Conditions: Healthy Participants
Allocation: RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 25
Healthy volunteers: yes

Brief summary:
This is a single-center, randomized, double-blind, placebo-controlled, first-in-human, single intravenous (IV) infusion of XTMAB-16 (formerly referred to as KBMAB-16) in normal healthy male and female participants.

Detailed description:
A total of 24 normal healthy adult participants will be enrolled and assigned into 2 treatment cohorts with 12 participants (9 on XTMAB-16 and 3 on placebo) in each cohort. Participants will receive a single IV infusion of 2 mg/kg or 4 mg/kg of XTMAB-16 or placebo on Day 1.

Arms:
arm 1: Single IV Infusion arm 2: Single IV Infusion arm 3: Single IV Infusion

Interventions: intervention 1: Placebo intervention 2: XTMAB-16 2 mg/kg intervention 3: XTMAB-16 4mg/kg
Intervention descriptions: intervention 1: Single dose of 2 or 4 mg/kg intervention 2: Single dose of 2 mg/kg intervention 3: Single dose of 4 mg/kg

Protocol document:
Prot_000.pdf: 
A Randomized, Double-blind, Placebo-controlled, First-
in-Human Study to Evaluate the Safety, Tolerability, and 
Pharmacokinetics of a Single Intravenous Infusion of 
XTMAB-16 in Healthy Adult Participants 
Protocol Number: XTMAB-16-101 
IND Number: 143210 
Principal Investigator: Ron Goldwater, MDCM, MSc(A) 
Sponsor: Xentria Inc. 
Version Number: 4.0 (Amendment 3) 
28 May 2021 
CONFIDENTIAL PROPERTY OF Xentria Inc. 
This document is a confidential communication of Xentria Inc. Acceptance of this document constitutes the 
agreement by the recipient that no information contained herein will be published or disclosed without written 
authorization from Xentria Inc. except to the extent necessary to obtain informed consent from those persons to 
whom the drug may be administered. Furthermore, the information is only meant for review and compliance by 
the recipient, his or her staff, and applicable institutional review committee and regulatory agencies to enable 
conduct of the study. 
NCT04971395   


CONFIDENTIAL 
Protocol XTMAB-16-101 
Version 4.0 (Amendment 3) 
 
 
28 May 2021 
 
2 
Amendment 3: Summary of Changes from Previous Version (version 3.0 dated 
14 May 2021): 
Affected Section(s) Summary of Revisions Made 
Rationale 
Cover Page, 
Investigator’s 
Agreement, 
1.1 Synopsis  
Study title updated to remove 
“two-part”.  
Updated in response to FDA 
request dated 28 May 2021. 
1.1 Synopsis, 
1.2 Schema, 
1.3 Schedule of 
Activities, 
3 Objectives and 
Endpoints, 
4.1 Overall Design, 
4.1 Dose Escalation, 
4.3 Justification for 
Dose, 
5.5 Replacement of 
Participants, 
9.2 Sample Size 
Determination, 
9.4.6 Planned Safety 
Review 
Study design updated and “two-
part” and relevant description on 
Part A and Part B removed. 
The number of cohorts updated 
from 4 to 2 (now Cohorts 1 and 2), 
and the total number of participants 
updated to 24 (12 participants each 
cohort). Dose of each cohort 
updated to 2 mg/kg for Cohort 1, 
and 4 mg/kg for Cohort 2.  
Study objective updated to reflect 
the dose. 
The randomization ratio of 
participants except for sentinel 
cohort updated to 4:1. 
Justification for dose updated 
accordingly to reflect the revised 
dose. 
Updated in response to FDA 
request dated 28 May 2021. 
6.1.2 Dosing and 
Administration 
Reference to the Pharmacy Manual 
added, and the dose of each cohort 
updated.  
To refer to the Pharmacy Manual 
for details. 
Updated in response to FDA 
request dated 28 May 2021. 
 


CONFIDENTIAL 
Protocol XTMAB-16-101 
Version 4.0 (Amendment 3) 
 
 
28 May 2021 
 
3 
Amendment 2: Summary of Changes from Previous Version (version 2.0 dated 
11 March 2021): 
Affected Section(s) Summary of Revisions Made 
Rationale 
Sponsor Signature 
Page 
Updated Sponsor Signature Page: 
Remove 
 and add 
 
Xentria staff changes. 
1.1 Synopsis 
Updated study description to 
remove dosage details for Cohort 3 
and Cohort 4 (6 and 10 mg/kg 
become x and y mg/kg) 
Added additional detail to explain 
Part B study start. Upon completion 
of Part A, PK modeling will be used 
to determine Part B’s dosing regimen 
for Cohort 3 and 4. 
Clarify that Part B will not resume 
enrollment until a full review of 
safety and PK are submitted, 
reviewed, and approved by FDA.  
Updated in response to FDA Full 
Clinical Hold Letter dated 
31 March 2021. 
1.2 Schema 
Update Study Schematic to remove 
Part B dosage details. Replace 6 and 
10 mg/kg with x and y mg/kg. 
Updated in response to FDA Full 
Clinical Hold Letter dated 
31 March 2021. 
1.3 Schedule of 
Assessments 
Provided additional detail in 
footnote k regarding data collection 
procedures. 
Administrative correction footnote l. 
Change made to accommodate 
site’s standard of care and per IRB 
Clarification Letter 
(February 2021). 
2.2.3 XTMAB-16 
Updated the result of completed 
study. 
13-week pre-clinical work 
completed and study data is 
updated. 
2.2.4 Toxicology 
Overview 
Updated the result of completed 
study. 
13-week pre-clinical work 
completed and study data is 
updated. 


CONFIDENTIAL 
Protocol XTMAB-16-101 
Version 4.0 (Amendment 3) 
 
 
28 May 2021 
 
4 
Affected Section(s) Summary of Revisions Made 
Rationale 
4.1.2.1 Criteria 
6.5.1 Rescue 
Medication 
Corrected Appendix 5 to Appendix 4 
Corrected Appendix 6 to Appendix 5 
Administrative correction. 
4.1 Overall Design 
Updated study description to 
remove dosage details for Cohort 3 
and Cohort 4 (6 and 10 mg/kg 
become x and y mg/kg) 
Added additional detail to explain 
Part B study start. Upon completion 
of Part A, PK modeling will be used 
to determine Part B’s dosing regimen 
for Cohort 3 and 4. 
Clarify that Part B will not resume 
enrollment until a full review of 
safety and PK are submitted, 
reviewed, and approved by FDA. 
Updated in response to FDA Full 
Clinical Hold Letter dated 
31 March 2021. 
Section 3 Objectives  Update Objectives to remove dosage 
details. Replace 6 and 10 mg/kg with 
x and y mg/kg. 
Updated in response to FDA Full 
Clinical Hold Letter dated 
31 March 2021. 
4.1 Overall Design 
4.1.1 Dose 
Escalation 
Updated study description to 
remove dosage details for Cohort 3 
and Cohort 4 (6 and 10 mg/kg 
become x and y mg/kg) 
Added additional detail to explain 
Part B study start. The study will be 
paused for any further enrollment 
after Cohort 2 has completed all 
follow-up visits. A full safety analysis 
of and PK report will be submitted to 
the FDA for review and approval to 
move forward with higher doses in 
Part B. The same protocol design will 
be repeated for Part B (Cohort 3 and 
Cohort 4). 
Updated in response to FDA Full 
Clinical Hold Letter dated 
31 March 2021. 


CONFIDENTIAL 
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Version 4.0 (Amendment 3) 
 
 
28 May 2021 
 
5 
Affected Section(s) Summary of Revisions Made 
Rationale 
Update Table 2 dose chart (removed 
6 and 10 mg/kg and replace with x 
and y mg/kg) 
Provide Part B information: PK 
modeling will determine doses to be 
tested in Cohorts 3 and 4.  
Reiterate that Part B will not begin 
until FDA approval. 
4.3 Justification for 
Dose 
Update the planned dosage for 
Part B, 6 and 10 mg/kg with x and 
y mg/kg. 
Justification for dose updated based 
on the completed 13-week GLP TgTC 
toxicology study. 
Updated in response to FDA Full 
Clinical Hold Letter dated 
31 March 2021. 
5.2 Exclusion 
Criteria 
Corrected Exclusion #21 lab values to 
align with Exclusion #12. 
Updated in response to FDA 
Information Request (IR) dated 
08 March 2021. 
5.3 Lifestyle 
Considerations 
Clarify subject position for vital signs. 
A semi-supine position during 
infusion. 
Change made to accommodate 
site’s standard of care and per IRB 
Clarification Letter 
(February 2021).  
6.2.2 Formulation, 
Appearance, 
Packaging, and 
Labeling 
The reconstituted solution is stable 
at room temperature for ≤4 hours. 
The reconstituted solution should be 
stored at 5° C or at room 
temperature prior to administration 
for ≤4 hours. This information is also 
detailed in the pharmacy manual. 
Updated in response to FDA Full 
Clinical Hold Letter dated 
31 March 2021. 
6.2.2 Formulation, 
Appearance, 
Packaging, and 
Labeling  
6.3.2 Preparation 
The information on the appearance 
updated from “colorless to 
pale-yellow and clear” to “colorless 
to pale-yellow and opalescent”. 
Administrative correction. 


CONFIDENTIAL 
Protocol XTMAB-16-101 
Version 4.0 (Amendment 3) 
 
 
28 May 2021 
 
6 
Affected Section(s) Summary of Revisions Made 
Rationale 
KBMAB-16 replaced with XTMAB-16 
6.2.3 Product 
Storage and 
Stability 
Update infusion timing. Infusion 
should begin within 1.5 hours of 
reconstitution and dilution. 
Updated based on shortened IP 
stability at room temperature. 
6.3.1.1 Unblinding 
Procedure 
Corrected header numbering and 
hyperlinks/references from 6.3.1.1 
to 6.3.1 
Administrative correction. 
6.5 Concomitant 
Therapy (Table 4) 
Corrected “study” to “study drug 
(XTMAB16 or placebo). 
Administrative correction. 
8.2.3 Vital Signs 
8.2.4 
Electrocardiograms 
Clarify subject position for data 
collection. 
Semi-supine/semi-reclined during 
infusion, supine for all other 
timepoints. 
Change made to accommodate 
site’s standard of care and per IRB 
Clarification Letter 
(February 2021).  
Section 10.1.5 Key 
Roles and Study 
Governance 
(Table 6) 
Study team update: 
 removed 
 added 
 AD, 
Clinical Operations removed  
 Clinical Affairs 
Manager added 
Updated to capture staff changes. 
 
Amendment 1: Summary of Changes from Previous Version (version 1.0 dated 
19 Jan 2021): 
Affected Section(s) Summary of Revisions Made 
Rationale 
Protocol Title 
Change 
Added “Two-part” to title. 
Title change to clarify that the 
study would be conducted in 2 
phases, with an FDA review of 
safety and PK data following 
completion of Part A, in response 
to FDA position on NOAEL and 


CONFIDENTIAL 
Protocol XTMAB-16-101 
Version 4.0 (Amendment 3) 
 
 
28 May 2021 
 
7 
Affected Section(s) Summary of Revisions Made 
Rationale 
Information Request (IR) dated 
08 Mar 2021. 
Synopsis (Study 
Description), 
Section 1.3, Section 
2.3, Section 4.1, 
Section 6.1.2, 
Section 6.5  
Removed pretreatment with 500 mg 
acetaminophen. 
Updated in response to FDA IR 
dated 08 Mar 2021. Participants 
will instead be closely monitored 
and treated symptomatically. 
Additional guidance has been 
added assessing and treating 
anaphylaxis. 
Synopsis (Study 
Design, Study 
Population, Phase, 
Study Duration, 
Sample Size, 
Description of Study 
Intervention, 
Section 4.1, Section 
4.3 
Text added that the study would be 
conducted in 2 phases (Part A and 
Part B). Part A will consist of the 
lower dose cohorts (1 and 3 mg/kg) 
and Part B will consist of the higher 
dose cohorts (6 and 10 mg/kg). The 
study will be paused after 
completion of Part A and an interim 
analysis of the data will be provided 
to the FDA. Upon approval to 
proceed, Part B will be initiated. 
Both phases will be conducted 
identically with the same Schedule 
of Assessments. 
Per FDA IR of 08 Mar 2021: 
Amended study design for 
conducting the FIH study in 
2 parts, including FDA review of 
the data following completion of 
Part A. This allows assessment of 
safety and PK data from human 
participants at a level consistent 
with the preclinical NOAEL before 
proceeding to higher doses in 
humans. 
Section 1.3,  
Appendix 1 (Table 7) 
New footnotes that tryptase levels 
will be assessed for all participants 
at Baseline, and additionally if a 
participant experiences anaphylaxis 
within 4 hours after completion of 
infusion. 
Added in response to FDA IR dated 
08 Mar 2021. Provides guidance 
for detailed monitoring of any 
anaphylactic response. 
Section 1.3, Section 
6.5 
Footnotes to clarify the timing of 
COVID-19 vaccination. The COVID-
19 vaccine may be given up to 30 
days prior to Day1 dosing, or at any 
time through study after the Week 4 
assessments are complete. 
Added in response to FDA IR dated 
08 Mar 2021. 


CONFIDENTIAL 
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8 
Affected Section(s) Summary of Revisions Made 
Rationale 
Additionally, at each visit a 
temperature check will be 
performed and participants will be 
asked if they have been exposed to 
someone known to have COVID-19. 
Temperatures over 100°F (37.7°C) 
will trigger an unscheduled COVID-
19 test. 
Section 2.3, Section 
6.5.1, Appendix 4, 
Appendix 5 
Text added regarding injection site 
reactions to be graded according to 
a new Appendix 4 added for toxicity 
grading (Grades 1-4) related to 
severity. Added text that 
appropriate personnel and 
medications for treating 
hypersensitivity reactions should be 
available, and added a new 
Appendix 5 for diagnosing and 
treating anaphylaxis. 
Updated in response to FDA IR 
dated 08 Mar 2021. Participants 
will instead be monitored closely 
and treated symptomatically. 
Additional guidance has been 
added assessing and treating 
anaphylaxis. 
Section 4.1.2.1 
Text added text for stopping 
infusion related to injection site 
reactions and/or anaphylaxis. 
Reactions of Grade 3 or higher will 
indicate termination of infusion. 
Updated in response to FDA IR 
dated 08 Mar 2021. Participants 
will instead be monitored closely 
and treated symptomatically. 
Section 4.2.1.2, 
Section 9.4.2.1 
Text added to clarify stopping rules 
in the event of liver function tests 
meeting Hy’s Law and the analysis 
of liver function test results. 
Updated in response to FDA IR 
dated 08 Mar 2021. While liver 
function tests were included as 
part of the protocol, the added 
text provides specificity. 
Section 4.3, Table 3 Removed Human PK simulation data 
from Table 3 
Updated in response to FDA IR 
dated 08 Mar 2021. 
Section 5.1, 
Inclusion criterion 
#6, Appendix 3 
Clarified that women of childbearing 
potential are eligible for enrollment. 
Clarified that restrictions for 
reproductive safety risks extend 
Updated in response to FDA IR 
dated 08 Mar 2021. Addressed 
existing discrepancies. 


CONFIDENTIAL 
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Version 4.0 (Amendment 3) 
 
 
28 May 2021 
 
9 
Affected Section(s) Summary of Revisions Made 
Rationale 
through 90 days after dosing. 
Clarified that highly effective 
methods of contraception are to be 
used. Updated the list of highly 
effective contraception. 
Section 5.2, 
Exclusion criterion 
#12 
Added specific criteria and 
acceptable normal limits for liver 
and renal laboratory screening and 
enrollment parameters. 
Updated in response to FDA IR 
dated 08 Mar 2021. Parameter 
limits were not previously 
specified. 
Section 6.5, Table 4 Clarified that prescription 
contraceptives and short-term 
antibiotics are allowed, that 
medications in the table are 
prohibited from the time shown 
through Day 8, and clarified 
COVID-19 vaccinations. 
Per FDA IR dated 08 Mar 2021. 
Section 9.4.6 
Interim analysis statement 
corrected as per revised study 
design; data after completion of 
Part A will be analyzed and 
summarized. 
Correction related to change in 
study design and to clarify that the 
study would be conducted in 
2 phases, including FDA review of 
the safety and PK data after Part A 
has been completed, in response 
to FDA IR dated 08 Mar 2021. This 
allows assessment of safety and PK 
data from human participants at a 
level consistent with the 
preclinical NOAEL prior to 
proceeding to Part B with higher 
doses evaluated in healthy 
volunteers. 


CONFIDENTIAL 
Protocol XTMAB-16-101 
Version 4.0 (Amendment 3) 
28 May 2021 
10 
SPONSOR SIGNATURE PAGE 
I confirm that I have read and approved this protocol in its entirety and will comply with the 
obligations as detailed in all applicable regulations and guidelines (eg, International Council on 
Harmonisation [ICH] Good Clinical Practice [GCP] guidelines) and the protocol. 
 
Chief Medical Officer 
Xentria Inc. 
Date 
2 June 2021


CONFIDENTIAL 
Protocol XTMAB-16-101 
Version 4.0 (Amendment 3) 
 
 
28 May 2021 
 
11 
INVESTIGATOR’S AGREEMENT 
PROTOCOL TITLE: A Randomized, Double-blind, Placebo-controlled, First-in-Human Study to 
Evaluate the Safety, Tolerability, and Pharmacokinetics of a Single Intravenous Infusion of 
XTMAB-16 in Healthy Adult Participants 
PROTOCOL NUMBER: XTMAB-16-101 
VERSION: Amendment 3 
This protocol is a confidential communication of the Sponsor. I confirm that I have read this 
protocol, I understand it, and I will work according to this protocol. I will also work consistently 
with the ethical principles that have their origin in the Declaration of Helsinki and that are 
consistent with GCPs and all applicable laws and regulations. Acceptance of this document 
constitutes my agreement that no unpublished information contained herein will be published 
or disclosed without prior written approval from the Sponsor. 
Instructions to the Investigator: Please SIGN and DATE this signature page. PRINT your name, 
title, and the name of the study center in which the study will be conducted. Return the 
signed copy to the Sponsor or designee. 
 
I have read this protocol in its entirety and agree to conduct the study accordingly. 
 
 
Signature of Investigator 
 
Date 
 
 
 
 
 
 
Ronald Goldwater, MDCM, MSC(A), CPI 
Principal Investigator 
 
 
 
Name/Address of Center: 
Parexel Baltimore Early Phase Clinical Unit 
 
MedStar Harbor Hospital 
 
3001 South Hanover Street – 7th floor 
 
Baltimore, MD 21115 


CONFIDENTIAL 
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Version 4.0 (Amendment 3) 
 
 
28 May 2021 
 
12 
TABLE OF CONTENTS 
Sponsor Signature Page .......................................................................................................................................... 10 
Investigator’s Agreement ......................................................................................................................................... 11 
TABLE OF CONTENTS ........................................................................................................................................... 12 
STATEMENT OF COMPLIANCE ........................................................................................................................... 15 
1 
PROTOCOL SUMMARY ............................................................................................................................. 16 
1.1 
Synopsis .............................................................................................................................................. 16 
1.2 
Schema ............................................................................................................................................... 19 
1.3 
Schedule of Assessments ................................................................................................................ 20 
2 
INTRODUCTION .......................................................................................................................................... 23 
2.1 
Study Rationale .................................................................................................................................. 23 
2.2 
Background......................................................................................................................................... 23 
2.2.1 
Sarcoidosis ......................................................................................................................................... 23 
2.2.2 
TNFα .................................................................................................................................................... 24 
2.2.3 
XTMAB-16 .......................................................................................................................................... 25 
2.2.4 
Toxicology Overview ......................................................................................................................... 25 
3 
OBJECTIVES AND ENDPOINTS .............................................................................................................. 29 
4 
STUDY DESIGN ........................................................................................................................................... 31 
4.1 
Overall Design .................................................................................................................................... 31 
4.1.1 
Dose Escalation ................................................................................................................................. 32 
4.1.2 
Stopping Rules ................................................................................................................................... 33 
4.2 
Scientific Rationale for Study Design.............................................................................................. 34 
4.3 
Justification for Dose ......................................................................................................................... 35 
4.4 
End of Study Definition ..................................................................................................................... 36 
5 
STUDY POPULATION ................................................................................................................................ 37 
5.1 
Inclusion Criteria ................................................................................................................................ 37 
5.2 
Exclusion Criteria ............................................................................................................................... 37 
5.3 
Lifestyle Considerations .................................................................................................................... 39 
5.4 
Screen Failures .................................................................................................................................. 40 
5.5 
Replacement of Participants ............................................................................................................ 40 
6 
STUDY INTERVENTION ............................................................................................................................ 42 
6.1 
Study Drug Administration ................................................................................................................ 42 
6.1.1 
Study Drug Description ..................................................................................................................... 42 
6.1.2 
Dosing and Administration ............................................................................................................... 42 
6.2 
Preparation/Handling/Storage/Accountability ................................................................................ 43 
6.2.1 
Acquisition and accountability .......................................................................................................... 43 
6.2.2 
Formulation, Appearance, Packaging, and Labeling .................................................................... 43 
6.2.3 
Product Storage and Stability .......................................................................................................... 44 
6.3 
Measures to Minimize Bias: Randomization and Blinding ........................................................... 44 
6.3.1 
Unblinding Procedure ........................................................................................................................ 45 
6.3.2 
Preparation ......................................................................................................................................... 45 
6.4 
Study Drug Compliance .................................................................................................................... 46 
6.5 
Concomitant Therapy ........................................................................................................................ 46 
6.5.1 
Rescue Medicine ............................................................................................................................... 47 
6.6 
Overdose............................................................................................................................................. 47 


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13 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL .................................................................................................................... 49 
7.1 
Discontinuation of Study Drug ......................................................................................................... 49 
7.2 
Participant Discontinuation/Withdrawal from the Study ............................................................... 49 
7.3 
Lost to Follow-Up ............................................................................................................................... 49 
8 
STUDY ASSESSMENTS AND PROCEDURES ..................................................................................... 51 
8.1 
Efficacy Assessments ....................................................................................................................... 51 
8.2 
Safety and Other Assessments ....................................................................................................... 51 
8.2.1 
Physical Examination ........................................................................................................................ 51 
8.2.2 
Height and Weight ............................................................................................................................. 51 
8.2.3 
Vital Signs ........................................................................................................................................... 51 
8.2.4 
Electrocardiograms ............................................................................................................................ 52 
8.2.5 
Clinical Laboratory Evaluations ....................................................................................................... 52 
8.3 
Pharmacokinetics .............................................................................................................................. 53 
8.4 
Immunogenicity .................................................................................................................................. 55 
8.5 
Biomarkers .......................................................................................................................................... 55 
8.6 
Adverse Events and Serious Adverse Events ............................................................................... 56 
8.6.1 
Definition of Adverse Events ............................................................................................................ 56 
8.6.2 
Definition of Serious Adverse Events ............................................................................................. 56 
8.6.3 
Classification of an Adverse Event .................................................................................................. 56 
8.6.4 
Time Period and Frequency for Event Assessment and Follow-Up .......................................... 57 
8.6.5 
Serious Adverse Event Reporting ................................................................................................... 58 
8.6.6 
Events of Special Interest ................................................................................................................. 59 
8.6.7 
Reporting of Pregnancy .................................................................................................................... 59 
8.7 
Unanticipated Problems .................................................................................................................... 60 
8.7.1 
Definition of Unanticipated Problems .............................................................................................. 60 
8.7.2 
Unanticipated Problem Reporting ................................................................................................... 60 
9 
STATISTICAL CONSIDERATIONS .......................................................................................................... 62 
9.1 
Statistical Hypotheses ....................................................................................................................... 62 
9.2 
Sample Size Determination .............................................................................................................. 62 
9.3 
Populations for Analyses .................................................................................................................. 62 
9.4 
Statistical Analyses............................................................................................................................ 62 
9.4.1 
General Approach .............................................................................................................................. 63 
9.4.2 
Safety Analyses ................................................................................................................................. 63 
9.4.3 
Pharmacokinetics .............................................................................................................................. 64 
9.4.4 
Biomarker Analysis ............................................................................................................................ 65 
9.4.5 
Baseline Descriptive Statistics ......................................................................................................... 66 
9.4.6 
Planned Safety Review ..................................................................................................................... 66 
9.4.7 
Handling of Protocol Deviations ...................................................................................................... 66 
9.4.8 
Handling of Dropouts or Missing Data ............................................................................................ 66 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 67 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ........................................................... 67 
10.1.1 
Informed Consent Process ............................................................................................................... 67 
10.1.2 
Study Discontinuation and Closure ................................................................................................. 67 
10.1.3 
Confidentiality and Privacy ............................................................................................................... 68 
10.1.4 
Future Use of Stored Specimens and Data ................................................................................... 69 


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10.1.5 
Key Roles and Study Governance .................................................................................................. 69 
10.1.6 
Safety Oversight ................................................................................................................................ 70 
10.1.7 
Clinical Monitoring ............................................................................................................................. 70 
10.1.8 
Quality Assurance and Quality Control........................................................................................... 71 
10.1.9 
Data Handling and Record Keeping ............................................................................................... 71 
10.1.10 
Protocol Deviations ............................................................................................................................ 72 
10.1.11 
Publication and Data Sharing Policy ............................................................................................... 72 
10.1.12 
Conflict of Interest Policy .................................................................................................................. 74 
10.2 
Abbreviations ...................................................................................................................................... 75 
11 
REFERENCES ............................................................................................................................................. 80 
Appendix 1: Clinical Laboratory Tests ................................................................................................................... 84 
Appendix 2: Pharmacokinetic, Anti-drug Antibody, and Biomarker Cytokine Collection Time Points .......... 86 
Appendix 3: Contraception ...................................................................................................................................... 88 
Appendix 4: Toxicity Grading for Injection Site Reactions, Vital Signs, and Laboratory Parameters .......... 91 
Appendix 5: Criteria for Diagnosing and REcommended Treatment for Anaphylaxis .................................... 94 
 
 
Table of Tables 
Table 1 
Schedule of Assessments .................................................................................................... 20 
Table 2 
Dose Cohorts ....................................................................................................................... 31 
Table 4 
Prohibited Medications and Dietary Products .................................................................... 47 
Table 5 
List of Pharmacokinetic Parameters and Definitions .......................................................... 54 
Table 6 
Key Study Personnel for Protocol XTMAB-16-101 .............................................................. 70 
Table 7 
Clinical Laboratory Parameters ........................................................................................... 85 
Table 8 
Pharmacokinetic, Anti-drug Antibody, Biomarker, and Telemetry Collection Time Points 86 
Table 9 
Grading for Injection Site Reactions .................................................................................... 91 
Table 10 
Grading for Vital Signs ......................................................................................................... 92 
Table 11 
Grading for Clinical Abnormalities ....................................................................................... 93 
Table 12 
Clinical Criteria for Diagnosing Anaphylaxis ........................................................................ 94 
 
Table of Figures 
Figure 1 
Study Schematic .................................................................................................................. 19 
Figure 2 
Algorithm for the Treatment of Acute Anaphylaxis ............................................................ 95 
 


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15 
STATEMENT OF COMPLIANCE 
The trial will be conducted in accordance with ICH GCP, applicable United States (US) Code of 
Federal Regulations (CFR), and applicable local regulations. The Principal Investigator will 
ensure that no deviation from, or changes to the protocol will take place without prior 
agreement from the Investigational New Drug (IND) Sponsor and documented approval from 
the Institutional Review Board (IRB), except where necessary to eliminate an immediate 
hazard(s) to the trial participants. All personnel involved in the conduct of this study have 
completed Human Subjects Protection and ICH GCP Training. 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the IRB for review and approval. Approval of both the protocol and the consent 
form must be obtained before any participant is enrolled. Any amendment to the protocol will 
require review and approval by the IRB before the changes are implemented to the study. All 
changes to the consent form will be IRB approved; a determination will be made regarding 
whether a new consent needs to be obtained from participants who provided consent, using a 
previously approved consent form. 




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completed. Participants will return to the CRU on Days 15, 29, 43, 57, and 
71 (End of Study/safety follow-up). 
Safety assessments will include adverse events (AEs), safety laboratory 
assessments, vital signs, electrocardiogram (ECG), immunogenicity, and 
physical examination. PK collection and analysis will also be completed in a 
similar manner during the course of this study. 
Objective: 
 
To evaluate the safety, tolerability, immunogenicity, PK, and selected 
clinical biomarkers after a single intravenous infusion of XTMAB-16 at 2 and 4 
mg/kg doses in normal healthy participants. 
Endpoints: 
Safety and Tolerability 
• 
The incidence of treatment-emergent adverse events (TEAEs) and 
serious adverse events (SAEs) 
• 
Observed values and change from Baseline in safety laboratory tests 
(hematology, clinical chemistry, urinalysis) by visit 
• 
Observed values and change from Baseline in ECG by visit 
• 
Time-matched Baseline and 50-hr postdose digital ECG monitoring  
• 
Observed values and change from Baseline in vital signs 
Immunogenicity 
• 
Number and percentage of participants by cohort who test positive for 
XTMAB-16 ADA at Baseline, Day 29, Day 57, and Day 71 
• 
Number and percentage of participants by cohort who test positive for 
XTMAB-16 nAb at Baseline, Day 29, Day 57, and Day 71 
Pharmacokinetics 
• 
Maximum observed XTMAB-16 concentration (Cmax) 
• 
XTMAB-16 serum concentration at the end of drug infusion (CT) 
• 
Time to maximum observed XTMAB-16 concentration (tmax) 
• 
Area under the XTMAB-16 concentration-time curve from time zero 
(predose) extrapolated to infinity (AUC0-∞) 
• 
Area under the XTMAB-16 concentration-time-curve from time zero to 
(predose) to the last quantifiable time point at t (AUC0-t) 
• 
Systemic clearance after IV dosing (CL) 
• 
Apparent terminal half-life (t1/2) 
• 
Volume of distribution following IV dosing (Vz) 
• 
Mean residence time (MRT) 


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Biomarkers 
• 
Absolute and percent change from Baseline in the following 
biomarkers 
o Angiotensin converting enzyme (ACE) 
o Soluble IL-2 receptor (sIL-2R) 
o Interleukin 6 (IL-6) 
o Soluble tumor necrosis factor (sTNFα) 
Study Population: 
A total of 24 male and female healthy adult participants aged 18 to 
45 years, inclusive. 
Phase: 
1  
Description of 
Sites/Facilities Enrolling 
Participants: 
This study will be performed at a single CRU in the US.  
Description of Study 
Intervention: 
XTMAB-16 is a chimeric human-murine IgG1κ anti-TNFα monoclonal 
antibody. The final dosage form is a sterile, white, lyophilized powder for IV 
infusion. Participants assigned to active treatment will receive a single 
dose of XTMAB-16 at a volume of 250 mL via IV infusion over 2 hours. The 
total dose received will be either 2 or 4 mg/kg, depending on treatment 
assignment.  
Placebo will be the same formulation as the active treatment, but without 
XTMAB-16. Participants assigned to placebo will receive a single dose of 
placebo at a volume of 250 mL via IV infusion over 2 hours. 
Study Duration: 
Study duration is expected to be approximately 4-5 months from First 
Patient First Visit to Last Patient Last Visit. 
Participant Duration: 
The study consists of an up to 28-day screening period, a 57-day treatment 
period, and a 14-day follow-up period, for a total duration of participation 
of up to 99 days. 
Statistical Methods 
Sample size: The selection of 24 participants was based on feasibility, first-
in-human (FIH) guidelines, industry standards, and empirical 
considerations. No sample size calculation was performed. 
Analysis Datasets: 
• 
The Enrolled Set (ES) will consist of all participants who have given 
informed consent. 
• 
The Full Analysis Set (FAS) will consist of all participants randomized 
into the study. 


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• 
The Safety Set: will consist of all study participants who are 
randomized and have received at least 1 dose of study medication. 
• 
The Pharmacokinetic Per-Protocol Set (PK-PPS) consists of all 
participants in the Safety Set who provide at least 1 quantifiable serum 
XTMAB-16 PK sample postdose without important protocol deviations 
that would affect the concentration. 
• 
Biomarker Set will consist of all participants in the PK-PPS who have at 
least 1 postdose biomarker measurement. 
Statistical Analysis: 
All safety, tolerability, laboratory, PK, biomarkers, and immunogenicity data 
will be summarized and listed using descriptive statistics.  
1.2 
SCHEMA 
 
Figure 1 
Study Schematic 
 
 
Abbreviations: FU = follow-up. 




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Abbreviations: ACE = angiotensin converting enzyme; ADA = anti-drug antibody; ECG = electrocardiogram; EOS = end of study; FU = follow-up; HBsAg = hepatitis 
B antigen; HCV = hepatitis C virus; HIV = human immunodeficiency virus; IL-6 = interleukin 6; nAb = neutralizing antibodies; PK = pharmacokinetics; sIL-2R = 
soluble IL-2 receptor; sTNFα = soluble tumor necrosis factor alpha; TB = tuberculosis. 
a 
Assessments at Day -2 may be performed on Day -1, as needed, by the clinical research unit, but must be performed no later than Day -1. 
b 
A full physical examination will be performed at Screening, Baseline, Day 8, and Day 71. An abbreviated physical examination will be performed 
predose on Day 1, and Days 15, 29, and 43. See Section 8.2.1 for a description of the physical examination. 
c 
For women of childbearing potential only. At Baseline, an FSH test will be run to confirm a postmenopausal state in women under 60 years old and not 
using hormonal contraception or hormone replacement therapy. 
d 
At each visit, participants will have a temperature check and will be asked if they have had exposure to someone known to have COVID-19. If the 
temperature is above 100°F (37.7°C) or the answer is “yes,” participants will be tested for COVID-19. Participants who receive a COVID-19 vaccine prior 
to study entry must receive the final vaccine at least 30 days before dosing and will be tested for COVID-19 as per the SoA. Participants who wish to 
receive the COVID-19 vaccine after dosing must wait until after Week 4 PK sampling and other assessments have been completed. COVID-19 
vaccination and any adverse reaction to the vaccine must be reported. 
e 
This will include a blood draw to test for blood alcohol levels. 
f 
From check-in at Day -2 to discharge from the unit on Day 8. Since the participants will be immunocompromised by administration of study treatment, 
the participants should be instructed to quarantine at home for 6 days after discharge from the clinical research unit. 
g 
When a meal, vital signs, ECG, or blood sample collection are scheduled at the same time as the study drug administration, the following order will be 
respected: ECG, vital signs, clinical biomarkers, PK, ADA, safety laboratory samples, and meal. To respect exact timing of PK samples (see Table 8), the 
other measurements will be done ahead of the scheduled time. The assessment schedule should be adapted to the design of the study. 
h 
During infusion, blood pressure and heart rate should be collected every 15 minutes for the first hour, every 30 minutes for the second hour, and 
hourly for 2 hours after the completion of infusion. 
i 
Blood samples will be collected for XTMAB-16 PK analysis at predose (Hour 0), at 1 hour after the start of infusion, 1 hour after the start of infusion, 
immediately after the 2-hour infusion (T; infusion termination), and at 3, 8, 14 hours on Day 1, and at 24 hours (Day 2), 50 hours (Day 3), 74 hours 
(Day 4), 170 hours (Week 2, Day 8), 338 hours (Week 3, Day 15), 674 (Week 4, Day 29), 1010 (Week 6, Day 43), 1346 hours (Week 8, Day 57), and 
1682 hours (Week 10, Day 71) postinfusion of XTMAB-16 or placebo. All sampling time points after time T refer to time from the start of infusion. 
Acceptable windows for PK sample collection are provided in Table 8. The exact time of sample collection must be recorded on the eCRF. 
j 
Blood samples will be collected to evaluate biomarker concentrations of ACE, sIL-2R, IL-6, and sTNFα. 
k 
Single 12-Lead ECGs will be collected at all time points. Additional ECGs will be performed at the discretion of the Investigator. Telemetry recording 
will begin on Day -1 and continue through 50 hours after the start of infusion. At specified time points, for extraction of telemetry data, participants 
should be in a semi-reclined resting position for at least 10 minutes prior to the target time of data extraction (at least 15 minutes when coinciding 
with PK/ADA/nAb blood collection). On Day -1, resting periods for telemetry data extraction should occur at 1, 2, 3, and 8 hours (corresponding to the 
projected time points on Day 1). On Day 1, resting periods for telemetry data extraction should occur at predose (to match the time point for 24 hours 
after the start of infusion) and 1, 2, 3, 8, and 24 hours after the start of infusion. A resting period for telemetry data extraction will also occur at 
50 hours after the end of infusion. During infusion, data will be collected in a semi-supine/semi-reclined position, and for all other readings, data will 
be collected in a supine position. 
l 
Tryptase levels will be assessed at Baseline for all participants. For any participant who experiences anaphylaxis within 4 hours after the end of 
infusion, and additional sample for assessment of tryptase levels should be collected as soon as is reasonable. See Appendix 5 for diagnosis and 
treatment of anaphylaxis. 


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m 
Blood samples for PK/ADA/nAb will be collected for analysis from participants who experience an SAE that is also considered related to study 
treatment. 
 
 
 
 


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2 
INTRODUCTION 
 
2.1 
STUDY RATIONALE 
The purpose of the study is to evaluate the safety, tolerability, immunogenicity, and 
pharmacokinetics (PK) of single ascending intravenous (IV) doses of XTMAB-16 in healthy adult 
subjects. This study is the first time that XTMAB-16 will be administered to humans. The safety, 
tolerability and PK results obtained from this study will inform future clinical development of 
XTMAB-16 for the treatment of sarcoidosis. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XTMAB-16 is being developed as a monoclonal antibody (mAb) tumor necrosis factor alpha 
(TNFα) blocker to address the treatment gap for patients with advanced pulmonary sarcoidosis 
with or without extrapulmonary involvement. 
2.2 
BACKGROUND 
2.2.1 SARCOIDOSIS 
Sarcoidosis is a chronic systemic disease of unknown etiology and uncertain prognosis that 
most commonly affects young and middle-aged adults. Sarcoidosis is characterized by the 
presence of noncaseating granulomas in 1 or more organs. While sarcoidosis is a systemic 
disease, the lungs, lymphatic system, and skin are most commonly affected.42 Patients 
frequently present with pulmonary infiltrates, bilateral hilar lymphadenopathy, and ocular and 
skin lesions.8 
A widely accepted hypothesis of the pathogenesis of sarcoidosis is that various unidentified 
antigens, either infectious or environmental, trigger an exaggerated immune response in 


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genetically predisposed individuals.3,36,42 In the lung, the antigen is presented to naive CD4+ 
lymphocytes and alveolar macrophages, activating both cell types, and subsequently triggers a 
complicated cascade of proinflammatory cytokines. The release of cytokines enhances the 
expression of tumor necrosis factor α (TNFα), a protein that plays a significant role in antigen-
stimulated, cell-mediated immune responses.7 High levels of TNFα released from alveolar 
macrophages have been shown to correlate with disease progression. 6,9 Notably, spontaneous 
release of TNFα by alveolar macrophages is greater in patients with active disease than in those 
with inactive or corticosteroid-treated disease.50 Similar inflammatory mechanisms are believed 
to underlie sarcoidosis involvement in other organs, such as the skin.20 
To prevent granuloma formation and limit tissue injury and fibrosis, targeted 
immunosuppression of proinflammatory cytokines such as TNFα is a clear goal of therapy, 
particularly in patients with chronic sarcoidosis. 
Please see the Investigator’s Brochure (IB) for additional details. 
2.2.2 TNFα 
TNFα is a proinflammatory cytokine widely recognized and implicated in inflammatory 
disorders including sarcoidosis. 
A model for granuloma formation in sarcoidosis patients suggests that macrophages, dendritic 
cells, and lymphocytes, with the aid of cytokines and chemokines, collaborate with one 
another. TNFα, one of the participating cytokines in the formation of the sarcoid granuloma, 
along with the successful use of immunomodulators inhibiting TNFα such as pentoxiphylline 
and thalidomide, led to the increasing utilization of anti-TNF agents in sarcoidosis patients. In 
patients with severe refractory sarcoidosis who do not respond to conventional 
immunosuppressive treatment, TNFα inhibitors infliximab and adalimumab are recommended 
by the World Association of Sarcoidosis and other Granulomatous Disorders (WASOG).12 
Comparisons between TNFα inhibitors have shown that infliximab is superior to other anti-TNF 
therapies.4,13,36 
 
 
 
 
Please see the IB for additional details. 




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(132 animals, 2/sex/dose/time point for 10 time points) to characterize a single IV dose TK 
profile. The findings are summarized below. 
KBMAB-16 was well tolerated up to 40 mg/kg after 3 biweekly IV injections. All animals survived 
in the toxicity study with no meaningful abnormal clinical and pathological findings. Thus, the no 
adverse effect level (NOAEL) of KBMAB-16/XTMAB-16 was considered to be 40 mg/kg via 
3 biweekly IV injections in TgTC mice. 
In the TK groups, a complete 6-week (1008 hours) TK profile following a single dose (10 mg/kg, 
20 mg/kg and 40 mg/kg) of KBMAB-16 was obtained. After a single 40 mg/kg IV injection, the 
maximum observed concentration (Cmax) was at 791.0 µg/mL and the area under the 
concentration-time curve (AUC)0- was at 124257.2 µg*hr/mL. The systemic exposure in terms 
of Cmax and AUC0-∞ were increased proportionally in the dose range from 10 to 40 mg/kg of 
KBMAB-16. The half-life (t1/2) of XTMAB-16 ranged from 9.4 days (226.9 hr) at 10 mg/kg to 
13.6 days (327.2 hr) at 40 mg/kg, which is comparable to the half-life of 10 mg/kg of infliximab 
in humans of 13.9 days (335.1 hr).21 
In a 13-week, repeated dose, GLP, toxicology study (Study 14042-20005) in hTNFα transgenic 
mice, KBMAB-16 was well tolerated up to 40 mg/kg after 7 bi-weekly IV injections in TgTC 
animals in the toxicity study with no meaningful test article related clinical and pathological 
abnormalities observed. The NOAEL of KBMAB-16 was considered to be 40 mg/kg after 7 doses 
biweekly IV injection in TgTC mice. In addition, safety pharmacology assessments of the central 
nervous system (CNS) and respiratory systems did not reveal adverse effects at any dose of 
KBMAB-16. After 40 mg/kg IV injection for 6 doses, the Cmax was 1104.9 µg/mL, the (AUC)0- was 
624865.9 µg*hr/mL and the (AUC)0-τ was 124878.7 µg*hr/mL. The systemic exposure in terms of 
Cmax and (AUC)0- increased in a dose proportional matter in the dose range from 10 to 40 
mg/kg of KBMAB-16.  
For further detailed nonclinical data for XTMAB-16, refer to the IB. 
Risk/Benefit Assessment 
This is the first time that XTMAB-16 will be administered to humans. XTMAB-16 is not expected 
to provide any clinical benefit to healthy participants. This study is designed primarily to 
generate safety, tolerability, immunogenicity, and PK data to provide the basis for further 
clinical development of XTMAB-16 as a potential new, pharmacological agent for the treatment 
of sarcoidosis. As such, data from this study may benefit people with sarcoidosis in the future. 
As of the issuance of this protocol, no specific human risks have been identified based on data 
gathered during a nonclinical study with XTMAB-16 using a transgenic mouse model (see IB). 
The clinical impact of any potential risks will be minimized through cautious dose escalation; 
that is, higher doses of XTMAB-16 will be administered only after lower doses have been found 
to be well tolerated with an acceptable safety profile. In addition, this study includes standard, 
intensive, inpatient monitoring of the participants following administration of single, IV doses of 
the investigational product. Clinical safety laboratory tests, thorough assessments of vital signs, 




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risks identified in association with XTMAB-16 are justified by the anticipated benefit, in terms of 
contribution to the process of developing new therapy in an area of unmet medical need. 








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Safety assessments will include AEs, safety laboratory assessments, vital signs, ECG, 
immunogenicity, and physical examination. PK collection and analysis will also be completed in 
a similar manner during the course of this study. 
4.1.1 DOSE ESCALATION 
For all cohorts, a sentinel group of 2 participants (1 assigned to XTMAB-16 and 1 assigned to 
placebo) will be dosed at least 48 hours before the remaining  participants in the same cohort. 
After blinded review of the available safety and laboratory data by the PI, if no notable safety 
signals are identified, the remaining  participants within the same cohort will be dosed. 
Participants within a cohort should be dosed at least 1 hour apart. 
As XTMAB-16 is a TNFα inhibitor, which have well-characterized clinical safety profiles, it can be 
given to participants in the 4 mg/kg dose group after 14 to 21 days clinical assessment of the 
participants at 2 mg/kg dose group, unless safety concerns arise.  
Dose escalation will be stopped as soon as safety signals or risks are identified or anticipated, 
based on: 
• Number of abnormal and clinically significant safety laboratory results 
• Number of SAEs and/or TEAEs with severity/intensity high enough for a meaningful 
decision 
• Proportion of TEAEs of the same type high enough to justify the decision 
The severity rating is adapted to healthy participants, taking into account event characteristics 
such as type, deleterious potential, occurrence, progression, and monitorability. A solitary SAE 
occurrence is not by itself a criterion for making a decision (assessment depends on the nature 
of the reported event). See Section 4.1.2 for details on stopping rules. 
A decision to proceed from dose “n” to the next higher “n+1” dose will be made jointly by the 
Sponsor and the Investigator based on a preliminary Investigator blinded safety report inclusive 
of the 12 participants in dose level cohort “n”. The relevant data for this decision should be, at a 
minimum, AEs, liver and kidney function tests, ECG, blood pressure, and heart rate.  
For safety purposes, the treatment of a specific participant may be unblinded before the next 
dose level is administered, after mutual agreement between the Sponsor and the Investigator. 
An unscheduled PK sample collection and analysis may be performed to support the clinical 
safety assessment, if needed in the event of a safety signal of concern. 
Depending on the tolerability profile and safety laboratory results observed in the dose level 
cohort “n,” one of the following decisions will be made for cohort “n+1”: 
• Dose escalation may continue as scheduled. 


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• A higher intermediate dose between the current dose (“n”) and the next planned dose 
(“n+1”) may be administered to the next cohort. 
• A lower intermediate dose between the current dose (“n”) and the previous dose 
(“n-1”) may be administered to the next cohort, including the possibility of 
administering a dose lower than the starting dose.  
• The study may be stopped. 
4.1.2 STOPPING RULES 
4.1.2.1 CRITERIA 
Participants who experience injection site reactions or vital signs changes of Grade 1 or 2 (see 
Appendix 4) during infusion may continue infusion or have infusion interrupted for treatment 
and then resumed, at the discretion of the Investigator. Participants who experience injection 
site reactions or vital signs changes of Grade 3 or 4 during infusion should have infusion 
terminated and will be treated, as needed, for the adverse events. Any participant who 
experiences anaphylaxis during infusion will have infusion terminated; diagnosis of and 
recommended treatment for anaphylaxis is provided in Appendix 5. 
In addition to the assessment of SAEs and the occurrence/severity of other AEs by the Sponsor 
and the Investigator, after exploring potential confounding factors, the following criteria should 
be considered as guidance for the decision to stop dose escalation or to stop administration of 
the study drug to additional participants: 
• 1 SAE for which the relationship to treatment cannot be reasonably excluded 
• 1 AE of severe intensity for which the relationship to treatment cannot be reasonably 
excluded 
• 3 or more participants with AEs of moderate intensity for which the relationship to 
treatment cannot be reasonably excluded 
• 1 participant in a cohort with potential Hy’s Law values  
o ALT or AST >8 × upper limit of normal (ULN) 
o ALT or AST >5 × ULN for more than 2 weeks 
o ALT or AST >3 × ULN and (total bilirubin >2 × ULN or INR >1.5) 
o ALT or AST >3 × ULN with the appearance of fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%) 
• QTcF ≥500 ms (men and women) 
• Any other clinically significant intolerance findings 


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If any of the above occur, the Contract Research Organization (CRO) and Sponsor should be 
notified within 24 hours of becoming aware of the event. Decisions to stop dose escalation or 
stop administration of study drug to additional participants will be determined collectively 
between the PI, CRO Medical Monitor, and Sponsor. 
4.1.2.2 ACTIONS 
At each dose level, if 1 of the above criteria is met at that dose level, the treatment blind will be 
broken by the Sponsor for the concerned participants as follows: 
• 
If 3 or more participants were given XTMAB-16 and no participant was given placebo, drug 
administration will be stopped for these participants and all other participants in that dose 
level; and either 
o One or more lower dose(s) may be considered, only if, after reviewing all data, the 
Investigator and the Sponsor agree that it is safe to do so, or 
o Study may be stopped. 
• 
Otherwise, drug administration per protocol may either continue as planned or be 
reconsidered if, after reviewing all data, the Sponsor and the Investigator agree that it is 
safe to do so; and either 
o The current dose level may be continued, or 
o One or more lower dose(s) may be considered, or 
o The study may be stopped 
The drug administration per protocol may either continue as planned or be reconsidered only 
if, after reviewing all data, the Sponsor and the Investigator agree that it is safe to do so. 
The treatment blind may be broken for other reasons, supported by a clear rationale. 
The Investigator and Sponsor may decide to stop study drug administration based on other 
safety signals not described in the above criteria. 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
The design of this Phase 1, SAD clinical trial is similar to other FIH studies evaluating TNFα 
inhibitors.39 
Based on TK results in the 6-week, GLP, toxicology study in hTNFα transgenic (TgTC) mice, the 
half-life (t1/2) of XTMAB-16 ranged from 9.4 days (226.9 hr) at 10 mg/kg to 13.6 days (327.2 hr) 
at 40 mg/kg, which is comparable to the half-life of 10 mg/kg of infliximab in humans of 
13.9 days (335.1 hr).21 Approximately 90% of XTMAB-16 after a single dosing is expected to be 
eliminated from the system in 8 weeks. Therefore, the 8-week study duration is considered 
adequate to support safety and PK, biomarker, and immunogenicity analyses. 


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In support of the effect of XTMAB-16 on TNFα, additional biomarkers associated with TNFα 
activity and sarcoidosis have been selected for investigation in this first-in-human (FIH) study. 
The biomarkers selected for this study are sIL-2R, ACE, TNFα, and IL-6. ACE is a common 
biomarker used in the diagnosis of sarcoidosis.43 sIL-2R is a surrogate marker for T cell 
activation, is significantly elevated in sarcoidosis patients, and has been shown to have a high 
and superior sensitivity and specificity, compared to ACE, for diagnosing sarcoidosis in 
patients.13 IL-6 is elevated in patients with sarcoidosis and may be involved in the initiation and 
maintenance of alveolitis by activating and causing the proliferation of T cells.36 TNFα induces 
IL-6 through the nuclear factor k B pathway and, thus, inhibition of TNFα through XTMAB-16 is 
likely to be reflected in a change in IL-6 circulating levels.25 These biomarkers are normally low 
or undetectable in healthy participants. However, as XTMAB-16 is intended for use in patients 
with pulmonary sarcoidosis (in whom these biomarkers are likely to be elevated), XTMAB-16 is 
expected to influence the levels of these biomarkers in patients. Measuring these biomarkers in 
healthy participants will establish relative baseline levels of these biomarkers for comparison in 
later trials in patients. 
4.3 
JUSTIFICATION FOR DOSE 
The participants in this study will receive a single IV infusion of placebo or 2 or 4 mg/kg of 
XTMAB-16 in 250 mL of 0.9% Sodium Chloride Injection, US Pharmacopeia (USP). 
 
 
 
 
 
 
 
Based on the clinical data from literature in sarcoidosis patients with pulmonary involvement, 
and safety data from the mouse toxicology study, the low doses of 2 to 4 mg/kg of XTMAB-16 in 
the current study are considered safe and expected to be relevant for PK and efficacy 
biomarker analyses to support further clinical development. Using mg/kg scaling from the 
40 mg/kg TgTC mouse NOAEL in the 13-wk toxicology study, the 2 and 4 mg/kg human dose 
cohorts provide a 5 and 10-fold safety margin respectively.  
Projected human safety margins were calculated by comparing the NOAEL exposure in the 
toxicology species (TgTC mice dosed at 40 mg/kg) to the projected clinical exposures. Using TK 
data generated from the 6-week GLP toxicology study in TgTC mice, a 2-compartmental model 
with first order absorption and elimination using a mixed ratio error model was developed for 
XT-MAB16. The model was allometrically scaled to humans using published allometric 
exponents. The allometrically scaled human model was then used to simulate the planned FIH 
doses for XTMAB-16 for a 70 kg human (Table 3).  
The projected human doses were then compared to the calculated Cmax and AUC0-∞ from the 
13-week NOAEL to generate exposure based safety margins (Table 3). Using a model built from 


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the 6-week toxicology study Comparing the AUC0-∞ (624865.9 hr•mg/mL) of the 40 mg/kg 
group dosed with XT-MAB16 in TgTC model toxicology study to the estimated AUC0-∞ of the 
2 mg/kg dose in humans (14000 hr•mg/mL) the safety margin for the starting dose is 
approximately 89-fold. Comparing the Cmax (1104.9 mg/mL) of 40 mg/kg dose of XTMAB-16 in 
TgTC to the estimated Cmax (47.8 mg/mL) of 2 mg/kg dose in humans, the safety margin for the 
starting dose is approximately 23-fold.  
In the repeat-dose 13-week toxicology study, the animals received 7 biweekly IV injections 
(Day 1, 15 and 29), while in the current study, only a single IV infusion will be administered to 
the human subjects. 
Therefore, the single administered doses of 2 and 4 mg/kg in the planned FIH study are 
considered scientifically reasonable and meet current guidance for Maximum Safe Starting 
Dose 2005 and appropriate safety margins for both the starting and highest dose based on the 
NOAEL exposure reported in the 13-week GLP TgTC toxicology study.  
The relevant human projected safety margins calculated from the 13-week toxicology study are 
summarized in Table 3 below. 
Table 3 
Allometrically Scaled Estimated Human PK Parameters  
PK Parameter 
2 mg/kg  
4 mg/kg  
Cmax (μg/mL) Mean 
47.8 
95.7 
Safety Margin for Cmax 
23 
12 
AUC0-∞ (μg/mL•hr) Mean 
14000 
28000 
Safety margin for AUC0-∞ 
45 
22 
 
4.4 
END OF STUDY DEFINITION 
A participant is considered to have completed the study if he or she has completed all phases of 
the study including the last visit shown in the Schedule of Assessments (SoA), Section 1.3. 


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5 
STUDY POPULATION 
5.1 
INCLUSION CRITERIA 
Participants must meet all of the following criteria to be eligible for participation in this study: 
1. In the opinion of the Investigator, the participant is capable of understanding and 
complying with protocol requirements. 
2. The participant is willing to sign and date a written, informed consent form and any 
required privacy authorization prior to the initiation of any study procedures, including 
requesting that a participant fast for any laboratory evaluations. 
3. The participant is a healthy adult male or female aged 18 to 45 years, inclusive, at the 
time of informed consent. 
4. The participant weighs between 45 kg (99 lbs) and 100 kg (220 lbs) and has a body mass 
index (BMI) between 18.0 and 30.0 kg/m2, inclusive, at the time of informed consent. 
5. The participant has physical examination, clinical laboratory values, and ECG results that 
are clinically acceptable. Laboratory results outside of the reference range must be 
documented as acceptable by the Investigator and Sponsor. 
6. A male participant who is nonsterilized and sexually active with a female partner of 
childbearing potential must agree to use highly effective contraception from the time of 
signing the informed consent throughout the duration of the study, and for 90 days after 
the last dose of study drug. See Appendix 3 for details on contraception requirements 
during the study. 
7. A female participant of childbearing potential who is sexually active with a nonsterilized 
male partner agrees to routinely use highly effective contraception from the time of 
signing the informed consent, throughout the duration of the study, and for 90 days 
after the last dose of study drug. See Appendix 3 for details on contraception 
requirements during the study. 
5.2 
EXCLUSION CRITERIA 
Participants who meet any of the following exclusion criteria will not be eligible for 
participation in this study: 
1. The participant has received any investigational compound within 90 days before 
dosing. 
2. The participant is an immediate family member, CRU employee, or is in a dependent 
relationship with a CRU employee who is involved in the conduct of this study (eg, 
spouse, parent, child, sibling) or may consent under duress. 


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3. The participant has any clinically significant illness, such as cardiovascular, neurologic, 
pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, 
endocrine, or psychiatric disease or disorder, or other abnormality, which may affect the 
participant’s safety, increase risk of seizure or lower the seizure threshold, or potentially 
confound the study results. It is the responsibility of the Investigator to assess the clinical 
significance of any conditions the participant may have; however, consultation with the 
Xentria Medical Monitor may be warranted. 
4. The participant has a known hypersensitivity to any component of the formulation of 
XTMAB-16. 
5. The participant has a positive result for drugs of abuse (defined as any illicit drug use) or 
alcohol at Screening or Baseline (Day -2). 
6. The participant has a history of drug abuse (defined as any illicit drug use) or a history of 
alcohol abuse within 1 year prior to Screening or is unwilling to agree to abstain from 
alcohol and drugs throughout the study. 
7. The participant has taken any excluded medication, supplements, or food products 
during the time periods listed in Table 4. 
8. If female, the participant is pregnant or lactating or intends to become pregnant before, 
during, or within 90 days after the last dose of study drug or intending to donate ova 
during such time period. 
9. If male, the participant intends to donate sperm during the study or within 90 days after 
the last dose of study drug. 
10. The participant has a history of autoimmune disease or respiratory disorders. 
11. The participant or any immediate family member has a history of cancer, except basal 
cell carcinoma, that has not been in remission for at least 5 years prior to Baseline 
(Day -2). 
12. The participant has a condition that can potentially reduce drug clearance (eg, renal or 
hepatic insufficiency). 
a. Glomerular filtration rate <60 
b. ALT >41 U/L 
c. AST > 34 U/L 
d. Alkaline phosphatase >117 U/L 
e. Total protein >8.2 g/dL 
f. Total bilirubin >11.9 mg/dL 
g. Gamma glutamyl transferase >43 U/L (female), >73 U/L (male) 


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h. Lactate dehydrogenase >246 U/L (female) or >241 (male) 
i. Prothrombin time >14.6 seconds 
13. The participant has current or recent (within 6 months) circulatory or hematologic 
disease that would be expected to influence the absorption of drugs (ie, a history of 
malabsorption, distribution, or clearance of investigational product). 
14. The participant has a positive test result for hepatitis B surface antigen (HBsAg), 
hepatitis B core antigen antibody, hepatitis C virus (HCV) antibody, COVID-19, TB, or a 
known history of human immunodeficiency virus (HIV) infection at Screening. 
15. The participant has used nicotine-containing products (including but not limited to 
cigarettes, pipes, cigars, chewing tobacco, nicotine patch, or nicotine gum) within 
28 days prior to Baseline. Cotinine test is positive at Screening or Baseline. 
16. The participant has poor peripheral venous access. 
17. The participant has donated or lost 450 mL or more of his or her blood volume 
(including plasmapheresis) or had a transfusion of any blood product within 90 days prior 
to dosing. 
18. The participant has a Screening or Baseline abnormal, clinically significant ECG. Entry of 
any participant with an abnormal, not clinically significant ECG must be approved and 
documented by signature of the PI or medically qualified sub-Investigator. In the case of 
a QTcF interval >450 ms (men) or >470 ms (women; participants with bundle branch 
block) or PR outside the range of 120 to 220 ms, the assessment may be repeated once at 
the Screening Visit or Baseline for eligibility determination. 
19. The participant has a supine blood pressure outside the ranges of 90 to 140 mm Hg for 
systolic and 50 to 90 mm Hg for diastolic. The assessment may be repeated once for 
eligibility determination at the Screening Visit or Baseline. 
20. The participant has a resting pulse outside the range of 50 to 90 bpm (not on ECGs). The 
assessment may be repeated once for eligibility determination at the Screening Visit or 
Baseline. 
21. The participant has abnormal Screening or Baseline laboratory values that suggest a 
clinically significant underlying disease or the participant has the following laboratory 
abnormalities: ALT >41 U/L and/or AST > 34 U/L. 
5.3 
LIFESTYLE CONSIDERATIONS 
From Day -2 and throughout the study duration, participants should refrain from excessive use 
of alcohol, tea, coffee, chocolate, quinine, or caffeine-containing beverages. 
Participants will be requested to follow a stable lifestyle with no intensive physical activity from 
Day -2 through the end of study (EOS) visit. 


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During the confinement, standardized breakfast when applicable, lunch, and dinner will be 
given as scheduled by the CRU, with every participant on the same meal schedule. There will be 
no water restrictions for participants; water supply will be at least 1500 mL for each 24-hour 
period. During the confinement period (Day -2 to Day 8), participants will be given a menu for 
the dosing period that includes 3 meals and an evening snack, not to exceed 30% fat (relative to 
the total calories). The meals served on the PK assessment days should be identical for each 
cohort in the study. The study menu should be recorded and submitted to the study file with a 
copy provided to the Sponsor prior to the start of the study. Whether the meal was fully 
consumed, or not, will be recorded. 
If a blood draw or any study procedure coincides with a meal, the blood draw will take 
precedence followed by the study procedure and then the meal. 
XTMAB-16 and placebo will be administered on Day 1 in same manner for each cohort (pre- or 
post-meal). Participants may consume water ad libitum following dosing. 
Vital signs will be collected in a supine position except for during the infusion, when the 
procedures will be performed in a semi-supine/semi-reclined position (see Section 8.2.3). 
Infusion will occur in a semi-supine/semi-reclined position. After dosing, the participant will be 
observed by staff for up to 2 hours—at the Investigator’s discretion for up to 4 hours, if 
necessary – except as necessitated by the occurrence of an AE or study procedures (eg, 
obtaining 12-lead ECG). 
Participants will be immunocompromised by administration of study treatment and should be 
instructed to quarantine at home for 6 days after discharge from the study unit. 
5.4 
SCREEN FAILURES 
Screen failures are defined as participants who consent to participate in the clinical trial but are 
not subsequently randomly assigned to the study intervention or entered in the study. A 
minimal set of screen failure information is required to ensure transparent reporting of screen 
failure participants, to meet the Consolidated Standards of Reporting Trials (CONSORT) 
publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, eligibility criteria, and any SAE. 
Individuals who do not meet the criteria for participation in this trial (screen failure) because of 
a nonclinically significant laboratory abnormality may be rescreened once at the discretion of 
the Investigator. Rescreened participants should be assigned the same participant number as 
for the initial screening; those who fail the drug test may not be rescreened. 
5.5 
REPLACEMENT OF PARTICIPANTS 
• 
Participants who sign the informed consent form and are randomized but do not receive 
the study intervention may be replaced. 


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• 
Participants who sign the informed consent form, are randomly assigned to treatment, 
receive the study intervention, and subsequently withdraw or are withdrawn or 
discontinued from the study before Week 2, will be replaced. 
• 
Participants who are lost-to-follow-up will be replaced. 
Replacement participants will be assigned to the same treatment assignment as the participant 
who discontinued. 


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6 
STUDY INTERVENTION 
6.1 
STUDY DRUG ADMINISTRATION 
6.1.1 STUDY DRUG DESCRIPTION 
 
 
 
 
 
 
 
 
 
 
 
Characterization studies were performed on XTMAB-16 drug substance batches produced in 
the commercial scale. Results include testing of chemical, physical, and biological properties to 
establish specifications in terms of identity, purity, and biological activity by a panel of 
orthogonal assays. 
Nonclinical studies of in-vitro biological activity of XTMAB-16 have been performed, including a 
potency assay, ligand binding assays to TNFα, tissue cross-reactivity, antibody-dependent 
cellular cytotoxicity, and complement-dependent cytotoxicity activity, and binding to Fc 
receptors. Please refer to the IB for details. 
6.1.2 DOSING AND ADMINISTRATION 
XTMAB-16 or placebo will be administered once on Day 1 by IV infusion at the required 
concentration in a volume outlined in the Pharmacy Manual  over a period of not less than 2 
hours (unless otherwise specified in the Pharmacy Manual). The dose to be administered (0 
[placebo], 2, or 4mg/kg) will be determined by the participant’s cohort and treatment 
assignment. 
Before XTMAB-16 infusion, the Investigator should carefully read the pretreatment checklist 
and go over the questions with the participant. Refer to the Administration Guide for the 
supplies needed, administration instructions, and important information on what to do in the 
event the participant experiences an infusion reaction. 
XTMAB-16 should be administered with an infusion kit and 1.2 micron filter via an infusion 
pump. See the Pharmacy Manual for details. 


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6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
6.2.1 ACQUISITION AND ACCOUNTABILITY 
The Sponsor will notify the Investigator and pharmacy prior to shipment of drug supplies and 
other related clinical supplies regarding the anticipated date of their arrival at the pharmacy. 
Shipment will be sent directly to the delegated personnel at the pharmacy. 
All shipped clinical supplies will be appropriately documented to ensure proper handling in case 
of emergency. 
Shipment will be sent under controlled conditions. Each shipment of clinical supplies for the 
trial will contain a certificate of analysis and a shipment certificate detailing the content of 
shipment. 
Transportation temperature will be monitored and recorded by temperature-monitoring 
devices. The CRU is required to acknowledge receipt of the study drug and verify the contents, 
quality, and temperature of the study drug. 
Initial clinical supply shipment will be sent automatically upon regulatory and Sponsor approval. 
XTMAB-16 must be kept in a secured area with access limited to designated study personnel. 
Only personnel under the supervision of either the Investigator or the local pharmacist are 
authorized to handle XTMAB-16. 
Refer to the Pharmacy Manual for additional information and details. 
6.2.2 FORMULATION, APPEARANCE, PACKAGING, AND LABELING 
 
 
 
 
 
 
 
 This information is 
also detailed in the pharmacy manual. 
The matching placebo has the same formulation as that the drug product except contains no 
XTMAB-16. 
 
 
 
 
The study drug and matching placebo will be packaged and labeled according to the current 
Good Manufacturing Practice (cGMP) guidelines for drugs used in clinical trials and any other 


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relevant local regulatory requirements. Details of the packaging and labeling will be found in 
the Pharmacy Manual provided by the Sponsor and/or delegate. 
6.2.3 PRODUCT STORAGE AND STABILITY 
XTMAB-16 drug product should be stored at 2°C to 8°C (refrigerate). The clinical supplies 
storage area at the CRU must be monitored by the CRU staff for temperature consistency with 
the above instructions. Documentation of temperature monitoring should be maintained at all 
times until study closure. 
Do not use beyond the expiry date provided by the Sponsor. 
Upon removal from refrigerated storage, XTMAB-16 cannot be returned to refrigerated storage. 
XTMAB-16 vials are for single use only. Any unused portion should be placed in quarantine for 
monitor review. No vials should be discarded without Sponsor approval. 
Infusion should begin within 1.5 hours of reconstitution and dilution. The infusion must be 
administered over a period of not less than 2 hours and must use an infusion set with an inline, 
sterile, non-pyrogenic, low-protein-binding filter (pore size of 1.2 μm or less). The vials do not 
contain antibacterial preservatives; therefore, any unused portion of the infusion solution 
should not be stored for reuse. 
The Investigator will be notified of any expiry date or retest date extension of Sponsor-supplied 
drug during the study conduct. On expiry date notification from the Sponsor or designee, the 
CRU must complete all instructions outlined in the notification, including segregation of expired 
Sponsor-supplied drug for destruction. 
In the event of expiry date extension of supplies already at the CRU, a memo will be provided 
by the Sponsor with the retest period and retest date. 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
In this study participants will be randomly assigned to treatment (XTMAB-16 or placebo) and 
treatment assignment will be double-blind: participants and all study staff will be blind to 
participant treatment assignment for the duration of the study except as specified. 
The randomization schedule will be generated by an unblinded statistician (third-party 
unblinded) and will be provided to the CRU pharmacist prior to the start of this study. All 
randomization information will be stored in a secured area, accessible only by authorized 
personnel. 
The Investigator (or designee) will assign participant numbers as participants are screened for 
the study. In accordance with the randomization numbers, the participant will receive the study 
treatment regimen assigned to the corresponding randomization number. 
To maintain the treatment blind, an otherwise uninvolved, third-party unblinded CRU staff 
member (eg, pharmacist) will be responsible for the preparation and dispensing of all study 


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treatment according to the randomization schedule and assigned treatment for the individual 
participant. The unblinded pharmacist will have no contact with study participants and will 
ensure that no treatment assignment information is transmitted to study unit staff except as 
defined in Section 6.3.1. 
6.3.1 UNBLINDING PROCEDURE 
The study drug blind shall not be broken by the Investigator unless information concerning the 
treatment assignment is necessary for the medical treatment of the participant. All study 
assessments and causality should be performed, if possible, prior to unblinding. In the event of 
a medical emergency, if possible, the Sponsor’s Medical Monitor should be contacted before 
the treatment assignment blind is broken to discuss the need for unblinding. 
For unblinding a participant, the treatment assignment blind can be obtained by contacting the 
dispensing pharmacist. Code break envelopes will be supplied for emergency unblinding when 
the pharmacist is unavailable. 
The Sponsor must be notified as soon as possible if the treatment assignment blind is broken. 
The date, time, and reason the blind is broken must be recorded in the source documents and 
the same information (except the time) must be recorded on the electronic case report form 
(eCRF). 
If the blind must be broken for the safety of the participant, the PI and CRO should refer to the 
Unblinding Plan for instructions and details for review of safety data for that cohort and the 
impact on dose escalation and/or stopping rules. 
If any CRU personnel are unblinded, study drug dosing must be stopped immediately and the 
participant must be withdrawn from the study. 
No change should be made to any assessment of the participant after unblinding. 
6.3.2 PREPARATION 
Reconstitute each XTMAB-16 or placebo vial with 10 mL of sterile WFI, USP, using a syringe 
equipped with a 21-gauge or smaller needle. Remove the flip-top from the vial and wipe the 
top with an alcohol swab. Insert the syringe needle into the vial through the center of the 
rubber stopper and direct the stream of sterile WFI, USP, to the glass wall of the vial. Gently 
swirl the solution by rotating the vial to dissolve the lyophilized powder. Avoid prolonged or 
vigorous agitation. DO NOT SHAKE. Foaming of the solution on reconstitution may occur and is 
not unusual. Allow the reconstituted solution to stand at room temperature for 5 minutes. The 
solution should be colorless to pale-yellow and opalescent and may develop a few translucent 
particles, as XTMAB-16 is a protein. Do not use if opaque particles, discoloration, or other 
foreign, particles are present. 
Please refer to additional instructions in the Pharmacy Manual. 


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The study drug will be prepared by a trained, unblinded CRU staff member using aseptic 
technique (eg, Pharmacist). Study drug will be prepared based on the treatment assignment. 
The Sponsor, Investigator, study center staff, and participants will be blinded to treatment 
assignment and only the unblinded pharmacist or designee will be aware of the treatment 
assignment. 
Dose preparation records will be completed and securely maintained by the dose preparer. 
Both XTMAB-16 and placebo have the same appearance after reconstitution and dilution, 
thereby ensuring that the CRU staff administering the study drug will remain blinded to 
treatment assignment. Details of the preparation of XTMAB-16 and placebo will be provided in 
the Laboratory Manual. 
6.4 
STUDY DRUG COMPLIANCE 
All doses of study drug in this study will be administered by CRU personnel. As such, no 
measures of study drug compliance are included for this study beyond study drug 
accountability, as previously described. 
If study drug administration is interrupted or stopped, the estimated total amount (percentage) 
of the study drug successfully administered will be recorded in the eCRF. 
6.5 
CONCOMITANT THERAPY 
Otherwise, the use of concomitant medication should not be allowed during the study unless 
specified in the inclusion criteria or study procedures. However, if a concomitant medication is 
required for any reason, the name of the medication, indication, dose, and duration of use will 
be recorded on the eCRF. The Sponsor must be informed within 48 hours via email or by 
telephone. 
Use of the agents in Table 4 (prescription or nonprescription) is prohibited from the time points 
specified until participant is discharged from the unit. 




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SAEs associated with overdose will be reported according to the procedure outlined in 
Section 8.6.5. 
All cases of overdose (with or without associated AEs) will be collected on the eCRF. 


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7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1 
DISCONTINUATION OF STUDY DRUG 
A single dose of study treatment will be administered in this study. Study treatment will only be 
discontinued if an unforeseen occurrence interrupts or prematurely stops the 2-hr IV infusion. 
Discontinuation from study treatment does not mean discontinuation from the study, and 
remaining study procedures should be completed as indicated by the study protocol. If a 
clinically significant finding is identified (including, but not limited to changes from Baseline) 
after enrollment, the Investigator or qualified designee will determine if any change in 
participant management is needed. All events or clinically relevant findings that cause the 
interruption or premature cessation of dosing will be reported as an AE. 
The data to be collected at the time of study treatment interruption or discontinuation will 
include the following: 
• 
Reason dosing was interrupted/stopped 
• 
Estimate of how much of the study treatment dose was delivered (%) 
• 
How long the participant was observed for safety after the event 
• 
Whether the participant continued in the study or was withdrawn. 
Participants who are withdrawn from the study after interruption or premature discontinuation 
of study treatment dosing should undergo EOS procedures as noted in the SoA (Section 1.3). 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Participants may withdraw from the study at any time and for any reason. The reason for 
participant discontinuation or withdrawal from the study will be recorded on the eCRF. 
Participants may be discontinued from the study for any of the following reasons: 
• 
Lost-to-follow-up 
• 
Study termination by the Sponsor 
7.3 
LOST TO FOLLOW-UP 
A participant will be considered lost to follow-up if he or she fails to return for 2 consecutively 
scheduled visits and is unable to be contacted by the CRU staff or fails to return for the Day 71 
visit. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 


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• 
The CRU will attempt to contact the participant and reschedule the missed visit within 
7 days and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain if the participant wishes to and/or should continue in the study. 
• 
Before a participant is deemed lost to follow-up, the Investigator or designee will make 
every effort to regain contact with the participant (where possible, 3 telephone calls 
and, if necessary, a certified letter to the participant’s last known mailing address or 
local equivalent methods). These contact attempts should be documented in the 
participant’s medical record or study file. 
• 
Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 


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8 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 
EFFICACY ASSESSMENTS 
There are no efficacy assessments for this Phase 1, FIH, clinical study. 
8.2 
SAFETY AND OTHER ASSESSMENTS 
Planned time points for all safety and other assessments are provided in the SoA (see Section 
1.3). 
8.2.1 PHYSICAL EXAMINATION 
• 
A complete physical examination will include assessments of general appearance, skin; 
head/neck; pulmonary, cardiovascular, gastrointestinal, external genitourinary 
(optional), lymphatic, and musculoskeletal systems; extremities; eyes (inspection and 
vision control); ears, nose; throat; and neurologic status. 
• 
An abbreviated physical examination will include assessments of general appearance; 
head, ears, eyes, nose, and throat; cardiovascular; respiratory; and gastrointestinal 
systems (including the abdomen). 
• 
A targeted physical examination may be conducted at any time at the Investigator’s 
discretion and should be limited to systems of clinical relevance (ie, cardiovascular, 
respiratory, lymph nodes, liver.) 
8.2.2 HEIGHT AND WEIGHT 
Height (cm) will be measured only at Screening. Weight will be measured in kilograms 
according to the SoA (Section 1.3). 
8.2.3 VITAL SIGNS 
Oral, tympanic or temporal body temperature, respiratory rate, pulse, and systolic and diastolic 
blood pressure will be assessed. The method of body temperature assessment chosen should 
be recorded and consistent throughout the study. 
If oral temperatures (°C) are taken, participants will have had no food or liquid for at least 
5 minutes before assessment. 
During the infusion, systolic/diastolic blood pressure and pulse should be measured in a semi-
spine/semi-reclined position. For all other readings, blood pressure and pulse will be taken in a 
supine position after 10 to 15 minutes rest. 


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Respiratory rate (breaths/min) will be taken after at least 5 minutes rest; breaths are counted 
for 30 seconds and multiplied by 2. Respiration rate will be taken concurrently with all ECGs. 
During the infusion, respiration rate will be taken in a semi-supine/semi-reclined position. 
 
8.2.4 ELECTROCARDIOGRAMS 
Participants will undergo telemetry beginning on Day -1 through 50 hours after the start of 
infusion (Table 8). Five-minute telemetry data extraction periods should begin after 10 minutes 
of rest in a semi-reclined position, and when applicable, at least 15 minutes prior to the 
nominal PK/ADA/nAb blood collection time point and to allow completion of the ECGs prior to 
collection of PK/ADA/nAb sample. 
Standard 12-lead ECGs will be recorded after the participant has been resting at least 10 
minutes using a CAM-14 module. Single ECGs will be collected at the time points noted in the 
SoA (Section 1.3). Additional ECGs will be performed at the discretion of the Investigator. 
Telemetry and ECG readings will be performed in a supine position after the allotted time 
specified above. During the infusion, procedures will be performed in a semi-
supine/semi-reclined position. 
The Investigator will be responsible for reviewing the ECG to assess whether the ECG is within 
the reference limits and to determine clinical significance of the results. If necessary, the 
Investigator has the right to override the interpretation and intervals as measured by the ECG 
machine. The ECG will be assessed for the following measures: P wave, QRS complex, U wave, 
QRS duration, QT interval, QTcF, T wave, ST segment, RR interval, PR interval, and qualitative 
results. 
8.2.5 CLINICAL LABORATORY EVALUATIONS 
Clinical laboratory assessments will be collected under appropriate conditions defined by the 
clinical unit’s standard of practice. 
• The research laboratory unit will be used to perform all clinical laboratory tests including 
serum pregnancy test, which will be assessed by the CRU staff. The Investigator should 
take immediate action for any safety concerns based on laboratory results. 
• The Investigator must review the laboratory report, document this review, and record 
any clinically relevant changes occurring during the study in the eCRF. The laboratory 
reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those that are not associated with an underlying disease, unless 
judged by the Investigator to be more severe than expected for the participant’s 
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• All laboratory tests with values considered clinically significantly abnormal during 
participation in the study, including the participant’s last EOS visit, should be repeated 
until the values return to normal or Baseline or are no longer considered clinically 
significant or follow-up is no longer needed per the judgment of the Investigator or 
Medical Monitor. 
o If such values do not return to normal/Baseline within a period of time judged 
reasonable by the Investigator, the etiology should be identified, and the Sponsor 
notified. 
• All protocol-required laboratory assessments, as defined in Appendix 1, must be 
conducted in accordance with the Laboratory Manual and the SoA (Section 1.3). 
Blood volumes for laboratory samples will be included in the Laboratory Manual. 
8.3 
PHARMACOKINETICS 
Whole blood samples will be collected for measurement of serum concentrations of XTMAB-16 
(Table 8). Instructions for the collection and handling of biological samples will be provided by 
the Sponsor in a separate Laboratory Manual. The actual date and time (24-hour clock) of each 
sample will be recorded in the eCRF. Samples will be used to evaluate the serum concentration 
and PK of XTMAB-16. Each serum sample will be divided into 2 aliquots (1 each for primary and 
back-up). 
Measurement of concentrations of XTMAB-16 will be performed using a validated assay 
method by or under the supervision of the Sponsor. The analytical methods used to measure 
concentrations of XTMAB-16 will be described in a separate bioanalytical report. Only samples 
that are within the window of sample stability will be analyzed. 
While PK samples must be collected from participants assigned to the placebo arm to maintain 
the blinding of treatment assignment, PK assay results for these participants are not needed for 
the safety conduct or proper interpretation of this trial and most samples will therefore not be 
analyzed. Personnel responsible for performing PK assays will be unblinded to participants’ 
treatment assignments to identify appropriate PK samples to be analyzed. Samples from 
participants assigned to placebo may be analyzed upon request (ie, to evaluate a possible error 
in dosing). 
Blood samples for PK/ADA/nAb will be collected for analysis from participants who experience 
an SAE that is also considered related to study treatment. If an SAE occurs prior to the 
validation of the XTMAB-16-specific PK assay, blood samples in these potential cases will be 
analyzed using the infliximab assay, as needed, on an individual basis. These samples from 
these participants will be re-analyzed as part of the batch analyses using the validated 
XTMAB-16-specific assay prior to completion of the study. 
Blood volumes for PK samples will be included in the Laboratory Manual. 


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Table 5 
List of Pharmacokinetic Parameters and Definitions 
Parameters 
Definition/Calculation 
Cmax 
Maximum observed serum concentration  
CT 
Serum concentration observed at the end of drug infusion, where T is the duration of 
infusion time 
tmax 
First time to reach Cmax after drug administration 
AUC0-t 
Area under the serum concentration versus time curve from time zero to the last 
quantifiable time point at t 
AUC0-∞ 
Area under the serum concentration versus time curve extrapolated to infinity 
according to the following equation: 
AUC0-∞ = AUC0-t + Ct / λz 
Values with a percentage of extrapolation >20% of AUC0-∞ will not be considered in 
the descriptive statistics  
z 
Terminal elimination rate constant (see t1/2 below) 
t1/2 
Terminal half-life associated with the terminal phase determined according to the 
following equation: 
t1/2 = 0.693/λz 
where λz is the slope of the regression line of the terminal phase of the serum 
concentration versus time curve, in semi-logarithmic scale. z will be calculated by 
taking the regression of at least 3 points. 
CL 
Total body clearance of a drug from the serum calculated using the following 
equation: 
CL = Dose / AUC0-∞ 
MRT 
Mean residence time of the drug in the body calculated as: 
MRT = AUMC0-∞ / AUC0-∞ 
where AUMC0-∞ is area under the serum concentration moment (C ∙ t) versus time 
curve extrapolated to infinity according to the following equation: 
AUMC0-∞ = AUMC0-t + (Ct ∙ t / z + Ct / z2) 
Vz 
Volume of distribution during the terminal phase calculated using the following 
equation: 
Vz = Dose/(z ∙ AUC0-∞) 
Vss 
Steady state volume of distribution following IV dosing calculated as: 
Vss = MRT • CL 
 


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8.4 
IMMUNOGENICITY 
Antibodies to XTMAB-16 will be evaluated in serum samples collected from all participants 
according to Table 8. Additionally, serum samples should also be collected at the final visit from 
participants who discontinue from the study. Instructions for the collection and handling of 
biological samples will be provided by the Sponsor in a separate Laboratory Manual. These 
samples will be tested by the Sponsor or Sponsor’s designee. Each serum sample will be divided 
into 2 aliquots (1 each for primary and a back-up). 
Serum samples will be tested in a multi-tiered approach. A validated screening assay for 
antibodies binding to XTMAB-16 will be initially used to assess serum samples. Samples that are 
determined putative positive in the screening assay will then be subjected to a confirmatory 
assay to demonstrate that antibodies are specific to XTMAB-16. Samples that are identified as 
positive in the confirmatory assay will be further characterized in a validated tier assay and titer 
of confirmed positive samples will be reported. Other analyses may be performed to verify the 
stability of antibodies to study treatment and/or to further characterize the immunogenicity of 
study treatment. Serum samples will be screened for antibodies binding to XTMAB-16 and the 
titer of confirmed positive samples will be reported. 
The detection and characterization of antibodies to XTMAB-16 will be performed using a 
validated assay method by or under the supervision of the Sponsor. The analytical methods 
used to measure immunogenicity will be described in a separate bioanalytical report. Only 
samples which are within the window of sample stability will be analyzed. 
Samples that are confirmed positive for antibodies binding to XTMAB-16 may be further 
evaluated for their ability to neutralize the activity of the study treatment using a validated 
assay method. 
Blood samples for PK/ADA/nAb will be collected for analysis from participants who experience 
an SAE that is also considered related to study treatment. 
Blood volumes for ADA/nAB samples will be included in the Laboratory Manual. 
8.5 
BIOMARKERS 
Whole blood samples will be collected for measurement of exploratory circulating biomarkers 
according to Table 8 and serum will be used for analysis. Circulating biomarkers that will be 
evaluated include ACE, sIL-2R, IL-6, and sTNFα. 
Instructions for the collection and handling of biological samples will be provided by the 
Sponsor in a separate Laboratory Manual. The actual date and time (24-hour clock time) of 
each sample will be recorded in the eCRF. Data collected from analyses of circulating 
biomarkers may be used to correlate exposure to safety or other parameters or after the study. 
Measurement of circulating biomarkers will be performed using a fit-for-purpose qualified 
assay method. The analytical methods used to measure these biomarker endpoints will be 


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described in separate bioanalytical reports. Only samples that are within the window of sample 
stability will be analyzed. 
Blood collection volumes for biomarker samples will be included in the Laboratory Manual. 
8.6 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
8.6.1 DEFINITION OF ADVERSE EVENTS 
An AE is any untoward medical occurrence associated with the use of an intervention in 
humans, whether or not considered intervention-related (21 CFR 312.32 (a)). 
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of study 
treatment. 
8.6.2 DEFINITION OF SERIOUS ADVERSE EVENTS 
An AE or suspected adverse reaction is considered "serious" if, in the view of either the 
Investigator or Sponsor, it results in any of the following outcomes: 
• Death 
• Life-threatening AE 
• Inpatient hospitalization or prolongation of existing hospitalization 
• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• 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 participant and may require medical or surgical intervention to prevent 
one of the outcomes listed in this 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. 
8.6.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.6.3.1 SEVERITY OF EVENT 
The Investigator will make an assessment of severity for each AE and SAE reported during the 
study and assign it to 1 of the following categories: 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
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Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or 
incapacitating. Of note, the term “severe” does not necessarily equate to “serious”. 
8.6.3.2 RELATIONSHIP TO STUDY INTERVENTION 
All AEs must have their relationship to the study drug assessed by the Investigator who 
examines and evaluates the participant based on temporal relationship and his/her clinical 
judgment. The degree of certainty about causality will be graded using the categories below. In 
a clinical trial, the study drug must always be suspect. 
• Related – The AE is known to occur with the study drug, there is a reasonable possibility 
that the study drug caused the AE, or there is a temporal relationship between the study 
drug administration and the event. Reasonable possibility means that there is evidence 
to suggest a causal relationship between the study drug and the AE. 
• Not Related – There is not a reasonable possibility that the administration of the study 
drug caused the event, there is no temporal relationship between the study drug and 
event onset, or an alternate etiology has been established. 
8.6.3.3 EXPECTEDNESS 
The Investigator will be responsible for determining whether an AE is expected or unexpected. 
XTMAB-16 has not previously been administered in humans. 
 
 
 
 
 
8.6.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
The occurrence of an AE or SAE may come to the attention of CRU personnel during study visits 
and interviews of a participant presenting for medical care, or upon review by a study monitor. 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be captured 
on the appropriate eCRF. Information to be collected includes event description, time of onset, 
clinician’s assessment of severity, relationship to study product (assessed only by those with 
the training and authority to make a diagnosis), and time of resolution/stabilization of the 
event. All AEs occurring while on study must be documented appropriately regardless of 
relationship. All AEs will be followed to adequate resolution. 


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Any medical condition that is present at the time that the participant is screened will be 
considered as Baseline and not reported as an AE. However, if the participant’s condition 
deteriorates at any time during the study, it will be recorded as an AE. 
Changes in the severity of an AE will be documented to allow an assessment of the duration of 
the event at each level of severity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode. 
The Investigator or designee will record all reportable events with start dates occurring any 
time after informed consent is obtained until 7 (for nonserious AEs) or 30 days (for SAEs) after 
the last day of study participation. At each study visit, the Investigator will inquire about the 
occurrence of AE/SAEs since the last visit. vents will be followed for outcome information until 
resolution or stabilization. 
8.6.5 SERIOUS ADVERSE EVENT REPORTING 
The PI or designee is responsible for providing notification to the Sponsor of any SAE, whether 
deemed study drug-related or not, that a participant experiences during the study within 
24 hours of becoming aware of the event. 
As a minimum requirement, the initial notification should provide the following information: 
• Study number 
• Participant number 
• Sex 
• Date of birth 
• Name of PI and full CRU address 
• Details of SAE 
• Criterion for classification as ‘serious’ 
• The study drug name, or code if unblinded, and treatment start date 
• Date of SAE onset 
• Causality assessment (if sufficient information is available to make this classification) 
All SAEs will be followed until satisfactory resolution, until the Investigator deems the event to 
be chronic, or the participant is stable. Other supporting documentation of the event may be 
requested by Parexel Safety Services/Sponsor and should be provided as soon as possible. 
The SAE form will be sent to: 
Parexel Safety Services 
Email:
 
FAX: 
 


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The Sponsor will be responsible for notifying regulatory authorities (eg, FDA, EMA, as 
applicable) of any unexpected fatal or life-threatening suspected adverse reaction, suspected 
unexpected serious adverse reaction (SUSAR), or other applicable SAE as soon as possible, but 
in no case later than 7 calendar days after the Sponsor's initial receipt of the information. In 
addition, the Sponsor must notify regulatory authorities and all participating Investigators in an 
IND safety report of potential serious risks, from clinical trials or any other source, as soon as 
possible, but in no case later than 15 calendar days after the Sponsor determines that the 
information qualifies for reporting. 
The Sponsor will notify the Investigator of relevant information about SUSARs that could 
adversely affect the safety of participants in a timely fashion. Follow-up information may be 
submitted if necessary. The Sponsor will also provide annual safety reports for submission to 
the regulatory authority and the IRB/IEC responsible for the clinical study. These updates will 
include information on SUSARs and other relevant safety findings. 
8.6.6 EVENTS OF SPECIAL INTEREST 
Based on clinical data from the TNFα inhibitor package inserts and nonclinical data to date for 
XTMAB-16, the adverse event of special interest (AESI) for this study is: 
• Anaphylactic shock 
AESIs will be reported using the appropriate eCRF. In addition, AESIs that are also SAEs will be 
reported using the SAE form and sent to Parexel Safety Services (see Section 8.6.5). 
8.6.7 REPORTING OF PREGNANCY 
• The Investigator will collect pregnancy information on any female participant or female 
partner of a male participant who becomes pregnant while the participant is in this 
study. 
• If a pregnancy is reported, the Investigator should inform Parexel Safety Services within 
24 hours of learning of the pregnancy using the SAE Form. 
• If a pregnancy occurs, the participant will be followed to determine the outcome of the 
pregnancy, but no longer than 6-8 weeks after the estimated delivery date. Any 
termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for the procedure. 
• Pregnancy is not considered an SAE but should be reported in the eCRF and on the 
Pregnancy Form in accordance with SAE reporting timelines as per Section 8.6.5. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, and ectopic pregnancy) are considered SAEs. 
• Any post-study pregnancy-related SAE considered reasonably related to the study 
treatment by the Investigator will be reported to the Sponsor as per Section 8.6.5. While 


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the Investigator is not obligated to actively seek this information in former study 
participants, he or she may learn of an SAE through spontaneous reporting. 
8.7 
UNANTICIPATED PROBLEMS 
8.7.1 DEFINITION OF UNANTICIPATED PROBLEMS 
The Office for Human Research Protections (OHRP) considers unanticipated problems (UPs) 
involving risks to participants or others to include, in general, any incident, experience, or 
outcome that meets all of the following criteria: 
• 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 form (ICF); and (b) the characteristics of the 
participant population being studied; 
• 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 involved in the research); and 
• Suggests that the research places participants or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was previously known 
or recognized. 
Investigators should refer to the Remicade (infliximab) package insert for known risks and AEs 
with the use of this class of drug (TNFα blockers).32 
8.7.2 UNANTICIPATED PROBLEM REPORTING 
The Investigator will report UPs to the IRB and to Parexel Safety Services. The UP report will 
include the following information: 
• Protocol identifying information: protocol title and number, PI’s name, and the IRB 
project number. 
• A detailed description of the event, incident, experience, or outcome. 
• An explanation of the basis for determining that the event, incident, experience, or 
outcome represents an UP. 
• A description of any changes to the protocol or other corrective actions that have been 
taken or are proposed in response to the UP. 
To satisfy the requirement for prompt reporting, UPs will be reported using the following 
timeline: 
• UPs that are SAEs will be reported to the IRB and to the Parexel Safety Services within 
24 hours of the Investigator becoming aware of the event. 


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• Any other UP will be reported to the IRB and to the Parexel Safety Services within 7 days 
of the Investigator becoming aware of the problem. 
All UPs should be reported to appropriate institutional officials (as required by an institution’s 
written reporting procedures), the supporting agency head (or designee), and the OHRP within 
7 days of the IRB’s receipt of the report of the problem from the Investigator. 


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9 
STATISTICAL CONSIDERATIONS 
9.1 
STATISTICAL HYPOTHESES 
Hypothesis testing will not be conducted for this study. 
9.2 
SAMPLE SIZE DETERMINATION 
The selection of 24 participants (12 per cohort) was based on feasibility and precision around 
the estimates for target variables associated with the primary and secondary endpoints. No 
sample size calculation was performed. 
9.3 
POPULATIONS FOR ANALYSES 
• Enrolled Set (ES): The ES will consist of all participants who have given informed 
consent. 
• Full Analysis Set (FAS): The FAS will consist of all participants randomized into the study. 
Participants in this analysis set will be used for analyzing demographics and other 
baseline characteristics. 
• Safety Set: The safety analysis set will consist of all participants who are randomized to 
treatment and have received 1 dose of study drug. Participants in this analysis set will 
be used for demographics, baseline characteristics, and safety summaries. 
• Pharmacokinetic Per-Protocol Set (PK-PPS): The PK-PPS set will consist of all 
participants in the Safety Set who provide at least 1 quantifiable serum XTMAB-16 PK 
sample postdose without important protocol deviations that would affect the 
concentration. 
• Biomarker Set: The PD set will consist of all participants in the PK-PPS who have at least 
1 postdose biomarker measurement. 
If any participants are found to be noncompliant in dosing schedule or with incomplete data, a 
decision will be made on a case-by-case basis as to their inclusion in the PK and biomarker 
analysis sets but nevertheless will be presented in the participant listings. 
9.4 
STATISTICAL ANALYSES 
Statistical analysis and generation of tables, figures, study participant data listings, and 
statistical output will be performed using SAS® Version 9.4 or higher. 
All original and derived parameters will be listed and described using summary statistics. For 
continuous parameters, number of participants with available measurements, mean, standard 
deviation (SD), median, minimum, and maximum and for categorical parameters, number of 
participants and percentages (to 1 decimal place) in each category will be presented. 


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All descriptive statistics will be presented by treatment where applicable (eg, biomarkers), 
including columns for all treated participants and all participants on demographics, baseline 
characteristics, and AE displays, and using the available data for the study population as 
observed. Summaries of concentration data will be based on geometric mean and geometric SD 
instead of arithmetic versions. All tabulations will be sorted by treatment, parameter, and Day 
(including time relative to dosing if applicable, unless otherwise stated). Only scheduled visits 
and times relative to dosing will be included in the tabulation. 
Categorical data will be summarized by Day/Week/Time and treatment. 
9.4.1 GENERAL APPROACH 
Details of the data analysis for this study will be provided in the Statistical Analysis Plan (SAP), 
which will be finalized prior to database lock. 
Unless otherwise specified, the last value obtained prior to infusion of study medication (Day 1) 
will be used as the baseline value. If a baseline measurement is missing, and a screening value 
available, the screening value will be utilized as Baseline instead. 
9.4.2 SAFETY ANALYSES 
9.4.2.1 LABORATORY EVALUATIONS, VITAL SIGNS AND ECG 
Laboratory evaluations, vital signs, and ECGs will be analyzed for the Safety Set for observed 
cases. Descriptive statistics will be presented by cohort and treatment at each time point: 
change from Baseline in vital signs, serum chemistry, hematology, and urinalysis. For laboratory 
data, changes between the Baseline or, if missing, screening value and each posttreatment 
assessment may be presented in shift tables or using other summaries as detailed in the SAP. 
Assessment of liver-related changes will include: 
• 3 ×-, 5 ×-, 10 ×-, and 20 × ULN elevations of AST, ALT, and either ALT or AST 
• Any elevations of bilirubin: elevated total bilirubin to >2 × ULN 
• Any elevations of ALP >1.5 × ULN 
• Elevation of AST or ALT (>3 × ULN) accompanied by elevated bilirubin (>1.5 × ULN, >2 × 
ULN) 
• Elevation of AST or ALT in temporal association with nausea, vomiting, anorexia, 
abdominal pain, or fatigue 
• Any liver-related deaths and liver-related treatment discontinuations. 
For ECG parameters, descriptive analysis and shift tables from predose will be performed. 
Further concentration QT analysis (eg, time-matched QT, and QTc analyses for XTMAB-16 and 


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placebo may be evaluated, including effect of XTMAB-16 concentration on QTc, and categorical 
analyses) and will be defined in a finalized SAP. 
9.4.2.2 ADVERSE EVENTS 
Safety variables will be analyzed for all study participants in the Safety Set. 
Adverse events will be coded by system organ class (SOC) and preferred term (PT) using the 
Medical Dictionary for Regulatory Activities (MedDRA) version 23 or higher. 
The frequency of all AEs during the study will be presented for each cohort and treatment 
separately by SOC and PT. The data will be displayed as the number of participants experiencing 
the AEs, percentage of participants, and the number of events. 
All TEAEs (defined as those AEs with an onset date/time on or after the start of infusion on 
Day 1 to end of safety follow-up), serious and nonserious, including deaths, will be tabulated 
and listed. Laboratory safety parameters that are reported as AEs will also be tabulated and 
listed. 
9.4.2.3 IMMUNOGENICITY 
Anti-drug antibodies and nAb at each sampling time will be summarized with descriptive 
statistics (N, mean, SD, coefficient of variation [CV], geometric mean, geometric CV, median, 
minimum, and maximum) for each dose. 
If ADA or nAb are detected, a direct link model may be used to describe the relationship 
between the serum concentration of XTMAB-16 and ADA or nAb levels, as AUC and time point 
concentration measurements to explore the time-dependence. 
9.4.3 PHARMACOKINETICS 
The PK analysis will be conducted for patients who have sufficient plasma concentration data to 
facilitate the calculation of at least one PK parameter and had no important protocol deviations 
affecting the PK variables as confirmed during a pre-analysis review of the data before database 
lock. The PK parameters will be calculated from the plasma concentration-actual time profiles. 
The non-compartmental analysis will be performed using Phoenix® WinNonlin® Software 
version 8.0 or higher (Certara, LP). 
9.4.3.1 SERUM CONCENTRATION-TIME DATA 
Individual serum concentrations of XTMAB-16 at each PK sampling time (predose, at 
completion of infusion, and all other timepoints after the start of infusion) will be summarized 
with descriptive statistics (N, mean, SD, CV, geometric mean [gMean], geometric coefficient of 
variation [gCV], median, minimum, and maximum) for each dose. For descriptive statistics of 
the concentration-time data summaries, the nominal times (ie, planned times) will be used. 


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Figures for individual serum concentration of XTMAB-16 versus time profiles will be generated 
on regular and semi-log scales with mean for each dose. Figures for mean ±SD serum 
concentration of XTMAB-16 versus time profiles will be generated on regular and semi-log 
scales together for all doses. 
9.4.3.2 PHARMACOKINETIC PARAMETERS 
For determination of PK parameters, the actual sampling times (taking into account the actual 
dates and times) will be used. The following PK parameters will be obtained: Cmax, tmax, AUC0-t, 
AUC0-ꚙ, % AUC0-ꚙ, CL, t2/1, z, Vz, Vss, and MRT. Individual dose-normalized parameters for Cmax, 
AUC0-t, and AUC0-ꚙ will also be summarized in terms of dose-normalized Cmax, AUC0-t, and 
AUC0-∞ (Cmax,norm, AUC0-t,norm, and AUC0-ꚙ,norm, respectively). Individual PK parameters of 
XTMAB-16 will be summarized with descriptive statistics (N, mean, SD, CV, gMean, gCV, 
median, minimum, and maximum) for each dose. 
Dose proportionality will be evaluated for these PK parameters, viz. Cmax, AUC0-t, and AUC0-ꚙ by 
the power model (PK parameter = α • doseβ). The power model will be fit on the 
log-transformed linear scale: log (PK parameter) = log(α) + β • log(dose). An estimate of unity 
for β will indicate perfect dose linearity. 
Details of the PK analysis, including PK Tables, Listings, and figures, will be provided in the SAP. 
9.4.4 BIOMARKER ANALYSIS 
Biomarkers (ACE, sIL-2R, IL-6, and sTNFα) at each sampling time (predose, at completion of 
infusion, and postinfusion timepoints) will be summarized with descriptive statistics (N, mean, 
SD, CV, geometric mean, geometric CV, median, minimum, and maximum) for each dose. 
Percent change from Baseline over time and total change from Baseline will be analyzed. 
Details of the biomarker analysis will be provided in the SAP. 
9.4.4.1 BIOMARKER-CONCENTRATION-TIME DATA 
All subjects without any major deviations related to study drug administration and for whom 
any biomarker (or effect) data are available will be included in the biomarker analysis. However, 
subjects being included in this population and having received only placebo will also be 
included as part of this data set. 
Details of the biomarker analysis will be provided in the SAP. 
9.4.4.2 PHARMACOKINETIC AND BIOMARKER RELATIONSHIP 
The relationship between each biomarker concentration and XTMAB-16 concentration 
collected at the same time point may be graphically displayed for individual subjects, and for 
mean data for each dose. In addition, these figures will also be generated for each biomarker 
with all the data pooled across all the doses. 


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Details of the PK and biomarker relationship analysis will be provided in the SAP. 
9.4.4.3 BIOMARKER PARAMETERS 
These biomarker (or effect) parameters will be obtained, if data permit: area under the effect-
time curve (AUEC), maximum observed effect (Emax,obs), and time to reach maximum observed 
effect (tEmax,obs). The overall results of the biomarker assessments will determine whether these 
specific analyses will be performed. 
If applicable, a PK/PD direct link model may be used to describe the relationship between 
biomarker levels and the XTMAB-16 concentrations at each time.  
Details of the biomarker analysis will be provided in the SAP. 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
Descriptive statistics (N, mean, SD, median, minimum, and maximum) will be used to present 
the continuous demographic variables and baseline characteristics for each XTMAB-16 dose 
level, pooled placebo, and overall total. For categorical variables, the number and percentage 
of participants will be tabulated for each XTMAB-16 dose level, pooled placebo, and overall 
total. Additional details will be presented in the SAP. 
9.4.6 PLANNED SAFETY REVIEW 
Blinded safety data of sentinel subjects for each cohort will be reviewed by the PI as a non-
comparative analysis at least 48 hours before enrollment of the remaining  participants in that 
cohort.  
9.4.7 HANDLING OF PROTOCOL DEVIATIONS 
Important protocol deviations are a subset of protocol deviations that may significantly impact 
the completeness, accuracy, and/or reliability of the study data or that may significantly affect a 
participant’s rights, safety, or well-being. The criteria for identifying important protocol 
deviations will be defined within the SAP. Important protocol deviations will be reviewed as 
part of the ongoing data cleaning process and data evaluation. All important deviations will be 
identified and documented prior to unblinding to confirm exclusion from analysis sets. 
9.4.8 HANDLING OF DROPOUTS OR MISSING DATA 
Missing data will not be imputed. See Section 5.5 for details on replacement of participants 
who discontinue prior to assessment of the primary PK endpoint. 


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10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
10.1.1 INFORMED CONSENT PROCESS 
10.1.1.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PARTICIPANTS 
Consent forms describing in detail the study intervention, study procedures, and risks are given 
to the participant and written documentation of informed consent is required prior to starting 
study intervention. 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
Informed consent is a process that is initiated prior to the participant’s agreeing to participate 
in the study and continues throughout the study participation. Consent forms will be IRB-
approved, and the participant will be asked to read and review the document. The Investigator 
will explain the research study to the participant and answer any questions that may arise. A 
verbal explanation will be provided in terms suited to the participant’s comprehension of the 
purposes, procedures, and potential risks of the study and of their rights as research 
participants. Participants will have the opportunity to carefully review the written consent form 
and ask questions prior to signing. 
The participants should have the opportunity to discuss the study with their family or 
surrogates or think about it prior to agreeing to participate. The participant will sign the 
informed consent document prior to any procedures being done specifically for the study. 
Participants must be informed that participation is voluntary and that they may withdraw from 
the study at any time, without prejudice. A copy of the informed consent document will be 
given to the participants for their records. 
The informed consent process will be conducted and documented in the source document 
(including the date), and the form signed, before the participant undergoes any study-specific 
procedures. The rights and welfare of the participants will be protected by emphasizing to them 
that the quality of their medical care will not be adversely affected if they decline to participate 
in this study. 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to study participants, 
Investigators, the IND Sponsor, and regulatory authorities. If the study is prematurely 
terminated or suspended, the PI will promptly inform study participants and the IRB and the 


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Sponsor and will provide the reason(s) for the termination or suspension. Study participants will 
be contacted, as applicable, and be informed of changes to study visit schedule. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to participants 
• Demonstration of efficacy that would warrant stopping 
• Insufficient compliance to protocol requirements 
• Data that are not sufficiently complete and/or evaluable 
• Determination that the primary endpoint has been met 
• Determination of futility 
The study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the Sponsor, IRB, and/or FDA or other regulatory authorities. 
10.1.3 CONFIDENTIALITY AND PRIVACY 
Participant confidentiality and privacy are strictly held in trust by the participating Investigators, 
their staff, and the Sponsor(s) and their interventions. This confidentiality is extended to cover 
testing of biological samples and genetic tests in addition to the clinical information relating to 
participants. Therefore, the study protocol, documentation, data, and all other information 
generated will be held in strict confidence. No information concerning the study or the data will 
be released to any unauthorized third party without prior written approval of the Sponsor. 
All research activities will be conducted in as private a setting as possible. 
The study monitor, other authorized representatives of the Sponsor, representatives of the IRB, 
regulatory agencies or pharmaceutical company supplying study product may inspect all 
documents and records required to be maintained by the Investigator, including but not limited 
to, medical records (office, clinic, or hospital) and pharmacy records for the participants in this 
study. The CRU will permit access to such records. 
The study participant’s contact information will be securely stored at the CRU for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure 
location for in accordance with Sponsor obligation (20 years from regulatory approval). 
Study participant research data, which is for purposes of statistical analysis and scientific 
reporting, will be transmitted to and stored at the data management company responsible for 
data management, analysis, and reporting. This will not include the participant’s contact or 
identifying information. Rather, individual participants and their research data will be identified 
by a unique study identification number. The study data entry and study management systems 
used by the CRU and by data management research staff will be secured and password 
protected. At the end of the study, all study databases will be de-identified and archived by the 
Sponsor. 


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All information generated in this study must be considered highly confidential and must not be 
disclosed to any people not directly concerned with the study without written prior permission 
from the Sponsor. Authorized regulatory officials and Sponsor personnel (or their 
representatives) will be allowed full access to inspect and copy the records. 
All study investigational product, participant bodily fluids, and/or other materials collected shall 
be used solely in accordance with this protocol, unless otherwise agreed to in writing by the 
Sponsor. Participants will only be identified by unique subject numbers on eCRFs. 
Every participant will be given a copy of each version of the form that he/she signs before and 
during the study. Each ICF may also include authorization allowing the institution, Investigator, 
and Sponsor to use and disclose personal health information in compliance with the Health 
Insurance Portability and Accountability Act of 1996 (HIPAA). 
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA 
Blood and serum specimen storage outside the study-required assessments is optional and 
requires participants to sign an ICF. Refusal to participate in this optional specimen storage 
does not affect a participant’s ability to be enrolled in the study. A participant may choose to 
participate in this specimen storage at Screening or any time during the study, up to and 
including the EOS visit. 
With the participant’s approval, and as approved by the central IRB, de-identified biological 
samples will be stored at a certified, licensed central laboratory. These samples could be used 
to research the causes of pulmonary sarcoidosis, its complications, and other conditions for 
which individuals with pulmonary sarcoidosis are at increased risk, and to improve treatment. 
The central laboratory will also be provided with a code-link that will allow linking the biological 
specimens with the phenotypic data from each participant, maintaining the blinding of the 
identity of the participant. 
During the conduct of the study, an individual participant can choose to withdraw consent to 
have biological specimens stored for future research. 
Once samples have been analyzed, specimens will be destroyed. If no analyses have been 
completed within 5 years following EOS, samples will be destroyed. 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 
Table 6 lists the key personnel for this study. Additional study contact information will be 
provided in the Study Operations Manual. 




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10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
The CRU will perform internal quality management of study conduct, data and biological 
specimen collection, documentation and completion. An individualized quality management 
plan will be developed to describe the CRU quality management. 
Quality control (QC) procedures will be implemented beginning with the data entry system and 
data QC checks that will be run on the database will be generated. Any missing data or data 
anomalies will be communicated to the CRU for clarification/resolution. 
Following written Standard Operating Procedures (SOPs), the monitors (blinded and unblinded) 
will verify that the clinical trial is conducted and data are generated and biological specimens 
are collected, documented (recorded), and reported in compliance with the protocol, ICH GCP, 
and applicable regulatory requirements (eg, GLP, GMP). 
The investigational CRU will provide direct access to all trial related sites, source 
data/documents, and reports for the purpose of monitoring and auditing by the Sponsor, and 
inspection by local and regulatory authorities. 
10.1.9 DATA HANDLING AND RECORD KEEPING 
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES 
Data collection is the responsibility of the clinical trial staff at the CRU under the supervision of 
the Investigator. The Investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. 
All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data. 
Hardcopies of the study visit worksheets will be provided for use as source document 
worksheets for recording data for each participant enrolled in the study. Data recorded in the 
eCRF derived from source documents should be consistent with the data recorded on the 
source documents. 
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) 
and clinical laboratory data will be entered into a 21 CFR Part 11-compliant data capture system 
provided by Parexel. The data system includes password protection and internal quality checks, 
such as automatic range checks, to identify data that appear inconsistent, incomplete, or 
inaccurate. Clinical data will be entered directly from the source documents. 
10.1.9.2 STUDY RECORDS RETENTION 
Study documents should be retained for a minimum of 2 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 until at least 2 years have elapsed since the formal 


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discontinuation of clinical development of the study drug. These documents should be retained 
for a longer period, however, if required by local regulations. No records will be destroyed 
without the written consent of the Sponsor. It is the responsibility of the Sponsor to inform the 
Investigator when these documents no longer need to be retained. Upon the request of the 
Sponsor, the study record may be delivered to the Sponsor from the CRO. 
10.1.10 
PROTOCOL DEVIATIONS 
A protocol deviation is any noncompliance with the clinical trial protocol, ICH GCP, or Clinical 
Operations Plan (COP) requirements. The noncompliance may be either on the part of the 
participant, the Investigator, or the CRU staff. If a deviation occurs, corrective actions are to be 
developed by the CRU and implemented promptly. 
It is the responsibility of the site Investigator to use continuous vigilance to identify and report 
deviations as soon as possible. All deviations must be addressed in study source documents and 
must be sent to the reviewing IRB per their policies. The CRU Investigator is responsible for 
knowing and adhering to the reviewing IRB requirements. Further details about the handling of 
protocol deviations will be included in the Protocol Deviation Plan, COP, Data and Medical 
Management Plans, blind data review documentation, and SAP. 
The study will be conducted as described in this protocol, except for an emergency situation in 
which the protection, safety, and well-being of the participant requires immediate intervention, 
based on the judgment of the Investigator (or a responsible, appropriately trained professional 
designated by the Investigator). In the event of a significant deviation from the protocol due to 
an emergency, accident, or mistake, the Investigator or designee must contact the Medical 
Monitor and the Sponsor at the earliest possible time by telephone. This will allow an early joint 
decision regarding the participant’s continuation in the study. This decision will be documented 
by the Investigator and the Medical Monitor. 
10.1.11 
PUBLICATION AND DATA SHARING POLICY 
This study will be conducted in accordance with the following publication and data sharing 
policies and regulations: 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access 
to the published results of NIH-funded research. It requires scientists to submit final peer-
reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed Central 
upon acceptance for publication. 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-
Funded Clinical Trial Information and the Clinical Trials Registration and Results Information 
Submission rule. As such, this trial will be registered at ClinicalTrials.gov, and results 
information from this trial will be submitted to ClinicalTrials.gov. In addition, every attempt will 
be made to publish results in peer-reviewed journals. Data from this study may be requested 


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from other researchers no sooner than 5 years after the completion of the primary endpoint by 
contacting the Sponsor. 
It is understood by the Investigator that the information generated in this study will be used by 
the Sponsor in connection with the development of the product. To allow for the use of 
information derived from the study, it is understood that the Investigator is obliged to provide 
the Sponsor with complete test results, all study data, and access to all study records. 
Any results of medical investigations with the Sponsor’s products and/or 
publication/lecture/manuscripts based thereon, shall be exchanged and discussed by the 
Investigator and Sponsor representative(s) 30 days before submission for publication or 
presentation. Due regard shall be given to the Sponsor’s legitimate interests (eg, manuscript 
authorship, obtaining optimal patent protection, coordinating and maintaining the proprietary 
nature of submissions to health authorities, coordinating with other ongoing studies in the 
same field, and protecting confidential data and information.) The Sponsor shall be furnished 
with a copy of any proposed publication. Comments shall be rendered without undue delay. 
In cases of publications or presentations of material arising from multicenter clinical 
investigations, the Sponsor is to serve as coordinator and referee. Individual Investigators who 
are part of a multicenter investigation may not publish or present data that are considered 
common to a multicenter investigation without the consent of the other participating 
Investigators and the prior review of the Sponsor. 
In case of disagreement among the Investigators participating in a multicenter investigation, 
the Sponsor will be the final arbiter. Comments shall be given without undue delay. If they are 
not accepted, the senior author of the manuscript and representatives of the Sponsor shall 
promptly meet to discuss further and endeavor to agree mutually on the final wording and/or 
disposition of the publication. The above procedure also applies to information on prematurely 
discontinued and other non-completed studies. 
Results from investigations shall not be made available to any third party by the investigating 
team outside the publication procedure as outlined previously. The Sponsor will not quote from 
publications by Investigators in its scientific information and/or promotional material without 
full acknowledgment of the source (ie, author and reference). 


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10.1.12 
CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who 
have a role in the design, conduct, analysis, publication, or any aspect of this trial will be 
disclosed and managed. Furthermore, persons who have a perceived conflict of interest will be 
required to have such conflicts managed in a way that is appropriate to their participation in 
the design and conduct of this trial. The study leadership has established policies and 
procedures for all study group members to disclose all conflicts of interest and will establish a 
mechanism for the management of all reported dualities of interest. 


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10.2 ABBREVIATIONS 
18F-FDG 
PET 
18-fluorodeoxyglucose-positron emission tomography 
z 
Terminal elimination rate constant 
ACE 
Angiotensin converting enzyme 
ADA 
Anti-drug antibodies 
AE 
Adverse Event 
AESI 
Adverse event of special interest 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of Covariance 
AST 
Aspartate aminotransferase 
AUC 
Area under the concentration-time curve 
AUC0-t,norm 
Dose-normalized AUC0-t 
AUC0-ꚙ 
Area under the serum XTMAB-16 concentration-time curve from time 0 
(predose) to the last quantifiable concentration time point t, and extrapolated 
to infinity 
AUC0-ꚙ,norm 
Dose-normalized AUC0-ꚙ 
AUEC0-t 
Area under the effect-time curve from time 0 (predose) to the last quantifiable 
effect-concentration time point, t  
BMI 
Body mass index 
CFR 
Code of Federal Regulations 
cGMP 
Current Good Manufacturing Practice 
CL 
Total body clearance after IV dosing 
Cmax 
Maximum observed concentration 


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Cmax,norm 
Dose-normalized Cmax  
CMP 
Clinical monitoring plan 
CNS 
Central nervous system 
CONSORT 
Consolidated Standards of Reporting Trials 
COP 
Clinical operations plan 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CRU 
Clinical research unit 
CT 
Serum concentration at the end of drug infusion 
CV 
Coefficient of variation 
eCRF 
Electronic Case Report Forms 
ECG 
Electrocardiogram 
Emax,obs 
Maximum observed effect 
EOS 
End of study 
ES 
Enrolled set 
EU 
European Union 
FAS 
Full analysis set 
FDA 
Food and Drug Administration 
FIH 
First-in-human 
FSH 
Follicle stimulating hormone 
GCP 
Good Clinical Practice 
gCV 
Geometric coefficient of variation 


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GLP 
Good Laboratory Practices 
gMean 
Geometric mean 
GMP 
Good Manufacturing Practices 
HCV 
Hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act  
HIV 
Human immunodeficiency virus 
HRT 
Hormone replacement therapy 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation  
IFN-γ 
Interferon gamma 
IgG1κ 
Immunoglobulin G 1 kappa 
IL-6 
Interleukin 6 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
IV 
Intravenous  
MedDRA 
Medical Dictionary for Regulatory Activities 
MRT 
Mean residence time 
NIH  
National Institutes of Health 
NIH IC 
NIH Institute or Center 
NOAEL 
No adverse effect level 
OHRP 
Office for Human Research Protections 


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PD 
Pharmacodynamic  
PI 
Principal Investigator 
PK 
Pharmacokinetics  
PT 
Preferred term 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard deviation 
sIL-2R 
Soluble IL-2 receptor 
SoA 
Schedule of Assessments 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SUSAR 
Suspected unexpected serious adverse reaction 
sTNFα 
Soluble tumor necrosis factor alpha 
t1/2 
Terminal elimination half-life 
TEAE 
Treatment-emergent adverse event 
tEmax,obs 
Time to reach maximum observed effect 
TgTC 
hTNFα transgenic mice 
TK 
Toxicokinetic  
tmax 
Time to reach maximum observed concentration 
tmTNF 
Transmembrane tumor necrosis factor 
TNFα 
Tumor necrosis factor alpha 


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TNF-R 
Tumor necrosis factor receptor 
ULN 
Upper limit of normal 
UP 
Unanticipated Problem 
US 
United States 
USP 
United States Pharmacopeia 
Vz 
Volume of distribution during the terminal phase following IV dosing 
WASOG 
World Association of Sarcoidosis and other Granulomatous Disorders 
WFI 
Water for injection 
WOCBP 
Women of childbearing potential 
 


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14. Eurelings LEM, Miedema JR, Dalm VASH, et al. Sensitivity and specificity of serum 
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28. Murdaca G, Spanò F, Contatore M, et al. Immunogenicity of infliximab and adalimumab: 
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35. Rossman MD, Newman LS, Baughman RP, et al. A Double-Blinded, Randomized, 
Placebo-Controlled Trial of Infliximab in Subjects with Active Pulmonary Sarcoidosis. 
Sarcoidosis Vasculitis and Diffuse Lung Diseases. 2006;23:201-208. 
36. Sahashi K, Ina Y, Takada K, et al. Significance of Interleukin 6 in Patients with Sarcoidosis. 
Chest. 1994;106:156-160. 
37. Schimmelpennink MC, Vorselaars ADM, van Beek FT, et al. Efficacy and safety of 
infliximab biosimilar Inflectra® in severe sarcoidosis. Resp Med. 2018;138:S7-S13. 
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39. Shin D, Kim Y, Kim YS, Körnicke T, Fuhr R. A Randomized, Phase I Pharmacokinetic Study 
Comparing SB2 and Infliximab Reference Product (Remicade(®) in Healthy Subjects. 
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40. Siljehult F, Ärlestig L, Eriksson C, Rantapää-Dahlqvist S. Concentrations of infliximab and 
anti-drug antibodies in relation to clinical response in patients with rheumatoid 
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41. Strik AS, van den Brink GR, Ponsioen C, Mathot R, Löwenberg M, D'Haens GR. 
Suppression of anti-drug antibodies to infliximab or adalimumab with the addition of an 
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42. Terwiel M, Coline HM, van Moorsel CHM. Clinical epidemiology of familial sarcoidosis: A 
systematic literature review. Respir Med. 2018;pii:S0954-6111(18)30394-9. 
43. Ungprasert P, Carmona EM, Crowson CS, Matteson EL. Diagnostic Utility of Angiotensin-
Converting Enzyme in Sarcoidosis: A Population-Based Study. Lung. 2016;194(1):91-95. 
44. Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet PY, Müller-Quernheim J. Sarcoidosis. 
Lancet. 2014;383:1155-1167. 
45. van Schaik T, Maljaars JP, Roopram RK, et al. Influence of combination therapy with 
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IBD. Inflamm Bowel Dis. 2014;20(12):2292-2298. 
46. Vorselaars AD, Crommelin HA, Deneer VH, et al. Effectiveness of Infliximab in Refractory 
FDG PET-Positive Sarcoidosis. Eur Respir J. 2015;46:175-185. 
47. Vorselaars AD, Wuyts WA, Vorselaars VMM, Zanen P, Deneer VHM Coline HM, et al. 
Methotrexate vs azathioprine in second-line therapy of sarcoidosis. Chest. 
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48. Vorselaars AD1, Verwoerd A, van Moorsel CH, Keijsers RG, Rijkers GT, Grutters JC. 
Prediction of relapse after discontinuation of infliximab therapy in severe sarcoidosis. 
Eur Respir J. 2014;43:602-609. 
49. Yanardag H, Pamuk ON, Karayel T. Cutaneous involvement in sarcoidosis: analysis of the 
features in 170 patients. Respiratory Med. 2003;97:978-982. 
50. Ziegenhagen MW, Benner UK, Zissel G, Zabel P, Schlaak M, Müller-Quernheimet J. 
Sarcoidosis: TNF-α Release from Alveolar Macrophages and Serum Level of sIL-2R Are 
Prognostic Markers. Am J Respir Crit Care Med. 1997;156:1586-1592. 


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APPENDIX 1: CLINICAL LABORATORY TESTS 
The tests detailed in Table 7 will be performed by the central laboratory. The time points are 
specified in the SoA (Section 1.3). 
Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5. 
Additional tests may be performed at any time during the study as deemed necessary by the 
Investigator or required by local regulations. 






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k 
Time-matched periods for telemetry data extraction corresponding to the projected time points on Day 1. 
The predose telemetry data extraction period on Day 1 should match the projected 24-hour time point 
after infusion.  


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APPENDIX 3: CONTRACEPTION 
Male Participant Reproductive Inclusion Criteria 
Male participants are eligible to participate if they agree to the following requirements during 
the intervention period and for at least 90 days after the last dose of study drug, which 
corresponds to the time needed to eliminate reproductive safety risk of the study 
intervention(s): 
• Refrain from donating sperm. 
PLUS either: 
• Be abstinent from heterosexual intercourse with a woman of childbearing potential as 
their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and 
agree to remain abstinent. 
OR 
• Must agree to use a male condom when engaging in any activity that allows for passage 
of ejaculate to another person. 
• In addition to male condom use, a highly effective method of contraception may be 
considered in WOCBP partners of male participants (refer to the list of highly effective 
methods below). 
Female Participant Reproductive Inclusion Criteria 
A female participant is eligible to participate whether she is of childbearing potential or is 
postmenopausal (see definitions below). A female participant of childbearing potential who is 
sexually active with a nonsterilized male partner must agree to use highly effective 
contraception from the time of signing the informed consent, throughout the duration of the 
study, and for 90 days after the last dose of study drug. 
The Investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy. 
Woman of Childbearing Potential 
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below). 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered. 
Women in the following categories are not considered WOCBP: 
1. Premenopausal female with 1 of the following: 


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a. Documented hysterectomy 
b. Documented bilateral salpingectomy 
c. Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other 
than the above, (eg, Müllerian agenesis, androgen insensitivity), Investigator 
discretion should be applied to determining study entry. 
Note: Documentation for any of the above categories can come from the CRU personnel’s 
review of the participant’s medical records, medical examination, or medical history interview. 
The method of documentation should be recorded in the participant’s medical record for the 
study. 
2. Postmenopausal female. 
a. A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. In addition: 
i. A high follicle stimulating hormone (FSH) level in the postmenopausal 
range must be used to confirm a postmenopausal state in women under 
60 years old and not using hormonal contraception or hormone 
replacement therapy (HRT). 
ii. Woman on HRT and whose menopausal status is in doubt will be required 
to use one of the nonestrogen hormonal highly effective contraception 
methods if they wish to continue their HRT during the study. Otherwise, 
they must discontinue HRT to allow confirmation of postmenopausal 
status before study enrollment. 
Contraception Methods 
Contraceptive use by men or women should be consistent with local availability/regulations 
regarding the use of contraceptive methods for those participating in clinical trials. 
Highly effective methods (according to Therapeutics Research Program Guidance for the 
Development of Protocol Procedures to Address Reproductive Risk, 21 Dec 2017): 
• Bilateral tubal ligation or tubal occlusion 
• An approved hormonal contraceptive such as oral contraceptives, patches, implants, 
injections, rings, or hormonally-impregnated intrauterine device (IUD) 
• IUD 
• Vasectomized partner 
o Vasectomized partner is a highly effective contraceptive method provided that 
the partner is the sole sexual partner of the WOCBP and the absence of sperm 


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has been confirmed. If not, an additional highly effective method of 
contraception should be used. The spermatogenesis cycle is approximately 
90 days. 
• Sexual abstinence 
o Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk 
associated with the study intervention. The reliability of sexual abstinence needs 
to be evaluated in relation to the duration of the study and the preferred and 
usual lifestyle of the participant. 


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28 May 2021 
 
91 
APPENDIX 4: TOXICITY GRADING FOR INJECTION SITE REACTIONS, VITAL SIGNS, AND 
LABORATORY PARAMETERS 
Table 9 
Grading for Injection Site Reactions 
 
 


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Table 10 
Grading for Vital Signs 
 
 


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Table 11 
Grading for Clinical Abnormalities 
 
Source: FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers enrolled in 
Preventive Vaccine Clinical Trials. September 2007. 


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28 May 2021 
 
94 
APPENDIX 5: CRITERIA FOR DIAGNOSING AND RECOMMENDED TREATMENT FOR 
ANAPHYLAXIS 
Table 12 
Clinical Criteria for Diagnosing Anaphylaxis 
 
Source: Sampson HA, Muñoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management 
of anaphylaxis: Summary report – Second National Institute of Allergy and Infectious Disease/Food Allergy and 
Anaphylaxis Network symposium. Am Acad Allergy, Asthma, Immunol. 2006. 
 


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95 
Figure 2 
Algorithm for the Treatment of Acute Anaphylaxis 
 
Abbreviations: ACLS = advanced cardiac life support; CPR = cardiopulmonary resuscitation; ICU = intensive care 
unit. 


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96 
Source: Lieberman P, Kemp SF, Oppenheimer J, et al. The diagnosis and management of anaphylaxis: An updated 
practice parameter. Am Acad Allergy, Asthma, Immunol. 2005. 

SAP_001.pdf: 
Parexel International 
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XTMAB-16-101 
 Statistical Analysis Plan 
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Parexel International 
Xentria Inc. 
XTMAB-16-101 
A Randomized, Double-blind, Placebo-controlled, First-in-Human Study to Evaluate the Safety, 
Tolerability, and Pharmacokinetics of a Single Intravenous Infusion of XTMAB-16 in Healthy 
Adult Participants  
Statistical Analysis Plan 
Version: Final 3.0 
Parexel Project Number: 251877 
NCT04971395   


Parexel International 
Xentria Inc. 
XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
TP-GDO-WW-133-02 
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Page 2 of 37 
 
SPONSOR SIGNATURE PAGE 
 
 
Approved by:  
_________________________ 
 
_______________ 
 
 
 
 
 
 
Date 
 
Clinical Lead, Xentria, Inc. 
 
 




Parexel International 
Xentria Inc. 
XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
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Project Document Version No. Final 3.0 
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TABLE OF CONTENTS 
1 
INTRODUCTION .................................................................................................................... 10 
2 
STUDY OBJECTIVES ............................................................................................................ 10 
2.1 
Primary Objective(s) ........................................................................................................ 10 
2.2 
Secondary Objective(s) .................................................................................................... 10 
2.3 
Exploratory Objective(s) ................................................................................................. 10 
3 
INVESTIGATIONAL PLAN................................................................................................... 10 
3.1 
Overall Study Design and Plan ........................................................................................ 10 
3.1.1 
Randomization and Blinding ...................................................................................... 12 
3.1.2 
Unblinding Procedure ................................................................................................. 12 
3.1.3 
Dose Escalation ........................................................................................................... 12 
3.2 
Endpoints and Associated Variables ............................................................................... 13 
3.2.1 
Primary Endpoints ...................................................................................................... 13 
3.2.2 
Secondary Endpoints .................................................................................................. 14 
3.2.3 
Exploratory Endpoints ................................................................................................ 14 
3.2.4 
Safety Variables .......................................................................................................... 14 
3.2.5 
Pharmacodynamic Variables ...................................................................................... 14 
3.2.6 
Immunogenicity Variables .......................................................................................... 14 
3.2.7 
Pharmacokinetic Variables ......................................................................................... 15 
3.2.8 
Biomarker Variables ................................................................................................... 16 
4 
STATISTICAL METHODS..................................................................................................... 17 
4.1 
Data Quality Assurance ................................................................................................... 17 
4.2 
General Presentation Considerations ............................................................................... 17 
4.3 
Software 18 
4.4 
Study Participants ............................................................................................................ 18 
4.4.1 
Disposition of Participants .......................................................................................... 18 
4.4.2 
Protocol Deviations ..................................................................................................... 19 
4.5 
Analysis Sets.................................................................................................................... 19 
4.6 
Demographics and Baseline Characteristics .................................................................... 20 
4.7 
Medical History and Concomitant Illnesses .................................................................... 20 
4.8 
Prior and Concomitant Medications ................................................................................ 20 
4.9 
Treatment Exposure ......................................................................................................... 21 
4.10 Pharmacokinetic Evaluation ............................................................................................ 21 
4.10.1 
Pharmacokinetic Concentrations ................................................................................ 21 
4.10.2 
Pharmacokinetics Parameters ..................................................................................... 23 
4.11 Safety Evaluation ............................................................................................................. 26 
4.11.1 
Adverse Events ........................................................................................................... 27 
4.11.2 
Deaths, Serious Adverse Events, and Adverse Events of Special Interest ................. 28 
4.11.3 
Clinical Laboratory Evaluation ................................................................................... 28 
4.11.4 
Vital Signs, Physical Findings and Other Observations Related to Safety ................ 29 
4.11.5 
Safety Monitoring (Independent Data Monitoring Committee [IDMC], Data Monitoring 
Committee [DMC], Data and Safety Monitoring Board [DSMB]) ............................ 32 
4.12 Other Analyses ................................................................................................................ 32 
4.12.1 
Immunogenicity .......................................................................................................... 32 
4.12.2 
Biomarker Analysis .................................................................................................... 32 
4.12.2.1 Biomarker Concentration-Time Data ..................................................................... 32 


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Xentria Inc. 
XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
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4.12.2.2 Biomarker Parameters ............................................................................................. 33 
4.13 Determination of Sample Size ......................................................................................... 33 
4.14 Changes in the Conduct of the Study or Planned Analysis ............................................. 33 
5 
REFERENCES ......................................................................................................................... 33 
6 
APPENDICES .......................................................................................................................... 34 
6.1 
Schedule of Assessments ................................................................................................. 34 
 
 
LIST OF TABLES 
 
Table 1            Dose Cohorts .............................................................................................................. 11 
Table 2 
Pharmacokinetic Parameters after Single Dose Administration ................................ 15 
Table 3 
Biomarker Parameters after Single Dose Administration .......................................... 16 
Table 4            Rounding Rules for Concentration Listings and Tables ............................................ 22 
Table 5  
Pharmacokinetic Parameter and Estimation .............................................................. 23 
Table 6            Rounding Rules for PK Parameter Listings and Tables ............................................ 25 
Table 7 
Grading for Vital Signs .............................................................................................. 30 
Table 8 
Schedule of Assessments ........................................................................................... 34 
Table 9 
Grading of Injection Site Reactions ........................................................................... 37 
 
 LIST OF FIGURES 
Figure 3-1 Study Design .................................................................................................................... 11 


Parexel International 
Xentria Inc. 
XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
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REVISION HISTORY 
. 
Version No. 
Effective Date 
Summary of Change(s) 
Final 1.0 
Date of Last 
Signature 
New Document 
2.0 
Date of Last 
Signature 
Clarification added on Exposure Response QT analysis  
3.0 
Date of Last 
Signature 
Addressed comments on Final 2.0 
 
 








Parexel International 
Xentria Inc. 
XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
TP-GDO-WW-133-02 
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1 
INTRODUCTION 
XTMAB-16 is a chimeric human-murine IgG1κ anti-TNFα monoclonal antibody. The final dosage 
form is a sterile, white, lyophilized powder for intravenous (IV) infusion. Participants assigned to 
active treatment will receive a single dose of XTMAB-16 at a volume of 250 mL via IV infusion over 
2 hours. The total dose received will be either 2 or 4 mg/kg, depending on treatment assignment. 
Placebo will be the same formulation as the active treatment but without XTMAB-16. Participants 
assigned to placebo will receive a single dose of placebo at a volume of 250 mL via IV infusion over 
2 hours. 
This is a single-center, randomized, double-blind, placebo-controlled, first-in-human (FIH), single IV 
infusion of sequential ascending doses of XTMAB-16 in normal healthy male and female 
participants. 
A total of 24 normal healthy adult participants will be enrolled and assigned into 2 treatment cohorts 
with 12 participants (9 on XTMAB-16 and 3 on placebo) in each cohort. Participants will receive a 
single IV infusion of 2 or 4 mg/kg of XTMAB-16 or placebo on Day 1. 
The Statistical Analysis Plan (SAP) details the statistical methodology to be used in analyzing study 
data related to safety, pharmacokinetic (PK) and outlines the statistical programming specifications 
for the Tables, Listings and Figures (TLFs). 
The analyses described in this SAP are based upon the following study documents: 
• 
Study Protocol, Version 4.0, Amendment 3 (May 28, 2021) 
This SAP will be finalized prior to database lock. Any changes after the finalization of this SAP will 
be documented in Statistical Method Modification Form. 
 
2 
STUDY OBJECTIVES 
2.1 
Primary Objective(s) 
To evaluate the safety, tolerability, immunogenicity, PK, and selected clinical biomarkers after a 
single intravenous infusion of XTMAB-16 at 2 and 4 mg/kg doses in normal healthy participants. 
2.2 
Secondary Objective(s) 
Not Applicable. 
2.3 
Exploratory Objective(s) 
Not Applicable. 
 
3 
INVESTIGATIONAL PLAN 
3.1 
Overall Study Design and Plan 
This is a single-center, randomized, double-blind, placebo-controlled, first-in-human (FIH), single IV 
infusion of sequential ascending doses of XTMAB-16 in normal healthy male and female 
participants. 
A total of 24 normal healthy adult participants will be enrolled and assigned into 2 treatment cohorts 
with 12 participants (9 on XTMAB-16 and 3 on placebo) in each cohort as shown in Table 1. 
Participants will receive a single IV infusion of 2 or 4 mg/kg of XTMAB-16 or placebo on Day 1. 


Parexel International 
Xentria Inc. 
XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
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Figure 3-1 Study Design 
 
Table 1 Dose Cohorts 
Cohort  
Dose  
Escalation 
Factor  
XTMAB-16  
Placeboa  
Total 
1  
2 mg/kg  
-  
9  
3  
12 
2  
4 mg/kg  
2 x  
9  
3  
12 
a The matching placebo will be identical to the XTMAB-16 in terms of volume and infusion duration. 
For all cohorts, a sentinel group of 2 participants (1 assigned to XTMAB-16 and 1 assigned to 
placebo) will be dosed at least 48 hours before the remaining participants in the same cohort. To 
maintain the treatment blind, study treatment will be prepared by an unblinded pharmacist according 
to the treatment assignment who will appropriately label the study drug for administration in a way 
that maintains the treatment blind to clinical research unit (CRU) staff and the participant. 
After blinded review of the available safety and laboratory data of the sentinel group by the Principal 
Investigator (PI), if no notable safety signals are identified, the remaining participants within the same 
cohort will be dosed. Participants within a cohort should be dosed at least 1 hour apart. If there are 
no safety concerns, the participants in Cohort 2 will receive XTMAB-16 after at least 14 to 21 days 
clinical assessment of the participants at Cohort 1.  
After a screening period of up to 28 days, participants will be admitted to the CRU on Day -2 for 
COVID-19 testing and baseline procedures. After confirmation of eligibility, participants will be 
randomly assigned to treatment (1:1 XTMAB-16 to placebo for sentinel cohort, 4:1 for remaining 
participants) and administered study drug on Day 1. Participants will remain at the CRU through Day 
8 for PK, biomarkers, anti-drug antibody (ADA), and safety assessments, and will be discharged on 
Day 8 once all procedures for that day have been completed. Participants will return to the CRU on 
Days 15, 29, 43, 57, and 71 (End of Study/safety follow-up). 
Safety assessments will include adverse events (AEs), safety laboratory assessments, vital signs, 12-
lead electrocardiogram (ECG), and physical examination. Samples for PK, Pharmacodynamic (PD) 
and immunogenicity will be collected and analysis will also be completed during the course of this 
study. 


Parexel International 
Xentria Inc. 
XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
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3.1.1 Randomization and Blinding 
In this study participants will be randomly assigned to treatment (XTMAB-16 or placebo) and 
treatment assignment will be double-blind: participants and all study staff will be blind to participant 
treatment assignment for the duration of the study except as specified. 
 
The randomization schedule will be generated by an unblinded statistician (third-party unblinded) 
and will be provided to the CRU pharmacist prior to the start of this study. All randomization 
information will be stored in a secured area, accessible only by authorized personnel. 
 
The Investigator (or designee) will assign participant numbers as participants are screened for the 
study. In accordance with the randomization numbers, the participant will receive the study treatment 
regimen assigned to the corresponding randomization number. 
 
To maintain the treatment blind, an otherwise uninvolved, third-party unblinded CRU staff member 
(e.g., pharmacist) will be responsible for the preparation and dispensing of all study treatment 
according to the randomization schedule and assigned treatment for the individual participant. The 
unblinded pharmacist will have no contact with study participants and will ensure that no treatment 
assignment information is transmitted to study unit staff except as defined in next Section. 
3.1.2 Unblinding Procedure 
Treatment assignment will be double-blind. Investigators, participants, CRO, and sponsor will be 
blinded throughout the study. Actual treatment assignment will be available after the occurrence of 
database lock for the purpose of performing statistical analyses of clinical trial data. 
3.1.3 Dose Escalation  
For all cohorts, a sentinel group of 2 participants (1 assigned to XTMAB-16 and 1 assigned to 
placebo) will be dosed at least 48 hours before the remaining participants in the same cohort. After 
blinded review of the available safety and laboratory data by the PI, if no notable safety signals are 
identified, the remaining participants within the same cohort will be dosed. Participants within a 
cohort should be dosed at least 1 hour apart. 
 
As XTMAB-16 is a TNFα inhibitor, which have well-characterized clinical safety profiles, it can be 
given to participants in the 4 mg/kg dose group after 14 to 21 days clinical assessment of the 
participants at 2 mg/kg dose group, unless safety concerns arise. 
 
Dose escalation will be stopped as soon as safety signals or risks are identified or anticipated, based 
on: 
• Number of abnormal and clinically significant safety laboratory results 
• Number of serious Adverse Events (AEs) , Serious Adverse Events (SAEs) and/or treatment-
emergent AEs (TEAEs) with severity/intensity high enough for a meaningful decision 
• Proportion of TEAEs of the same type high enough to justify the decision. 
The severity rating is adapted to healthy participants, taking into account event characteristics such 
as type, deleterious potential, occurrence, progression, and monitorability. A solitary SAE occurrence 
is not by itself a criterion for making a decision (assessment depends on the nature of the reported 
event).  
 


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Xentria Inc. 
XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
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A decision to proceed from dose “n” to the next higher “n+1” dose will be made jointly by the Sponsor 
and the Investigator based on a preliminary Investigator blinded safety report inclusive of the 12 
participants in dose level cohort “n”. The relevant data for this decision should be, at a minimum, 
AEs, liver and kidney function tests, ECG, blood pressure, and heart rate. 
 
For safety purposes, the treatment of a specific participant may be unblinded before the next dose 
level is administered, after mutual agreement between the Sponsor and the Investigator. 
 
An unscheduled PK sample collection and analysis may be performed to support the clinical safety 
assessment, if needed in the event of a safety signal of concern. 
 
Depending on the tolerability profile and safety laboratory results observed in the dose level cohort 
“n,” one of the following decisions will be made for cohort “n+1”: 
• Dose escalation may continue as scheduled. 
• A higher intermediate dose between the current dose (“n”) and the next planned dose (“n+1”) 
may be administered to the next cohort. 
• A lower intermediate dose between the current dose (“n”) and the previous dose (“n-1”) may 
be administered to the next cohort, including the possibility of administering a dose lower 
than the starting dose. 
• The study may be stopped as per stopping rule mentioned in protocol. 
3.2 
Endpoints and Associated Variables 
3.2.1 Primary Endpoints 
Safety and Tolerability 
• The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events 
(SAEs). 
• Observed values and change from Baseline in safety laboratory tests (hematology, clinical 
chemistry, urinalysis) by visit. 
• Observed values and change from Baseline in ECG parameters by visit. 
• Time-matched Baseline and 50-hr post dose digital ECG parameters monitoring. 
• Observed values and change from Baseline in vital signs. 
Immunogenicity 
• Number and percentage of participants by cohort who test positive for XTMAB-16 anti-drug 
antibody (ADA) at Baseline, Day 29, Day 57, and Day 71 
• Number and percentage of participants by cohort who test positive for XTMAB-16 
neutralizing antibody (nAb) at Baseline, Day 29, Day 57, and Day 71 
Biomarkers 
Absolute and percent change from Baseline in the following biomarkers: 
• Angiotensin converting enzyme (ACE) 
• soluble IL-2 receptor (sIL-2R) 
• Interleukin 6 (IL-6) 
• soluble TNFα (sTNFα) 
Other relevant biomarkers may be assessed to better understand PK/PD relationships. 
 


Parexel International 
Xentria Inc. 
XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
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3.2.2 Secondary Endpoints 
Not Applicable 
 
Pharmacokinetics 
 
Serum PK of XTMAB-16 will be assessed after single dose administration of XTMAB-16 as below: 
• Cmax: Maximum observed XTMAB-16 serum concentration  
• CT: XTMAB-16 serum concentration at the end of drug infusion  
• tmax: Time to maximum observed XTMAB-16 concentration  
• AUC0-inf: Area under the XTMAB-16 concentration-time curve from time zero extrapolated 
to infinity  
• AUC0-last: Area under the XTMAB-16 concentration-time curve from time zeroto the last 
quantifiable concentration  
• CL: Systemic clearance after IV dosing  
• λz: Terminal elimination rate constant 
• t1/2: Terminal elimination half-life calculated as: ln2/λz  
• Vz: Volume of distribution during the terminal phase calculated as: Dose/(λz ∙ AUC0-inf) 
• Vss: Steady state volume of distribution following IV dosing calculated as: MRT∙CL  
• MRT: Mean residence time  
*Dose normalized Cmax, AUC0-t, and AUC0-inf will be also calculated  
3.2.3 Exploratory Endpoints 
Not Applicable 
3.2.4 Safety Variables 
• Vital signs (supine blood pressure [BP] and pulse, tympanic (ear), oral  and temporal body 
temperature, respiratory rate) 
• 12-lead electrocardiograms (ECG): P wave, QRS complex, U wave, QRS duration, QT 
interval, QTcF, T wave, ST segment, RR interval, PR interval, and qualitative results. 
• Telemetry 
• Clinical laboratory tests (hematology, biochemistry, urinalysis, Virology, Urine Drug abuse 
Screening, Serum Pregnancy Test) 
• Adverse event (AE) assessments 
• Physical examinations 
3.2.5 Pharmacodynamic Variables 
Not Applicable 
3.2.6 Immunogenicity Variables  
Immunogenicity testing XTMAB-16  of ADA and nAb using designated serum samples from each 
participant is planned to be conducted. 
An individual sample result will be designated “antibody positive” based on both positive screening 
and confirmation assay results (i.e., confirmed positive result), and otherwise will be deemed 
“antibody negative” or “inconclusive.” The titer assay will be performed for antibody-positive 
samples. For (anti-drug XTMAB-16  antibodies) positive samples, the presence of neutralizing 
antibodies may be determined using the (anti-drug XTMAB-16  antibodies) neutralizing assays.   


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Xentria Inc. 
XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
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Study participants will be given “positive” status if they have at least one antibody positive sample 
result at any time post baseline (during either the Treatment and Observation Period or the Safety 
Follow-up Period). A study participant will be given “negative” status if all evaluated 
immunogenicity sample results during the Postbaseline Period are antibody negative. 
The antibody response in antibody-positive participants can be further classified by the following 
criteria: 
• “Treatment-induced”: Has at least one antibody positive sample at any time after treatment 
(for participants with antibody-negative status at Baseline) 
• “Treatment-boosted”: Has at least one antibody-positive sample at any time after treatment 
with a titer of four-fold or greater compared to Baseline (for participants with antibody-
positive status at Baseline) 
3.2.7 Pharmacokinetic Variables 
Blood samples will be collected for XTMAB-16 PK analysis at pre dose (Hour 0), at 1 hour after the 
start of infusion, immediately after the 2-hour infusion (T; infusion termination), and at 3, 8, 14 hours 
on Day 1, and at 24 hours (Day 2), 50 hours (Day 3), 74 hours (Day 4), 170 hours (Week 2, Day 8), 
338 hours (Week 3, Day 15), 674 hours (Week 4, Day 29), 1010 hours (Week 6, Day 43), 1346 hours 
(Week 8, Day 57), and 1682 hours (Week 10, Day 71) post infusion of XTMAB-16 or placebo. All 
sampling time points after time T refer to time from the start of infusion. Acceptable windows for PK 
sample collection are provided in Window Allowance Document. The exact time of sample collection 
must be recorded on the eCRF. 
Unless otherwise stated, derivation of PK parameters will be the responsibility of Clinical 
Pharmacology, Modeling and Simulation (CPMS, formerly Quantitative Clinical Development 
(QCD), Parexel International. If calculable, the PK parameters listed in (Table 2) will be determined 
for XTMAB-16 in serum following single IV dose administration: 
Table 2 
Pharmacokinetic Parameters after Single Dose Administration 
Parameter 
Definition 
CT 
XTMAB-16 serum concentration at the end of drug infusion 
Cmax 
Maximum observed serum concentration determined directly from the 
concentration-time profile 
tmax 
Time of maximum serum concentration determined directly from the 
concentration-time profile 
AUC0-inf 
Area under the concentration-time curve from time zero extrapolated 
to infinity 
AUC0-last 
Area under the concentration-time curve up to last measurable 
concentration 
λz 
Terminal elimination rate constant 
t½ 
Terminal elimination half-life calculated as: ln2/λz 


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Xentria Inc. 
XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
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Parameter 
Definition 
CL  
Total body clearance calculated as: Dose/AUCinf 
Vz  
Volume of distribution during the terminal phase calculated as: 
Dose/(λz ∙ AUC0-inf) 
MRT 
Mean residence time of the drug in the body 
Vss 
Steady state volume of distribution following IV dosing calculated as: 
MRT∙CL  
DNCmax,  
DNAUC0-last,  
DNAUC0-inf 
Dose-normalized Cmax, AUC0-t, and AUC0-inf  
Additional PK parameters may be calculated if needed.  
3.2.8 Biomarker Variables 
Absolute and percent change from baseline in the following biomarkers will be analyzed.  
• Angiotensin converting enzyme (ACE) 
• soluble IL-2 receptor (sIL-2R) 
• Interleukin 6 (IL-6) 
• soluble TNFα (sTNFα) 
Biomarker samples will be corrected for biomarker analysis at pre dose (Hour 0), and at 8 hours on 
Day 1, 24 hours (Day 2), 50 hours (Day 3), 74 hours (Day 4), 170 hours (Week 2, Day 8), 338 hours 
(Week 3, Day 15), 674 hours (Week 4, Day 29), 1010 hours (Week 6, Day 43), 1346 hours (Week 8, 
Day 57), and 1682 hours (Week 10, Day 71) post infusion of XTMAB-16 or placebo. All sampling 
time points after time T refer to time from the start of infusion. 
Unless otherwise stated, derivation of biomarker parameters will be the responsibility of Clinical 
Pharmacology, Modeling and Simulation (CPMS, formerly Quantitative Clinical Development 
(QCD), Parexel International.  The following biomarker parameters, if data permit, will be determined 
for XTMAB-16 in serum following single IV dose administration: 
Table 3 
Biomarker Parameters after Single Dose Administration 
Parameter  
Definition 
AUEC 
Area under the effect-time curve 
Emax,obs 
Maximum observed effect 
tEmax,obs 
Time to reach maximum observed effect 
 


Parexel International 
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XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
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4 
STATISTICAL METHODS 
4.1 
Data Quality Assurance 
All tables, figures and data listings to be included in the report will be independently checked for 
consistency, integrity and in accordance with standard Parexel procedures. 
4.2 
General Presentation Considerations 
This section is applicable to all non-PK assessments.  
 
TLF outputs will be generated for XTMAB-16 and pooled placebo by the planned treatment duration. 
 
The participants, who received “Placebo” in each cohort, will be pooled into a single placebo group 
(Pooled Placebo) in each respective part for all summaries and presentation related to safety for this 
study. The PK outputs will be generated for each XTMAB-16 dose. 
 
‘Baseline’ is defined as the last observed value of the parameter of interest prior to dosing (this 
includes unscheduled visits) for each XTMAB-16 dose and pooled placebo group. ‘End of Study’ for 
a participant is defined as the last available post-treatment assessment. ‘Study Day’ will be calculated 
relative to the date of randomization i.e. Study Day = Assessment Date -Randomization Date + 1. 
 
In case of any unscheduled repeated assessments occurred during the period, the following rule will 
be applied, unless specified otherwise: 
 
If unscheduled repeated measurement of a specific parameter occurs prior to the first XTMAB-16 
administration (Day 1), then the last obtained value prior to dosing will be considered in the 
descriptive statistics and in the calculation of change from baseline. 
 
If unscheduled repeated measurement of a specific parameter occurs after Day 1 or XTMAB-16 or 
Placebo administration, then the first (non-missing) value after dosing will be used in descriptive 
statistics and in the calculation of change from baseline. 
 
All data will be listed according to the number of decimal places presented in the source data with a 
limitation on maximum of 3 decimal places. Continuous data will be summarized in terms of the 
mean, standard deviation (SD), median, minimum, maximum and number of observations, unless 
otherwise stated. 
 
The minimum and maximum will be reported to the same number of decimal places as the raw data 
recorded in the database. The mean and median will be reported to one more decimal place than the 
raw data recorded in the database. The SD will be reported to two more decimal places than the raw 
data recorded in the database. In general, the maximum number of decimal places reported shall be 
four for any summary statistic. 
 
Departure from these general rules will be specified in the output shell document. 
 
Categorical data will be summarized in terms of the number of participants providing data at the 
relevant time point (n), frequency counts and percentages. Any planned collapsing of categories will 
be detailed in the SAP text and the data displays. 


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XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
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Percentages will be presented to one decimal place. Percentages as “0.0” will be presented for zero 
counts. Percentages will be calculated using n as the denominator. If sample sizes are small, the data 
displays will show the percentages, but any textual report will describe frequencies only. 
 
Changes from baseline in categorical data will be summarized using shift tables where appropriate. 
Confidence intervals will be presented to same decimal place as of associated estimate. 
4.3 
Software 
All report outputs will be produced using SAS® version 9.4 or a later version in a secure and validated 
environment. 
 
PK analyses will be produced using Phoenix® WinNonLin version 8.2 or a later version in a secure 
and validated environment.  
 
All report outputs will be provided to the Sponsor in Microsoft Word document/RTF format. 
4.4 
Study Participants 
4.4.1 Disposition of Participants 
A clear accounting of the disposition of all participants who entered into the study will be provided, 
from screening to study completion. 
 
The participant disposition summaries may include the following: 
 
• A summary of the number of participants screened for entry into the study and the number 
and percentage of screened failure participants, number and percentage of participants 
randomized and dosed will be presented for all screened population by XTMAB-16 dose/ 
pooled placebo group and overall. 
• All screened failure participants who did not meet the inclusion criteria and participants who 
did meet the exclusion criteria will be listed. 
• The number and percentage of participants who completed the trial and those who 
discontinued study (including reasons for early withdrawal) will be presented by XTMAB-16 
dose / pooled placebo group for all randomized set. 
• Participant disposition will be listed for each participant, including the participant completion 
status, reason of discontinuation, date of discontinuation on all randomized population set. 
• A randomization listing will be presented and include the following: each participant’s 
randomization number, the participant’s full Screening number, the treatment to which the 
participant has been randomized and the location of the clinical unit. 
 
Primary reason of study discontinuation, as recorded on eCRF will be presented as one of 
the following: 
• Adverse Event 
• Death 
• Loss to Follow-up 
• Protocol Violation 
• Participant withdrew at own request 
• Other 


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XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
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4.4.2 Protocol Deviations 
Protocol deviations defined as those deviations from the clinical study protocol relating to a 
participant likely to have an impact on the perceived pharmacokinetic, pharmacodynamic and safety 
of study treatments and include the following: 
• Inclusion/exclusion criteria deviations 
• Dosing deviations (e.g., incorrect treatment received, participant was not fasted as per the 
protocol requirements prior to and after dosing). 
• Time window deviations for safety. 
• Participants receiving prohibited concomitant medications. 
• Sample processing 
• Other procedural and study conduct deviations recorded by the Clinical Unit on a protocol 
deviation log. 
Protocol deviations that may potentially impact PK parameter derivations include, but are not limited 
to: 
• More than three emetic episodes and the volunteer was not discontinued 
• Missed PK samples that are evaluated to impact estimation of PK parameter(s) 
• Time window deviation for PK samplings that may impact the estimation of PK parameter(s). 
• Concomitant medications not authorized by protocol (drugs of abuse) 
The criteria for the assessment and reporting of protocol deviations will be stipulated in a separate 
study specific protocol deviation specification (PDS) document. This will include a Windows 
Allowance Document (WAD) which stipulates tolerance windows for safety and PK assessments. 
Measurements performed within these tolerance windows will not be considered as protocol 
deviations and will not be reported as such. 
All protocol deviations will be discussed at the data review meeting prior to final database hard lock 
in order to define the analysis population for the study. Prior to database lock, protocol deviation and 
analysis population outputs will be produced and will be sent to Sponsor for review. Analysis 
population classifications will be discussed in Data Review Meeting to discuss the outputs and to 
decide which participants and/or participant data will be excluded from certain analyses. 
Protocol Deviation will be classified as Major/Minor. Minor deviations are defined as those that 
deviate from accepted procedures that will not adversely affect subject/data, but should be dealt with 
appropriately. Major deviations are defined as those that deviate from the protocol that are likely to 
have an impact on the participants rights, safety, well-being, and/or on the validity of the data for 
analysis. 
Important protocol deviations are a subset of protocol deviations that may significantly impact the 
completeness, accuracy, and/or reliability of the study data or that may significantly affect a 
participant’s rights, safety, or well-being. Important protocol deviations will be reviewed as part of 
the ongoing data cleaning process and data evaluation. All important deviations will be identified and 
documented prior to unblinding to confirm exclusion from analysis sets. 
 
All protocol deviations will be listed by participant on all full analysis sets. Protocol Deviations 
related to COVID-19 will be listed separately. 
 
4.5 
Analysis Sets 
Following analysis, sets are defined in this study. 


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Enrolled Set (ES): The ES will consist of all participants who have given informed consent. 
Full Analysis Set (FAS): The FAS will consist of all participants randomized into the study. 
Participants in this analysis set will be used for analyzing demographics and other baseline 
characteristics. 
Safety Set: The safety analysis set will consist of all participants who are randomized to treatment 
and have received 1 dose of study drug. Participants in this analysis set will be used for demographics, 
baseline characteristics, and safety summaries. If all participants in the FAS received actual study 
drug as randomly assigned, summaries of demographics and baseline characteristics will not be 
presented for the Safety Set.  
Pharmacokinetic Per-Protocol Set (PK-PPS): The PK-PPS set will consist of all participants in the 
Safety Set who provide at least 1 quantifiable serum XTMAB-16 PK sample post dose without 
important protocol deviations related to study drug administration that would affect the concentration. 
Participants who receive placebo will not be part of the statistical analysis and summary statistics for 
PK data. PK-PPS will be used to conduct the PK analysis to calculate PK parameters, descriptive 
summaries of PK parameters, statistical analysis for comparison of PK parameters, and create Tables 
and Figures. PK-PPS will be finalized after unblinding of the study. Any data excluded will be 
discussed in the CSR. Any excluded subject must have their concentration and PK parameter data 
listed only and footnoted with reason of exclusion.  
Biomarker Set: All participants without any major deviations related to study drug administration 
and for whom any biomarker (or effect) data are available will be included in the biomarker analysis. 
However, subjects being included in this population and having received only placebo will also be 
included as part of this data set. 
A summary of classification to analysis population will be presented in a listing by participant 
including reason of exclusion on all randomized population set. The number and percentage of 
participants included in each analysis population will be summarized on all randomized population 
set by dose cohort/ pooled placebo group and overall. 
4.6 
Demographics and Baseline Characteristics 
Demographic and anthropometric variables (age, sex, ethnicity, race, height, weight and BMI) will 
be listed by participant. Demographic characteristics (age, sex, ethnicity and race) and anthropometric 
characteristics (height, weight and BMI) will be summarized by XTMAB-16 dose / pooled placebo 
group and overall, for all participants in the safety analysis set. The denominator for percentages will 
be the number of participants in the safety analysis set for each treatment or for all participants as 
applicable. 
Age will be calculated as the number of complete years between a participant's birth date and the date 
of informed consent. 
4.7 
Medical History and Concomitant Illnesses 
Medical history data will be listed by participant including visit, description of the disease/procedure, 
Medical Dictionary for Regulatory Activities (MedDRA Version 24.0 or latest) system organ class 
(SOC), MedDRA preferred term, start date, and stop date (or ongoing if applicable). 
 
4.8 
Prior and Concomitant Medications 
Prior medications are those that started and stopped prior to the dose of IMP. Concomitant 


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medications are those taken before or after dosing (including medications that started prior to 
dosing and continued after) and up to end of trial. 
 
Prior and concomitant medications will be presented based on safety analysis population and will be 
listed by participant and will include the following information: reported name, preferred term, the 
route of administration, dose, frequency, start date/time, duration, and indication. 
 
Prior and concomitant medication will be coded according to the World Health Organization Drug 
Dictionary (WHO-DD) (Version March 1, 2021 B3 or latest) and will be classified by Anatomical 
Therapeutic Chemical (ATC) categories. 
 
If missing data prevents the medication being classified as prior or concomitant, the medication will 
be considered as concomitant for the data listings. 
 
Medication start and stop dates will be compared to the date of dose of study medication to allow 
medications to be classified as either Prior only, or Concomitant only. Medications starting after the 
completion/withdrawal date will be listed but will not be classified or summarized. 
 
Medications that start and stop prior to the date of dose of study medication will be classified as 
Prior only. Medications will be classified as Concomitant only if they have a start date before or after 
the date of dose of study medication and up to end of trial. 
 
If medication start and/or stop dates are missing or partial, the dates will be compared as far as 
possible with the date of dose of study medication. Medications will be assumed to be 
Concomitant only, unless there is clear evidence (through comparison of partial dates) to suggest that 
the medication started prior to the dose of study medication. If there is clear evidence to suggest 
that the medication stopped prior to the dose of study medication, the medication will be assumed 
to be Prior only. 
4.9 
Treatment Exposure  
A listing of drug administration will be created and will include the dose cohort, treatment received, 
date and time of administration, dose (unit), dose form, route of administration. 
4.10 Pharmacokinetic Evaluation  
4.10.1 Pharmacokinetic Concentrations 
Concentration Listings: 
Pharmacokinetic concentration data for XTMAB-16, will be listed by treatment and subject for the 
Safety Set. Concentration listings will include nominal PK sampling time, actual sampling time 
relative to start of infusion, infusion duration, deviation from start of nominal infusion time, percent 
deviation from nominal time and concentrations. Serum concentrations below the lower limit of 
quantification (LLOQ) will be presented as below the limit of quantification (BLQ) in the listings and 
the LLOQ value presented as a footnote. Missing PK samples will be reported as no sample (NS) 
and/or not reportable (NR) and considered excluded from PK analysis. 
 
 
 
 


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XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
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Concentration Summary tables: 
Source data as reported from the laboratory will be used for calculation of concentration summary 
statistics. Tabular summaries for concentration-time data will report N (number of participants who 
received treatment), n (number of participants with non-missing values) ), and n(BLQ) (the number 
of participants with BLQ). 
 
Serum concentrations for XTMAB-16 will be summarized by treatment, and nominal timepoint using 
the PK-PPS set. The following descriptive statistics will be presented for serum concentrations 
obtained at each nominal time point: N, n, n(BLQ), arithmetic mean, SD, coefficient of variation 
(CV%), geometric mean, geometric CV% (calculated as: gCV% =SQRT(es² -1)*100; where s is the 
standard deviation of the log-transformed values), median, minimum and maximum values. 
 
For summary tables, all BLQs will be considered zero, and the number of BLQs and non-BLQs at 
each scheduled time point will be reported.  Summary Statistics will not be calculated if non-BLQ 
concentrations at a scheduled time point is <3 and will be reported as NC. If for any time point any 
value is zero in this case Geometric mean and Geometric CV(%) for respective time point will not be 
calculated and reported ad NC. 
The rules followed for calculation and presentation of concentration data with regards to the number 
of decimal places/significant digits for the listings of subject level concentrations and summary tables 
of concentration are as follows:  
Table 4 Rounding Rules for Concentration Listings and Tables 
Serum Concentration Listings and Tables 
Rounding 
Individual concentrations 
n s f. as supplied by bioanalytical laboratory 
Minimum and Maximum 
n s.f. capped at 4 
Mean/SD/Median/Geomean 
n+1 s.f. capped at 4 
CV%/gCV% 
1 d.p. 
N/n 
Whole number 
s f = significant figures, d.p. = decimal place 
Concentration Figures: 
For arithmetic mean linear/linear graphs, all BLQ values will be substituted with zero for calculation 
of arithmetic mean and for log/linear graphs the log transformed arithmetic mean will be displayed 
(this should not include zero). 
Individual linear/linear and log/linear graphs all BLQ values will be substituted as follows: 
• BLQs at the beginning of a subject profile (ie, before the first incidence of a measurable 
concentration) will be assigned to zero (except for intravenous administration when these 
BLQs should not be displayed). When using log/linear scale, these timepoints will be 
considered missing. 
• BLQs at the end of a subject profile (ie, after the last incidence of a measurable concentration) 
will be set to missing. 
• Single BLQs which fall between two measurable concentrations will be set to missing.  
• Consecutive BLQs which fall between measurable concentrations will be set to missing. 
Measurable concentrations after consecutive BLQs will be set to missing. 


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XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
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To visualize subject-level concentrations and the comparison between each cohort, the descriptive 
PK graphs listed below will be generated.   
• Figure xx.1: Individual XTMAB-16 Serum Concentration-Time Profiles (Linear and Semi-
Logarithmic Scale), (Safety Set) 
• Figure xx.2: Combined Individual XTMAB-16 Serum Concentration-Time Profiles (Linear 
and Semi-Logarithmic Scale) by Treatment, (Safety Set) 
• Figure xx.3: Mean (± SD) XTMAB-16 Serum Concentration-Time Profiles (Linear and Semi-
Logarithmic Scale) by Treatment, (PK-PPS) 
Figures will be generated in black and white or color using unique line style and marker for each plot 
in the graph. Actual times will be used for individual and combined individual serum concentration-
time profiles on Safety Set, and nominal times will be used for mean (± SD) serum concentration-
time profiles (no SD for semi-logarithm plot) on PK-PPS. All plots will be presented on a linear and 
semi-logarithm scale.  
4.10.2 Pharmacokinetics Parameters 
Pharmacokinetic parameters will be calculated by non-compartmental analysis methods from the 
concentration-time data using Phoenix® WinNonlin® (Version 8.2) or higher following these 
guidelines: 
• Actual sampling times relative to the start of infusion rather than nominal times will be used 
in the calculation of all derived pharmacokinetic parameters except when parameters are 
calculated for safety/dose escalation meetings when nominal times may be used to calculate 
PK parameters. 
• There will be no imputation of missing data. 
• Handling of BLQ data for the derivation of serum PK Parameters 
o BLQs at the beginning of a subject profile (i.e. before the first incidence of a measurable 
concentration) will be assigned to zero. 
o BLQs at the end of a subject profile (i.e. after the last incidence of a measurable 
concentration) will be set to missing. 
o Single BLQs which fall between two measurable concentrations will be set to missing. 
o Consecutive BLQs which fall between measurable concentrations will be set to missing. 
Measurable concentrations after consecutive BLQs will also be set to missing. 
 
Pharmacokinetic parameters will be estimated according to the guidelines presented in Table 3. 
Table 5  
Pharmacokinetic Parameter and Estimation 
Parameter 
Guideline for Derivation 
Cmax, tmax, CT 
Obtained directly from the observed concentration-time data. 
AUC0-t or AUC0-
last 
The AUC from zero time (pre-dose) to the time of last quantifiable concentration will be 
calculated by a combination of linear and logarithmic trapezoidal methods. Unless 
specifically requested and justified, the linear up/log down trapezoidal method will be 
employed. 
The AUC0-t is the sum of areas up to the time of the last quantifiable sample: 
 
AUC0-t=∫𝐶last ∗𝑑𝑡
 t
0
 


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XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
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Parameter 
Guideline for Derivation 
AUC0-inf 
The area from zero time extrapolated to infinite time will be calculated as follows:  
AUC0-inf = AUC0-t+
𝐶last
𝜆𝑧 
where Clast is the last observed quantifiable concentration.  
%AUCex 
The percentage of AUC0-inf obtained by extrapolation will be calculated as follows:  
%AUCex =
AUC0-inf  ꟷ 𝐴𝑈𝐶0-t 
AUC0-inf
x100 . Unless otherwise determined by PK Scientist’s best knowledge 
and judgment, if the %AUCex is greater than 30% the value, %AUCex, and all dependent 
parameters (ie, AUC0-inf, MRT, Vz and CL) will be flagged in listings and excluded from 
summary tables and statistical analysis of PK parameters. The reason for exclusion will be 
listed/footnoted in parameter listings.  
λz and t½ 
1. 
The apparent terminal phase rate-constant (λz) will be estimated by linear regression 
of concentration versus time data presented in a log-linear scale. 
2. 
Data are primarily monotonically decreasing in magnitude and are representative of 
the actual decline in the log concentration-time curve. 
3. 
Only those data points that are judged to describe the terminal log-linear decline will 
be used in the regression.  
4. 
A minimum number of three data points in the terminal phase will be used in 
calculating λz with the line of regression starting at any post-Cmax data point (Cmax should not 
be part of the regression slope, if possible). Unless otherwise determined by PK Scientist’s best 
knowledge and judgment, if the adjusted correlation coefficient (R2 adjusted) is <0.8, it will be 
excluded from the summary tables and statistical analysis of PK parameters, and λz and all the 
λz dependent parameters (i.e. t½, AUC0-inf, CL, MRT, and Vz) will also be flagged and 
excluded from summary tables and statistical analysis. The reason for exclusion will be 
listed/footnoted in parameter listings. 
5. 
Unless otherwise determined by PK Scientist’s best knowledge and judgment, the 
interval used to determine λz should be equal or greater than 1.5-fold the estimated t½, and if 
less than 1.5-fold, λz will be flagged in listings and excluded from summary tables and 
statistical analysis of PK parameters. All the derived parameters (i.e. t½, AUC0-inf, CL, MRT, 
and Vz) will also be flagged from listings and excluded from statistical analysis of PK 
parameters. The reason for exclusion will be listed/footnoted in parameter listings.  
 
6. 
The t½ will be calculated as follows:  
 
 
 
t½ =  ln2/λz = 0.693/ λz 
7. 
Data points may be dropped from the linear regression if the PK Scientist considers 
the reported values to be anomalous.  Any data points so designated should remain in the 
listings with a footnote and be identified in the study report with a rationale for exclusion. 
CL 
Following IV administration, systemic clearance of drug will be calculated from:  
CL = 
Dose
AUC0-inf 
Vz 
Volume of distribution at terminal phase following IV dosing may be calculated from: 
 
Vz = 
Dose
λz×AUC0-inf = CL / z  
Vss 
Following IV administration, the volume of distribution at steady state of drug will be 
calculated from:  
V,ss = CL × MRTiv 
MRT 
Mean residence time of the drug is calculated as: 
 
 
MRT = [AUMC0-inf /AUC0-inf – TI/2] 
where AUMC0-inf is area under the serum concentration moment (C ∙ t) versus time curve 
extrapolated to infinity according to the following equation: 
AUMC0-inf = AUMC0-t + (Ct ∙ t / λz + Ct / λz2) 
TI is the length of infusion 
DNCmax,  
DNAUC0-last,  
DNAUC0-inf 
Dose-normalized Cmax,AUC0-t, and AUC0-inf calculated as:  
parameter value/Dose 
 


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PK Parameters Listings: 
Pharmacokinetic parameters will be listed by treatment and subject for the Safety Set. PK parameters 
that will be excluded from summary tables and statistical analyses of PK parameters will be flagged 
and footnoted with reason for exclusion.  
PK Parameter Summary Tables: 
PK parameters will be provided by CPMS group. Biostatistics group will consider this the PK 
parameters source data and will use this data without rounding for calculation of PK parameter 
summary statistics tables.  
PK parameters will be summarized by treatment for the PK-PPS. 
Tabular summaries for PK parameters will report N (number of participants who received treatment) 
and n (number of participants with non-missing values). 
Descriptive statistics for calculated PK parameters will include: N, n, arithmetic mean, SD, CV%, 
geometric mean, geometric CV%, median, minimum and maximum values. For tmax, only median, 
minimum and maximum values will be presented. No descriptive statistics will be determined when 
fewer than three individual PK parameters are available. 
The rules followed for presentation of PK parameters data with regards to the number of decimal 
places/significant digits for the listings of subject level PK parameters and summary tables of PK 
parameters are as follows:  
Table 6 Rounding Rules for PK Parameter Listings and Tables 
PK Parameter Listings and Tables 
Rounding  
Derived Individual parameters 
4 s f. 
Directly Derived Individual parameters (Cmax, 
CT) 
n s f. as supplied by the analytical laboratory but not 
more than 4 s f. 
Minimum and Maximum 
4 s f. 
Mean/SD/Median/Geomean 
4 s f. 
CV%/gCV% 
1 d.p. 
Comparative estimates 
3 d.p. 
CI and other percentages 
2 d.p. 
p-values 
4 d.p. 
N/n 
Whole number 
Exceptions for PK Tables 
  
tmax individuals and min/max 
2 d.p 
tmax median only 
2 d.p 
s f = significant figures, d.p. = decimal place 
PK Parameter Figures: 
The following plots will also be generated: 
• Boxplots for dose normalized PK parameters (e.g., Cmax, AUC0-last, and AUC0-inf) versus 
treatment 
Assessment of Dose Proportionality  
• Power Model using ANOVA Method: 


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An ANOVA of the natural log-transformed PK parameters, ln-transformed dose as a fixed and 
participant as random effect. 
Dose-proportionality based on the power model will be accepted (“not rejected”, in terms of statistical 
inference) if each of the 95% CIs of the slope of the effect of dose level on each of PK parameters 
includes 1. 
For each of the parameters (Cmax and AUCs) a plot of the log-transformed PK parameter against the 
log-transformed dose will be constructed including the fitted line from the linear regression and the 
line of unity. 
Sample SAS Code: 
ODS OUTPUT lsmeans=lsm estimates=est Diffs=diff1; 
PROC MIXED DATA=PKDATA; 
BY ANALYTE PKPARAM ; 
CLASS SUBJECT; 
MODEL LN_PK= LNDOSE/ddfM=KR; 
RANDOM SUBJECT; 
ESTIMATE "LNDOSE" LNDOSE/CL= 0.05; 
RUN; 
where: 
LN_PK: natural log-transformed PK parameter  
LNDOSE: natural log-transformed dose level of <drug>  
ANALYTE: analyte (LICO FG-459) 
PKPARAM: PK parameter  
SUBJECT: participant 
4.11 Safety Evaluation 
All safety summaries and analyses will be based upon the Safety Set. All Safety and tolerability 
parameters  (AEs, laboratory data (hematology, biochemistry, and urinalysis parameters), vital signs, 
physical exam findings and ECG parameters will be evaluated as following. 


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4.11.1 Adverse Events 
An AE is any untoward medical occurrence in a study participant administered an IMP which does 
not necessarily have a causal relationship with this treatment.  
A treatment-emergent adverse event (TEAE) is defined as an AE that begins or that worsens in 
severity after at least one dose of the study drug has been administered. 
All related TEAEs will be defined as Adverse drug reaction (ADR). 
Any AEs with incomplete start and end dates/times will be treated as follows: 
• Adverse events with unknown start times, but with start date known, will be imputed with a 
time of 00:00, unless the start date corresponds to any given dosing date. In this case the start 
time will be imputed with the time of dosing. If this results in a start date/time after end 
date/time of the AE, then the time will also be imputed with 00:00.  
• Adverse events with completely unknown start dates will be imputed with the date and time 
of first dosing, unless the end date is known and prior to dosing; in that case the start date will 
be imputed as the date of Screening and a time of 00:00.  
• Adverse events with partially known start dates/times will be treated as follows: 
▪ If only the day is missing, then the day will be imputed with the first day of the month, 
unless the month and year in which the AE started is a month and year in which study 
drug was administered, then the day will be imputed with the first day on which study 
drug was administered in that month. If this results in a start date after the end date, 
then the day will be imputed with the first day of the month. 
▪ If only the month is missing, and the year is a year in which study drug was 
administered, then the month will be imputed with the first month in which study drug 
was administered. If this results in a start date after the end date of the AE, then the 
month will be imputed with JAN. If the known year part is not a year in which study 
drug was administered, then the month will also be imputed with JAN. 
▪ If both the day and month is missing and the year is a year in which study drug was 
administered, then the day and month will be imputed with the day and month of 
dosing. If this results in a start date after end date, then the day and month will be 
imputed with 01JAN. If the year is not a year in which study drug was administered, 
then the day and month will also be imputed with 01JAN. 
▪ If only the year is missing, then the year will be imputed with the year of dosing. 
Unknown dates and times will be shown as NK and NK:NK in the listings (where NK = Not Known), 
respectively. 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
Version 24.0 or higher.   
Unless specified otherwise, all adverse event summaries will include the TEAEs only and adverse 
event summary counts will be the number of participants reporting adverse events and not the number 
of events reported.  
If more than one event occurred with the same preferred term for the same participant, then the 
participant will be counted only once for maximum severity level or for most causality level of that 
preferred term for the summarization of severity or causality accordingly. This table will be sorted 
alphabetically by SOC and PT.   
The following summaries will be presented: 


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• A table of number (percentage) of participants and number of adverse events with an overview 
of treatment emergent adverse events (TEAE), severe AEs,ADR, SAE, and AE leading to 
discontinuation will be presented by XTMAB-16 dose, pooled placebo and overall. 
• A table of number (percentage) of participants and number of adverse events with treatment 
emergent adverse events (TEAE), and SAE summarized by SOC and PT, XTMAB-16 dose, 
pooled placebo and overall. This table will be sorted by decreasing frequency of the overall 
column. 
• A table of number (percentage) of participants and number of adverse events with TEAEs 
summarized by SOC, PT, relationship, XTMAB-16 dose, pooled placebo and overall. If more 
than one event with the same preferred term occurred for the same participant, then the 
participant was counted only once for that preferred term under the strongest causality. This 
table will be sorted by decreasing frequency of the overall column. 
• Tables of number (percentage) of participants and number of adverse events with TEAEs 
summarized by SOC, PT maximum severity, XTMAB-16 dose, pooled placebo and overall 
will be presented. If more than one event occurred with the same preferred term for the same 
participant, then the participant was counted only once for maximum severity level of that 
preferred term for the summarization of severity. This table will be sorted by decreasing 
frequency of the overall column. 
• A listing will be created for all Adverse Events (AEs), which will include: treatment received, 
treatment period, preferred term (PT), system organ class (SOC), AE onset date (and time), 
AE end date (and time), measure taken on AE, relationship to IMP, AE outcome, severity, 
frequency, action taken, concomitant medication (if administered), TEAE indicator flag and 
SAE indicator flag. 
• A table of grading of injection site reaction (Table 5) will be summarized by dose cohort and 
overall. 
• A by subject listing of TEAE leading to discontinuation, TEAE expectedness and SAE will 
be created. 
Adverse event summaries will be ordered in terms of decreasing frequency for SOC, and PT within 
SOC, and then alphabetically for SOC, and PT within SOC. 
4.11.2 Deaths, Serious Adverse Events, and Adverse Events of Special Interest 
A by-participant listing of death, adverse of special interest (AESI) and all serious adverse events will 
be created.  
4.11.3 Clinical Laboratory Evaluation 
The following safety laboratory parameters will be measured: 
Hematology: Hematocrit, Hemoglobin, Platelet count, Red blood cell count, White blood cell count 
with differential, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes, Activated partial, 
thromboplastin time. 
Clinical Chemistry: Albumin, Alkaline phosphatase, Alanine aminotransferase, Aspartate 
aminotransferase, Bilirubin (total and conjugated), C-reactive protein, Calcium, Chloride, Creatinine, 
Creatine phosphokinase, Gamma-glutamyl transferase, Glucose, Potassium, Sodium, Total 
cholesterol, Total protein, Triglycerides, Tryptasea, WOCBP Only (per SoA): Human chorionic, 
gonadotropin. 


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XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
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Viral Serology: Hepatitis B surface antigen, Hepatitis B core antigen antibody, Hepatitis C virus 
antibody, HIV antibody (HIV1 and HIV2), COVID-19, Tuberculosis (quantiFERON Gold™ test). 
Urinalysis: Protein, Glucose, Red blood cells, White blood cells, Ketone bodies, pH. 
At discretion of Investigator based on urinalysis results: 
• Microbiology 
• Urine microscopy 
Drugs of Abuse: Alcohol, Amphetamines/methamphetamines, Barbiturates, Benzodiazepines, 
Cannabinoids, Cocaine, Opiates. 
Individual data listings of all the laboratory results will be presented for each participant. Flags will 
be attached to values outside of the laboratory’s reference limits along with the investigator’s 
assessment. Clinically significant laboratory test abnormalities that were considered adverse events 
by the investigator will be presented in the adverse event listings.  
Any laboratory parameters with results from the laboratory given as '<xx' or '>xx' in the database will 
be imputed with the absolute value of the number without the sign (e.g., < 9.2 will be imputed as 9.2) 
for the descriptive statistics and changes from baseline.  
Safety laboratory tests (observed values and change from baseline) will be summarized descriptively 
in tabular format by dose cohort and pooled placebo group. The baseline for the laboratory parameters 
will be the measurement obtained prior to administration of IV of XTMAB-16.  . 
In order to compare a before-and-after effect for selected laboratory parameters, shift tables with 
regards to reference ranges will be provided for each dose step, and for all participants. 
The number and percentage of participants with newly occurring liver enzyme abnormalities 
occurring at any time post-baseline will be summarized by dose cohort and by overall. 
4.11.4 Vital Signs, Physical Findings and Other Observations Related to Safety 
Vital Signs 
Oral, tympanic or temporal body temperature, respiratory rate, pulse, and systolic and diastolic blood 
pressure will be assessed.  
Vital signs data will be listed by participant including changes from baseline. The baseline for the 
vital signs’ measurements will be the measurement obtained prior to administration of IV of 
XTMAB-16. 


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XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
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Table 7 
Grading for Vital Signs  
 
Toxicity grading of vital signs will be summarized by dose cohort. 
Descriptive statistics (n, mean, SD, median, minimum, maximum) for absolute values and changes 
from baseline will be presented by dose cohort. 
ECG 
Standard safety 12-lead ECGs will be performed as shown in the Schedule of Assessments. 
The following ECG parameters will be recorded: 
P wave, QRS complex, U wave, QRS duration, QT interval, QTcF, T wave, ST segment, RR interval, 
PR interval, and qualitative results. 
The ECG will be evaluated by the Investigator as ‘Normal’, ‘Abnormal, NCS’ or ‘Abnormal, CS’. 
All ECG parameters will be listed by participant for each dose cohort and time point including 
changes from baseline. The baseline for the ECG measurements will be obtained prior to 
administration of IV of XTMAB-16. 
Descriptive statistics (n, mean, SD, median, lower quartile, upper quartile, minimum, maximum) for 
absolute values and changes from baseline will be presented by dose cohort and pooled placebo group. 
A categorical QTc analysis will also be performed. 
A summary of the number and percentage of participants with QTcF intervals exceeding some 
predefined upper limits (e.g. >450ms, >480ms, >500ms for measured values as well as. >30ms, 
>60ms for changes from baseline) of ECG parameters will be displayed in a frequency table. 


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XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
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Mean QTcF values (±SD) over time per dose and pooled placebo will be presented graphically on 
Safety set.  
If findings on telemetry are identified, a further concentration QT analysis (tie-matched QT and QTc 
analysis for XTMAB-16 and placebo) may be further evaluated. ER analysis consists of the 
following: 
1. A linear mixed effects model with ΔQTcF as the dependent variable, drug plasma 
concentration as a continuous covariate, treatment (active or placebo) as categorical factor, 
and a random intercept for each participant. Note: concentration values are set to 0 for placebo 
participants. 
2. The predicted mean ΔΔQTcF (placebo corrected, change from baseline) at the observed 
geometric mean Cmax (i.e., the product with the slope estimate treatment effect [active – 
placebo]) will be calculated. Two-sided 90% CIs of the estimate will be calculated using a 
bias-corrected nonparametric bootstrap with 1,000 resamples and participant as the unit of 
resampling. Note: Bootstrap is used to provide robust estimate for the 90% CI.  
Resampling will be done independently for the active and the placebo participants. For each 
resample, the model will be fitted and the predicted mean ΔΔQTcF will be computed at the 
geometric mean Cmax determined from the resampled data. The 90% CI will be determined 
from the distribution of resampled predicted values. 
3. Decisions to classify the risk QTprolongation induced by XTMAB-16, the upper bound of 
the two-sided 90% CI for the ΔΔQTcF effect of XTMAB-16 as estimated by ER model 
should be <10ms at the observed geometric mean Cmax  to exclude a risk QT prolongation 
induced by XTMAB-16. (reference: ICH E14 Guideline: The Clinical Evaluation of 
QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs 
Questions & Answers (R3)) 
Physical Examination 
• A complete physical examination will include assessments of general appearance, skin; 
head/neck; pulmonary, cardiovascular, gastrointestinal, external genitourinary (optional), 
lymphatic, and musculoskeletal systems; extremities; eyes (inspection and vision control); 
ears, nose; throat; and neurologic status. 
• An abbreviated physical examination will include assessments of general appearance; head, 
ears, eyes, nose, and throat; cardiovascular; respiratory; and gastrointestinal systems 
(including the abdomen). 
• A targeted physical examination may be conducted at any time at the Investigator’s discretion 
and should be limited to systems of clinical relevance (ie, cardiovascular, respiratory, lymph 
nodes, liver.) 
Abnormal physical examination findings will be listed. 
Assessment of liver-related changes will include: 
• 3 ×-, 5 ×-, 10 ×-, and 20 × ULN elevations of AST, ALT, and either ALT or AST 
• Any elevations of bilirubin: elevated total bilirubin to >2 × ULN 
• Any elevations of ALP >1.5 × ULN 
• Elevation of AST or ALT (>3 × ULN) accompanied by elevated bilirubin (>1.5 × ULN, >2 × ULN) 
• Elevation of AST or ALT in temporal association with nausea, vomiting, anorexia, abdominal pain, 
or fatigue 


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Xentria Inc. 
XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
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Project Document Effective Date: Date of last signature 
Related to:  SOP-GDO-WW-019 
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• Any liver-related deaths and liver-related treatment discontinuations. 
Assessment of liver-related changes will be summarized. 
4.11.5 Safety Monitoring (Independent Data Monitoring Committee [IDMC], Data 
Monitoring Committee [DMC], Data and Safety Monitoring Board [DSMB])  
Not Applicable. 
4.12 Other Analyses 
4.12.1 Immunogenicity  
If ADA or nAb are detected, a direct link model may be used to describe the relationship between the 
serum concentration of XTMAB-16 and ADA or nAb levels, as AUC and time point concentration 
measurements to explore the time-dependence. 
If ADA or nAb are detected, a summary table of PK parameter by ADA and nAb status (Positive or 
Negative) will be provided using PK analysis set. 
Anti-drug antibodies and nAb at each sampling time will be summarized with descriptive statistics 
(N, mean, SD, coefficient of variation [CV], geometric mean, geometric CV, median, minimum, and 
maximum) for each dose cohort and Day. 
4.12.2 Biomarker Analysis 
Biomarker analysis of ACE, sIL-2R, IL-6, and sTNFα will be based on Biomarker Set.  
All participants without any major deviations related to study drug administration and for whom any 
biomarker (or effect) data are available will be included in the biomarker analysis. However, 
participants being included in this population and having received only placebo will also be included 
as part of this data set. 
Percent change from Baseline over time and total (absolute) change from Baseline will be analyzed. 
4.12.2.1 Biomarker Concentration-Time Data 
Biomarkers (ACE, sIL-2R, IL-6, and sTNFα) at each biomarker sampling times will be summarized 
with descriptive statistics (N, mean, SD, CV%, geometric mean, geometric CV%, median, minimum, 
and maximum) for treatment, day, and nominal timepoint. 
 
For presentation in biomarker summary tables if less than 4 significant digits, all summary statistics 
will be tabulated to one more significant digit compared to the source data, otherwise up to a 
maximum of 4 significant digits, with exception of N, and n that will be presented as whole numbers, 
CV% and geometric CV% that will be presented to 1 decimal place. 
 
To visualize the comparison between treatment, the following descriptive biomarker graphs will be 
generated. For each figure participants belonging to each category will be shown on the same plot 
with separate figures for each level of dose. Figures will be displayed in unique line and marker color, 
line style and marker for each plot in the graph. For all biomarker-time plots, linear scale will be used 
for both x-axis and y-axis. The following plots will be generated for each of biomarkers.  
 
• Figure xx.1: Individual Biomarker-Time Profiles (Absolute change and percent change from 
Baseline) (Biomarker Set) 
• Figure xx.2: Mean (± SD) Biomarker-Time Profiles (Absolute change and percent change 
from Baseline) by dose and placebo groups (Biomarker Set) 


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XTMAB-16-101                                                                                                                              Statistical Analysis Plan 
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Project Document Version No. Final 3.0 
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Project Document Effective Date: Date of last signature 
Related to:  SOP-GDO-WW-019 
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4.12.2.2 Biomarker Parameters 
These biomarker (or effect) parameters will be obtained, if data permit: area under the effect-time 
curve (AUEC), maximum observed effect (Emax,obs), and time to reach maximum observed effect 
(tEmax,obs). The overall results of the biomarker assessments will determine whether these specific 
analyses will be performed. 
Biomarker parameters will be provided by CPMS group. Biostatistics group will use this data for 
calculation of biomarker parameter summary statistics tables. 
Biomarker parameters will be calculated by non-compartmental analysis methods from the 
biomarker-time data using Phoenix® WinNonlin® (Version 8.2) or higher following these 
guidelines: 
• Actual sampling times relative to the start of infusion rather than nominal times will be used 
in the calculation of all derived biomarker parameters. 
• There will be no imputation of missing data. 
Biomarker parameters will be listed by treatment and subject for the Biomarker Set. Biomarker 
parameters will be summarized by different dose and placebo groups.  
For presentation in biomarker parameter summary tables if less than 4 significant digits, all summary 
statistics will be tabulated to one more significant digit compared to the source data, otherwise up to 
a maximum of 4 significant digits, with exception of N, and n that will be presented as whole numbers, 
CV% and geometric CV% that will be presented to 1 decimal place. 
4.13 Determination of Sample Size 
The selection of 24 participants (12 per cohort) was based on feasibility and precision around the 
estimates for target variables associated with the primary and secondary endpoints. No sample size 
calculation was performed. 
4.14 Changes in the Conduct of the Study or Planned Analysis 
None. 
5 
REFERENCES 
[1] SAS® Version 9.4 of the SAS System for Personal Computers. Copyright © 2002-2003. SAS 
Institute Inc. SAS and all other SAS Institute Inc. product or service names are registered 
trademarks or trademarks of SAS Institute Inc., Cary, NC, USA. 
[2] Phoenix®WinNonlin® Professional Software Version 8.2. https://www.certara.com 
 
 


Parexel International 
Xentria Inc. 
XTMAB-16-101                                                                                                                                                                                                                               Statistical Analysis Plan 
TP-GDO-WW-133-02                                                                                CONFIDENTIAL                                                                              Project Document Version No. Final 3.0 
Effective Date:  26 Nov 19                                                                                                                                                             Project Document Effective Date: Date of last signature 
Related to:  SOP-GDO-WW-019                                                                                                                                                                                                                        Page 34 of 37 
6 
APPENDICES 
6.1 
Schedule of Assessments 
Table 8 
Schedule of Assessments 
 


Parexel International 
Xentria Inc. 
XTMAB-16-101                                                                                                                                                                                                                               Statistical Analysis Plan 
TP-GDO-WW-133-02                                                                                CONFIDENTIAL                                                                              Project Document Version No. Final 3.0 
Effective Date:  26 Nov 19                                                                                                                                                             Project Document Effective Date: Date of last signature 
Related to:  SOP-GDO-WW-019                                                                                                                                                                                                                        Page 35 of 37 
 


Parexel International 
Xentria Inc. 
XTMAB-16-101                                                                                                                                                                                                                               Statistical Analysis Plan 
TP-GDO-WW-133-02                                                                                CONFIDENTIAL                                                                              Project Document Version No. Final 3.0 
Effective Date:  26 Nov 19                                                                                                                                                             Project Document Effective Date: Date of last signature 
Related to:  SOP-GDO-WW-019                                                                                                                                                                                                                        Page 36 of 37 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Parexel International 
Xentria Inc. 
XTMAB-16-101                                                                                                                                                                                                                               Statistical Analysis Plan 
TP-GDO-WW-133-02                                                                                CONFIDENTIAL                                                                              Project Document Version No. Final 3.0 
Effective Date:  26 Nov 19                                                                                                                                                             Project Document Effective Date: Date of last signature 
Related to:  SOP-GDO-WW-019                                                                                                                                                                                                                        Page 37 of 37 
Table 9 
Grading of Injection Site Reactions 
Local 
Reaction 
to 
Injectable Product 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Potentially 
Life 
Threatening (Grade 4) 
Pain 
Does not Interfere with 
activity 
Repeated use of non-
narcotic pain reliver > 24 
hours or interferes with 
activity 
Any use of narcotic pain 
reliever or prevents daily 
activity 
Emergency room (ER) 
visit or hospitalization 
Tenderness 
Mild discomfort to touch Discomfort 
with 
movement 
Significant discomfort at 
rest 
ER 
visit 
or 
hospitalization 
Erythema/Redness* 
2.5 - 5 cm 
5 – 10 cm 
>10 cm  
Necrosis or exfoliative 
dermatitis 
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 
Necrosis 
*  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 actual measurement. 
 
 
 


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