA® 
Medical Dictionary for Regulatory Activities® 
 
mg 
Milligram 
 
mL 
Milliliter 
 
mmHg 
Millimeter of mercury 
 
MRT 
Mean residence team 
 
msec 
Millisecond 
 
N 
Sample size 
 
No. 
Number 
 
PBMC 
Peripheral blood mononuclear cells  
 
PD 
Pharmacodynamics 
 
PI 
Principal Investigator 
 


CONFIDENTIAL 
CA23900 (3G3-18-02), Final Protocol Amendment 1 14June 2018 
 
Page 18 
PK 
Pharmacokinetic(s) 
 
PT 
Prothrombin time 
 
QA 
Quality Assurance 
 
QTc 
Corrected value of the interval between the Q and T waves on the 
electrocardiogram tracing 
 
SAE 
Serious adverse event 
 
SAP 
Statistical analysis plan 
 
TEAE 
Treatment emergent adverse event 
 
Tmax 
Time to reach maximum observed concentration 
 
t½ 
Apparent terminal elimination half-life 
 
URR 
Urea reduction ratio 
 
US 
United States 
 
USA 
United States of America 
 
Vz 
Apparent volume of distribution during the terminal elimination phase 
after oral (extravascular) administration 
 
WHO 
World Health Organization 
 
 


CONFIDENTIAL 
CA23900 (3G3-18-02), Final Protocol Amendment 1 14June 2018 
 
Page 19 
8 
INTRODUCTION 
This study will be conducted in compliance with the protocol, Good Clinical Practice (GCP), 
and applicable regulatory requirements. The study population will be comprised of adult 
male and/or female patients with end stage renal disease. 
A brief overview of available information regarding xisomab 3G3 follows below. Details can 
be found in the xisomab 3G3 Investigator’s Brochure (IB 2018). 
8.1 Background 
Xisomab 3G3 is a novel, injectable, therapeutic recombinant humanized IgG4 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 (F) XII on negatively charged surfaces. Activated FXII (FXIIa) then activates FXI 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 
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, including FIX. 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 of 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 
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 


CONFIDENTIAL 
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Page 20 
as determined by GLP toxicity studies in both rats and nonhuman primates, the therapeutic 
index has not been determined. 
8.2 Nonclinical Studies 
8.2.1 
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 other antithrombotics, 
currently marketed or under development, that target the functionality of coagulation cascade 
components downstream of FXII and important for both thrombosis and normal hemostasis, 
xisomab 3G3 is designed to prevent or treat thrombosis by selectively interfering with the 
interaction of FXII and FXI, thereby without impeding hemostasis. 
8.2.2 
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 postdose 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 
recovery animals. Consequently, individual t½ were longer and ranged from 61.4 to 


CONFIDENTIAL 
CA23900 (3G3-18-02), Final Protocol Amendment 1 14June 2018 
 
Page 21 
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. Intravenous 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 and females, respectively 
and the clearance (CL) was 0.202 and 0.170 mL/h/kg for the males and females, respectively. 
8.2.3 
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 tested and 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 postdose (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 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. 
8.3 
Clinical Studies 
A first-in-human (FIH) study (Study No. 3G3-15-01 [Celerion Project No.: CA19214]) was 
completed in the United-States on January 16, 2018. This study was a single ascending dose 
study in healthy adult male and female subjects with the purpose of collecting safety, 
tolerability, PK, and PD information in order to support further development of 
xisomab 3G3. 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]) were dosed. Subjects received a 
single IV infusion (less than 5 minutes) of 0.1 mg/kg (Cohort 1), 0.5 mg/kg (Cohort 2), 
2 mg/kg (Cohort 3), or 5 mg/kg (Cohort 4) xisomab 3G3 or placebo. 


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Page 22 
A total of 21 subjects entered the study, received the study medication or placebo, and 
completed the study per protocol. Below is a summary of the preliminary data from this FIH 
study as of 07 of May 2018. 
8.3.1 
Safety Data 
There were no deaths or SAEs experienced in this study. No subjects were discontinued due 
to AEs. Overall, 10 (48%) of 21 subjects experienced a total of 20 TEAEs in this study, with 
7 (44%) of 16 subjects following active treatment and 3 (60%) of 5 subjects following 
placebo. The highest incidence of TEAEs by system organ class was skin and subcutaneous 
tissue disorders, experienced by 3 (19%) active-treatment subjects and 1 (20%) placebo 
subject. The most common TEAE in this study was productive cough, considered unrelated 
or unlikely treatment related and experienced by 2 (13%) active treatment subjects. All other 
TEAEs were experienced by 1 subject. The majority of events (17) were mild (Grade 1) in 
severity and 3 were moderate (Grade 2). Moderate events included increased diastolic BP 
(2 mg/kg xisomab 3G3), productive cough (5 mg/kg xisomab 3G3), and upper respiratory 
tract infection (0.5 mg/kg xisomab 3G3). As expected, increases from baseline in aPTT were 
noted following all treatments, with greater magnitude and duration of these increases 
following administration of the higher doses of xisomab 3G3. 
A single IV dose of xisomab 3G3 up to 5 mg/kg appeared to be safe and generally well 
tolerated by the healthy male and female subjects in this study. 
8.3.2 
Pharmacokinetics and Pharmacodynamics Data 
The plasma xisomab 3G3 PK profiles were best characterized at the 5 mg/kg dose level. The 
PK profiles and PK parameters in the 0.1 mg/kg dose level were not well characterized since 
the majority of concentrations fell below the LLOQ; thus, an insufficient number of time 
points were available to characterize the elimination phase from 3 out of 4 subjects at that 
dose level. Terminal phase PK may have not been reliable at the doses below 5 mg/kg, noting 
that Vss appeared to be underestimated (were less than physiological blood volumes), and 
that half-life estimations increased when xisomab 3G3 was quantifiable for longer intervals. 
Plasma xisomab 3G3 exposure (AUCs and Cmax) increased with increasing dose levels. 
Although a dose proportionality analysis was not performed in this study, the mean PK 
parameter values indicated that plasma xisomab 3G3 exposure appeared to increase in a 
slightly more than dose-proportional manner from 0.5 to 5 mg/kg. The PK parameters 
calculated from the 0.1 mg/kg dose were less robust as most parameters were estimated in 
only 1 subject due to the absence of an observable elimination phase in 3 out of 4 subjects. 
The maximal concentrations peaked early, with Tmax values achieved before 1 hour 
following start of infusion. Elimination of the drug was decreased with increasing 
xisomab 3G3 doses, as shown by a lower Kel, longer t½, and lower CL. A summary of mean 
PK parameters and mean concentration profile can be found in Table 1 and Figure 1. 


CONFIDENTIAL 
CA23900 (3G3-18-02), Final Protocol Amendment 1 14June 2018 
 
Page 23 
Table 1: Key PK Parameters 
 
Dose 
Parameters (units) 
0.1 mg /kg 
0.5 mg/kg 
2 mg/kg 
5 mg/kg 
N 
3* 
4 
4 
4 
AUC0-t 
(ng•h/mL) 
60.47 ± 38 
368 500 ± 23 
5 657 000 ± 24 
28 270 000 ± 12 
AUC0-inf 
(ng•h/mL) 
- 
370 400 ± 23 
5 668 000 ± 24 
28 290 000 ± 12 
Cmax 
(ng/mL) 
124.9 ± 23 
11 250 ± 9 
42 750 ± 12 
127 300 ± 3 
Tmax 
(h) 
0.084 ± 2.4 
1.15 ± 113  
0.13 ± 65 
1.01 ± 132 
t½ 
(h) 
- 
16.638 ± 9 
60.63 ± 7 
121.49 ± 85 
CL 
(L/h) 
- 
0.09 ± 20 
0.026 ± 13 
0.014 ± 23 
Vss 
(L) 
- 
2.52 ± 24 
3.72 ± 11 
4.31 ± 18 
AUC = area under the concentration-time curve; CL = apparent body clearance; Cmax = maximum observed plasma 
concentration; N = number of subjects; CV% = coefficient variation; t½= elimination half-life; Tmax = time of observed 
Cmax; Vss = apparent volume of distribution.  
Data presented as mean ± CV% 
* Non-zero concentration data from only 3 of 4 subjects was available for PK analysis. 
Figure 1: Mean Concentration Profile  
 


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CA23900 (3G3-18-02), Final Protocol Amendment 1 14June 2018 
 
Page 24 
aPTT was prolonged in all cohorts after xisomab 3G3 IV administration, and near-saturation 
of the effect was observed around the 0.5 mg/kg dose. Results showed that the maximum 
aPTT values achieved increased with increasing xisomab 3G3 dose levels, and the aPTT 
values decreased towards baseline values over time as depicted in Figure 2. The time for 
aPTT to return to baseline (±10%) increased as the dose levels increased. This may be 
correlated to a slower in elimination rate of xisomab 3G3 from the plasma as the doses 
increased.  
Figure 2: Mean aPTT Profile Over Time 
0
7
14
21
28
35
42
49
56
63
70
77
84
91
1.0
1.2
1.4
1.6
1.8
2.0
2.2
placebo
0.1 mg/kg
0.5 mg/kg
2 mg/kg
5 mg/kg
*
*
(3)**
(2)**(2)**
(1)
(1)
(1)
Time  Relative to Dosing (d)
aPTT (fold change)
0
24
48
72
96
120
1.0
1.2
1.4
1.6
1.8
2.0
2.2
placebo
0.1 mg/kg
0.5 mg/kg
2 mg/kg
5 mg/kg
hours
aPTT (fold change)
A
B
 
Legend: 
(A) aPTT of Cohorts 1 to 4 for the duration of the Phase 1 clinical trial to date in days (d) 
(B) aPTT data from the first 120 hours (h) post-dose.  
Numbers in parentheses indicate the number of subjects at that time point. *blood sample taken within 24 hours 
of time point indicated. **blood sample taken within 48 hours of time point indicated. 
 


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8.4 Rationale 
8.4.1 Rationale for this Study and Study Design 
A FIH study was conducted in healthy subjects and concluded that a single dose of 
xisomab 3G3 up to 5 mg/kg was safe and generally well tolerated. Results also confirmed 
that xisomab 3G3 prolonged aPTT values; the magnitude and duration of which were 
dose-related. This study will explore the potential utility of single infusion doses of xisomab 
3G3 in ESRD patients who are on chronic HD. 
Thromboembolic disease and bleeding are common comorbidities in subjects with chronic 
kidney diseases (Lutz et al., 2017). In most ESRD patients, heparin is routinely used during 
outpatient HD to reduce clotting in the dialyzer cartridge and to improve HD efficiency. 
However, administration of heparin during HD temporally increases the risk of bleeding. A 
safe alternative for patients with active bleeding, or that are at a high risk for bleeding 
complications, is heparin-free dialysis (Schwab et al., 1987; Stamatiadis et al., 2004; and 
Caruana et al., 1987) and the majority of HD patients that are admitted to the hospital are 
routinely dialyzed without heparin due to bleeding concerns.  
In this study design, subjects will be confined to the clinic for the majority of the trial and 
will not receive heparin during their HD sessions. While heparin-free HD can increase 
clotting within the dialyzer, resulting in the need for exchange of the dialyzer cartridge 
during HD in 5-7% of the procedures (Cronin and Reilly, 2010), there is no evidence that HD 
without heparin results in increased thromboembolic complications. Indeed, heparin 
anticoagulation during HD is not intended for systemic thromboprophylaxis and a recent 
retrospective analysis of data from the United States Renal Data System and electronic 
medical records shows that heparin-free HD is not associated with increased risk of 
thromboembolic events in ESRD patients (Shen et al., 2013). Therefore, the removal of 
standard of care heparin anticoagulation in either arm for the short duration of the study is 
not expected to place the patients at an increased risk for development of thromboembolic 
complications, and additionally enables the most rigorous assessment of safety and efficacy 
for xisomab 3G3 that would not be possible if heparin treatment was maintained. 
Xisomab 3G3 is expected to prevent pathologic thrombogenesis by selectively inhibiting 
thrombotic contact pathway activation without interrupting normal hemostasis or the 
hemostatic feedback activation of FXI by thrombin, or other mechanisms. As both 
thromboembolism and bleeding are common comorbidities in ESRD patients, safe 
anticoagulation is currently an unmet need for this patient population. Xisomab 3G3 is a 
fundamentally novel anticoagulant that is expected to reduce clot formation in vascular 
devices, including the hemodialyzer apparatus, without the increased risk of bleeding 
associated with heparin. In addition, data to date suggest that xisomab 3G3 may also reduce 
the incidence and severity of thromboembolic events in these patients. Further, non-clinical 
data suggest that xisomab 3G3 reduces systemic inflammatory responses, which may be 
detrimental, and has been associated with contact activation of the blood that is perfused 
through devices during external organ support. As such, xisomab 3G3 stands as a promising 
alternative to other anticoagulants in this population. It is therefore of interest to assess 
xisomab 3G3 safety and effectiveness in ESRD patients on chronic HD. 


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A placebo arm is included in this study design in order to robustly demonstrate the safety and 
efficacy of xisomab 3G3 while not placing the subjects at unnecessary risk, as mentioned 
above. The primary endpoint in this study is safety, measured as the number of adverse 
events that occur during the observation period.  A heparin free inpatient HD observation 
period (Study Days -7 to 1) is included in the trial design to establish a baseline for the 
heparin-free procedure. Continuation of the heparin-free HD procedure during the 
subsequent trial period and inclusion of a placebo arm allows for the determination of 
whether an adverse event is drug-related or not and permits accurate assessment of the safety 
of the study drug. The addition of a placebo arm also removes potential bias from the 
interpretation of AEs by the PIs and the subjects. The secondary endpoint for this study is 
efficacy of xisomab 3G3 on hemodialysis efficiency which may be more clearly observed 
with a placebo control instead of an active control (e.g., heparin). While the placebo arm may 
be at the same risk of clotting within the dialysis circuit as during the pre-dosing period 
(Study Days -7 to 1), data cited above suggests that these patients will not be at higher risk 
for either thromboembolic or bleeding complications. Should clotting occur within the 
dialyzer cartridge during a hemodialysis session that results in dialyzer failure, the dialyzer 
cartridge will be replaced, and the patient will be closely monitored by the PI. It is important 
to note that replacement of the dialyzer cartridge during HD is safe for the patient and a 
routine procedure in cases of dialyzer failure.  
8.4.2 Rationale for the Dose Selection  
Doses of 0.25 mg/kg and 0.5 mg/kg were selected for this phase 2 study in order to provide 
adequate PD and PK characterization but still allowing a safety margin should the results 
differ in this population compared to healthy subjects. The 0.25 mg/kg xisomab 3G3 dose is 
2.5-fold higher than the lowest dose in the FIH study. The 0.1 mg/kg dose in the FIH study 
had a short and modest, yet detectable PD effect (several seconds of temporal aPTT 
prolongation). The 0.25 mg/kg dose is expected to provide an initial plasma concentration 
that is within the range of average FXI concentration, the molecular target of xisomab 3G3, 
in human subjects, and may approach saturation in some individuals after full distribution. 
Therefore, it has the potential to exert brief pharmacological (anti-inflammatory, 
antithrombotic) activity, possibly lasting up to a day, until elimination of the antibody and 
hepatic FXI secretion that neutralizes the antibody. 
The 0.5 mg/kg dose was safely administered in the FIH study and allowed adequate 
characterization of the PK profile in healthy adults. In addition, following a 0.5 mg/kg a 
prolongation of aPTT was seen, with highest values measured at 24 hours postdose and 
having a sustained effect for at least 72 hours postdose. The 0.5 mg/kg xisomab 3G3 dose is 
expected to provide, after complete distribution, a plasma concentration that is approximately 
twice the average human plasma concentration of the FXI antigen. Therefore, this dose is 
expected to be overcome by FXI generation later, and have pharmacological activity that 
lasts longer than the lower dose level. 


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8.5 Risks and/or Benefits to Patients 
ESRD patients are often ill, and are prone to a variety of adverse events on or off HD, 
ranging, for example, from infections to hypertension to bleeding to thromboembolism to 
acute ischemic cardiovascular emergencies, even if they are apparently stable on chronic HD. 
A temporal and modest increase in blood pressure was observed in one study subject in the 
FIH study after xisomab 3G3 administration, and the event was deemed potentially related to 
the study drug. 
Xisomab 3G3 is a purified protein produced by recombinant DNA technology in a 
mammalian cell culture system, and these types of drugs can, occasionally and unpredictably 
evoke acute allergic reactions. Some ESRD patients develop chronic HD- and uremia-related 
moderate hemorrhagic diathesis or hemostasis impairment. Even though currently available 
data do not indicate a hemostatic function for the FXI/FXII interaction, there remains a 
theoretical possibility of contact activation-mediated enhancement of hemostasis. Thus, the 
hemostatic safety of xisomab 3G3 in the complex conditions of ESRD and chronic HD is not 
yet known. The safety monitoring practices employed by this protocol (i.e., 12-lead ECG, 
vital signs, blood pressure, clinical laboratory tests, AE questioning, vascular access site (AV 
fistula or AV graft) monitoring, and physical examination) are adequate to protect the 
patients’ safety and should detect all expected and unexpected treatment-emergent AEs 
(TEAEs). In addition, the cohorts will be dosed in a sequential manner, starting with the 
lower dose level, Cohort 1.  
Patients undergoing heparin-free HD may be at higher risk of developing clots within the 
hemodialyzer. Should this occur, site standard operating procedures will be followed to 
replace the clotted dialyzer and resume HD under the supervision of the PI. It is important to 
note that replacement of the dialyzer cartridge is a safe procedure for the patient. While 
studies suggest that there is no risk of thromboembolic complications should this occur, 
clotting of the dialyzer circuit could result in up to ~228 mL of blood loss. 
There may be direct health benefit for study participants from receipt of study drug, some 
evaluated among the secondary outcome measures. Xisomab 3G3 and its murine precursor, 
14E11, have shown anti-inflammatory and antithrombotic effects in non-clinical studies. 
Both inflammatory responses to exposure of blood to the foreign surfaces of the HD 
equipment, and thrombus formation-related consumption of blood components, anywhere in 
the body, or thrombus layer entrapment in the dialyzer equipment, especially in the absence 
of systemic anticoagulation with heparins, may be reduced in the presence of 
pharmacologically active levels of xisomab 3G3. Reduced thrombus accumulation on the 
dialyzer surface may potentially improve the efficiency of hemodialysis as well. An indirect 
health benefit for study participants enrolled in this study is the free medical tests received at 
screening and during the study. 
 
 


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9 
OBJECTIVES AND ENDPOINTS 
9.1 Objectives 
The primary objective of this study is: 
• To assess the safety and tolerability of a single dose of xisomab 3G3 when injected 
through a port into the proximal (arterial) dialysis line immediately after initiation of a 
HD procedure in patients with ESRD. 
The secondary objectives of this study are: 
• To assess the PD of a single dose of xisomab 3G3 when injected through a port into the 
proximal (arterial) dialysis line immediately after initiation of a HD procedure in 
patients with ESRD. 
• To assess the efficacy of a single dose of xisomab 3G3 on HD efficiency when injected 
through a port into the proximal (arterial) dialysis line immediately after initiation of a 
HD procedure in patients with ESRD. 
• To assess the PK of a single dose of xisomab 3G3 when injected through a port into the 
proximal (arterial) dialysis line immediately after initiation of a HD procedure in 
patients with ESRD. 
9.2 Endpoints 
Primary outcome measures: 
• The safety and tolerability of xisomab 3G3 will be evaluated versus pre-treatment and 
placebo by reviewing number and severity of adverse events and use of concomitant 
medications, physical examination, vascular access site reaction, bleeding time, and 
changes in vital signs, ECGs, and clinical laboratory evaluations. 
Secondary outcome measures: 
• PD using dose-dependency of drug potency, determined by measuring changes in 
coagulation parameters, and thrombus accumulation (assessed and ranked by visual 
inspection) within the dialyzer cartridges and total protein accumulation in the HD filter 
after xisomab 3G3-treatment versus pre-treatment and placebo. 
• Efficacy on hemodialysis efficiency using BUN and potassium levels before and after 
hemodialysis, length of HD, measurement of urea removed by 3 hours of dialysis, and 
total dialysate urea (single pool Kt/V and URR) after xisomab 3G3-treatment versus pre-
treatment and placebo. 
Other outcome measures: 
• PK parameters of xisomab 3G3, calculated, as appropriate: AUC0-t, AUC0-inf, 
AUC%extrap, Cmax, Tmax, Kel, t½, CL, and Vss. 
• Development of immunity or antibodies against xisomab 3G3 after drug exposure. 


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10 STUDY DESIGN 
10.1 Overall Study Design and Plan 
This is a phase 2, randomized, double-blind, placebo-controlled, single-dose study of 
xisomab 3G3 designed to evaluate the safety, efficacy/potency, and PK at 2 dose levels 
administered to patients with ESRD undergoing HD.  
A total of up to 24 adult male and female patients will be enrolled; 9-12 patients are planned 
for each cohort. In each cohort, an attempt will be made to enroll at least 50% of females and 
at least 30% of a race/ethnicity minority group. Patients will be enrolled into Cohort 1 or 
Cohort 2; cohorts will be dosed sequentially. Within a cohort, patients will be randomized to 
active drug or placebo as summarized below: 
Table 2: Cohort and Treatment Randomization 
Cohort 
Treatment 
Active:Placebo 
Cohort Size 
1 
Infusion dose of 0.25 mg/kg 
xisomab 3G3 or placebo 
2:1 
9-12 
2 
Infusion dose of 0.5 mg/kg 
xisomab 3G3 or placebo 
2:1 
9-12 
This study includes a screening period of 28 days prior to checking-in to the clinical research 
unit on Day -8.  From Day -7 (one week prior to dosing on Day 1) through Day -1, all 
patients will undergo HD 3 times and will be assessed for all scheduled procedures and 
endpoints before and after each HD session as per the Study Events Flow Chart (Section 6).  
On Study Day 1, prior to dosing, patients will undergo baseline measurements followed by 
initiation of a regular HD procedure, consistently using only one type of dialyzer cartridge in 
each patient. Immediately after the start of blood perfusion, a single dose of xisomab 3G3 or 
matching placebo will be injected through a port into the flowing arterial blood in the 
proximal dialysis line. Patients will continue to undergo HD procedures and scheduled 
assessments from Day 1 through Day 12. 
Study assessments will include physical examinations, vital signs, ECGs, clinical laboratory 
tests, HD vascular access site (AV fistula or AV graft) reaction, antibody titer 
(immunogenicity), AEs, PD blood sampling (coagulation parameters), and PK blood 
sampling to be performed throughout the study according to the Study Events Flow Chart 
(Section 6). On Days -7, -5, and -3 and Days 1, 3, 5, and 12, bleeding time from the HD 
vascular access sites on the AV fistula or AV graft (ladder or buttonhole technique) will be 
evaluated at the end of the HD session. The dialyzer cartridge will be rinsed and visually 
inspected at the end of the HD procedure and graded against a standardized visual assessment 
scale. After visual assessment, the used and rinsed dialyzer cartridge will be frozen and saved 
for later retained content (deposited blood-derived material) analysis. The number of dialyzer 
cartridges used for the HD session will be recorded. 
Patients who withdraw prematurely from the study may be replaced at the discretion of the 
Investigator and Aronora, Inc. to ensure that up to 24 patients (9 to 12 patients per cohort) 
complete the study. 


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10.1.1 Confinement and Follow-Up 
Patients will be housed on Day -8, at the time indicated by the CRU, until after completion of 
study procedures on Day 6 as indicated in the Study Events Flow Chart (Section 6). Patients 
will return to the CRU as per the Study Events Flow Chart (Section 6) for additional HD 
sessions and study procedures. At all times, a patient may be required to remain at the CRU 
for longer at the discretion of the Principal Investigator (PI) or designee. 
All patients who received the study drug or placebo (including patients who terminate the 
study early) will undergo follow-up procedures at the CRU approximately 12 days after 
dosing. 
10.1.2 End of Study Definition 
The end of study is defined as the date of the last scheduled study procedure as outlined in 
the Study Events Flow Chart (Section 6). 
 
 


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11 STUDY POPULATION 
11.1 Inclusion Criteria 
Patients must fulfill all of the following inclusion criteria to be eligible for participation in 
the study: 
1. ESRD maintained on stable outpatient HD regimen, using an established (> 3 months) 
and normally functioning, regular flow, uninfected first mature AV fistula (or AV graft) 
and skin consistent with standard chronic HD access injuries, and HD stability defined as 
Kt/V ≥ 1.2 within 3 months prior to screening at a healthcare center for > 3 months from 
screening. 
2. On HD regimen at least 3 times per week for a minimum of 3 hours per dialysis session, 
using a complication-free well maintained AV fistula (or AV graft), expected and plan to 
continue this throughout and for at least 3 months beyond the study.   
3. Is capable of understanding the written informed consent, provides signed and witnessed 
written informed consent, and agrees to comply with protocol requirements and 
study-related procedures. 
4. Willing to be confined to the CRU for the duration of the study, able to comply with all 
study-related requirements, and able to adhere to study restrictions and visit schedules. 
5. Male or female, between 18 and 80 years of age (inclusive) at the time of screening.  
6. BMI of ≥ 18 at the time of screening. 
7. Considered by the PI to be clinically stable with respect to underlying ESRD, based on 
medical evaluation that includes medical and surgical history, and a complete physical 
examination including vital signs, ECG, and clinical laboratory test results at screening. 
Repeat assessments are permitted for any laboratory, ECG, or vital sign parameter 
required for enrollment. 
8. Female patients must be of non-childbearing potential and 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. 


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9. Male patients must either be sterile (vasectomy with history of a negative sperm count 
following the procedure); practice total abstinence from sexual intercourse as the 
preferred lifestyle (periodic abstinence is not acceptable); use a male condom with any 
sexual activity; or agree to use a birth control method considered to be appropriate by the 
Investigator (such as one of the methods identified above for female patients) from the 
time of screening until 90 days after study drug administration. Male patients must agree 
not to donate sperm for a period of 90 days after study drug administration. 
11.2 Exclusion Criteria 
Patients must not be enrolled in the study if they meet any of the following criteria: 
1. Documented history of acute vasoocclusive thrombotic event (acute coronary syndrome, 
stroke or transient ischemic attack, venous thromboembolic event), or vascular access 
fistula or AV graft failure in the past 3 months.  
2. With the exception of unfractionated heparin during HD, concomitant or prior use of 
anticoagulant/antiplatelet agents (e.g., low molecular weight heparins, warfarin, 
apixaban, bivalirudin, ticagrelor, edoxaban, dabigatran, rivaroxaban, clopidogrel, 
prasugrel, ticlopidine, eptifibatide, tirofiban, dipyridamole, diclofenac, and all other 
NSAIDs) that may affect hemostasis for 2 weeks prior to check-in on Day -8 and 
throughout the study. 
3. Use of unfractionated heparin for HD sessions from check-in on Day -8 and throughout 
the study. 
4. Any clinically significant (CS) concomitant disease or condition (including treatment for 
such conditions) that, in the opinion of the PI, could either interfere with the study drug, 
compromise interpretation of study data, or pose an unacceptable risk to the patient. 
5. Any other CS abnormalities in laboratory test results at screening that would, in the 
opinion of the PI, increase the patient's risk of participation, jeopardize complete 
participation in the study, or compromise interpretation of study data. 
6. Pregnant (positive pregnancy test) at screening or check-in on Day -8. If serum human 
chorionic gonadotropin (hCG) pregnancy test results are indeterminate, follow-up testing 
should be performed to determine eligibility. 
All female patients will not be pregnant and will have a negative pregnancy test at 
screening and check-in on Day -8, with the following exception: females receiving 
dialysis with an indeterminate pregnancy test result or persistently low hCG resulting in a 
false positive pregnancy test may be included in the study at the discretion of the PI. 
Postmenopausal patients with a result outside the postmenopausal range or an 
indeterminate pregnancy test will undergo additional testing with FSH to confirm 
postmenopausal status prior to study enrollment. 
7. Treatment with another investigational drug or device study within 30 days (or 
5 half-lives, whichever is longer) prior to check-in on Day -8. 


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8. Acute illness that is considered by the PI to be CS within 2 weeks of check-in on Day -8. 
9. Currently have established underlying inherited or acquired symptomatic bleeding 
disorders and/or are at risk for excessive bleeding per PI judgment or current active 
bleeding (e.g., gastrointestinal, intracranial), aside from minor bleeding from the puncture 
site on the AV fistula or AV graft, which would be expected to occur during the dialysis 
procedure, with the following values: 
• Platelet count < 100,000 cells/mm3 (if < 100,000 but > 75,000 cells/mm3, with 
permission of PI and medical monitor) at screening  
• INR > 1.4 at screening 
• aPTT up to 1.2 x ULN (if >1.2x ULN up to < 1.5 x ULN, with permission of PI and 
medical monitor) at screening 
• ALT or AST > 2 x ULN at screening 
• Total bilirubin > 1.2 ULN at screening 
• Hemoglobin concentration < 10 g/dL at screening 
10. Seated blood pressure < 90/40 mmHg at screening and check-in on Day -8.  
11. Exclusion criteria for ECG at screening and check-in on Day -8: 
Heart rate 
< 45 and > 110 bpm 
QTcF interval  
> 500 msec 
bpm = beats per minute; msec = milliseconds; QTcF = QT interval corrected using Fridericia’s 
formula 
• Any significant arrhythmia or conduction abnormality, (including but not specific to 
atrioventricular block [2nd degree or higher], Wolff Parkinson White syndrome [unless 
curative radio ablation therapy]), which, in the opinion of the PI and Medical 
Monitor, could interfere with the safety for the individual patient. 
• Non-sustained or sustained ventricular tachycardia (> 2 consecutive ventricular 
ectopic beats at a rate of > 1.7/second). 
12. History of a CS allergy to recombinant biologic drug, rodents, or a known sensitivity or 
idiosyncratic reaction to any compound present in xisomab 3G3, its related compounds, 
or any compound listed as being present in the study formulation. 
13. Participate in strenuous exercise from 48 hours prior to check-in on Day -8 and 
throughout the study. 
14. Positive test for drugs of abuse and/or positive alcohol test at screening or check-in on 
Day -8 if not accounted for by a prescription medication.  Patients with a positive test 
based on a prescribed medication may be enrolled. 


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15. Positive test at screening for hepatitis B surface antigen (HBsAg) or human 
immunodeficiency virus (HIV). If a patient with ESRD has positive test results for 
hepatitis C virus (HCV) but liver function tests are otherwise not clinically significant, 
the patient may be included at the PI’s discretion. 
16. Receiving blood purification therapy other than HD. 
17. Any other reason that would render the patient unsuitable for study enrollment at the 
discretion of the PI. 
11.3 Early Termination of Patients from the Study 
Patient participation in this study may be discontinued for any of the following reasons: 
1. Occurrence of any medical condition or circumstance that exposes the patient to 
substantial risk and/or does not allow the patient to adhere to the requirements of the 
protocol. 
2. If the patient clots the hemodialyzer twice they may be discontinued from the study at the 
discretion of the PI. If the patient fully clots the hemodialyzer, continuation of the patient 
in the study will be at the PIs discretion. 
3. 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 patient. 
4. Patient's decision to withdraw. 
5. Requirement of prohibited concomitant medication. 
6. Patient failure to comply with protocol requirements or study related procedures. 
7. Termination of the study by the Sponsor, FDA, Celerion, CRU, or other regulatory 
authorities.  
The clinical report will include reason(s) for patient withdrawals as well as details relevant to 
the patient withdrawal.  
If a patient is withdrawn from the trial prior to study completion, the patient will undergo all 
procedures scheduled for early termination as the situation allows (see the Study Events Flow 
Chart (Section 6). Any patient 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. 


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11.4 Study Restrictions 
11.4.1 Prohibitions and Concomitant Medication 
Consumption of foods and beverages containing the following substances will be prohibited 
as indicated: 
• Xanthines/caffeine: 48 hours prior to dosing and throughout the period of sample 
collection (small amounts of caffeine derived from normal foodstuffs e.g., 
250 mL/8 oz./1 cup 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 prior to dosing and throughout the period of sample collection; 
Concomitant medications will be listed, recorded, and allowed except for those listed as 
prohibited in the exclusion criteria in Section 11.2. It is understood and will be considered 
that treatment with certain drugs or cessation of treatment with certain drugs (e.g., drugs for 
hypertension) may have adverse effects and could interfere with the evaluation of the 
primary outcome measures of the study.  
After randomization, acetaminophen (up to 2 g per 24 hours) may be administered, for fever 
or chronic pain control, at the discretion of the PI or designee. Administration of opioids for 
certain types of pain management may be allowed. 
If deviations occur, the PI or designee in consultation with the Sponsor if needed will decide 
on a case-by-case basis whether the patient may continue participation in the study. 
11.4.2 Meals 
At the CRU, meals and/or snacks and fluids will be provided at appropriate times following 
check-in and throughout the study as per the clinical site standard procedure. 
11.4.3 Activity 
On Day 1, as dosing will be immediately after the start of the hemodialysis session, patients 
will be dosed in the same position as required for their hemodialysis session. Patients will 
maintain that position for the whole hemodialysis session, as per standard HD procedure, 
except when they are supine or semi-reclined for other study procedures. At other times, 
there will be no specific activity restrictions. However, should AEs occur at any time, 
patients may be placed in an appropriate position. 
Patients will be instructed to refrain from strenuous exercise which could cause muscle aches 
or injury, including contact sports at any time from 48 hours prior to check-in on Day -8 and 
throughout the study. 
 
 


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12 TREATMENTS 
12.1 Treatments Administered 
A separate dosing manual will detail the drug preparation and treatment administration to be 
followed for this study. 
Xisomab 3G3 and matching placebo will be supplied as sterile powder for injection via the 
IV route, upon reconstitution. 
Investigational materials will be provided by the Sponsor as in Table 3. 
Table 3: Identity of Investigational Products 
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) 
 
An unblinded pharmacist will be responsible for providing xisomab 3G3 or placebo to the 
blinded study personnel for administration via injection into the proximal hemodialysis line 
as per the randomization scheme. 
Patients will be enrolled into Cohort 1 or Cohort 2. Within a cohort, patients will be 
randomized to active drug or placebo as summarized in Table 2. 
Patients will receive a single infusion dose of 0.25 mg/kg xisomab 3G3, 0.5 mg/kg 
xisomab 3G3, or matching placebo on Day 1 at Hour 0. The dose will be administered 
proximal to the dialyzer cartridge, into the arterial line immediately after start of HD. 
Hour 0 will correspond to the start of the xisomab 3G3 infusion. The time at which the 
infusion is started and stopped must be recorded. 
The patient weight recorded at check-in will be used to calculate the study drug dose. 
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. 
12.2 Dose Modification 
The dose and administration of the study drug to any patient within a cohort may not be 
modified. If necessary, a patient must be discontinued for the reasons described in 
Section 11.3. 


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12.3 Method of Assigning Patients to Treatment Groups 
Each patient will be assigned a unique identification number upon screening. Patients who 
complete the study screening assessments and meet all the eligibility criteria will be assigned 
a unique randomization identification number at the time of dosing, different from the 
screening number, and will receive the corresponding product, according to a randomization 
scheme generated at Celerion. 
Patients will be enrolled to Cohort 1 or Cohort 2 with Cohort 1 conducted prior initiation of 
Cohort 2. In each cohort, an attempt will be made to enroll at least 50% of females and at 
least 30% of a race/ethnicity minority group. An attempt will also be made to approximately 
match key characteristics, including sex, average age, and weight per cohort. 
In each cohort, patients will be randomized to receive either xisomab 3G3 or placebo 
maintaining a 2:1 ratio  
If replacement patients are used, the replacement patient number will be 100 more than the 
original (e.g., Patient No. 101 will replace Patient No. 1).  
12.4 Blinding 
This is a double-blind, placebo-controlled study. 
12.4.1 Maintenance of Randomization 
A computerized randomization scheme will be created by a Celerion statistician and it shall 
be considered blinded as per the following: the randomization is available only to the CRU 
pharmacy staff that is preparing the drug who will not be involved in any other aspect of the 
study including administration of the drug. It will not be made available to the Sponsor, 
patients, or members of the staff responsible for the monitoring and evaluation of safety 
assessments. 
12.4.2 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 patient.  
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 patient only. In the event that the emergency is one, in which it appears 
that the other patients may be at imminent risk, the blind may be broken for all patients dosed 
at that dose level. The unblinding will be properly documented in the study file. 


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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. 
12.4.3 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, 
CRFs signed by the PI, and the database is officially locked.  
12.5 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 patient 
has received the entire dose. In the case of an incomplete dosing a few milliliters of blood 
could be drawn back into the dosing syringe and carefully reinjected to ensure administration 
of the complete dose; this will be reported. 


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13 STUDY ASSESSMENTS AND PROCEDURES 
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 patient 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, 
vascular access site reaction, 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. 
13.1 Screening 
Within 28 days prior to check-in on Day -8, medical history and demographic data, including 
name, sex, age, race, ethnicity, body weight (kg), height (cm), BMI (kg/m2) and history of 
tobacco use will be reported. Each patient will have a physical examination, vital sign 
measurements (heart rate, blood pressure, temperature, and respiratory rate), 12-lead ECG, 
and the laboratory tests of hematological, coagulation, hepatic and renal function and 
additional tests as noted in Section 13.2.7. 
13.2 Safety and Tolerability Assessments 
13.2.1 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. 


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13.2.2 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. 
Vital signs will be performed with patients in a seated position following a 5 minute rest 
period, except when they are supine or semi-reclined because of study procedures and/or AEs 
(e.g. nausea, dizziness) or if deemed necessary by the PI or designee. 
When scheduled postdose, vital signs will be performed within approximately 15 minutes of 
the scheduled time point.  
13.2.3 ECG 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 patients in a semi-recumbent position following a 5 minute rest 
period. All ECG tracings will be reviewed by the PI or designee. 
When scheduled postdose, ECGs will be performed within approximately 20 minutes of the 
scheduled time point. 
13.2.4 Body Weight 
Body weight (kg) will be measured daily up to Day 6, and before and after each HD session, 
as outlined in the Study Events Flow Chart (Section 6).  
13.2.5 Vascular Access Site Reaction Assessment 
The monitoring of AEs will pay special attention to vascular access fistula (or AV graft) site 
reactions. The preferred vascular access is an established AV fistula (or AV graft). Well 
established and reaction-free AV graft is an alternative, but less preferred access option, as it 
is more prone to complications. Patients who are hemodialyzed through catheters are not 
included in the study. Therefore, inspection of the AV fistula (or AV graft) and surrounding 
area will be performed. Any new abnormal findings inconsistent with past skin injuries as 
expected in patients on chronic HD will be reported as AEs. AV fistula (or AV graft) site 
reactions will be evaluated as outlined in the Study Events Flow Chart (Section 6). Prior to 
HD, the AV fistula (or AV graft) site will be examined for inflammation, infection, or flow 
abnormalities. When scheduled postdose, injection site examinations will be performed 
within approximately 20 minutes after completion of the HD session. 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 (FDA Guidance 2007) 
as follows: 


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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. 
13.2.6 Bleeding of Access Site 
Evaluation of bleeding and bleeding time from the HD vascular access sites on the AV fistula 
or AV graft using the ladder or buttonhole technique will be performed as per Study Events 
Flow Chart (Section 6).  
Following hemodialysis, the needle will be removed from the vascular access site and 
immediately followed by the placement of the dressing (i.e., gauze). Pressure will be applied 
manually by a clinical associate for 10 minutes before checking for evidence of bleeding 
around the dressing. If there is still some bleeding, pressure will be applied back at the site 
for 5 minutes. The site will then be checked again for evidence of bleeding; this procedure 
will be repeated every 5 minutes until bleeding has stopped. Once bleeding has stopped, a 
new gauze dressing is applied and then taped. To ensure consistency when applying the 
pressure, the clinical staff will have received adequate training and an attempt will be made 
to have the same associates perform this test.  
The time to clot will be recorded. 


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13.2.7 Clinical Laboratory Tests 
All tests listed below will be performed as outlined in the 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 or saliva drug screen 
➢ Opiates 
➢ Amphetamines 
➢ Cocaine  
➢ Cannabinoids  
• 
Urine, breathalyzer, or saliva alcohol screen 
• 
Serum pregnancy test  
(for females only) 
• 
FSH (for postmenopausal females only) 
 
* 
Serum chemistry tests will be performed after at least a 4-hour fast; however, in case of dropouts or 
rechecks, patients may not have fasted for 4 hours prior to 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. 
┼ 
For anuric patients, urinalysis may not be performed. 


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13.2.8 Adverse Events  
13.2.8.1 Adverse Event Definition 
AE will be defined as any untoward medical occurrence during the study, associated or not 
with the use of xisomab 3G3 in the study patients, whether or not considered drug related. 
TEAE is an AE that occurs after administration of the study drug or placebo.  
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 study drug. (FDA Guidance, 2012) 
Prolonged aPTT is an expected pharmacodynamic effect of xisomab 3G3 and will, therefore, 
not be considered an AE. 
13.2.8.2 Monitoring 
Patients will be monitored for AEs from check-in through completion of the study. Patients 
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 serious adverse events (SAEs) will be performed by a licensed medical 
provider, either at the CRU 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). 
13.2.8.3 Reporting 
All AEs that occurred during this clinical study (i.e., before, during, and after exposure of 
ESRD patients to xisomab 3G3) will be recorded. This design is to improve Sponsor ability 
to obtain reliable initial information about drug safety yet reducing the number of study 
patients needed to generate useful data.  
Adverse events and SAEs that are related to study participation (e.g., protocol-mandated 
intervention) will be recorded from the time the patient check-in until study completion. All 
other AEs and SAEs will be recorded from Day -8 until exit from the study. 
AEs will be coded using the most current MedDRA® available at Celerion. 


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The PI or designee will review each event and assess its relationship to study drug (likely, 
probably, possibly, unlikely, or unrelated) and severity. The date and time of onset, time 
relationship to drug dosing, duration, and outcome of each event will be noted. 
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 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). (FDA Guidance 2007) 
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 
Severe (Grade 3)  
The AE prevents daily activity and requires medical intervention 
Potentially Life-threatening 
(Grade 4) 
Emergency room visit or hospitalization is required 
 


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13.2.8.4 Serious Adverse Event 
If any AEs are serious, as defined by the Food and Drug Administration (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. The institutional review board (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 patient on this study, contact the Sponsor personnel listed in Section 3. 
13.3 Hemodialysis Procedure and Blood Clots in the Dialyzer Cartridge 
Patients will undergo hemodialysis 3 times a week as delineated in the Study Events Flow 
Chart (Section 6). For each patient, the hemodialysis will last at least 3 hours as per patient 
standard schedule which will be the same throughout the study. 
Patients undergoing heparin-free hemodialysis may be at higher risk of developing clots 
within the hemodialysis circuit. In order to monitor clotting within the HD circuit, venous 
pressure will be continuously monitored. Should clotting within the dialyzer occur, site 
standard operating procedures will be followed to replace the clotted dialyzer and resume 
hemodialysis under the supervision of the PI, if appropriate. It is important to note that 
replacement of the dialyzer cartridge is a safe procedure for the patient. While studies 


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Page 46 
suggest that there is no risk of thromboembolic complications should this occur, clotting of 
the dialyzer circuit could result in up to ~228 mL of blood loss. 
The hemoglobin levels will be followed more closely. 
If the patient clots the hemodialyzer twice they may be discontinued from the study at the 
discretion of the PI. If the patient fully clots the hemodialyzer, the continuation of the patient 
in the study will be at the PIs discretion.  
13.4 Immunogenicity Assessment 
Blood samples for immunogenicity assessment will be performed from the PK blood 
collection tubes as delineated in the  Study Events Flow Chart (Section 6). 
Instruction for blood sampling, collection, and processing will be provided separately. 
13.5 Pharmacodynamic Assessments 
Pharmacodynamic assessment will include evaluation of drug potency and efficiency of HD. 
For all patients, PD assessments will be performed at scheduled time points as delineated in 
the Study Events Flow Chart (Section 6). 
Drug potency will be evaluated using the following PD markers: 
• thrombus accumulation will be evaluated by a visual inspection of the dialyzer 
membrane at the end of HD procedures and by a gradation using a standardized visual 
assessment scale (e.g., Ronco et al., 2017);  
• total protein accumulation within the HD filter will be evaluated using appropriate 
methods; 
• coagulation parameters. 
Efficiency of HD will be assessed by: 
• Blood BUN and potassium levels before and after dialysis; 
• length of HD; 
• total dialysate urea (measurement of BUN removed over 3 hours of dialysis) will be 
computed; 
o single pool Kt/V (where Kt = volume of fluid completely cleared of urea 
[K = dialyzer clearance (mL/min), t=time of dialysis] and V=volume of water a 
patient’s body contains. 
o URR measured as the difference between urea pre-dialysis and post-dialysis 
expressed as a percentage. 


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13.6 Dialysate Analysis 
A 10 mL dialysate sample will be taken as delineated in the Study Events Flow Chart 
(Section 6). 
The samples will be sent to Aronora and will be stored for up to 5 years following the last 
dosing for future analysis (e.g., xisomab 3G3 levels and or urea).  
Instruction for the sample collection, processing, and sample shipment will be provided 
separately. 
13.7 Pharmacokinetic Assessments 
13.7.1 Blood Sampling and Processing 
For all patients, blood samples for the determination of free (active) xisomab 3G3 will be 
collected at scheduled time points as delineated in the Study Events Flow Chart (Section 6). 
The sample times for PK collection are in relation to the start of infusion. 
Instruction for blood sampling, collection, processing, and sample shipment will be provided 
separately. 
Following completion of the samples analysis, leftover plasma samples will be shipped to the 
Sponsor, as per their instructions provided separately. Additional analysis for exploratory 
purposes, including but not limited to factor XI activity, will be performed on leftover plasma 
samples at the Sponsor’s discretion; samples will be stored for up to 5 years following the 
last dosing for future analysis. 
13.7.2 Plasma Pharmacokinetic Parameters 
The following PK parameters will be computed, as appropriate, for plasma free xisomab 3G3 
from the individual plasma concentrations using a non-compartmental 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. 
AUC%extrap: 
Percent of AUC0-inf extrapolated, represented as (1 – AUC0-
t/AUC0-inf)*100. 
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. 


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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. 
Vss: 
Total apparent volume of distribution following single IV dose 
administration calculated as Vss = MRT x CL. 
MRT*: Mean residence time = AUMC0-inf/AUC0-inf (for IV infusion) 
AUCM0-inf*: Area under the moment curve from time 0 to the last measurable 
concentration, = AUMC0-t + [(tlast x Ct)/ Kel]+ Ct/(Kel)2 
* 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. 
Plasma concentrations below the limit of quantitation will be treated as missing for all PK 
calculations. 
No PK parameters will be calculated for patients 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-time profile. 
Individual and mean plasma concentration time curves (both linear and log-linear) will be 
included in the final report. 
13.7.3 Analytical Method 
PK plasma sample analysis will be performed using validated bioanalytical methods.  
Samples from patients to be assayed are specified in Section 14.2. 


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13.8 Blood Volume Drawn for Study Assessments 
Table 4: 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 patients only) and serum pregnancy 
(for female patients only). 
1 
16  
16 
On-study hematology and serum 
chemistry(this includes serum pregnancy for 
female patients only when scheduled at the 
same time) 
4 
12.5 
60 
On-study coagulation (PT/INR and aPTT)  
16 
3.5 
56 
On-study platelet count only ** 
Up to 14 
3.5 
Up to 49 
On-study BUN and potassium only ** 
Up to 14 
3.5 
Up to 49 
Blood for PD (aPTT only) ** 
Up to 17 
2.7 
Up to 45.9 
Blood for PK (free xisomab 3G3) 
16 
10 
160 
Blood for Immunogenicity 
2 
*** 
*** 
Total Blood Volume (mL)→ 
Up to 435.9 † 
 
* 
Represents the largest collection tube that may be used for this (a smaller tube may be used). 
** 
Platelet count, BUN and potassium, and aPTT value will be taken from the hematology, serum 
chemistry, and coagulation sample, respectively, when these are scheduled to be collected at the same 
time. Samples will not be taken twice at a same timepoint 
*** 
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 50 mL; 
this volume could be exceeded only with agreement of the PI on a case-by-case basis). 


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14 STATISTICAL CONSIDERATIONS 
Data will be handled and processed according to Celerion Standard Operating Procedures, 
which are written based on the principles of GCP. 
14.1 Sample Size Determination 
The sample size chosen for this study was selected without statistical considerations. The 
sample size of up to 24 patients in total (9-12 per cohort with a ratio of 2:1 of active study 
drug:placebo) has been determined adequate to meet the study safety, tolerability, PD, and 
PK objectives.  
14.2 Population for Analyses 
Safety Population: All patients who received the study drug (active or placebo) will be 
included in the safety evaluations. 
PD Population: All patients who received the study drug (active or placebo) and had at least 
one postdose measurement of any of the PD assessment will be included in the statistical 
analyses. 
PK Population: Samples from all patients receiving the active drug will be assayed even if 
the patients do not complete the study. All patients receiving the active drug 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.  
14.3 Statistical Analyses 
Detailed methodology for summary and statistical analyses of the data collected in this study 
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.  
14.3.1 Safety and Tolerability Analyses 
All safety data will be populated in the individual CRFs. All safety data will be listed by 
patients. 
The placebo patients from all cohorts will be pooled into a single placebo group for all 
summaries and presentations 
Dosing dates and times will be listed by patient. 


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Incidence and time of bleeding from the HD access sites on the AV fistula (or AV graft), as 
described in Section 13.2.6, will be counted and recorded. Treatment versus pre-treatment, 
placebo, and post-treatment results will be compared. 
AEs will be coded using the most current version of Medical Dictionary for Regulatory 
Activities (MedDRA®) available at Celerion and summarized by treatment (2 active dose 
levels and pooled placebo) for the number of patients reporting the treatment emergent 
adverse event (TEAE) and the number of TEAEs reported. A by-patient AE data listing 
including verbatim term, coded term, treatment, severity, and relationship to study drug will 
be provided.  
Safety data including ECGs, vital signs assessments, clinical laboratory results and vascular 
access site reaction, will be summarized by treatment (2 active dose levels and pooled 
placebo) and point of time of collection. 
Descriptive statistics using appropriate summary statistics will be calculated for quantitative 
safety data as well as for the difference to baseline, when appropriate. In addition, a shift 
table describing out of normal range shifts will be provided for clinical laboratory results.  
Concomitant medications will be listed by patient and treatment (2 active dose levels and 
pooled placebo) and coded using the most current version of WHO drug dictionary available 
at Celerion. Medical history will be listed by patient. 
14.3.2 Immunogenicity Analyses 
ADA titer will be reported and summarized descriptively.  
14.3.3 Pharmacodynamic Analyses 
Placebo patients from Cohort 1 and Cohort 2 will be pooled for analysis.   
The PD analysis will include assessments of drug potency and efficiency of HD. These will 
include change in aPTT, BUN, and potassium levels. Change in thrombus accumulation, in 
total dialysate urea, URR, and Kt/V after xisomab 3G3 levels versus pre-treatment and 
placebo will also be evaluated. Total protein accumulation within HD filter will be evaluated. 
The change from baseline in PD endpoints will be summarized by treatment (2 active dose 
levels and pooled placebo) and at each scheduled time point using descriptive statistics. The 
baseline values are any value observed from Day -7 to Day 1, prior to xisomab 3G3 
administration. Any values after a single dose of xisomab 3G3 are regarded as post baseline 
values.   
The change from baseline variables will be calculated as the post-baseline value minus the 
value at baseline. 
Additional analyses may be performed as deemed necessary upon review of the data. 


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14.3.4 Pharmacokinetic Analyses 
Values will be calculated for the plasma concentrations and the PK parameters listed in 
Section 13.7.2 using appropriate summary statistics to be fully outlined in the SAP.  
Pharmacokinetic parameter listings and statistical summaries will be generated separately for 
each cohort. 
Plasma concentration data will also be displayed graphically on the linear and semi-
logarithmic scales. Figures will be created to display mean and individual free xisomab 3G3 
concentration-time curves, stratified by dose level. 
Additional analyses may be performed as deemed necessary upon review of the data. 


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15 STUDY ADMINISTRATION 
15.1 Ethics 
15.1.1 Institutional Review Board  
This protocol will be reviewed by the 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 Council on 
Harmonisation (ICH) guidelines. 
15.1.2 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). 
15.1.3 Patient Information and Consent 
The purpose of the study, the procedures to be carried out and the potential hazards will be 
described to the patients in non-technical terms. Patients will be required to read, sign and 
date an ICF summarizing the discussion prior to screening, and will be assured that they may 
withdraw from the study at any time without jeopardizing their medical care. 
Patient will be given a copy of their signed ICF. 
15.2 Termination of the Study 
Celerion/CRU reserves the right to terminate the study in the interest of patient welfare. 
Sponsor reserves the right to suspend or terminate the study at any time. 
15.3 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 study is conducted, and that data are generated, documented and reported in 
compliance with the study protocol, GCP and Good Laboratory Practice requirements as well 
as applicable regulatory requirements and local laws, rules and regulations relating to the 
conduct of the clinical study. 
The Clinical Study Report will be audited by the QA department and the QA audit certificate 
will be included in the study report. 


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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® 
or comparable statistical program to check for missing data, data inconsistencies, data ranges, 
etc. Corrections are made prior to database lock. 
15.4 Direct Access to Source Data/Documents 
The PI must maintain, at all times, the primary records (i.e., source documents) of each 
patient’s data. Examples of source documents are laboratory reports, drug inventory, study 
drug label records, and CRFs that are used as the source. 
Celerion/CRU will ensure that the Sponsor, IRB, and inspection by domestic and foreign 
regulatory authorities will have direct access to all study-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 study-related monitoring should be done by other 
parties, they will be required to sign a confidentiality agreement prior to any monitoring and 
auditing. 
15.5 Drug Supplies, Packaging and Labeling 
The Sponsor will supply sufficient quantities of investigational drug and matching placebo to 
allow completion of this study. The lot numbers, manufacture dates, and expiration dates (if 
available) of the study drugs supplied will be recorded in the final report. 
The investigational product and matching placebo will be shipped to a designee at the CRU 
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 (active and placebo) 
supplied. At the conclusion of the study, any unused study drugs as well as original 
containers (even if empty),will be retained by the study site, 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. 
15.6 Data Handling and Record Keeping 
Celerion standard CRFs will be supplied. CRFs are printed off directly from the database. 
Each CRF is reviewed and signed by the PI. 
All raw data generated in connection with this study, together with the original copy of the 
final report, will be retained by CRU 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. 


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CA23900 (3G3-18-02), Final Protocol Amendment 1 14June 2018 
 
Page 55 
15.7 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).  
15.8 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. 
15.9 Publication Policy 
All unpublished information given to Celerion or the CRU 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. 


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Page 56 
16 REFERENCES 
Caruana R. J., Raja M.R., and Bush J.V., et al. Heparin free dialysis: comparative data and 
results in high risk patients. Kidney Int. 1987;31:1351-1355. 
Cronin R.E., and Reilly R.F. Unfractionated heparin for hemodialysis: still the best option. 
Semin Dial 2010;23(5):510-515. Doi: 10.1111/j.1525-139X.2010.00770.x. 
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/GuidanceComplianceRegulatoryInf
ormation/Guidances/Vaccines/ucm091977.pdf 
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  
Lutz J., Jurk K., and Schinzel H. Direct oral anticaoagulants in patients with chronic kidney 
disease: patient selection and special considerations. Int J Nephrol Renovasc Dis. 
2018;10:135-143. doi: 10.2147/ijnrd.s105771 
Ronco C., Brendolan A., Nalesso F., et al. Prospective, randomized, multicenter, controlled 
trial (TRIATHRON 1) on a new antithrombogenic hydrophilic dialysis membrane. Int J Artif 
Organs 2017;40(5):234-9. 
Schwab S.J., Onorato J.J., Sharar L.R., et al. Hemodialysis without anticoagulation. One-year 
prospective Trial in Hospitalized Patients at Risk for Bleeding. Am J Med. 1987;83:405-410.  
Shen J.I., Mitani A.A., Chang T.I., et al. Use and safety of heparin-free maintenance 
hemodialysis in the USA. Nephrol Dial Transplant. 2013 Jun;28(6):1589-602. doi: 
10.1093/ndt/gft067. 
Stamatiadis D.N., Helioti H., Mansour M., et al. Hemodialysis for patients bleeding or at risk 
for bleeding, can be simple, safe and efficient Clin Nephrol. 2004;62(1):29-34. 
Xisomab 3G3. Aronora, Inc. Investigator Brochure. Version Number 2; 24 May 2018. 
 

SAP_001.pdf: 
Statistical Analysis Plan 
 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and 
Efficacy/Potency of a Single Dose of Xisomab 3G3, Administered at the Beginning of a 
Regular Hemodialysis Procedure, in Patients with End-Stage R14.3.5.3enal Disease on 
Chronic Hemodialysis 
 
Protocol No: 3G3-18-02 
Final Protocol Date: 25 May 2018 
Amendment One Date: 14 June 2018 
 
Compound Name: xisomab 3G3 
 
 
Celerion Project CA23900 
Final Version 1.0 
Date: 20 December 2018 
 
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  
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 2 of 96 
Statistical Analysis Plan Signature Page 
Compound Name: xisomab 3G3 
Protocol: 3G3-18-02 
Study Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Safety 
and Efficacy/Potency of a Single Dose of Xisomab 3G3, Administered at the 
Beginning of a Regular Hemodialysis Procedure, in Patients with End-Stage 
Renal Disease on Chronic Hemodialysis 
Issue Date: 20 December 2018 
 
Signature:_____________________________________ 
Date:_______________ 
Mohammad Abu-Rashid, BPharm, MPhil 
Senior Scientist, Clinical Pharmacology & Pharmacometrics,  
Data Management and Biometrics, Celerion 
100 Alexis Nihon Blvd., Suite 360 
Montreal, Quebec H4M 2N8, Canada 
 
Signature:_____________________________________ 
Date:_______________ 
Nancy Wang, PhD 
Associate Director, Biostatistics 
Data Management and Biometrics, Celerion 
Lincoln, Nebraska, USA 
 
Signature:_____________________________________ 
Date:_______________ 
Christina Lorentz, PhD 
Senior Scientist 
Aronora, Inc. 
Portland, Oregon 97239, USA 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 3 of 96 
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 .....................................................................7 
5. 
TREATMENT DESCRIPTIONS .......................................................................................7 
6. 
PHARMACOKINETIC ANALYSIS .................................................................................8 
6.1 
Measurements and Collection Schedule ...................................................................8 
6.2 
Bioanalytical Method ................................................................................................8 
6.3 
Investigational Product and PK Analyte Information ...............................................9 
6.3.1 Xisomab 3G3 ................................................................................................9 
6.4 
Pharmacokinetic Concentrations ...............................................................................9 
6.5 
Noncompartmental Pharmacokinetic Analysis and Parameter Calculation..............9 
6.5.1 Plasma Pharmacokinetic Parameters .............................................................9 
6.6 
Data Summarization and Presentation of PK Parameters .......................................11 
7. 
PHARMACODYNAMICS ..............................................................................................12 
7.1 
Pharmacodynamic Assessment ...............................................................................12 
7.1.1 Drug potency ...............................................................................................12 
7.1.2 Efficiency of HD .........................................................................................12 
7.2 
Data Summarization and Presentation of PD Parameters .......................................13 
7.2.1 aPTT 13 
7.2.2 BUN and Potassium: ...................................................................................14 
7.2.3 URR and KT/V ...........................................................................................14 
7.2.4 Clotting in the Drip Chamber and Dialysis Filter .......................................15 
7.2.5 Dialysate Analysis .......................................................................................15 
8. 
SAFETY ...........................................................................................................................15 
8.1 
Subject Discontinuation ..........................................................................................15 
8.2 
Demographics .........................................................................................................16 
8.3 
Adverse Events .......................................................................................................16 
8.4 
Clinical Laboratory Tests (Serum Chemistry, Hematology, Coagulation 
and Urinalysis) ........................................................................................................16 
8.5 
Vital Signs ...............................................................................................................17 
8.6 
Electrocardiogram ...................................................................................................17 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
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8.7 
Concomitant Medications .......................................................................................17 
8.8 
Physical Examination ..............................................................................................17 
8.9 
Vascular Access Site Reaction ................................................................................18 
8.10 Bleeding Time .........................................................................................................18 
8.11 Medical History .......................................................................................................18 
8.12 Immunogenecity ......................................................................................................18 
9. 
SUMMARY OF CHANGES FROM PROTOCOL-PLANNED ANALYSIS ................18 
10. SUMMARY TABLES AND FIGURES ..........................................................................18 
10.1 In-text Summary Tables and Figures ......................................................................19 
10.2 Section 14 Summary Tables and Figures ................................................................20 
10.3 Section 16 Data Listings .........................................................................................26 
11. TABLE AND FIGURE SHELLS .....................................................................................29 
11.1 In-text Summary Tables Shells ...............................................................................30 
11.2 Figures Shells ..........................................................................................................40 
11.3 Section 14 Summary Tables Shells .........................................................................47 
12. LISTING SHELLS ...........................................................................................................69 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 5 of 96 
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 the 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 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 a single 
dose of xisomab 3G3 when injected through a port into the proximal (arterial) dialysis 
line immediately after initiation of a hemodialysis (HD) procedure in patients with 
end stage renal disease (ESRD). 
The secondary objectives of the study are as follows: 
• To assess the pharmacodynamics (PD) of a single dose of xisomab 3G3 when 
injected through a port into the proximal (arterial) dialysis line immediately after 
initiation of a HD procedure in patients with ESRD. 
• To assess the efficacy of a single dose of xisomab 3G3 on HD efficiency when 
injected through a port into the proximal (arterial) dialysis line immediately after 
initiation of a HD procedure in patients with ESRD. 
• To assess the pharmacokinetics (PK) of a single dose of xisomab 3G3 when 
injected through a port into the proximal (arterial) dialysis line immediately after 
initiation of a HD procedure in patients with ESRD.  
2.2 
Endpoints 
Primary outcome measures: 
• The safety and tolerability of xisomab 3G3 will be evaluated versus pre-treatment 
and placebo by reviewing number and severity of adverse events and use of 
concomitant medications, physical examination, vascular access site reaction, 
bleeding time, and changes in vital signs, ECGs, and clinical laboratory 
evaluations. 
Secondary outcome measures: 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 6 of 96 
• PD using dose-dependency of drug potency, determined by measuring changes in 
the coagulation parameter (aPTT), and thrombus accumulation (assessed and 
ranked by visual inspection) within the dialyzer cartridges and total protein 
accumulation in the HD filter after xisomab 3G3-treatment versus pre-treatment 
and placebo. 
• Hemodialysis efficiency using blood urea nitrogen (BUN) and potassium levels 
will be measured before and after hemodialysis to calculate URR and Kt/V. 
Note:   Kt/V = volume of fluid completely cleared of urea [K = dialyzer clearance 
(mL/min), t = time of dialysis] and V = volume of water a patients body 
contains. Formulas to calculate Kt/V and URR are located under Section 
7.2.3. 
 
Other outcome measures: 
 
• The following PK parameters will be calculated for xisomab 3G3 in plasma, as 
appropriate: AUC0-t, AUC0-inf, AUC%extrap, Cmax, Tmax, Kel, t½, CL, and 
Vss. 
• Development of immunity or antibodies against xisomab 3G3 after drug 
exposure. 
3. STUDY DESIGN 
This is a phase 2, randomized, double-blind, placebo-controlled, single-dose study of 
xisomab 3G3 designed to evaluate the safety, efficacy/potency, and PK at 2 dose 
levels administered to patients with ESRD undergoing HD.  
Patients will be enrolled into Cohort 1 or Cohort 2; cohorts will be dosed 
sequentially. Within a cohort, patients will be randomized to active drug or placebo as 
summarized below: 
Cohort 
Treatment 
Active:Placebo Cohort Size 
1 
Infusion dose of 0.25 mg/kg xisomab 3G3 or placebo 
2:1 
9-12 
2 
Infusion dose of 0.5 mg/kg xisomab 3G3 or placebo 
2:1 
9-12 
This study includes a screening period of 28 days prior to checking-in to the clinical 
research unit on Day -8.  From Day -7 (one week prior to dosing on Day 1) through 
Day -1, all patients will undergo HD 3 times and will be assessed for all scheduled 
procedures and endpoints before and after each HD session.  
On Study Day 1, prior to dosing, patients will undergo baseline measurements 
followed by initiation of a regular HD procedure, consistently using only one type of 
dialyzer cartridge in each patient. Immediately after the start of blood perfusion, a 
single dose of xisomab 3G3 or matching placebo will be injected through a port into 
the flowing arterial blood in the proximal dialysis line. Patients will continue to 
undergo HD procedures and scheduled assessments from Day 1 through Day 12.   


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
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Study assessments will include physical examinations, vital signs, electrocardiogram 
(ECGs), clinical laboratory tests, HD vascular access site (AV fistula or AV graft) 
reaction, antibody titer (immunogenicity), adverse events (AEs), PD blood sampling 
(coagulation parameters), and PK blood sampling to be performed throughout the 
study. On Days -7, -5, and -3 and Days 1, 3, 5, and 12, bleeding time from the HD 
vascular access sites on the AV fistula or AV graft (ladder or buttonhole technique) 
will be evaluated at the end of the HD session. The dialyzer cartridge will be rinsed 
and visually inspected at the end of the HD procedure and graded against a 
standardized visual assessment scale. After visual assessment, the used and rinsed 
dialyzer cartridge will be frozen and saved for later retained content (deposited 
blood-derived material) analysis. The number of dialyzer cartridges used for the HD 
session will be recorded.  
All patients who received the study drug or placebo (including patients who terminate 
the study early) will undergo follow-up procedures at the Clinical Research Unit 
(CRU) approximately 12 days after dosing. 
4. ANALYSIS POPULATIONS 
4.1 
Analysis Populations 
Safety Population 
The safety population will include all patients who received at least one dose of study 
drug (active or placebo). 
 
Pharmacokinetic Population 
Samples from all patients receiving the active drug will be assayed even if the 
patients do not complete the study. All patients receiving the active drug 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. 
 
Pharmacodynamic Population 
All patients who received the study drug (active or placebo) and had at least one 
postdose measurement of any of the PD assessment will be included in the statistical 
analyses. 
4.2 
Preliminary Data and Interim Analysis 
Celerion has not been contracted to complete any interim safety, PK, and PD 
analyses. 
5. TREATMENT DESCRIPTIONS 
Patients will receive a single infusion dose of 0.25 mg/kg xisomab 3G3, 0.5 mg/kg 
xisomab 3G3, or matching placebo on Day 1 at Hour 0. The dose will be 
administered proximal to the dialyzer cartridge, into the arterial line immediately after 
start of HD. 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 8 of 96 
Planned doses for each cohort of the study are as follows: 
Cohort 1:  0.25 mg/kg xisomab 3G3 or matching placebo 
Cohort 2:  0.5 mg/kg xisomab 3G3 or matching placebo 
The patients’ 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 & 2 
P 
Placebo (Pooled) 
Single IV Infusion of Placebo 
(Pooled) 
Cohort 1 
A 
0.25 mg/kg 
xisomab 3G3 
Single IV Infusion of 0.25 
mg/kg xisomab 3G3 
Cohort 2 
B 
0.5 mg/kg 
xisomab 3G3 
Single IV Infusion of 0.5 
mg/kg xisomab 3G3 
 
6. PHARMACOKINETIC ANALYSIS 
6.1 
Measurements and Collection Schedule 
For all patients, blood samples for the determination of free xisomab 3G3 will be 
collected at predose (hour 0, at least 1 hour prior the start of HD session) and at 
0.167, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 120, 144, and 192 hours after xisomab 
3G3 start of infusion. 
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, 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 9 of 96 
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 and matching placebo was supplied as sterile powder for injection via 
the IV route, upon reconstitution.  
The quantity referenced for doses are based on active drug substance (i.e., xisomab 
3G3); therefore, dose adjustment is not required for calculation of dose-dependent PK 
parameters for the parent drug. 
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. 
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 
free xisomab 3G3 concentration-time data using Phoenix® WinNonlin® Version 7.0 
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. 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 10 of 96 
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 
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 
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 
Percent of AUC0-inf extrapolated  
 
AUC%extrap =  
(1 - AUC0-t/AUC0-
inf)*100 
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 
The maximum observed concentration 
Taken directly from 
bioanalytical data 
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 
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  
 
Calculated as: 0.693/ Kel 
CL 
The apparent total plasma clearance after IV 
administration 
Calculated as: 
Dose/(AUC0-inf)  
 
MRT* 
Mean residence time of free drug in the systemic 
circulation when the drug concentrations are 
extrapolated to infinity 
Calculated as:  
(AUMC0-inf/AUC0-inf ) – 
(T1/2) 
Where TI is the duration of 
infusion 
Vss 
Total apparent volume of distribution following 
single IV dose administration 
Calculated as:  
MRT x CL 


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* 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 patients with 2 or fewer consecutive time 
points with detectable 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 summary statistics. 
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 0.75. In cases 
where the Kel interval is not assigned, the values of AUC0-inf, AUC%extrap, 
AUMC0-inf, t½, CL, MRT, and Vss are considered not calculable and will not be 
reported. Wherever the resulting t½ is more than half as long as the sampling interval, 
the Kel values and associated parameters (AUC0-inf, AUC%extrap, AUMC0-inf, t½, 
CL, MRT, and Vss) may not be presented as judged appropriate and in accordance 
with Celerion SOPs.  
6.6 
Data Summarization and Presentation of PK Parameters 
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.  


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Statistical Analysis Plan, 20 December 2018 
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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 t½ 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 
7. 
PHARMACODYNAMICS  
7.1 
Pharmacodynamic Assessment 
Pharmacodynamic (PD) assessment will include evaluation of drug potency and 
efficiency of HD.  
7.1.1 Drug potency 
Drug potency will be evaluated using the following PD markers: 
• Thrombus accumulation will be evaluated by a visual inspection of the dialyzer 
membrane at the end of HD procedures and by a gradation using a standardized 
visual assessment scale;  
• Total protein accumulation within the HD filter will be evaluated using 
appropriate methods; 
• Coagulation parameter (activated partial thromboplastin time [aPTT]). 
7.1.2 Efficiency of HD 
Efficiency of HD will be assessed by: 
• Blood BUN and potassium levels before and after dialysis; 
• Length of HD – will be calculated as end time minus start time in hours and 
presented in individual and mean tables for each treatment; 


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• Total dialysate urea (measurement of BUN removed over 4 hours of dialysis) 
will be used to calculate; 
o Single pool Kt/V. The formula to calculate Kt/V is listed under Section 7.2.3. 
o URR measured as the difference between urea pre-dialysis and post-dialysis 
expressed as a percentage. The formula to calculate URR is listed under 
Section 7.2.3. 
7.2 
Data Summarization and Presentation of PD Parameters 
7.2.1 aPTT 
Sample Collection: Samples for the coagulation parameter (aPTT) will be collected 
at screening, pre- and post-dialysis on Days -7, -5, -3, 1, 3, 5, and 12. Additional 
samples for aPTT will be collected following xisomab 3G3/placebo dosing on Day 1 
at predose (hour 0, at least 1 hour prior the start of HD session) and at 0.167, 0.5, 1, 2, 
3, 4, 6, 8, 12, 16, 24, 48, 96, 120, 144, and 192, hours after xisomab 3G3 start of 
infusion. 
Baseline Calculation Method Following Day 1 Dosing: Following xisomab 3G3 
dosing on Day 1, aPTT change from baseline will be calculated by dividing postdose 
aPTT values from average of pre-dose baseline (the average of pre-dialysis aPTT 
values on Days -7, -5, -3, and 1 will be calculated as pre-dose baseline).  
Fold change in aPTT values: The fold change in aPTT values on Days -7, -5, -3, 1 
(only pre- and post-dialysis aPTT values on Day 1), 3, 5, and 12 will be calculated by 
dividing the post-dialysis aPTT/pre-dialysis aPTT values for each day separately.  
aPTT values will be extracted from the clinical laboratory database and descriptive 
statistics will be generated using SAS® version 9.3 or higher. Following Day 1 
xisomab 3G3 dosing, a table will be presented for the aPTT change from baseline 
with descriptive statistics.  
aPTT values will be listed and summarized by treatment and time points in Tables 
and Figures for all subjects in the Safety Population (2 active dose levels and pooled 
placebo). 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 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:  


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xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
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• 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 
 
7.2.2 BUN and Potassium: 
Sample Collection: Samples for BUN and potassium will be collected pre- and 
post-dialysis on Days -7, -5, -3, 1, 3, 5, and 12.  
 
Change in BUN and Potassium values: The change in BUN values on 
Days -7, -5, -3, 1, 3, 5, and 12 will be calculated by subtracting the post-dialysis BUN 
from the pre-dialysis BUN values for each day separately. The same method will be 
used for potassium. 
 
Potassium and BUN values will be listed and summarized by treatment and Day in 
Tables and Figures for all subjects in the Safety Population (2 active dose levels and 
pooled placebo).  
 
The level of precision for potassium and BUN summary statistic will be the same as 
per aPTT values listed in Section 7.2.1. 
7.2.3 URR and KT/V 
The derived PD parameters (URR and KT/V) will be calculated from the pre- and 
post-dialysis BUN values on Days -7, -5, 1, 3, 5, and 12.  
URR will be calculated using the following formula:  
URR = (1-(post-dialysis BUN/ pre-dialysis BUN))*100 
 
Kt/V will be calculated using the following formula:  
𝑠𝑝𝐾𝑡
𝑉= ln(𝑅−(0.008 × 𝑡)) + (4 −(3.5 × 𝑅)) × 𝑈𝐹
𝑊𝑡 
Where  
R = BUN Post-dialysis/BUN Pre-dialysis 
 
 
 
t = Time of HD  
 
 
 
UF = Pre-dialysis Weight – Post-dialysis Weight 
 
 
 
Wt = Post-dialysis weight of patient. 
 
URR and Kt/V values will be listed and summarized by treatment and Day in Tables 
for all subjects in the Safety Population (2 active dose levels and pooled placebo).  
 
The level of precision for URR and Kt/V summary statistic will be the same as per 
aPTT values listed in Section 7.2.1 


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7.2.4 Clotting in the Drip Chamber and Dialysis Filter  
Visual inspection of clotting in the drip chamber will be recorded 2 hours after start 
of dialysis and at the end of dialysis on Days -7, -5, -3, 1, 3, 5, and 12. 
 
Visual inspection of clotting in the dialysis filter will be recorded at the end of 
dialysis on Days -7, -5, -3, 1, 3, 5, and 12. 
 
Summary of clotting values will be listed and summarized by treatment and Day in 
Tables for all subjects in the Safety Population (2 active dose levels and pooled 
placebo). 
  
7.2.5 Dialysate Analysis  
A 10 mL dialysate sample will be taken at the start and at the end of HD on 
Days -7, -5, 3, 12 and at 0.5 and 4 hours post dosing on Day 1.  
The samples will be sent to Aronora and will be stored for up to 5 years following the 
last dosing for future analysis (e.g., xisomab 3G3 levels and or urea). 
 
8. SAFETY  
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. Percentages of total frequency counts, if presented, will be 
reported as whole numbers. 
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 (two dose levels and 
pooled placebo and study overall. 


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8.2 
Demographics 
Descriptive statistics will be calculated for continuous variables (age, weight, height, 
and body mass index) and frequency counts will be provided for categorical variables 
(race, ethnicity, and sex) by treatment and overall. Age will be derived from date of 
birth to date of first dosing. 
8.3 
Adverse Events 
All adverse events (AEs) occurring during this clinical trial will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA®), Version 21.1.  
All AEs captured in the database will be listed in by-subject data listings including 
verbatim term, coded term, treatment, severity, relationship to study medication, 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 time of or after study 
drug administration. Each TEAE will be attributed to a treatment based on the onset 
date and time of the AE. If the onset time of an AE is missing and the onset date is 
the same as 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 and overall. 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.  
Serious adverse events (SAEs), if present, will also be listed. Applicable narratives 
will be included in the CSR.  
8.4 
Clinical Laboratory Tests (Serum Chemistry, Hematology, Coagulation and 
Urinalysis) 
Safety serum chemistry, hematology and urinalysis tests are performed at Screening, 
Day -8 check-in, Day 1 predose, Day 6 and Day 12.  For anuric patients, urinalysis 
may not be performed. Platelet count are collected at start and end of HD on Days -7, 
-5, -3, 1, 3, 5 and 12 and on Day 6. Platelet count are collected at start and end of HD 
on Days -7, -5, -3, 1, 3, 5 and 12 and Day 6. aPTT results are presented and discussed 
in the PD Section 7.2.  
Out-of-range values and clinically significant results will be listed.  
For all numeric laboratory values, descriptive statistics will be presented for each 
laboratory test by assessment time point and treatment. Change from baseline will be 
summarized in a similar manner. Baseline is defined as the result closest and prior to 


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xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
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dose which may include unscheduled results. This will typically be the result 
collected at predose on Day 1. Postdose unscheduled events or 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.  
Coagulation parameters and platelet count will be listed and presented together since 
they have the same timepoints. Urinalysis test results will be listed only. 
8.5 
Vital Signs 
Vital signs tests (HR, BP, RR and T) will be assessed at Screening, Day -8 check-in, 
start of HD on Days -7, -5, -3, 1, 3, 5, 8, 10 and 12, 1 hour postdose on Day1, Day 6 
discharge or early term and Day 12 follow-up.  
 
Vital sign results will be summarized by dose level, pooled placebo, and time point. 
Change from baseline will be summarized in a similar way. Baseline is defined as the 
result closest and prior to the dose on Day 1, which may include unscheduled results, 
whichever is later. Postdose unscheduled events or early termination results will not 
be included in summaries. 
8.6 
Electrocardiogram  
Safety ECGs (HR, PR, QRS, QT and Fridericia correction QTcF) will be assessed at 
Screening, Day -8 check-in, Day 1 predose, Day 6 (discharge or early term) and Day 
12 follow-up. 
 
ECG parameters will be summarized by dose level, pooled placebo, and time point. 
Change from baseline will be summarized in a similar way. Baseline is defined as the 
result closest and prior to the dose on Day 1, which may include unscheduled results, 
whichever is later. Postdose unscheduled events or early termination results will not 
be included in summaries. 
 
The QTcF values that are > 450 ms and increase from baseline > 30 ms, will be 
flagged in the data listings. 
8.7 
Concomitant Medications 
All concomitant medications recorded during the study will be coded with the WHO 
Dictionary Version September 2018, B3 and listed. 
8.8 
Physical Examination 
Full physical examinations will be performed at Screening and Day -8 check-in and 
abbreviated physical examination will be performed on Days 1, 6 and 12. Abnormal 
findings will be reported as medical history or adverse events. All data found in the 
CRF will be listed.  


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Celerion, Clinical Study Report No. CA23900 
 
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8.9 
Vascular Access Site Reaction 
Vascular access site reaction will be assessed at predose on Day 1 and end of HD on 
Days 1, 3 and 5. Any new abnormal findings inconsistent with past skin injuries as 
expected in patient on chronic HD will be reported as AEs. 
8.10 
Bleeding Time 
The time to clot (bleeding time) will be recorded following hemodialysis after the 
needle is removed from the vascular access site on Days -7, -5, -3, 1, 3, 5 and 12.  
Summary statistics will be calculated for time to clot by treatment and assessment 
timepoint. 
8.11 
 Medical History 
All medical and surgical histories recorded in the study will be coded with 
MedDRA®, Version 21.1. and listed. 
8.12 
Immunogenecity 
Development of antibodies against the study drug will be evaluated by determining 
the anti-drug antibody (ADA) titer.  
Blood samples will be collected from each subject for ADA detection prior to dosing 
on Day 1 and at the end of HD on Day 12. Immunogenicity testing will be done at 
Celerion, Lincoln, Nebraska.  
Summary counts of positive and negative ADA detection will be presented by 
collection time and treatment.  
 
9. SUMMARY OF CHANGES FROM PROTOCOL-PLANNED ANALYSIS 
The length of HD was 3 hours in the protocol and should be approximately 4 hours. 
The samples collected for BUN and potassium will be at the end of dialysis 
(approximately 4 hours).  
The analyses described in this SAP are aligned with those analyses described in the 
protocol. 
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, 
immunogenicity and Safety summary tables and figures will be generated using SAS® 


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Version 9.3 or higher and/or using Phoenix® WinNonlin® Version 7.0 or higher for 
summary PK TFLs, as appropriate.  
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 
Subject Disposition Summary  
Section 11: 
Table 11-1 
Demographic Summary  
Table 11-2 
Summary of Plasma Xisomab 3G3 Pharmacokinetics Following a 
Single IV Infusion of 0.25 and 0.5 mg/kg Xisomab 3G3 
(Pharmacokinetic Population) 
Efficiency of HD: 
Table 11-3 
Summary of Difference Between Pre- and Post-dialysis BUN and 
URR – Days -7 to 12 (Safety Population) 
Table 11-4 
Summary of Difference Between Pre- and Post-dialysis Potassium – 
Days -7 toSummary 12 (Safety Population) 
Table 11-5 
Summary of Kt/V Values (Safety Population) 
Drug Potency: 
Table 11-6 
Summary of Difference Between Pre- and Post-dialysis aPTT – 
Days -7 to 12 (Safety Population) 
Table 11-7 
Summary of Clotting in the Drip Chamber – Days -7 to 12 (Safety 
Population) 
Table 11-8 
Summary of Clotting in the Dialysis Filter – Days -7 to 12 (Safety 
Population) 
Figures 
Figure 11-1 
Arithmetic Mean Plasma Xisomab 3G3 Concentration Versus Time 
Following a Single IV Infusion of 0.25 and 0.5 mg/kg Xisomab 3G3 
(Linear Scale) (Pharmacokinetic Population) 
Figure 11-2 
Arithmetic Mean Pre- and Post-dialysis BUN Values – Days -7 to 12 
(Linear Scale) (Safety Population) 
Figure 11-3 
Arithmetic Mean Pre- and Post-dialysis Potassium Values – Days -7 to 
12 (Linear Scale) (Safety Population) 


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Celerion, Clinical Study Report No. CA23900 
 
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Figure 11-4 
Arithmetic Mean aPPT Values Versus Time Following a Single IV 
Infusion of 0.25 and 0.5 mg/kg Xisomab 3G3 and Placebo (Pooled) – 
Day 1 (Linear Scale) (Safety Population) 
Figure 11-5 
Arithmetic Mean aPPT Values Versus Time During the Course of the 
Study – Days -7 to 12 (Linear Scale) (Safety Population) 
Figure 11-6 
Arithmetic Mean aPPT Change From Baseline Versus Time Following 
a Single IV Infusion of 0.25 and 0.5 mg/kg Xisomab 3G3 and Placebo 
(Pooled) – Day 1 (Linear Scale) (Safety Population) 
Figure 11-7 
Arithmetic Mean pre- and Post-dialysis aPTT Values – Days -7 to 12 
(Linear Scale) (Safety Population) 
Section 12: 
Table 12-1 
Adverse Event Frequency by Treatment - Number of Subjects 
Reporting the Event (% of Subjects Dosed) 
Table 12-2 
Summary of Difference Between Pre- and Post-dialysis PT – Days -7 
to 12 (Safety Population) 
Table 12-3 
Summary of Difference Between Pre- and Post-dialysis INR – Days -7 
to 12 (Safety Population) 
Table 12-4 
Summary of Difference Between Pre- and Post-dialysis PT/INR – 
Days -7 to 12 (Safety Population) 
Table 12-5 
Summary of Post-dialysis Bleeding Time – Days -7 to 12 (Safety 
Population) 
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 re-numbered as appropriate during the 
compilation of the report.  
14.1 
Demographic Data Summary Tables  
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. 
Table 14.1.1 Summary of Disposition (Safety Population) 
Table 14.1.2 Summary of Demographics (Safety Population) 
14.2 
Pharmacokinetic and Pharmacodynamic Data Summary Tables and 
Figures  
Pharmacokinetic Tables and Figures 


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14.2.1. Plasma Pharmacokinetic Xisomab 3G3 Tables and Figures 
Table 14.2.1.1.1 Plasma Xisomab 3G3 Concentrations (ng/mL) Following a 
Single IV Infusion of 0.25 mg/kg Xisomab 3G3 
(Pharmacokinetic Population) 
Table 14.2.1.1.2 Plasma Xisomab 3G3 Concentrations (ng/mL) Following a 
Single IV Infusion of 0.5 mg/kg Xisomab 3G3 
(Pharmacokinetic Population) 
Table 14.2.1.1.3 Plasma Xisomab 3G3 Concentrations (ng/mL) Following a 
Single IV Infusion of Placebo (Pooled)  
Table 14.2.1.1.4 Plasma Xisomab 3G3 Pharmacokinetic Parameters 
Following a Single IV Infusion of 0.25 mg/kg Xisomab 3G3 
(Pharmacokinetic Population) 
Table 14.2.1.1.5 Plasma Xisomab 3G3 Pharmacokinetic Parameters 
Following a Single IV Infusion of 0.5 mg/kg Xisomab 3G3  
(Pharmacokinetic Population) 
Table 14.2.1.1.6 Intervals (Hours) Used for Determination of Plasma Xisomab 
3G3 Kel Values (Pharmacokinetic Population) 
 
Figure 14.2.1.2.1 Arithmetic Mean (SD) Plasma Xisomab 3G3 Concentration 
Versus Time Profiles Following a Single IV Infusion of 0.25 
and 0.5 mg/kg Xisomab 3G3 (Linear Scale) 
(Pharmacokinetic Population) 
Figure 14.2.1.2.2 Arithmetic Mean Plasma Xisomab 3G3 Concentration 
Versus Time Profiles Following a Single IV Infusion of 0.25 
and 0.5 mg/kg Xisomab 3G3 (Linear Scale) 
(Pharmacokinetic Population) 
Figure 14.2.1.2.3 Arithmetic Mean Plasma Xisomab 3G3 Concentration 
Versus Time Profiles Following a Single IV Infusion of 0.25 
and 0.5 mg/kg Xisomab 3G3 (Semi-Log Scale) 
(Pharmacokinetic Population) 
Pharmacodynamic/Immunogenicity Tables and Figures 
14.2.2 
BUN Tables and Figures  
Table 14.2.2.1.1 Individual and Mean Difference Between Pre- and 
Post-dialysis BUN Values (unit) and URR – Days -7 to 12 – 
0.25 mg/kg Xisomab 3G3 on Day 1 (Safety Population) 
Table 14.2.2.1.2 Individual and Mean Difference Between Pre- and Post-
dialysis BUN Values (unit) and URR – Days -7 to 12 – 0.5 
mg/kg Xisomab 3G3 on Day 1 (Safety Population) 


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Table 14.2.2.1.3 Individual and Mean Difference Between Pre- and Post-
dialysis BUN Values (unit) and URR – Days -7 to 12 –
Placebo (Pooled) (Safety Population) 
Programmer Note:  
For Tables 14.2.2.1.1 through 14.2.2.1.3, the difference will 
be calculated as follows: (Pre-dialysis – Post-dialysis). 
 
Figure 14.2.2.2.1 Arithmetic Mean Pre- and Post-dialysis BUN Values – Days 
-7 to 12 (Linear Scale) (Safety Population) 
Figure 14.2.2.2.2 Arithmetic Mean (SD) Pre- and Post-dialysis BUN Values – 
Days -7 to 12 (Linear Scale) (Safety Population) 
14.2.3 
Potassium Tables and Figures  
Table 14.2.3.1.1 Individual and Mean Difference Between Pre- and Post-
dialysis Potassium Values (unit) – Days -7 to 12 – 0.25 
mg/kg Xisomab 3G3 on Day 1 (Safety Population) 
Table 14.2.3.1.2 Individual and Mean Difference Between Pre- and 
Post-dialysis Potassium Values (unit) – Days -7 to 12 – 0.5 
mg/kg Xisomab 3G3 on Day 1 (Safety Population) 
Table 14.2.3.1.3 Individual and Mean Difference Between Pre- and Post-
dialysis Potassium Values (unit) – Days -7 to 12 – Placebo 
(Pooled) (Safety Population) 
Programmer Note:  
For Tables 14.2.3.1.1 through 14.2.3.1.3, the difference will 
be calculated as follows: (Pre-dialysis – Post-dialysis). 
 
Figure 14.2.3.2.1 Arithmetic Mean Pre- and Post-dialysis Potassium Values – 
Days -7 to 12 (Linear Scale) (Safety Population) 
Figure 14.2.3.2.2 Arithmetic Mean (SD) Pre- and Post-dialysis Potassium 
Values – Days -7 to 12 (Linear Scale) (Safety Population) 
14.2.4 
Kt/V Tables  
Table 14.2.4.1.1 Individual and Mean Kt/V Values (unit) – 0.25 mg/kg 
Xisomab 3G3 on Day 1 (Safety Population) 
Table 14.2.4.1.2 Individual and Mean Kt/V Values (unit) – 0.5 mg/kg 
Xisomab 3G3 on Day 1 (Safety Population) 
Table 14.2.4.1.3 Individual and Mean Kt/V Values (unit) – Placebo (Pooled) 
(Safety Population) 
14.2.5 
aPTT Tables and Figures  
Table 14.2.5.1.1 Individual and Mean aPTT Values (unit) During the Course 
of the Study (Days -7 to 12) and Following a Single IV 


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Statistical Analysis Plan, 20 December 2018 
Page 23 of 96 
Infusion of 0.25 mg/kg Xisomab 3G3 on Day 1 (Safety 
Population) 
Table 14.2.5.1.2 Individual and Mean aPTT Values (unit) During the Course 
of the Study (Days -7 to 12) and Following a Single IV 
Infusion of 0.5 mg/kg Xisomab 3G3 on Day 1 (Safety 
Population) 
Table 14.2.5.1.3 Individual and Mean aPTT Values (unit) During the Course 
of the Study (Days -7 to 12) and Following a Single IV 
Infusion of Placebo (Pooled) on Day 1 (Safety Population) 
 
Table 14.2.5.1.4 Individual and Mean aPTT Change From Baseline Values 
(unit) Following a Single IV Infusion of 0.25 mg/kg Xisomab 
3G3 on Day 1 (Safety Population) 
Table 14.2.5.1.5 Individual and Mean aPTT Change From Baseline Values 
(unit) Following a Single IV Infusion of 0.5 mg/kg Xisomab 
3G3 on Day 1 (Safety Population) 
Table 14.2.5.1.6 Individual and Mean aPTT Change From Baseline Values 
(unit) Following a Single IV Infusion of Placebo (Pooled) – 
Day 1 (Safety Population) 
Programmer Note:  
For Tables 14.2.5.1.4 through 14.2.5.1.6, aPTT baseline 
will be the average of all pre-dialysis aPTT value on 
Days -7, -5, -3 and 1, and the change from baseline will be 
calculated as follows: (post-dialysis/baseline). 
 
Table 14.2.5.1.7 Individual and Mean Difference Between Pre- and Post-
dialysis aPTT Values (unit) – Days -7 to 12 – 0.25 mg/kg 
Xisomab 3G3 on Day 1 (Safety Population) 
Table 14.2.5.1.8 Individual and Mean Difference Between Pre- and Post-
dialysis aPTT Values (unit) – Days -7 to 12 – 0.5 mg/kg 
Xisomab 3G3 on Day 1 (Safety Population) 
Table 14.2.5.1.9 Individual and Mean Difference Between Pre- and Post-
dialysis aPTT Values (unit) – Days -7 to 12 – Placebo 
(Pooled) (Safety Population) 
Programmer Note:  
For Tables 14.2.5.1.7 through 14.2.5.1.9, the fold change 
will be calculated by follows: (post-dialysis/pre-dialysis 
aPTT values) for each day. 
 
Figure 14.2.5.2.1 Arithmetic Mean aPPT Values Versus Time Following a 
Single IV Infusion of 0.25 and 0.5 mg/kg Xisomab 3G3 and 
Placebo (Pooled) – Day 1 (Linear Scale) (Safety Population) 


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Statistical Analysis Plan, 20 December 2018 
Page 24 of 96 
Figure 14.2.5.2.2 Arithmetic Mean (SD) aPPT Values Versus Time Following 
a Single IV Infusion of 0.25 and 0.5 mg/kg Xisomab 3G3 
and Placebo (Pooled) – Day 1 (Linear Scale) (Safety 
Population) 
Figure 14.2.5.2.3 Arithmetic Mean aPPT Values Versus Time During the 
Course of the Study – Days -7 to 12 (Linear Scale) (Safety 
Population) 
Figure 14.2.5.2.4 Arithmetic Mean (SD) aPPT Values Versus Time During the 
Course of the Study – Days -7 to 12 (Linear Scale) (Safety 
Population) 
 
Figure 14.2.5.2.5 Arithmetic Mean aPPT Change From Baseline Versus Time 
Following a Single IV Infusion of 0.25 and 0.5 mg/kg 
Xisomab 3G3 and Placebo (Pooled) – Day 1 (Linear Scale) 
(Safety Population) 
Figure 14.2.5.2.6 Arithmetic Mean (SD) aPPT Change From Baseline Versus 
Time Following a Single IV Infusion of 0.25 and 0.5 mg/kg 
Xisomab 3G3 and Placebo (Pooled) – Day 1 (Linear Scale) 
(Safety Population) 
 
Figure 14.2.5.2.7 Arithmetic Mean Pre- and Post-dialysis aPTT Values – Days 
-7 to 12 (Linear Scale) (Safety Population) 
Figure 14.2.5.2.8 Arithmetic Mean (SD) Pre- and Post-dialysis aPTT Values – 
Days -7 to 12 (Linear Scale) (Safety Population) 
 
14.2.6  Clotting in the Drip Chamber Tables 
Table 14.2.6.1 Summary of Clotting in the Drip Chamber (Safety 
Population) 
14.2.7  Clotting in Dialysis Filter Tables 
Table 14.2.7.1 Summary of Clotting in the Dialysis Filter (Safety 
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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Statistical Analysis Plan, 20 December 2018 
Page 25 of 96 
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 is 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/Coagulation  (Safety Population) 
Table 14.3.4.3 Out-of-Range Values and Recheck Results – Urinalysis 
(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 and Change from Baseline – 
Serum Chemistry (Safety Population) 
Table 14.3.5.2 Clinical Laboratory Shift from Baseline – Serum Chemistry 
(Safety Population) 
Table 14.3.5.3 Clinical Laboratory Summary and Change from Baseline – 
Hematology (Safety Population) 
Table 14.3.5.4 Clinical Laboratory Shift from Baseline – Hematology 
(Safety Population) 
Table 14.3.5.5 Clinical Laboratory Summary and Change from Baseline – 
Coagulation and Platelet Count (Safety Population) 
Table 14.3.5.6 Clinical Laboratory Shift from Baseline – Coagulation and 
Platelet Count (Safety Population) 
Table 14.3.5.7 Vital Sign Summary and Change from Baseline (Safety 
Population)  


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Statistical Analysis Plan, 20 December 2018 
Page 26 of 96 
Table 14.3.5.8 12-Lead Electrocardiogram Summary and Change from 
Baseline (Safety Population) 
Table 14.3.5.9 Frequency of Immunogenicity - ADA Titer (Safety 
Population) 
10.3 
Section 16 Data Listings 
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 
Study Completion/Early Termination  (Safety 
Population) 
16.2.2 
Protocol Deviations 
Appendix 16.2.2 
Protocol Deviations 
16.2.3 
Subjects Excluded from Pharmacokinetic/Pharmcodynamic 
Analyses 
Appendix 16.2.3 
Subjects Excluded from 
Pharmacokinetic/Pharmacodynamic Analyses 
<Note: Appendices 16.2.2 and 16.2.3 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 and Surgical History (Safety Population) 
Appendix 16.2.4.4 
Alcohol Screen (Safety Population) 
Appendix 16.2.4.5 
Drug Screen (Safety Population) 
16.2.5 
Compliance and/or Drug Concentration Data 


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Statistical Analysis Plan, 20 December 2018 
Page 27 of 96 
Appendix 16.2.5.1 
Subject Eligibility (Safety Population) 
Appendix 16.2.5.2 
Subject Eligibility at Check-In (Safety Population) 
Appendix 16.2.5.3 
Test Compound Administration (Safety Population) 
Appendix 16.2.5.4 
Blood Draw Times for Free xisomab 3G3 PK (Safety 
Population) 
Appendix 16.2.5.5 
Blood Draw Times for Free xisomab 3G3 PD (aPTT)  
(Safety Population) 
Appendix 16.2.5.6 
Blood Draw Times for Immunogenicity (Safety 
Population) 
Appendix 16.2.5.7 
Blood Draw Times for Dialysate Analysis for Kt/V and 
URR (Safety Population) 
Appendix 16.2.5.8.1 Dialyzer Assessment (I of V) (Safety Population) 
Appendix 16.2.5.8.2 Dialyzer Assessment (II of V) (Safety Population) 
Appendix 16.2.5.8.3 Dialyzer Assessment (III of V) – (Safety Population 
Number and Volume of Saline Flushes) 
Appendix 16.2.5.8.4 Dialyzer Assessment (IV of V) – Clotting in Drip 
Chamber (Safety Population) 
Appendix 16.2.5.8.5 Dialyzer Assessment (V of V) – Clotting in Dialysis 
Filter (Safety Population) 
Appendix 16.2.5.9 
Non-Study Procedures (Safety Population) 
Appendix 16.2.5.10 
Prior and Concomitant Medications (Safety Population) 
 
16.2.6 
Individual Pharmacokinetic Response Data 
Individual Xisomab 3G3 Figures 
Appendix 16.2.6.1.1 Individual Plasma Xisomab 3G3 Concentrations Versus 
Time Profiles Following a Single IV Infusion of 0.25 
mg/kg Xisomab 3G3 (Linear and Semi-Log Scale) for 
<Subject #> 
Appendix 16.2.6.1.2 Individual Plasma Xisomab 3G3 Concentrations Versus 
Time Profiles Following a Single IV Infusion of 0.5 
mg/kg Xisomab 3G3 (Linear and Semi-Log Scale) for 
<Subject #> 
Appendix 16.2.6.2.1 Individual aPTT Values Versus Time Profiles During 
the Course of the Study (Linear Scale) for <Subject #> 
 
16.2.7 
Adverse Events Listings 


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Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 28 of 96 
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 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 – Coagulation and Platelet 
Count (Safety Population) 
Appendix 16.2.8.1.4 Clinical Laboratory Report - Urinalysis (Safety 
Population) 
Appendix 16.2.8.1.5 Clinical Laboratory Report – Additional Tests (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 ADA Titer (Safety Population) 
 
 


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Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 29 of 96 
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 of the Celerion ADaM Version 2.1 data structure.   
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 30 of 96 
11.1 
In-text Summary Tables Shells 
In-text Table 10-1 will be in the following format: 
 
Table 10-1 
Subject Disposition Summary 
 
Table 10-1  
Subject Disposition Summary (Safety Population) 
 
 
Dose Level of xisomab 3G3 
Pooled 
Placebo 
Overall 
Disposition 
0.25 mg/kg 
0.5 mg/kg 
Dosed 
XX (XX%) 
XX (XX%) 
XX (XX%) 
XX (XX%) 
Completed 
XX (XX%) 
XX (XX%) 
XX (XX%) 
XX (XX%) 
Discontinued 
X (XX%) 
X (XX%) 
X (XX%) 
X (XX%) 
 
<Reason1> 
X (XX%) 
X (XX%) 
X (XX%) 
X (XX%) 
 
<Reason2> 
X (XX%) 
X (XX%) 
X (XX%) 
X (XX%) 
Source: Table 14.1.1 
Program:  /CAXXXXX/sas_prg/stsas/intext/t_disp.sas  DDMMMYYYY  HH:MM 
 
 
 
 


Aronora, Inc. 
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Statistical Analysis Plan, 20 December 2018 
Page 31 of 96 
In-text Table 11-1 will be in the following format: 
 
Table 11-1 
Demographic Summary  
 
Trait 
Category/ 
Statistics 
Dose Level of xisomab 3G3 
Pooled 
Placebo 
 
0.25 mg/kg 
0.5 mg/kg 
Overall 
Sex 
Male 
XX (XX%) 
XX (XX%) 
XX (XX%) 
XX (XX%) 
Female 
XX (XX%) 
XX (XX%) 
XX (XX%) 
XX (XX%) 
Race 
Asian 
XX (XX%) 
XX (XX%) 
XX (XX%) 
XX (XX%) 
 
Black or African American 
XX (XX%) 
XX (XX%) 
XX (XX%) 
XX (XX%) 
 
White 
XX (XX%) 
XX (XX%) 
XX (XX%) 
XX (XX%) 
Ethnicity 
Hispanic or Latino 
XX (XX%) 
XX (XX%) 
XX (XX%) 
XX (XX%) 
 
Not Hispanic or Latino 
XX (XX%) 
XX (XX%) 
XX (XX%) 
XX (XX%) 
Age* (yrs) 
n 
XX 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
 
SD 
X.XX 
X.XX 
X.XX 
X.XX 
 
Minimum 
XX 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
XX 
Weight (kg) 
n 
XX 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
 
SD 
X.XX 
X.XX 
X.XX 
X.XX 
 
Minimum 
XX 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
XX 
*Age is calculated at the time of first dosing. 
BMI = Body mass index 
Source: Table 14.1.2 
Program:  /CAXXXXX/sas_prg/stsas/intexttest/t_dem.sas  DDMMMYYYY  HH:MM 
 
Programmer note:  also include height and BMI 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 32 of 96 
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 0.25 and 0.5 mg/kg Xisomab 3G3 (Pharmacokinetic Population) 
 
 
Pharmacokinetic 
Parameters  
Single IV Infusion of 0.25 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] 
AUCs and Cmax values are presented as geometric mean and geometric CV%, when available. 
Tmax values are presented as median (minimum, maximum). 
Other parameters are presented as arithmetic mean (± SD), or just mean when SD is not available.  
Source: Tables 14.2.1.4 through 14.2.1.5 
 
  
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 
 
 
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. 
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Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 33 of 96 
 
Table 11-3 
Summary of Difference Between Pre- and Post-dialysis BUN and URR – Days -7 to 12 (Safety Population) 
 
Mean Blood Urea Nitrogen (Reference Range xx – xx <units>) and  URR (Reference Range xx – xx <%>) 
 
 
Time 
Point 
Treatments 
Single IV Infusion of 0.25 mg/kg xisomab 
3G3 
Single IV Infusion of 0.5 mg/kg xisomab 
3G3 
Placebo (Pooled) 
 
Pre-
dialysis 
 
(Unit) 
[n=xx] 
 
Post-
dialysis 
 
(Unit) 
[n=xx] 
 
Difference 
 
 
(Unit) 
[n=xx] 
 
URR 
(%) 
 
(Unit) 
[n=xx] 
 
Pre-
dialysis 
 
(Unit) 
[n=xx] 
 
Post-
dialysis 
 
(Unit) 
[n=xx] 
 
Difference 
 
 
(Unit) 
[n=xx] 
 
URR 
(%) 
 
(Unit) 
[n=xx] 
 
Pre-
dialysis 
 
(Unit) 
[n=xx] 
 
Post-
dialysis 
 
(Unit) 
[n=xx] 
 
Difference 
 
 
(Unit) 
[n=xx] 
 
URR 
(%) 
 
(Unit) 
[n=xx] 
Day -7 
XXX.X 
XXX.X 
XX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
XX.X 
Day -5 
XXX.Xa 
XXX.X  
XX.X 
XX.X 
XXX.X  
XXX.X  
XX.X 
XX.X 
XXX.X  
XXX.X  
XX.X 
XX.X 
Day -3 
XXX.X  
XXX.X  
XX.X 
XX.X 
XXX.X  
XXX.X  
XX.X 
XX.X 
XXX.X  
XXX.X  
XX.X 
XX.X 
Day 1* 
XXX.X 
XXX.X 
XX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
XX.X 
Day 3 
XXX.X 
XXX.X 
XX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
XX.X 
Day 5 
XXX.X  
XXX.X  
XX.X 
XX.X 
XXX.X  
XXX.X  
XX.X 
XX.X 
XXX.X  
XXX.X  
XX.X 
XX.X 
Day 12 
XXX.X  
XXX.X  
XX.X 
XX.X 
XXX.X  
XXX.X  
XX.X 
XX.X 
XXX.X  
XXX.X  
XX.X 
XX.X 
Difference = Pre-dialysis - Post-dialysis 
a-n = xx 
URR = (1-(post-dialysis BUN/ pre-dialysis BUN))*100 
* -  Single IV infusion of 0.25, 0.5 mg/kg xisomab 3G3 or placebo was administered on Day 1 
Values will be presented as arithmetic mean  
 
Source: Tables 14.2.2.1.1 through 14.2.2.1.3 
Program:  /CAXXXXX/sas_prg/stsas/intext/t_ae.sas  DDMMMYYYY  HH:MM 
 
Notes for Generating the Actual Table: 
 
• 
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, with the following changes: n will be presented in the column title with more additional columns to be 
created. 
 
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, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 34 of 96 
Table 11-4 will be in the following format: 
Table 11-4 
Summary of Difference Between Pre- and Post-dialysis Potassium – Days -7 to 12 (Safety Population) 
 
                  Mean Potassium (Reference Range xx – xx <units>)  
 
 
Time 
Point 
Treatments 
Single IV Infusion of 0.25 mg/kg 
xisomab 3G3 
Single IV Infusion of 0.5 mg/kg 
xisomab 3G3 
Placebo (Pooled) 
 
Pre-
dialysis  
 
(Unit) 
[n=xx] 
 
Post-
dialysis 
 
(Unit) 
 [n=xx] 
 
Difference 
 
 
(Unit) 
 [n=xx] 
 
Pre-
dialysis  
 
(Unit) 
 [n=xx] 
 
Post-
dialysis 
 
(Unit) 
 [n=xx] 
 
Difference 
 
 
(Unit) 
 [n=xx] 
 
Pre-
dialysis  
 
(Unit) 
 [n=xx] 
 
Post-
dialysis 
 
(Unit) 
 [n=xx] 
 
Difference 
 
 
(Unit) 
 [n=xx] 
Day -7 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
Day -5 
XXX.X 
XXX.X a 
XX.X 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
Day -3 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
Day 1* 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
Day 3 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
Day 5 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
Day 6 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
Day 12 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
Difference = Pre-dialysis - Post-dialysis 
a-n = xx 
* -  Single IV infusion of 0.25, 0.5 mg/kg xisomab 3G3 or placebo was administered on Day 1 
Values will be presented as arithmetic mean  
 
Source: Tables 14.2.3.1.1 through 14.2.3.1.3 
Program:  /CAXXXXX/sas_prg/stsas/intext/t_ae.sas  DDMMMYYYY  HH:MM 
 
Notes for Generating the Actual Table: 
 
• 
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, with the following changes: n will be presented in the column title with additional columns to be created. 
 
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, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 35 of 96 
Tables 11-6, 12-2 through 12-4 will be in the following format: 
Table 11-6 
Summary of Difference Between Pre- and Post-dialysis aPTT – Days -7 to 12 (Safety Population) 
                  Mean aPTT (Reference Range xx – xx <units>)  
 
 
Time 
Point 
Treatments 
Single IV Infusion of 0.25 mg/kg 
xisomab 3G3 
Single IV Infusion of 0.5 mg/kg 
xisomab 3G3 
Placebo (Pooled) 
 
Pre-
dialysis  
 
(Unit) 
[n=xx] 
 
Post-
dialysis 
 
(Unit) 
 [n=xx] 
 
Fold 
Change 
 
(Unit) 
 [n=xx] 
 
Pre-
dialysis  
 
(Unit) 
 [n=xx] 
 
Post-
dialysis 
 
(Unit) 
 [n=xx] 
 
Fold 
Change 
 
(Unit) 
 [n=xx] 
 
Pre-
dialysis  
 
(Unit) 
 [n=xx] 
 
Post-
dialysis 
 
(Unit) 
 [n=xx] 
 
Fold 
Change 
 
(Unit) 
 [n=xx] 
Day -7 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
Day -5 
XXX.X 
XXX.X a 
XX.X 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
Day -3 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
Day 1* 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
Day 3 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
Day 5 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
Day 6 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
Day 12 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
XXX.X 
XXX.X 
XX.X 
Fold Change = Post-dialysis/Pre-dialysis  
a-n = xx 
* -  Single IV infusion of 0.25, 0.5 mg/kg xisomab 3G3 or placebo was administered on Day 1 
Values will be presented as arithmetic mean  
 
Source: Tables 14.2.5.1.7 through 14.2.5.1.9 
Program:  /CAXXXXX/sas_prg/stsas/intext/t_ae.sas  DDMMMYYYY  HH:MM 
 
Notes for Generating the Actual Table: 
• 
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, with the following changes: n will be presented in the column title with additional columns to be created. 
 
For Table 12-2 through 12-5 the source tables will be 14.3.5.5 
 
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, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 36 of 96 
Table 11-5 
Summary of Kt/V Values (Safety Population) 
Single pool Kt/V 
 
 
Time 
Point 
Treatments 
Single IV Infusion of 0.25 mg/kg 
xisomab 3G3 
Single IV Infusion of 0.5 mg/kg xisomab 
3G3 
Placebo (Pooled) 
R 
(unit) 
[n=xx] 
t 
(unit) 
[n=xx] 
UF 
(unit) 
[n=xx] 
Wt 
(unit) 
[n=xx] 
Kt/V 
(unit) 
[n=xx] 
R 
(unit) 
[n=xx] 
t 
(unit) 
[n=xx] 
UF 
(unit) 
[n=xx] 
Wt 
(unit) 
[n=xx] 
Kt/V 
(unit) 
[n=xx] 
R 
(unit) 
[n=xx] 
t 
(unit) 
[n=xx] 
UF 
(unit) 
[n=xx] 
Wt 
(unit) 
[n=xx] 
Kt/V 
(unit) 
[n=xx] 
Day -7 
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 
Day -5 
XX.X XX.X 
XX.X 
XX.Xa 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X XX.X XX.X 
XX.X 
XX.X 
Day -3 
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 
Day 1* 
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 
Day 3 
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 
Day 5 
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 
Day 12 
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 
a-n=xx 
* -  Single IV infusion of 0.25, 0.5 mg/kg xisomab 3G3 or placebo was administered on Day 1 
Values will be presented as arithmetic mean  
 
R= post-dialysis BUN/pre-dialysis BUN))*100 
t = Time of HD 
UF =  Pre-dialysis Weight – Post-dialysis Weight 
Wt = Post-dialysis weight of patient 
Kt/V = ln(R −(0.008 × t)) + (4 −(3.5 × R)) ×
UF
Wt 
 
Source: Tables 14.2.4.1.1 through 14.2.4.1.3 
Program:  /CAXXXXX/sas_prg/stsas/intext/t_ae.sas  DDMMMYYYY  HH:MM 
 
Notes for Generating the Actual Table: 
• 
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, with the following changes: n will be presented in the column title with more additional columns to be 
created. 
 
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, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 37 of 96 
Table 11-7 
Summary of Clotting in the Drip Chamber – Days -7 to 12 (Safety Population) 
Clotting in the Drip Chamber 
 
 
 
Time 
Point 
Treatments 
Single IV Infusion of 0.25 mg/kg xisomab 3G3 
Single IV Infusion of 0.25 mg/kg xisomab 3G3 
Placebo (Pooled) 
 
Category 
 
2 Hours after Start of 
Dialysis 
 
[n=xx] 
 
 
Category 
 
Post-dialysis 
 
 
[n=xx] 
 
Category 
 
2 Hours after Start of 
Dialysis 
 
[n=xx] 
 
 
Category 
 
Post-dialysis 
 
 
[n=xx] 
 
Category 
 
2 Hours after Start of 
Dialysis 
 
[n=xx] 
 
 
Category 
 
Post-dialysis 
 
 
[n=xx] 
 
1 
2 
3a 
3b 
4 
1 
2 
3a 
3b 
4 
1 
2 
3a 
3b 
4 
1 
2 
3a 
3b 
4 
1 
2 
3a 
3b 
4 
1 
2 
3a 
3b 
4 
Day -7 
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 
Day -5 
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 
Day -3 
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 
Day 1* 
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 
Day 3 
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 
Day 5 
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 
Day 12 
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 
Day x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a-n=xx 
* -  Single IV infusion of 0.25, 0.5 mg/kg xisomab 3G3 or placebo was administered on Day 1 
Values will be presented as arithmetic mean  
 
Source: Table 14.2.6.1  
Program:  /CAXXXXX/sas_prg/stsas/intext/t_ae.sas  DDMMMYYYY  HH:MM 
 
Notes for Generating the Actual Table: 
 
• 
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, with the following changes: n will be presented in the column title with more additional columns to be 
created. 
 
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, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 38 of 96 
Table 11-8 
Summary of Clotting in the Dialysis Filter – Days -7 to 12 (Safety Population) 
 
Clotting in Dialysis Filter 
 
 
 
Time 
Point 
Treatments 
Single IV Infusion of 
0.25 mg/kg xisomab 3G3 
Single IV Infusion of 
0.25 mg/kg xisomab 3G3 
Placebo (Pooled) 
 
Category 
 
Post-dialysis 
 
[n=xx] 
 
Category 
 
Post-dialysis 
 
[n=xx] 
 
Category 
 
Post-dialysis 
 
[n=xx] 
 
1 
2 
3a 
3b 
4 
1 
2 
3a 
3
b 
4 
1 
2 
3a 
3b 
4 
Day -7 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X X 
X 
X 
Day -5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X X 
X 
X 
Day 1* 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X X 
X 
X 
Day 3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X X 
X 
X 
Day 5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X X 
X 
X 
Day 12 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X X 
X 
X 
Day x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a-n=xx 
* -  Single IV infusion of 0.25, 0.5 mg/kg xisomab 3G3 or placebo was administered on Day 1 
Values will be presented as arithmetic mean  
 
Source: Table 14.2.7.1  
Program:  /CAXXXXX/sas_prg/stsas/intext/t_ae.sas  DDMMMYYYY  HH:MM 
 
Notes for Generating the Actual Table: 
 
• 
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, with the following changes: n will be presented in the column title with more additional columns to be 
created. 
 
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, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 39 of 96 
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) 
 
 
Dose Level of xisomab 3G3 
Pooled 
Placebo 
Overall 
Adverse Event* 
0.25 mg/kg 
0.5 mg/kg 
Number of Subjects With TEAEs 
XX (XX%) 
XX (XX%) 
XX (XX%) 
XX (XX%) 
Number of Subjects Without TEAEs 
XX (XX%) 
XX (XX%) 
XX (XX%) 
XX (XX%) 
System Organ Class 1 
     X (X%) 
     X (X%) 
     X (X%) 
     X (X%) 
 
Preferred Term 1 
     X (X%) 
     X (X%) 
     X (X%) 
     X (X%) 
 
Preferred Term 2 
     X (X%) 
     X (X%) 
     X (X%) 
     X (X%) 
System Organ Class 2 
     X (X%) 
     X (X%) 
     X (X%) 
     X (X%) 
 
Preferred Term 1 
     X (X%) 
     X (X%) 
     X (X%) 
     X (X%) 
 
Preferred Term 2 
     X (X%) 
     X (X%) 
     X (X%) 
     X (X%) 
*Adverse events are classified according to MedDRA Version 21.1. 
TEAEs = Treatment-emergent adverse events 
If a subject has 2 or more clinical adverse events, 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  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 40 of 96 
11.2 
Figures Shells 
In-text Figures 11-1, 11-4 through 11-6, post-text Figures 14.2.1.2.1 through 14.2.1.2.3, 
14.2.5.2.1 through 14.2.5.2.6 and Individual Listings in 16.2.6.1.1, 16.2.6.1.2, and 16.2.6.2.1 
will be in the following format: 
 
Figure 14.2.1.2.1 
 
Arithmetic Mean (SD) Plasma Xisomab 3G3 Concentration Versus Time 
Profiles Following a Single IV Infusion of 0.25 and 0.5 mg/kg Xisomab 3G3 
(Linear Scale) (Pharmacokinetic Population) 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 41 of 96 
Figure 14.2.1.2.2 
 
Arithmetic Mean Plasma Xisomab 3G3 Concentration Versus Time Profiles 
Following a Single IV Infusion of 0.25 and 0.5 mg/kg Xisomab 3G3 (Linear 
Scale) (Pharmacokinetic Population) 
 
 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 42 of 96 
Figure 14.2.1.2.3  
 
Arithmetic Mean Plasma Xisomab 3G3 Concentration Versus Time Profiles 
Following a Single IV Infusion of 0.25 and 0.5 mg/kg Xisomab 3G3 (Semi-
Log Scale) (Pharmacokinetic Population) 
 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 43 of 96 
Notes for Generating the Actual Mean Figure: 
 
• 
Figures 11-1, 14.2.1.2.1 through 14.2.1.2.3 
o  y-axis: Plasma Xisomab 3G3 Concentration (ng/mL) 
o  X-axis: Hours From Start of Infusion 
• 
Figures 11-4 and 11-5, 14.2.5.2.1 through 14.2.5.2.4 
o  y-axis: Arithmetic Mean aPTT (sec) 
o  X-axis: Hours From Start of Infusion 
• 
Figures 11-6, 14.2.5.2.5 and 14.2.5.2.6 
o  y-axis: aPTT Mean Change from Baseline (sec) 
o  X-axis: Hours From Start of Infusion 
 
 
Figure Legend: Use the Short Description as presented in Section 5. 
 
 
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, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 44 of 96 
Figures 11-2, 11-3, 11-7, 14.2.2.2.1, 14.2.2.2.2, 14.2.3.2.1, 14.2.3.2.2, 14.2.5.2.7, and 
14.2.5.2.8 will be listed as per the above formats with connecting the mean results between 
the pre- and post-dialysis results within the same day but without connecting the values 
between days. 
 
o y-axis: <aPTT, Bun, potassium> (unit) 
o  X-axis: Day 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 45 of 96 
Figures in Appendices 16.2.6.1 and 16.2.6.2 will be in the following format:  
 
Appendix 16.2.6.1.1 
 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 <#> 
 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 46 of 96 
Notes for Generating the Actual Individual Figure: 
 
• 
Appendix 16.2.6.1  
o  y-axis: Arithmetic Mean aPTT (sec) 
o  X-axis: Hours From Start of Infusion 
 
• 
Appendix 16.2.6.2  
o  y-axis: Plasma Xisomab 3G3 Concentration (ng/mL) 
o  X-axis: Hours From Start of Infusion 
 
 
Figure Legend: Use the Short Description as presented in Section 5. 
 
 
 
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, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 47 of 96 
11.3 
Section 14 Summary Tables Shells 
                                                                                                                            
                                                                                        Page 1 of X 
 
                             Table 14.1.1  Subject Disposition Summary (Safety Population) 
 
                                                           Dose Level of Xisomab 3G3  
                                                          ---------------------------- Pooled 
                                    Disposition               0.25 mg/kg  0.5 mg/kg    Placebo   Overall       
                                    --------------------------------------------------------------------- 
                                    Dosed                       X (XX%)     X (XX%)     X (XX%)   X (XX%) 
                                    Completed                   X (XX%)     X (XX%)     X (XX%)   X (XX%) 
                                    Discontinued                X (XX%)     X (XX%)     X (XX%)   X (XX%) 
                                      <Reason 1>                X (XX%)     X (XX%)     X (XX%)   X (XX%) 
                                      <Reason 2>                X (XX%)     X (XX%)     X (XX%)   X (XX%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program:  /CAXXXXX/sas_prg/stsas/tab PROGRAMNAME.sas  DDMMMYYYY  HH:MM  
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 48 of 96 
    
                                                                                                                                 Page 1 of X 
 
Table 14.1.2  Summary of Demographics (Safety Population) 
 
                                                                     Dose Level of Xisomab 3G3 
                                           Category/                 -----------------------------  Pooled 
                         Trait             Statistics                0.25 mg/kg      0.5 mg/kg     Placebo    Overall                
                         --------------------------------------------------------------------------------------------- 
                         Sex                Male                       X ( XX%)     X ( XX%)       X (XX%)    X (XX%) 
                                            Female                     X ( XX%)     X ( XX%)       X (XX%)    X (XX%) 
 
 
                         Race               Asian                      X ( XX%)     X ( XX%)       X (XX%)    X (XX%) 
                                            Black or African           X ( XX%)     X ( XX%)       X (XX%)    X (XX%) 
                                            American       
                                            White                      X ( XX%)     X ( XX%)       X (XX%)    X (XX%) 
 
                         Ethnicity          Hispanic or Latino         X ( XX%)     X ( XX%)       X (XX%)    X (XX%) 
                                            Not Hispanic or Latino     X ( XX%)     X ( XX%)       X (XX%)    X (XX%) 
 
                         Age* (yrs)         n                                X            X              X         X 
                                            Mean                          XX.X         XX.X           XX.X      XX.X 
                                            SD                            X.XX         X.XX           X.XX      X.XX 
                                            Minimum                         XX           XX             XX        XX 
                                            Median                        XX.X         XX.X           XX.X      XX.X 
                                            Maximum                         XX           XX             XX        XX 
 
                         Weight (kg)        n                                X            X              X         X 
                                            Mean                          XX.X         XX.X           XX.X      XX.X 
                                            SD                            X.XX         X.XX           X.XX      X.XX 
                                            Minimum                         XX           XX             XX        XX 
                                            Median                        XX.X         XX.X           XX.X      XX.X 
                                            Maximum                         XX           XX             XX        XX 
 
Programmer Note:  This is just a mock table shell. Please use the race categories listed in the CRF. 
                  Please also include Height (cm) and BMI (kg/m2). 
 
 
 
 
Note: *Age is calculated at the time of first dosing. 
 
Program:  /CAXXXXX/sas_prg/stsas/tab PROGRAMNAME.sas  DDMMMYYYY  HH:MM 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 49 of 96 
 
Tables 14.2.1.1.1 through 14.2.1.1.3, 14.2.5.1.1 through 14.2.5.1.6 will be in the following format:  
 
Table 14.2.1.1.1  Plasma Xisomab 3G3 Concentrations (ng/mL) Following a Single IV Infusion of 0.25 mg/kg Xisomab 3G3 (Pharmacokinetic 
Population)       
 
Subject --------------------------------- Sample Times (hr) -------------------------------- 
 
Number Predose 
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 
X 
BLQ 
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 <X> ng/mL are treated as 0 
before the first quantifiable concentration and as missing elsewhere. 
. = Value missing or not reportable. 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 50 of 96 
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, Minimum and Maximum +0, CV% to 1 decimal 
• 
PK Time points are: predose (hour 0) and 0.167, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 120, 144, and 192 hours postdose 
(additional time points might be added depending on the conduct of the study) 
• 
For Tables 14.2.5.1.1 through 14.2.5.1.3, aPTT values will be reported during the course of the study from Days -7 through 12 with 
adding “Day” above the “Sampling Time”. 
• 
For Tables 14.2.5.1.3 and 14.2.5.1.6, there will be no summary statistics 
 
 
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, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 51 of 96 
 
Tables 14.2.1.1.4 and 14.2.1.1.5 will be in the following format:  
Table 14.2.1.1.4  Plasma Xisomab 3G3 Pharmacokinetic Parameters Following a Single IV Infusion of 0.25 mg/kg Xisomab 3G3    
(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, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 52 of 96 
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, Minimum and Maximum = +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, Minimum and Maximum = +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, Minimum and Maximum = +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, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 53 of 96 
Table 14.2.1.1.6 will be in the following format:  
 Table 14.2.1.1.6 Intervals (Hours) Used for Determination of Plasma Xisomab 3G3 Kel Values (Pharmacokinetic Population) 
Subject 
Number 
Treatment 
Interval 
R2 
n 
                      ----------------------------------------------------------------------- 
X 
0.25 mg/kg 
XX.X - XX.X 
X.XXX 
X 
X     0.5 mg/kg 
XX.X - XX.X 
X.XXX 
X 
X 
x 
XX.X - XX.X 
X.XXX 
X 
X 
X 
XX.X - XX.X 
X.XXX 
X 
X 
X 
XX.X - XX.X 
X.XXX 
X 
X 
X 
XX.X - XX.X 
X.XXX 
X 
                      ----------------------------------------------------------------------- 
 
 
0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
 0.5 mg/kg: Single IV Infusion of 0.5 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, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 54 of 96 
Tables 14.2.2.1.1 through 14.2.2.1.3, 14.2.3.1.1 through 14.2.3.1.3 will have the following format: 
 
Table 14.2.3.1.1 
Individual and Mean Difference Between Pre- and Post-dialysis Potassium Values (unit) – Days -7 to 12 – 0.25 mg/kg 
Xisomab 3G3 on Day 1 (Safety Population) 
 
                                        0.25 mg/kg                         0.5 mg/kg                               Placebo                   . 
 
Subject 
 
Pre- 
dialysis 
Post- 
dialysis Difference 
Pre- 
dialysis 
Post- 
dialysis Difference 
Pre- 
dialysis 
Post- 
dialysis Difference 
Number 
Day 
(units) 
(units) 
(units) 
(units) 
(units) 
(units) 
(units) 
(units) 
(units) 
    ------------------------------------------------------------------------------------------------------------------------------------------- 
X 
-7 
XXX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
XXX 
XX.X 
X.XXX 
X 
-7 
XX.X 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
XXX 
XX.X 
X.XXX 
X 
-7 
XX.X 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
XXX 
XX.X 
X.XXX 
X 
-7 
X.XX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
XXX 
XX.X 
X.XXX 
X 
-7 
XXX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
XXX 
XX.X 
X.XXX 
    ------------------------------------------------------------------------------------------------------------------------------------------- 
n 
 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
 
XXX.X 
X.XXX 
XXX.X 
XXX.X 
XX.XX 
X.XXXX 
XXX.X 
XX.XX 
X.XXXX 
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 
XX.X 
SEM 
 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Minimum 
 
XX.X 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
XXX 
XX.X 
X.XXX 
Median 
 
XX.XX 
X.XXX 
XXX.X 
XXX.X 
XX.XX 
X.XXXX 
XXX.X 
XX.XX 
X.XXXX 
Maximum 
 
XXX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
XXX 
XX.X 
X.XXX 
    --------------------------------------------------------------------------------------------------------------------------------------------- 
 
0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
  
0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
  
Placebo = pooled placebo  
 
Difference = Pre-dialysis - Post-dialysis 
Single IV infusion of 0.25, 0.5 mg/kg xisomab 3G3 or placebo was administered on Day 1 
 
Programmer Notes:   
For the BUN Tables 14.2.2.1.1 through 14.2.2.1.3 values will be reported at pre- and post-dialysis on Days -7, -5, -3, 1, 3, 5, 6, and 12. 
The screening values to be reported if not presented in other tables. 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 55 of 96 
For the BUN Tables 14.2.2.1.1 through 14.2.2.1.3, additional column of “URR” will be reported at the right of the “Difference” column (as 
per Table 11-3 shell), with the following footnotes: 
• 
Difference = Pre-dialysis - Post-dialysis  
• 
Single IV infusion of 0.25, 0.5 mg/kg xisomab 3G3 or placebo was administered on Day 1 
• 
URR = (1-(post-dialysis BUN/ pre-dialysis BUN))*100 
 
 
Program:  /CAXXXXX/sas_prg/pksas/xxxxxxxx.sas   DDMMMYYYY  HH:MM 
Program:  /CAXXXXX/sas_prg/pksas/xxxxxxxxx.sas   
DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 56 of 96 
Tables 14.2.5.1.7 through 14.2.5.1.9, 14.2.4.1.1 through 14.2.4.1.3 will have the following format: 
 
Table 14.2.5.1.7 
Individual and Mean Difference Between Pre- and Post-dialysis aPTT Values (unit) – Days -7 to 12 – 0.25 mg/kg Xisomab 
3G3 on Day 1 (Safety Population) 
 
                                        0.25 mg/kg                         0.5 mg/kg                               Placebo                   . 
 
Subject 
 
Pre- 
dialysis 
Post- 
dialysis 
Fold 
Change 
Pre- 
dialysis 
Post- 
dialysis 
Fold 
Change 
Pre- 
dialysis 
Post- 
dialysis 
Fold 
Change 
Number 
Day 
(units) 
(units) 
(units) 
(units) 
(units) 
(units) 
(units) 
(units) 
(units) 
    ------------------------------------------------------------------------------------------------------------------------------------------- 
X 
-7 
XXX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
XXX 
XX.X 
X.XXX 
X 
-7 
XX.X 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
XXX 
XX.X 
X.XXX 
X 
-7 
XX.X 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
XXX 
XX.X 
X.XXX 
X 
-7 
X.XX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
XXX 
XX.X 
X.XXX 
X 
-7 
XXX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
XXX 
XX.X 
X.XXX 
    ------------------------------------------------------------------------------------------------------------------------------------------- 
n 
 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
 
XXX.X 
X.XXX 
XXX.X 
XXX.X 
XX.XX 
X.XXXX 
XXX.X 
XX.XX 
X.XXXX 
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 
XX.X 
SEM 
 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Minimum 
 
XX.X 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
XXX 
XX.X 
X.XXX 
Median 
 
XX.XX 
X.XXX 
XXX.X 
XXX.X 
XX.XX 
X.XXXX 
XXX.X 
XX.XX 
X.XXXX 
Maximum 
 
XXX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
XXX 
XX.X 
X.XXX 
    --------------------------------------------------------------------------------------------------------------------------------------------- 
 
0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
  
0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
  
Placebo = pooled placebo  
 
Fold Change = Post-dialysis / Pre-dialysis  
Single IV infusion of 0.25, 0.5 mg/kg xisomab 3G3 or placebo was administered on Day 1 
 
 
Programmer Notes:   
Values will be reported at pre- and post-dialysis on Days -7, -5, -3, 1, 3, 5, 6, and 12. 
The screening values to be reported if not presented in other tables. 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 57 of 96 
For Tables 14.2.4.1.1 through 14.2.4.1.3, Kt/V will be reported on Days -7, -5, -3, 1, 3, 5, and 12. Column titles will be the same as per 
Table 11-5 shell (ie., R, t, UF, Wt, and Kt/V) with the following footnotes: 
• 
Single IV infusion of 0.25, 0.5 mg/kg xisomab 3G3 or placebo was administered on Day 1 
• 
R = post-dialysis BUN/pre-dialysis BUN))*100 
• 
t = Time of HD 
• 
UF =  Pre-dialysis Weight – Post-dialysis Weight 
• 
Wt = Post-dialysis weight of patient 
• 
Kt/V = ln(R −(0.008 × t)) + (4 −(3.5 × R)) ×
UF
Wt 
 
 
For the bleeding time table in Section 14.3, values will be reported post-dialysis on Days screening (if available), -7, -5, -3, 1, 3, 5, 8, 
10 and 12. There will be only one column underneath each dose as per Table 11-4 shell with the following footnote: 
• 
Single IV infusion of 0.25, 0.5 mg/kg xisomab 3G3 or placebo was administered on Day 1 
 
 
Program:  /CAXXXXX/sas_prg/pksas/xxxxxxxx.sas   DDMMMYYYY  HH:MM 
Program:  /CAXXXXX/sas_prg/pksas/xxxxxxxxx.sas   
DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 58 of 96 
Tables 14.2.6.1 will be in the following format: 
 
                                                                                                                                               Page 1 of X 
 
  
  
 
 
Table 14.2.6.1  Summary of Clotting in the Drip Chamber – Days -7 to 12 (Safety Population) 
 
 
                                   0.25 mg/kg Xisomab 3G3   0.5 mg/kg Xisomab 3G3     Pooled Placebo 
                                   ----------------------  ----------------------   ---------------------- 
                                          Category*            Category*                 Category*    
                                   ----------------------  ----------------------   ----------------------                                         
         Day       Time Point       1   2   3a   3b    4   1   2   3a   3b    4      1   2   3a   3b    4 
  -------------------------------------------------------------------------------------------------------- 
         Day -7    2 hr after HD    X   X    X    X    X    X   X    X    X    X     X   X    X    X    X    
 
                   Post HD          X   X    X    X    X    X   X    X    X    X     X   X    X    X    X 
 
         Day  X    2 hr after HD    X   X    X    X    X    X   X    X    X    X     X   X    X    X    X    
 
                   Post HD          X   X    X    X    X    X   X    X    X    X     X   X    X    X    X 
 
 
 
 
        <include all days and timepoints> 
 
 
 
 
 
 
   Note: *Category:1=No detectable clotting, 2=Presence of fibrinous ring or minimum clot affecting less than 5% of chamber space, 
                   3a=Clot formation (affecting more than 5% of but less than 30% of chamber space) but dialysis still possible, 
                   3b=Clot formation (affecting more than 30% of chamber space) but dialysis still possible, 
                   4=Complete occlusion of chamber 
         HD: hemodialysis 
 
 
Program:  /AAXXXXX/ECR/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 59 of 96 
Tables 14.2.7.1 will be in the following format: 
 
                                                                                                                                               Page 1 of X 
 
  
Table 14.2.7.1  Summary of Clotting in the Dialysis Filter – Days -7 to 12 (Safety Population) 
 
 
                    0.25 mg/kg Xisomab 3G3   0.5 mg/kg Xisomab 3G3     Pooled Placebo 
                    ----------------------  ----------------------   ---------------------- 
                           Category*            Category*                 Category*    
                    ----------------------  ----------------------   ----------------------                                         
         Day         1   2   3a   3b    4   1   2   3a   3b    4      1   2   3a   3b    4 
  ----------------------------------------------------------------------------------------- 
         Day -7      X   X    X    X    X    X   X    X    X    X     X   X    X    X    X    
 
         Day  X      X   X    X    X    X    X   X    X    X    X     X   X    X    X    X    
 
 
 
 
 
        <include all days> 
 
 
 
 
 
 
   Note: *Category:1= No clotting, clean filter, 2= Few blood streaks (affecting less than 5% of the fibers seen at the surface of dialyzer), 
                   3a= More blood streaks (affecting more than 5% but less than 30 % of the fibers seen at the surface of the dialyzer), 
                   3b= More blood streaks (affecting more than 30% of the fibers seen at the surface if the dialyzer), 
                   4=Complete occlusion 
 
 
Program:  /AAXXXXX/ECR/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 60 of 96 
 
 
Page 1 of X 
 
Table 14.3.1.1 Treatment-Emergent Adverse Event Frequency by Treatment - Number of Subjects Reporting the Event  
(% of Subjects Dosed) (Safety Population) 
 
                                                                          
                                                    Dose Level of Xisomab 3G3 
                                                    -------------------------  Pooled 
     Adverse Event*                                 0.25 mcg/kg    0.5 mcg/kg   Placebo     Overall 
     ----------------------------------------------------------------------------------------------- 
     Number of Subjects Dosed                        XX ( XX%)    XX (XXX%)    XX ( XX%)   XX (XXX%) 
     Number of Subjects With TEAEs^                   X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
     Number of Subjects Without TEAEs^               XX ( XX%)    XX (XXX%)    XX ( XX%)   XX (XXX%) 
     ----------------------------------------------------------------------------------------------- 
     Nervous system disorders                         X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
          Dizziness                                   X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
          Headache                                    X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
          Presyncope                                  X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
     Respiratory, thoracic and mediastinal disorders  X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
          Dry throat                                  X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
          Oropharyngeal pain                          X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
          Sinus congestion                            X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
          Sneezing                                    X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
     General disorders and administration site        X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
     conditions 
          Fatigue                                     X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
          Thirst                                      X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
 
 
   
Note:  *Adverse events are classified according to MedDRA Version 21.1. ^ = Treatment-emergent adverse events 
        If a subject has 2 or more clinical adverse events, the subject is counted only once within a category. The same subject may appear  
        in different categories. 
 
Program:  /CAXXXXX/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 61 of 96 
Page 1 of X 
 
Table 14.3.1.2  Treatment-Emergent Adverse Event Frequency by Treatment - Number of Adverse Events  
(% of Total Adverse Events) (Safety Population) 
 
                                                           
                                                 
                                                     Dose Level of Xisomab 3G3 
                                                     ------------------------- Pooled 
     Adverse Event*                                  0.25 mg/kg    0.5 mg/kg   Placebo     Overall 
     ----------------------------------------------------------------------------------------------- 
     Number of TEAEs                                  X (100%)     X (100%)     X ( XX%)    X ( XX%) 
     ----------------------------------------------------------------------------------------------- 
     Nervous system disorders                         X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
          Dizziness                                   X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
          Headache                                    X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
          Presyncope                                  X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
     Respiratory, thoracic and mediastinal disorders  X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
          Dry throat                                  X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
          Oropharyngeal pain                          X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
          Sinus congestion                            X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
          Sneezing                                    X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
     General disorders and administration site        X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
     conditions 
          Fatigue                                     X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
          Thirst                                      X ( XX%)     X ( XX%)     X ( XX%)    X ( XX%) 
 
  
 
 
  
Note: *Adverse events are classified according to MedDRA Version 21.1. ^ = Treatment-emergent adverse events 
 
Program:  /CAXXXXX/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 62 of 96 
 
                                                                                                                       Page 1 of X 
 
Table 14.3.1.3  Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Study Drug -  
Number of Adverse Events (Safety Population) 
 
 
                                                                  Severity                            Relationship to Study Drug 
                       Dose    Number of    Number   ---------------------------------------  --------------------------------------------- 
                       Level/  Subjects      of                        
 Adverse Event*        Placebo With TEAEs   TEAEs    Grade 1   Grade 2     Grade 3   Grade 4  Unrelated Unlikely Possibly  Probably  Likely 
 ------------------------------------------------------------------------------------------------------------------------------------------ 
 Dizziness               X         X          X         X          X          X          X        X        X        X        X        X 
                         X         X          X         X          X          X          X        X        X        X        X        X 
 Dry eye                 X         X          X         X          X          X          X        X        X        X        X        X  
 Dry mouth               X         X          X         X          X          X          X        X        X        X        X        X 
 Dry throat              X         X          X         X          X          X          X        X        X        X        X        X 
 Ear pain                X         X          X         X          X          X          X        X        X        X        X        X 
                         X         X          X         X          X          X          X        X        X        X        X        X 
 Fatigue                 X         X          X         X          X          X          X        X        X        X        X        X 
 Headache                X         X          X         X          X          X          X        X        X        X        X        X 
 Dizziness               X         X          X         X          X          X          X        X        X        X        X        X 
                         X         X          X         X          X          X          X        X        X        X        X        X 
 Hyperhidrosis           X         X          X         X          X          X          X        X        X        X        X        X 
 Laceration              X         X          X         X          X          X          X        X        X        X        X        X 
 Limb crushing injury    X         X          X         X          X          X          X        X        X        X        X        X 
 Muscle twitching        X         X          X         X          X          X          X        X        X        X        X        X 
 ------------------------------------------------------------------------------------------------------------------------------------------ 
                0.25 mg/kg         X          X         X          X          X          X        X        X        X        X        X 
                 0.5 mg/kg         X          X         X          X          X          X        X        X        X        X        X 
                   Placebo        XX         XX         X          X          X          X        X        X        X        X        X 
                   Overall        XX         XX         X          X          X          X        X        X        X        X        X 
 ------------------------------------------------------------------------------------------------------------------------------------------ 
 
Note:  0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
        0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
        Placebo = pooled placebo  
*Adverse events are classified according to MedDRA Version 21.1. TEAE = Treatment-emergent adverse events 
        If a subject experience the same adverse event (AE) at more than one level of severity during a treatment, each AE is counted  
        separately. If a subject experience the same AE at more than one level of drug relationship during a treatment, each AE is  
        counted separately. 
        Severity: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially life-threatening 
 
Program:  /CAXXXXX/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 63 of 96 
Tables 14.3.4.1 to 14.3.4.3 will have the following format: 
Page 1 of X 
                
                               Table 14.3.4.1  Out-of-Range Values and Clinically Significant Results - Serum Chemistry (Safety Population) 
  
                                                                        Parameter1  Parameter2   Parameter3  Parameter4   Parameter5  
 Dose Level/  Subject Age#/  Study                                        <Range>     <Range>      <Range>      <Range>     <Range>   
 Placebo      Number  Sex    Period   Day   Hour    Date       Time       (Unit)      (Unit)       (Unit)      (Unit)       (Unit)   
 ----------------------------------------------------------------------------------------------------------------------------------- 
 XXX <units>    X     XX/X   Screen    .      .     DDMMMYYYY  HH:MM:SS    XX H +                                             XX L   
                               1      -X   -XX.XX   DDMMMYYYY  HH:MM:SS    XX L        XX L        XX H          XX L              
                             Recheck                DDMMMYYYY  HH:MM:SS                                          XX              
 
 
Programmer Notes:  Replace Parameter1, 2 etc. with actual lab tests in the study. Sort unscheduled assessment and early termination 
chronologically with other scheduled assessments.  
 
 
 
 
 
 
 
Note:  0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
        0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
        Placebo = pooled placebo  
        #Age is calculated at the time of first dosing. F = Female; M = Male  
        H = Above reference range, L = Below reference range                                                                     
        PI Interpretation: + = Clinically significant 
 
Program:  /CAXXXXX/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 64 of 96 
Tables 14.3.5.1, 14.3.5.3 and 14.3.5.5 will be in the following format: 
                                                                                                             Page 1 of X 
Table 14.3.5.1  Clinical Laboratory Summary and Change from Baseline - Serum Chemistry (Safety Population) 
 
                                                                                                   Change from Baseline* 
                                                                                                --------------------------- 
    Laboratory Test   Reference                                       0.25     0.5                0.25     0.5       
    (unit)            Range       Time Point          Statistic      mg/kg   mg/kg    Placebo    mg/kg   mg/kg    Placebo  
    -------------------------------------------------------------------------------------------  --------------------------  
    XXXXXXXXX (unit)  X.X-XX.X#   Screen              n                  XX       XX       XX     
                                                      Mean             X.XX     X.XX     X.XX     
                                                      SD              X.XXX    X.XXX    X.XXX    
                                                      Minimum          X.XX     X.XX     X.XX     
                                                      Median            X.X      X.X      X.X     
                                                      Maximum          XX.X     XX.X     XX.X     
 
                                  Baseline*           n                  XX       XX       XX     
                                                      Mean             X.XX     X.XX     X.XX     
                                                      SD              X.XXX    X.XXX    X.XXX    
                                                      Minimum          X.XX     X.XX     X.XX     
                                                      Median            X.X      X.X      X.X     
                                                      Maximum          XX.X     XX.X     XX.X     
 
                                  Day X, Hour X.XX    n                  XX       XX       XX      XX       XX       XX 
                                                      Mean             X.XX     X.XX     X.XX    X.XX     X.XX     X.XX 
                                                      SD              X.XXX    X.XXX    X.XXX   X.XXX    X.XXX    X.XXX 
                                                      Minimum          X.XX     X.XX     X.XX    X.XX     X.XX     X.XX 
                                                      Median            X.X      X.X      X.X     X.X      X.X      X.X 
                                                      Maximum          XX.X     XX.X     XX.X    XX.X     XX.X     XX.X 
 
                                 <include all timepoints>       
 
Programmer Note: Table 14.3.5.5 will not include timepoints that are summarized in PD endpoint tables in 14.2.  
 
Note:  0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
       0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
       Placebo = pooled placebo  
   # = Lowest of the lower ranges and highest of the higher ranges are used. Refer to Appendix 16.1.10.1 for the breakdown. 
       * Baseline is defined as the result closest and prior to dose on Day 1. 
Programmer note: for PT, INR and PT/INR, the pre-dialysis value will be the baseline value for that day and the “change from baseline” will 
be the fold change from baseline “ie. Post-dialysis / Pre-dialysis. 
 
Program:  /AAXXXXX/ECR/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 65 of 96 
 
Tables 14.3.5.2, 14.3.5.4 and 14.3.5.6 will be in the following format: 
Page 1 of X 
 
Table 14.3.5.2  Clinical Laboratory Shift From Baseline - Serum Chemistry (Safety Population)  
 
                                                      
                  Dose                                    Baseline* L                      Baseline* N                      Baseline* H 
Laboratory Test   Level/                           -------------------------------   -----------------------------   ------------------------------ 
(unit)            Placebo         Time Point          L         N          H            L         N          H          L          N          H  
-------------------------------------------------- -------------------------------   -----------------------------   ------------------------------ 
XXXXXXX (unit)    XXX <units>   Day X, Hour X.XX     X         XX          X           X         XX         X          X          XX         X  
 
 
 
 
 
 
 
 
 
 
 
Programmer Note: Table 14.3.5.6 will not include timepoints that are summarized in PD endpoint tables in 14.2.  
 
 
 
 
 
 
Note:  0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
       0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
       Placebo = pooled placebo  
   N = Within Normal Range, L = Below Normal Range, H = Above Normal Range 
       # = Lowest of the lower ranges and highest of the higher ranges are used. Refer to Appendix 16.1.10.1 for the breakdown. 
       * Baseline is defined as the result closest and prior to dose on Day 1. 
 
Program:  /AAXXXXX/ECR/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 66 of 96 
 
                                                                                                                                               Page 1 of X 
 
                            Table 14.3.5.7  Vital Sign Summary and Change from Baseline(Safety Population) 
 
 
                                                                                         Change from Baseline* 
                                                                                     ---------------------------- 
                                                            0.25     0.5                0.25     0.5        
    Vital Sign(unit)      Time Point          Statistic     mg/kg   mg/kg    Placebo    mg/kg   mg/kg    Placebo 
    ------------------------------------------------------------------------------------------------------------- 
    XXXXXXXXX (unit)      Screen              n               XX        XX       XX    
                                              Mean          X.XX      X.XX     X.XX    
                                              SD           X.XXX     X.XXX    X.XXX    
                                              Minimum       X.XX      X.XX     X.XX    
                                              Median         X.X       X.X      X.X    
                                              Maximum       XX.X      XX.X     XX.X    
 
                          <Also include Days -7, -5 and -3> 
 
                          Baseline*           n               XX        XX       XX    
                                              Mean          X.XX      X.XX     X.XX    
                                              SD           X.XXX     X.XXX    X.XXX    
                                              Minimum       X.XX      X.XX     X.XX    
                                              Median         X.X       X.X      X.X    
                                              Maximum       XX.X      XX.X     XX.X    
 
                          Day X, Hour X.XX    n               XX        XX       XX      XX        XX       XX 
                                              Mean          X.XX      X.XX     X.XX    X.XX      X.XX     X.XX 
                                              SD           X.XXX     X.XXX    X.XXX   X.XXX     X.XXX    X.XXX 
                                              Minimum       X.XX      X.XX     X.XX    X.XX      X.XX     X.XX 
                                              Median         X.X       X.X      X.X     X.X       X.X      X.X 
                                              Maximum       XX.X      XX.X     XX.X    XX.X      XX.X     XX.X 
 
                          <include all postdose timepoints> 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
  * Baseline is defined as the result closest and prior to the dose on Day 1. 
 
Program:  /AAXXXXX/ECR/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM  
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 67 of 96 
                                                                                                                                               Page 1 of X 
 
         
Table 14.3.5.8  12-Lead Electrocardiogram Summary and Change from Baseline (Safety Population) 
 
                                                                                                          
                                                                                         Change from Baseline* 
                                                                                     ---------------------------- 
                                                            0.25     0.5                0.25     0.5        
    Measurement (unit)    Time Point          Statistic     mg/kg   mg/kg    Placebo    mg/kg   mg/kg    Placebo 
    ------------------------------------------------------------------------------------------------------------- 
    XXXXXXXXX (unit)      Screen              n               XX        XX       XX    
                                              Mean          X.XX      X.XX     X.XX    
                                              SD           X.XXX     X.XXX    X.XXX    
                                              Minimum       X.XX      X.XX     X.XX    
                                              Median         X.X       X.X      X.X    
                                              Maximum       XX.X      XX.X     XX.X    
 
                          Baseline*           n               XX        XX       XX    
                                              Mean          X.XX      X.XX     X.XX    
                                              SD           X.XXX     X.XXX    X.XXX    
                                              Minimum       X.XX      X.XX     X.XX    
                                              Median         X.X       X.X      X.X    
                                              Maximum       XX.X      XX.X     XX.X    
 
                          Day X, Hour X.XX    n               XX        XX       XX      XX        XX       XX 
                                              Mean          X.XX      X.XX     X.XX    X.XX      X.XX     X.XX 
                                              SD           X.XXX     X.XXX    X.XXX   X.XXX     X.XXX    X.XXX 
                                              Minimum       X.XX      X.XX     X.XX    X.XX      X.XX     X.XX 
                                              Median         X.X       X.X      X.X     X.X       X.X      X.X 
                                              Maximum       XX.X      XX.X     XX.X    XX.X      XX.X     XX.X 
 
                          <include all postdose timepoints> 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
  * Baseline is defined as the result closest and prior to the dose on Day 1. 
 
Program:  /AAXXXXX/ECR/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
Tables 14.2.12 will be in the following format: 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 68 of 96 
                                                                                                                                               Page 1 of X 
 
  
Table 14.5.5.9  Frequency of Immunogenicity - ADA Titer (Safety Population) 
 
 
                    0.25 mg/kg Xisomab 3G3   0.5 mg/kg Xisomab 3G3      Pooled Placebo 
                    ----------------------  ----------------------   ---------------------- 
         Day          Positive   Negative    Positive   Negative       Positive   Negative  
  ----------------------------------------------------------------------------------------- 
         Day 1          X (%)      X (%)       X (%)      X (%)          X (%)      X (%)    
 
         Day 12         X (%)      X (%)       X (%)      X (%)          X (%)      X (%)    
 
 
 
 
Note:  % is percentage of total subject dosed in each treatment. 
 
 
Program:  /AAXXXXX/ECR/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 69 of 96 
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 CSR. These listings will be generated off of the 
Celerion SDTM Tabulation Model 1.4 mapped in accordance with SDTM Implementation 
Guide 3.2. All listings will be presented in Courier New size font 9. 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 70 of 96 
Page 1 of X 
 
                                   Appendix 16.1.10.1  Clinical Laboratory Reference Ranges  
 
                                                                                           Reference 
        Laboratory Group           Test Name                     Sex         Age Category  Range           Unit      
        -------------------------------------------------------------------------------------------------------- 
        Serum Chemistry            Test Name                     XXXXXX      XX            XX – XX         units 
                                   Test Name                     XXXXXX      XX            XX – XX         units 
                                   Test Name                     XXXXXX      XX            XX – XX         units 
                                   Test Name                     XXXXXX      XX            XX – XX         units 
                                   Test Name                     XXXXXX      XX            XX – XX         units 
                                   Test Name                     XXXXXX      XX            XX – XX         units 
                                                                                                                     
        Hematology                 Test Name                     XXXXXX      XX            XX – XX         units 
                                   Test Name                     XXXXXX      XX            XX – XX         units 
                                   Test Name                     XXXXXX      XX            XX – XX         units 
                                   Test Name                     XXXXXX      XX            XX – XX         units 
                                   Test Name                     XXXXXX      XX            XX – XX         units 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
<similar for remaining Laboratory Groups and Test Names> 
 
Program:  /CAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 71 of 96 
 
                                                                                                                                 Page 1 of X 
 
           
 
 
 
Appendix 16.2.1  Study Completion/Early Termination (Safety Population) 
 
              Dose Level/  Subject  Completed                Date of   
              Placebo      Number   Study?      Date       Last Contact  Reason for Discontinuation  Comments 
              -------------------------------------------------------------------------------------------------------------- 
              XXX <units>       X   Yes        DDMMMYYYY    DDMMMYYYY    
                                X   Yes        DDMMMYYYY    DDMMMYYYY    
                                X   Yes        DDMMMYYYY    DDMMMYYYY    
                                X   Yes        DDMMMYYYY    DDMMMYYYY    
                                X   No         DDMMMYYYY    DDMMMYYYY     XXXXXXXXXXXXXX             XXXXXXXX 
                                X   Yes        DDMMMYYYY    DDMMMYYYY    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 72 of 96 
                                                                                                                                 Page 1 of X 
 
                                              Appendix 16.2.4.1  Demographics (Safety Population) 
                                                                                                                                
                                                                                                              Body Mass   Informed                    
       Dose Level/  Subject    Date of      Age*                                         Height    Weight      Index      Consent 
       Placebo      Number     Birth       (yrs)    Sex       Race        Ethnicity      (cm)      (kg)       (kg/m2)       Date 
       --------------------------------------------------------------------------------------------------------------------------- 
       XXX <units>    X        MMMYYYY       XX     AAAAAA    AAAAAAAA    AAAAAAAAAA      XXX      XX.XX       XX.XX     DDMMMYYYY 
                      X        MMMYYYY       XX     AAAAAA    AAAAAAAA    AAAAAAAAAA      XXX      XX.XX       XX.XX     DDMMMYYYY 
                      X        MMMYYYY       XX     AAAAAA    AAAAAAAA    AAAAAAAAAA      XXX      XX.XX       XX.XX     DDMMMYYYY 
                      X        MMMYYYY       XX     AAAAAA    AAAAAAAA    AAAAAAAAAA      XXX      XX.XX       XX.XX     DDMMMYYYY 
                      X        MMMYYYY       XX     AAAAAA    AAAAAAAA    AAAAAAAAAA      XXX      XX.XX       XX.XX     DDMMMYYYY 
                      X        MMMYYYY       XX     AAAAAA    AAAAAAAA    AAAAAAAAAA      XXX      XX.XX       XX.XX     DDMMMYYYY 
                      X        MMMYYYY       XX     AAAAAA    AAAAAAAA    AAAAAAAAAA      XXX      XX.XX       XX.XX     DDMMMYYYY 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
      *Age is calculated from the date of first dosing. 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 73 of 96 
Page 1 of X 
 
 
Appendix 16.2.4.2  Physical Examination (Safety Population) 
 
  
    Dose Level/  Subject                                                                                             Clinical     
    Placebo      Number   Period   Day    Time    Date        Body System            Result   Abnormality            Significance 
  ----------------------------------------------------------------------------------------------------------------------------------------- 
    XXX <units>    X      Screen                  DDMMMYYYY   1. General Appearance  Abnormal XXXXXXXXXXXXXXXXXXXXX    NCS      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 74 of 96 
 
                                                                                                                                 Page 1 of X 
 
 
                      Appendix 16.2.4.3  Medical and Surgical Histories (Safety Population) 
  
 
                                                         Date of Diagnosis/Surgery 
  Dose Level/  Subject                                   -------------------------                                         
  Placebo      Number   Seq # Description                   Start           End          Ongoing?                            
-------------------------------------------------------------------------------------------------------- 
  XXX <units>     X      X    XXXXXX  XXXXX XXXXXXX        DDMMMYYYY                       Yes                                   
                         X    XXXXXXXXX                    DDMMMYYYY     DDMMMYYYY         No 
                         X    XXXXXXXX XXXXX XXXXXX        DDMMMYYYY     DDMMMYYYY         No   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 75 of 96 
 
 
                                                                                                                                 Page 1 of X 
 
 
         Appendix 16.2.4.4  
Alcohol Screen (Safety Population) 
  
 
                                                      
  Dose Level/  Subject    Visit                       Actual                                           
  Placebo      Number     Date       Type of Sample    Time     Result                           
-------------------------------------------------------------------------- 
  XXX <units>     X      DDMMMYYYY       Urine        HH:MM     Negative                                   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 76 of 96 
 
                                                                                                                                 Page 1 of X 
 
 
           
 
 
 
Appendix 16.2.4.5  
Drug Screen (Safety Population) 
  
 
                                                      
  Dose Level/  Subject    Visit                       Actual                                           
  Placebo      Number     Date       Type of Sample    Time     Result    If Positive, list all that were positive:                       
--------------------------------------------------------------------------------------------------------------------- 
  XXX <units>     X      DDMMMYYYY       Urine        HH:MM     Negative                                   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 77 of 96 
 
                                                                                                                               Page 1 of X 
 
                                           Appendix 16.2.5.1  Subject Eligibility (Safety Population) 
  
                                 
             Dose Level/  Subject  Study                       Did subject meet 
             Placebo      Number   Period    Date         all eligibility criteria?    Criterion Not Met*      Specify  
             ----------------------------------------------------------------------------------------------------------------------- 
             XXX <units>    X      Screen    DDMMMYYYY              Yes         
                            X      Screen    DDMMMYYYY              Yes  
                            X      Screen    DDMMMYYYY              No                  EXCLUSION X             XXXXXXXXXXXXXXX XXXX        
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
 
                                                                      
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 78 of 96 
                                                                                                                               Page 1 of X 
 
                                           Appendix 16.2.5.2  Subject Eligibility at Check-In (Safety Population) 
  
                                 
             Dose Level/  Subject  Study                  Does subject continue to meet 
             Placebo      Number   Period    Date         criteria since Screening?        If No, specify  
             ----------------------------------------------------------------------------------------------------------------------- 
             XXX <units>    X      Check-In  DDMMMYYYY              Yes         
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
 
                                                                      
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 79 of 96 
 
                                                                                                                                 Page 1 of X 
 
                               Appendix 16.2.5.3  Test Compound Administration Times (Safety Population) 
  
  Dose Level/  Subject                         Dose            Start     End                                                                             
  Placebo      Number   Period  Day  Time      Date      Administered?   Time      Time        Route        Form      Frequency                 
-------------------------------------------------------------------------------------------------------------------------- 
  XXX <units>    X       XXXX    XX   XX      DDMMMYYYY      Yes         HH:MM:SS  HH:MM:SS  IV Infusion   Injection    Once       
  
                                                                                              
 
  
 
 
 
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
 
 
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 80 of 96 
                                                                                                                                 Page 1 of X 
 
Appendix 16.2.5.4 Blood Draw Times for Free XISOMAB 3G3 PK (Safety Population) 
  
Dose Level/  Subject                               Actual                                         
Placebo      Number    Day   Hour     Date         Time       Comments                                      
------------------------------------------------------------------------- 
XXX <units>    X        X   -X.XX     DDMMMYYYY    XX:XX    XXXXXXXXXXX                                  
                            XX.XX     DDMMMYYYY    XX:XX                                            
                            XX.XX     DDMMMYYYY    XX:XX                                         
                            XX.XX     DDMMMYYYY    XX:XX    XXXXXXXXXX                                 
                            XX.XX     DDMMMYYYY    XX:XX                                                  
                            XX.XX     DDMMMYYYY    XX:XX                              
                            XX.XX     DDMMMYYYY    XX:XX    XXXXXXXXXXX                     
                            XX.XX     DDMMMYYYY    XX:XX   
                            XX.XX     DDMMMYYYY    XX:XX   
                            XX.XX     DDMMMYYYY    XX:XX                                                  
                            XX.XX     DDMMMYYYY    XX:XX   
                            XX.XX     DDMMMYYYY    XX:XX   
                        X   XX.XX     DDMMMYYYY    XX:XX   
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
 
 
 
Program:  /AAXXXXX/ECR/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 81 of 96 
                                                                                                                                 Page 1 of X 
 
Appendix 16.2.5.5 Blood Draw Times for Free XISOMAB 3G3 PD (aPTT) (Safety Population) 
  
Dose Level/  Subject                               Actual                                         
Placebo      Number    Day   Hour     Date         Time       Comments                                      
------------------------------------------------------------------------- 
XXX <units>    X        X   -X.XX     DDMMMYYYY    XX:XX    XXXXXXXXXXX                                  
                            XX.XX     DDMMMYYYY    XX:XX                                            
                            XX.XX     DDMMMYYYY    XX:XX                                         
                            XX.XX     DDMMMYYYY    XX:XX    XXXXXXXXXX                                 
                            XX.XX     DDMMMYYYY    XX:XX                                                  
                            XX.XX     DDMMMYYYY    XX:XX                              
                            XX.XX     DDMMMYYYY    XX:XX    XXXXXXXXXXX                     
                            XX.XX     DDMMMYYYY    XX:XX   
                            XX.XX     DDMMMYYYY    XX:XX   
                            XX.XX     DDMMMYYYY    XX:XX                                                  
                            XX.XX     DDMMMYYYY    XX:XX   
                            XX.XX     DDMMMYYYY    XX:XX   
                        X   XX.XX     DDMMMYYYY    XX:XX   
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
 
 
 
Program:  /AAXXXXX/ECR/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 82 of 96 
                                                                                                                                 Page 1 of X 
 
Appendix 16.2.5.6 Blood Draw Times for Immunogenicity (Safety Population) 
  
Dose Level/  Subject                               Actual                                         
Placebo      Number    Day   Hour     Date         Time       Comments                                      
------------------------------------------------------------------------- 
XXX <units>    X        1   Predose   DDMMMYYYY    HH:MM      XXXXXXXXXXX                                  
                       12   Follow-up DDMMMYYYY    HH:MM                                            
 
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
 
 
 
Program:  /AAXXXXX/ECR/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 83 of 96 
                                                                                                                                 Page 1 of X 
 
Appendix 16.2.5.7 Blood Draw Times for Dialysate Analysis for Kt/V and URR (Safety Population) 
  
Dose Level/  Subject                                Actual                                         
Placebo      Number    Day     Hour     Date         Time       Comments                                      
-------------------------------------------------------------------------------------------------- 
XXX <units>    X       -7    3 hours   DDMMMYYYY    HH:MM      XXXXXXXXXXX                                  
                       -5    3 hours   DDMMMYYYY    HH:MM                                            
                        1    3 hours   DDMMMYYYY    HH:MM                                            
                        3    3 hours   DDMMMYYYY    HH:MM                                            
                       12    3 hours   DDMMMYYYY    HH:MM                                            
 
 
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
 
 
 
Program:  /AAXXXXX/ECR/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 84 of 96 
                                                                                                                                 Page 1 of X 
 
Appendix 16.2.5.8.1 Dialyzer Assessment (I of V) (Safety Population) 
 
                                      Hemodialysis Time 
Dose Level/  Subject                 -------------------   Interrupted                                                             
Placebo      Number   Period  Day    Start  End   Total*   Prematurely?  Reason for Interruption   Specify                                      
-------------------------------------------------------------------------------------------------- 
XXX <units>    X       XXXX    X     HH:MM HH:MM  HH:MM      Yes 
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
      *Total = End time – Start time 
 
 
 
Program:  /AAXXXXX/ECR/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 85 of 96 
                                                                                                                                 Page 1 of X 
 
Appendix 16.2.5.8.2 Dialyzer Assessment (II of V) (Safety Population) 
 
                                                                   Blood 
                                   Atrial Pressure  Venus Pressure Flow    Time to Hemostasis    
Dose Level/  Subject               ---------------  -------------- Rate   -------------------   Dialysis Filter                                              
Placebo      Number    Day   Hour   Time     mmHg    Time    mmHg  mL/min  Time   Length (min)   Collected*?                                
----------------------------------------------------------------------------------------------------------------- 
XXX <units>    X        X     X     HH:MM     XX     HH:MM    XX    XX     HH:MM     XX             Yes 
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
      * Was the dialysis fi lter collected, sealed and stored < -20 C until shipment? 
 
 
Program:  /AAXXXXX/ECR/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 86 of 96 
                                                                                                                                 Page 1 of X 
 
Appendix 16.2.5.8.3 Dialyzer Assessment (III of V) - Number and Volume of Saline Flushes(Safety Population) 
 
 
 
                                   Saline Time 
Dose Level/  Subject               Flush   of    Volume      Total Volume        Total Number                                           
Placebo      Number    Day   Hour  Number Flush   (mL)      of Flushes (mL)      of Flushes                     
-------------------------------------------------------------------------------------------------- 
XXX <units>    X        X     X      1    HH:MM    XX          XXX                   XX 
                                     2    HH:MM    XX      
                                     3    HH:MM    XX      
                                     4    HH:MM    XX      
                                     5    HH:MM    XX      
                                     6    HH:MM    XX      
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
 
 
 
Program:  /AAXXXXX/ECR/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 87 of 96 
                                                                                                                                 Page 1 of X 
 
Appendix 16.2.5.8.4 Dialyzer Assessment (IV of V) – Clotting in the Drip Chamber(Safety Population) 
 
 
 
                                   2 Hours after Start of Dialysis                 End of Dialysis 
                                  ----------------------------------- ----------------------------------- 
                                                 Category*                            Category* 
Dose Level/  Subject                     ----------------------------         ----------------------------                                 
Placebo      Number    Day   Hour  Time     1   2   3a  3b   4          Time     1   2   3a  3b   4                 
---------------------------------------------------------------------------------------------------------- 
XXX <units>    X        X     X    HH:MM    X   X    X   X   X          HH:MM    X   X    X   X   X    
  
                                   
                                   
                                   
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
      *Category:1=No detectable clotting, 2=Presence of fibrinous ring or minimum clot affecting less than 5% of chamber space, 
                3a=Clot formation (affecting more than 5% of but less than 30% of chamber space) but dialysis still possible, 
                3b=Clot formation (affecting more than 30% of chamber space) but dialysis still possible, 
                4=Complete occlusion of chamber 
 
 
Program:  /AAXXXXX/ECR/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 88 of 96 
                                                                                                                                 Page 1 of X 
 
Appendix 16.2.5.8.5 Dialyzer Assessment (V of V) – Clotting in Dialysis Filter(Safety Population) 
 
 
 
                                             End of Dialysis 
                                       (or premature interruption) 
                                   ----------------------------------- 
                                                   Category* 
Dose Level/  Subject                       ----------------------------                                 
Placebo      Number    Day   Hour    Time     1   2   3a  3b   4                 
----------------------------------------------------------------------- 
XXX <units>    X        X     X      HH:MM    X   X    X   X   X    
  
                                   
                                   
                                   
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
      *Category:1= No clotting, clean filter, 2= Few blood streaks (affecting less than 5% of the fibers seen at the surface of dialyzer), 
                3a= More blood streaks (affecting more than 5% but less than 30 % of the fibers seen at the surface of the dialyzer), 
                3b= More blood streaks (affecting more than 30% of the fibers seen at the surface if the dialyzer), 
                4=Complete occlusion 
 
 
Program:  /AAXXXXX/ECR/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 89 of 96 
 
                                                                                                                                 Page 1 of X 
 
Appendix 16.2.5.9 Non-Study Producers (Safety Population) 
 
                                                      Procedure 
Dose Level/  Subject                   Assessment ----------------    Due to Medical Due to AE,  Overall Procedure     Procedure                             
Placebo      Number    Procedure         Date     Date       Time     History, seq#  AE page#     Interpretation    Findings/Comments                        
------------------------------------------------------------------------------------------------------------------------------------------ 
XXX <units>    X       None 
                       XXXXXXXXXXXXX   DDMMMYYYY  DDMMMYYYY  HH:MM      XXXXXXX        XX        XXXXXXXXXXXXXXXX   XXXXXXXXXXXXXXXXXXXX   
 
 
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
 
 
 
Program:  /AAXXXXX/ECR/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 90 of 96 
 
                                                                                                                                 Page 1 of X 
 
                                           Appendix 16.2.5.10  Prior and Concomitant Medications (Safety Population) 
                                                                                                                                     
                                                                     Start              Stop                                    Prior   Due 
Dose Level/ Subject  Any    Medication     Dosage/               ---------------  -----------------  Fre-               Con-      to    to 
Placebo     Number   Med?   (WHO* Term)    Strength  Form Route  Date      Time   Date       Time   quency Indication tinuing?  Study?  AE? 
-------------------------------------------------------------------------------------------------------------------------------------------- 
XXX <units>  X       No     None                                                                                                  
             X       Yes    ACETAMINOPHEN  620 mg/X  XXX  Oral   DDMMMYYYY HH:MM  DDMMMYYYY  HH:MM   Once  Toothache    No        X     XX  
                           (ACETAMINOPHEN) 
           
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
      *Concomitant medications are coded with World Health Organization (WHO) Drug Dictionary Version September 2018, B3. 
      Med = Medication  
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 91 of 96 
                                                                                                                                 Page 1 of X 
 
                                        Appendix 16.2.7.1.1  Adverse Events (I of II) (Safety Population) 
 
                                                                     Time From                                             
                                                                     Last Dose       Onset             Resolved         Duration  
Dose Level/ Subject                                                 ----------  ----------------   ----------------  ------------- 
Placebo     Number   TE?^   Adverse Event*    Preferred Term         (DD:HH:MM)  Date       Time    Date       Time    (DD:HH:MM) 
----------------------------------------------------------------------------------------------------------------------------------- 
XXX <units>   X             None                                                                                                
              X      Yes    XXXXXXXXXXXXX     XXXXXXXXXX XXXXXXX      XX:XX:XX   DDMMMYYYY  XX:XX   DDMMMYYYY  XX:XX    XX:XX:XX  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
      *Adverse events are classified according to MedDRA Version 21.1. 
      ^TE = Treatment-emergent 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 92 of 96 
 
                                                                                                                                 Page 1 of X 
 
                                       Appendix 16.2.7.1.2  Adverse Events (II of II) (Safety Population) 
 
                                                                                                                  
                                                        Onset                                                         
  Dose Level/  Subject        Adverse             -----------------        Severity/                      Relationship to 
  Placebo      Number   TE?^  Event               Date        Time  Freq*  Intensity  Serious  Outcome    Study Drug         Action 
  ------------------------------------------------------------------------------------------------------------------------------------- 
  XXX <units>    X            None                                                                                       
                 X      Yes   XXXXXXXXXXXXXXXXXX  DDMMMYYYY   XX:XX Inter.  Grade 1   Not      Resolved   XXXXXXXXXXXXXXXX   XXXXXXXXX 
                                                                            Mild      serious 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
      ^TE = Treatment-emergent 
      *Freq represents Frequency:  SI = Single Episode, Inter. = Intermittent, Cont. = Continuous                            
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 93 of 96 
 
 
 
                                                                                                                                Page 1 of X 
 
                              Appendix 16.2.7.2  Adverse Event Preferred Term Classification (Safety Population) 
 
                                                                                                                   Onset      
 Dose Level/  Subject        Adverse                                                                          ------------------ 
 Placebo      Number   TE?^  Event*                      Preferred Term             System Organ Class        Date       Time  
 ------------------------------------------------------------------------------------------------------------------------------- 
 XXX <units>    X      Yes   XXXXXXX XXXXX XXXX XXXXXX   XXXXXXXXXX XXXXXXX         XXXXXXXXXXXXXXXXXXXXX     DDMMMYYYY  XX:XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
      *Adverse events are classified according to MedDRA Version 21.1. 
      ^TE = Treatment-emergent 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM                                                                


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 94 of 96 
Appendices 16.2.8.1.1 to 16.2.8.1.5 will have the following format. 
 
                                                                                                                                 Page 1 of X 
 
                                   Appendix 16.2.8.1.1  Clinical Laboratory Report - Serum Chemistry (Safety Population) 
  
                                                                                                                                                
                                                              Parameter1  Parameter2  Parameter3  Parameter4  Parameter5 Parameter6  
  Dose Level/ Subject   Age#/  Study                           < Range>   < Range>    < Range>     < Range>   < Range>    < Range>        
  Placebo     Number    Sex    Period  Day   Hour   Date        (Unit)     (Unit)      (Unit)       (Unit)     (Unit)     (Unit)      
  ---------------------------------------------------------------------------------------------------------------------------------- 
  XXX <units>   X       XX/X   Screen   .      .    DDMMMYYYY   XX H        XX          XX           XX         XX H       XX        
                                X      -X   -XX.X   DDMMMYYYY   XX L +      XX L        XX           XX L       XX         XX        
 
 
 
Programmer Note:  Replace Parameter1, 2 etc. with actual lab tests in the study. Sort unscheduled assessment and early term chronologically 
with other scheduled assessments.   
 
 
 
 
Programmer Note: All timepoints for coagulation and platelet count should be listed with results and flags.  
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
      #Age is calculated from the date of first dosing. F = Female; M = Male 
H = Above reference range, L = Below reference range                                                                                         
PI interpretation: + = Clinically Significant 
                      
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 95 of 96 
 
                                                                                                                                Page 1 of X 
 
                                              Appendix 16.2.8.2  Vital Signs (Safety Population) 
  
 
                                                              Blood Pressure (mmHg)  Heart  Respi-    Tempera-                       
 Dose Level/  Subject                                         ---------------------  Rate   ration    ture     Weight           
 Placebo      Number  Period  Day  Hour     Date       Time      Systolic/Diastolic   (bpm)  (bpm)     (°C)     (kg)    Position    
 ----------------------------------------------------------------------------------------------------------------------------- 
 XXX <units>     X    Screen   .     .      DDMMMYYYY  XX:XX          XXX/ XX           XX    XX        XX       XX     XXXX                        
                       XXX    -X  -XX.X     DDMMMYYYY  XX:XX          XXX/ XX           XX    XX        XX       XX     XXXXXXXXX 
                       XXX     X   XX.X     DDMMMYYYY  XX:XX          XXX/ XX           XX            
 
 
 
 
 
 
Programmer Note: Sort unscheduled assessment and early term chronologically with other scheduled assessments.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Aronora, Inc. 
xisomab 3G3, Protocol 3G3-18-02 
Celerion, Clinical Study Report No. CA23900 
 
Statistical Analysis Plan, 20 December 2018 
Page 96 of 96 
 
                                                                                                                                 Page 1 of X 
 
                                            Appendix 16.2.8.3  12-Lead Electrocardiogram (Safety Population) 
 
                                                                        Heart                                                                      
  Dose Level/ Subject                                                   Rate     PR     QRS    QT    QTcF*                                       
  Placebo     Number   Period Day   Hour  Date       Time   Result      (bpm)   (ms)   (ms)   (ms)   (ms)    Comments                             
  -------------------------------------------------------------------------------------------------------------------- 
  XXX <units>  X       Screen  .      .   DDMMMYYYY  XX:XX  Normal       XX     XXX     XX    XXX    XXX^#   XXXXXXXXX                         
                         X     X    XX.X  DDMMMYYYY  XX:XX  Normal       XX     XXX     XX    XXX    XXX                  
                         X     X    XX.X  DDMMMYYYY  XX:XX  Normal       XX     XXX     XX    XXX    XXX                 
 
 
 
 
Programmer Note: Sort unscheduled assessment and early term chronologically with other scheduled assessments.   
 
 
 
 
 
 
 
 
 
 
 
Note: 0.25 mg/kg: Single IV Infusion of 0.25 mg/kg xisomab 3G3 
      0.5 mg/kg: Single IV Infusion of 0.5 mg/kg xisomab 3G3 
      Placebo = pooled placebo  
QTcF* = QT corrected for heart rate using Fridericia’s correction. 
Abnormal, NCS = Abnormal, Not clinically significant 
^ = QTcF is > 450 ms 
# = QTcF change from baseline is > 30 ms 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM