Clinical trial NCT04351243
Conditions: COVID-19
Keywords: Granulocyte macrophage-colony stimulating factor (GM-CSF) Immunomodulator Cytokine storm COVID-19 Coronavirus Severe Acute Respiratory Syndrome (SARS) Lung Injury Monoclonal antibody
Sponsor: Kinevant Sciences GmbH
Start date: 2020-04-15; Completion date: 2021-04-01
Enrollment: 227 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Study KIN-1901-2001 is a multi-center, adaptive, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of gimsilumab in subjects with lung injury or acute respiratory distress syndrome (ARDS) secondary to COVID-19.

Detailed description:
Gimsilumab is a monoclonal antibody against granulocyte macrophage-colony stimulating factor (GM-CSF), which is a myeloid cell growth factor and pro- inflammatory cytokine. Late stages of COVID-19 can be marked by a "cytokine storm" and the overactivation of inflammatory myeloid cells that infiltrate and damage tissue, such as the lungs. Inhibition of GM-CSF may be able to reverse this pathology. The anti-GM-CSF mechanism is distinct from antiviral therapeutic mechanisms and may provide synergistic effects when used in combination.

Study KIN-1901-2001 will consist of a 2-week treatment period (last dose Day 8, if administered) and a 22-week follow-up period, for a total study duration of 24 weeks for each subject. A total of 270 subjects (135 subjects per arm) who have a confirmed diagnosis of COVID-19 with clinical evidence of acute lung injury or ARDS will be entered into the trial.

Subjects will receive a 400 mg dose of gimsilumab on Day 1 and a 200 mg dose of gimsilumab on Day 8, or matching placebo (saline solution) on Day 1 and on Day 8. The Day 8 dose will be omitted if the subject is discharged from the hospital prior to the dose or is no longer in need of supplemental oxygen or ventilatory support for \>48 hours.

The primary objective of Study KIN-1901-2001 is to evaluate the impact of IV treatment with gimsilumab on mortality in subjects with lung injury or ARDS secondary to COVID-19.

Arms: arm 1: Gimsilumab 400 mg on Day 1 Gimsilumab 200 mg on Day 8 arm 2: Normal saline on Day 1 Normal saline on Day 8
Interventions: intervention 1: Gimsilumab intervention 2: Placebo
Intervention descriptions: intervention 1: Gimsilumab is a fully human monoclonal antibody (mAb). intervention 2: Normal saline

Protocol documents:
Prot_000.pdf: 
 
 
 
 
 
Study Number: KIN-1901-2001 
 
Study Title: A Multi-Center, Adaptive, Randomized, Double-blind, Placebo-controlled Study to 
Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute 
Respiratory Distress Syndrome (ARDS) Secondary to Coronavirus Disease 2019 (COVID-19) 
 
 
 
Clinical Study Protocol 
 
Version 5.0 (Amendment 4): 17-Aug-2020 
NCT04351243 


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CLINICAL STUDY PROTOCOL 
Study Title: 
A Multi-Center, Adaptive, Randomized, Double-blind, 
Placebo-controlled Study to Assess the Efficacy and Safety of 
Gimsilumab in Subjects With Lung Injury or Acute Respiratory 
Distress Syndrome (ARDS) Secondary to Coronavirus Disease 2019 
(COVID-19) 
Protocol Number: 
KIN-1901-2001 
Compound Name 
and/or Number: 
Gimsilumab (KIN-1901, formerly MORAb-022) 
Sponsor: 
Kinevant Sciences GmbH (“KSG”), a Swiss Limited Liability 
Company, is the sponsor of this study. Kinevant Sciences, Inc. 
(“KSI”), a Delaware corporation and an affiliate of KSG, has been 
engaged by KSG to manage the day-to-day operations of the study. 
All references to “Sponsor” contained herein shall refer to KSI, 
acting pursuant to a services agreement with KSG. 
Development Phase: 
2 
Indication: 
For the treatment of lung injury or ARDS secondary to COVID-19 
Current Version and 
Effective Date: 
Version 5.0 (Amendment 4): 17-Aug-2020 
Previous Version(s) 
and Effective Date(s): 
Version 1.0 (Original): 22-March-2020 
Version 2.0 (Amendment 1): 05-April-2020 
Version 3.0 (Amendment 2): 06-May-2020 
Version 4.0 (Amendment 3): 12-Jun-2020 
Study Director: 
 
CONFIDENTIALITY STATEMENT 
The information contained in this document, particularly unpublished data, is the property or under 
control of Sponsor, and is provided to you in confidence as an investigator, potential investigator or 
consultant, for review by you, your staff, and an applicable Institutional Review Board or Independent 
Ethics Committee. The information is only to be used by you in connection with authorized clinical 
studies of the investigational drug described in the protocol. You will not disclose any of the information 
to others without written authorization from Sponsor, except to the extent necessary to obtain informed 
consent from those persons to whom the drug may be administered. 


DocuSign Envelope ID: CEEE68B0-D48A-4243-B942-66973BA5270B 
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SPONSOR SIGNATURE PAGE 
Study Title: A Multi-Center, Adaptive, Randomized, Double-blind, Placebo-controlled 
Study to Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung 
Injury or Acute Respiratory Distress Syndrome (ARDS) Secondary to 
Coronavirus Disease 2019 (COVID-19) 
 
Protocol Number: KIN-1901-2001 
 
This protocol has been approved by a representative of Kinevant Sciences GmbH. The following 
signature documents this approval. 
 
 
 
 
 
8/17/2020 
 
Date 


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MEDICAL CONTACT/SPONSOR INFORMATION PAGE 
Sponsor Medical Contact/SAE Contact Information: 
 
Role 
Name 
 
Contact for Serious Adverse 
Events (SAEs) 
On discovery, all SAEs should be immediately reported (latest within 24 hours of 
knowledge of the event) to 
 
 
 
 
Study Sponsor 
Kinevant Sciences GmbH (“KSG”), a Swiss Limited Liability Company, is the sponsor of this 
study. Kinevant Sciences, Inc. (“KSI”), a Delaware corporation and an affiliate of KSG, has been 
engaged by KSG to manage the day-to-day operations of the study. All references to “Sponsor” 
contained herein shall refer to KSI, acting pursuant to a services agreement with KSG. 
 
Kinevant Sciences GmbH Registered Address: 
Viaduktstrasse 8 
4051 Basel 
Switzerland 
 
Kinevant Sciences, Inc. Address: 
151 West 42nd Street, 15th floor 
New York, NY, 10036 
USA 
Primary Medical Monitor 
(Europe) 
Primary Medical Monitor 
(US) 
Secondary Medical Monitor 


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INVESTIGATOR STATEMENT 
• I confirm agreement to conduct the study in compliance with the protocol. 
• I acknowledge that I am responsible for overall study conduct. I agree to personally 
conduct or supervise the described study. 
• I agree to ensure that all associates, colleagues, and employees assisting in the conduct of 
the study understand their obligations and will comply with the study protocol. 
Mechanisms are in place to ensure that site staff receives the appropriate training and 
information throughout the study. 
 
 
 
 
 
 
 
Principal Investigator Name (Printed) 
Signature 
 
 
 
 
 
Date 
Site 
 
 
 
Study Site 
Name of Primary Investigator Site 
 
Address Line 1 
Address Line 2 
City, State, Country, Zip Code 


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TABLE OF CONTENTS 
Clinical Study Protocol ............................................................................................................... 1 
Sponsor Signature Page ............................................................................................................ 2 
Medical Contact/Sponsor Information Page ............................................................................ 3 
Investigator Statement ............................................................................................................... 4 
Table of Contents ........................................................................................................................ 5 
List of Tables ............................................................................................................................... 7 
List of Figures ............................................................................................................................. 8 
1. 
Protocol Summary for Study KIN-1901-2001 .................................................................... 9 
2. 
Introduction ....................................................................................................................... 20 
2.1. 
Study Rationale ........................................................................................................... 20 
2.1.1. 
COVID-19 Background, Clinical Course, and Immunopathogenesis .................. 20 
2.1.2. 
Rationale for Targeting GM-CSF in COVID-19 ................................................... 20 
2.2. 
Dose Rationale ............................................................................................................ 21 
2.3. 
Benefit/Risk Assessment ............................................................................................. 24 
3. 
Objectives and Endpoints ................................................................................................ 25 
4. 
Investigational Plan .......................................................................................................... 27 
4.1. 
Overall Study Design ................................................................................................... 27 
4.2. 
Scientific Rationale for Study Design .......................................................................... 28 
4.3. 
Treatment Arms and Duration ..................................................................................... 28 
5. 
Subject Population ........................................................................................................... 29 
5.1. 
Type and Number of Subjects ..................................................................................... 29 
5.2. 
Inclusion Criteria .......................................................................................................... 29 
5.3. 
Exclusion Criteria ........................................................................................................ 30 
5.4. 
Other Eligibility Criteria Considerations ....................................................................... 31 
5.5. 
Screening/Baseline ..................................................................................................... 31 
5.6. 
Lifestyle and/or Dietary Restrictions ............................................................................ 31 
5.6.1. 
Contraception ...................................................................................................... 31 
5.7. 
Withdrawal Criteria ...................................................................................................... 33 
5.7.1. 
Reasons for Withdrawal ...................................................................................... 33 
5.7.2. 
Subject Withdrawal Procedures .......................................................................... 33 
5.8. 
Toxicity Management Criteria ...................................................................................... 34 
5.8.1. 
Liver Chemistry Management Criteria ................................................................. 34 
5.8.2. 
Individual Stopping Criteria ................................................................................. 35 
5.8.3. 
Study Stopping Criteria ....................................................................................... 35 
5.8.4. 
Other Management Criteria ................................................................................. 35 
5.9. 
Subject and Study Completion .................................................................................... 35 
6. 
Study Treatment ................................................................................................................ 35 
6.1. 
Study Treatment .......................................................................................................... 35 
6.2. 
Administration of Study Treatments ............................................................................ 36 
6.3. 
Randomization / Study Treatment Assignment ........................................................... 36 
6.4. 
Blinding........................................................................................................................ 37 
6.5. 
Packaging and Labeling .............................................................................................. 38 
6.6. 
Preparation/Handling/Storage/Accountability .............................................................. 38 


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6.7. 
Compliance with Study Treatment Administration ....................................................... 39 
6.8. 
Treatment of Study Treatment Overdose .................................................................... 39 
6.9. 
Concomitant Medications and Non-Drug Therapies ................................................... 39 
6.9.1. 
Permitted Medications and Non-Drug Therapies ................................................ 39 
6.9.2. 
Prohibited Medications and Non-Drug Therapies ................................................ 40 
7. 
Study Assessments and Procedures .............................................................................. 40 
7.1. 
Schedule of Assessments (Treatment and Follow-up Periods) .................................. 42 
7.2. 
Informed Consent ........................................................................................................ 47 
7.3. 
Inclusion/Exclusion Criteria Eligibility Review ............................................................. 47 
7.4. 
Study Assessments and Procedures .......................................................................... 47 
7.4.1. 
Efficacy Assessments .......................................................................................... 47 
7.4.2. 
Safety and Other Assessments ........................................................................... 49 
8. 
Data Management ............................................................................................................. 53 
9. 
Statistical Considerations and Analyses ........................................................................ 54 
9.1. 
Sample Size Determination ......................................................................................... 54 
9.2. 
Randomization ............................................................................................................ 54 
9.3. 
Analysis Endpoints ...................................................................................................... 55 
9.3.1. 
Efficacy Endpoints ............................................................................................... 55 
9.3.2. 
Safety Endpoints ................................................................................................. 56 
9.3.3. 
Pharmacokinetic Endpoints ................................................................................. 56 
9.3.4. 
Biomarker Endpoints ........................................................................................... 56 
9.4. 
Analysis Populations ................................................................................................... 56 
9.5. 
Statistical Analyses/Methods ....................................................................................... 57 
9.5.1. 
Primary Efficacy Analyses ................................................................................... 57 
9.5.2. 
Sensitivity Analysis of the Primary Endpoint ....................................................... 57 
9.5.3. 
Analysis of the Key and Other Secondary Endpoints .......................................... 58 
9.5.4. 
Adjustment of Multiple Comparisons and Interim Analyses ................................. 58 
9.5.5. 
Handling of Missing Data ..................................................................................... 59 
9.5.6. 
Safety Analyses ................................................................................................... 59 
9.5.7. 
Sub-Group Analyses ........................................................................................... 59 
9.5.8. 
Timing of Analyses .............................................................................................. 60 
9.5.9. 
Pharmacokinetic, Biomarker, and Immunogenicity Analyses .............................. 60 
10. 
Adverse Events (AE) and Serious Adverse Events (SAEs) ....................................... 60 
10.1. Special Consideration for Assessment of Adverse Events ......................................... 60 
10.2. Definition of an Adverse Event .................................................................................... 61 
10.3. Definition of a Serious Adverse Event ......................................................................... 62 
10.4. Time Period and Frequency for Collecting AE and SAE Information .......................... 62 
10.5. Method of Detecting AEs and SAEs ............................................................................ 63 
10.6. Assessing Severity of AEs and SAEs ......................................................................... 63 
10.7. Assessing Causalities of AEs and SAEs ..................................................................... 64 
10.8. Follow-up of (non-serious) AEs and Serious AEs ....................................................... 64 
10.9. Regulatory Reporting Requirements for SAEs ............................................................ 64 
11. 
Pregnancy Reporting .................................................................................................... 65 
12. 
Responsibilities ............................................................................................................. 65 
12.1. Principal Investigator Responsibilities ......................................................................... 65 
12.1.1. 
Good Clinical Practice ......................................................................................... 65 
12.1.2. 
Institutional Review Board/Independent Ethics Committee Approval .................. 66 
12.1.3. 
Informed Consent ................................................................................................ 66 


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12.1.4. 
Confidentiality ...................................................................................................... 66 
12.1.5. 
Study Files and Retention of Records ................................................................. 66 
12.1.6. 
Electronic Case Report Forms (eCRF) ................................................................ 68 
12.1.7. 
Drug Accountability.............................................................................................. 68 
12.1.8. 
Inspections .......................................................................................................... 68 
12.1.9. 
Protocol Compliance ........................................................................................... 68 
12.2. Sponsor Responsibilities ............................................................................................. 68 
12.2.1. 
Protocol Modifications ......................................................................................... 68 
12.2.2. 
Study Report and Publications ............................................................................ 69 
12.3. Joint Investigator/Sponsor Responsibilities ................................................................. 69 
12.3.1. 
Access to Information for Monitoring ................................................................... 69 
12.3.2. 
Access to Information for Auditing or Inspections ................................................ 69 
12.3.3. 
Study Discontinuation .......................................................................................... 69 
13. 
References ..................................................................................................................... 70 
14. 
Appendices .................................................................................................................... 73 
14.1. Appendix 1: Abbreviations and Trademarks ............................................................... 73 
14.2. Appendix 2: Liver Safety Required Actions and Follow up Assessments ................... 77 
14.3. Appendix 3: Summary of Changes for Protocol Amendments .................................... 79 
 
 
LIST OF TABLES 
Table 2-1: Predicted Gimsilumab Exposure and Exposure Margins after Gimsilumab 
400 mg IV Compared to Highest IV Dose Studied in Study MORAb-022- 
001 in Humans and the NOEL IV Dose Studied in Cynomolgus Monkeys .......... 23 
Table 4-1: Treatment Arms for KIN-1901-2001 ........................................................................... 28 
Table 6-1: Treatment Descriptions for KIN-1901-2001 ............................................................... 36 
Table 6-2: Randomization Schema for KIN-1901-2001 .............................................................. 37 
Table 7-1: Estimated Sample Requirements Per Subject .......................................................... 40 
Table 7-2: Schedule of Assessments ......................................................................................... 42 
Table 7-3: List of Clinical Laboratory Analyses ........................................................................... 51 
Table 14-1: Summary of Changes: Amendment 1 ...................................................................... 79 
Table 14-2: Summary of Changes: Amendment 2 ...................................................................... 97 
Table 14-3: Summary of Changes: Amendment 3 .................................................................... 103 
Table 14-4: Summary of Changes: Amendment 4 .................................................................... 108 


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LIST OF FIGURES 
Figure 2-1: 
Simulated Serum Gimsilumab PK Profile After Gimsilumab 400 mg IV 
Day 1 and 200 mg IV Day 8a ............................................................................... 24 
 
Figure 4-1: 
Study Schematic ................................................................................................. 27 
 
Figure 7-1: 
National Early Warning Score ............................................................................. 49 


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1. 
PROTOCOL SUMMARY FOR STUDY KIN-1901-2001 
Synopsis 
 
Study Rationale 
In December 2019, the city of Wuhan, China experienced an outbreak of 
coronavirus disease 2019 (COVID-19), caused by a novel coronavirus, 
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of 
March 2020, COVID-19 has become a global pandemic, and there are 
currently no approved agents available to treat coronaviruses [World 
Health Organization (WHO) COVID-19 Situation Report, 2020]. 
SARS-CoV-2 infection often induces an overactive immune response that 
causes significant lung damage, leading to acute respiratory distress 
syndrome (ARDS) and ultimately death. Granulocyte macrophage-colony 
stimulating factor (GM-CSF), a hematopoietic growth factor and 
immunomodulatory cytokine, is believed to be a key driver of cytokine 
storm and lung hyper-inflammation [Molfino, 2016; Sterner, 2019; Zhou, 
2020]. Targeting GM-CSF using an anti-GM-CSF antibody, gimsilumab 
(KIN-1901), represents a promising strategy to treat patients who have 
developed lung injury or ARDS secondary to COVID-19. 
Study Design 
Randomized, double-blind, placebo-controlled 
Study Objectives 
Primary Objective: 
• The primary objective is to evaluate the impact of intravenous (IV) 
treatment with gimsilumab on mortality in subjects with lung injury or 
ARDS secondary to COVID-19. 
Key Secondary Objectives: 
• To assess the effect of gimsilumab on ventilation requirements 
• To assess the effect of gimsilumab on overall duration of 
hospitalization 
Additional Secondary Objectives: 
• To assess the effect of gimsilumab on the need for Intensive Care Unit 
(ICU) level of care 
• To assess the effect of gimsilumab as measured by the National Early 
Warning Score (NEWS) 
• To assess the effect of gimsilumab as assessed by the Sequential 
Organ Failure Assessment (SOFA) score 
• To assess the effect of gimsilumab as measured by the 7-point ordinal 
scale 
• To assess the effect of gimsilumab on peripheral capillary oxygen 
saturation / fraction of inspired oxygen (SpO2/FiO2) 
• To assess the effect of gimsilumab on oxygenation requirements 
• To assess changes in on-treatment viral load 
• To assess the effect of gimsilumab on biomarkers of inflammation 
• To determine the pharmacokinetic (PK) properties of gimsilumab 
• To assess the immunogenicity of gimsilumab 
• To determine the safety and tolerability of gimsilumab 


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Exploratory Objectives: 
• To explore the effect of gimsilumab on serum cytokine concentrations 
and surfactant protein D (SP-D) 
• To explore the effect of gimsilumab on other measurements of lung 
injury that may be performed during standard care (e.g., Lung Injury 
Score [LIS], chest radiography, PaO2/FiO2 [P/F ratio], need for 
extracorporeal membrane oxygenation [ECMO]) 
• To explore the effect of gimsilumab on cardiac function (if measured) 
• To assess the effect of gimsilumab on renal function 
Study Population 
270 subjects (135 subjects per arm) who have a confirmed diagnosis of 
COVID-19 with clinical evidence of acute lung injury or ARDS 
Number of Planned 
Subjects 
270 total subjects are planned for this study. 
Arm 1 (Active drug): 135 subjects 
Arm 2 (Placebo): 135 subjects 
Study Treatments 
Gimsilumab 400 mg IV on Day 1 and 200 mg IV on Day 8, or matching 
placebo (saline solution) IV on Day 1 and on Day 8. The Day 8 dose will 
be omitted if the subject is discharged from the hospital or is no longer in 
need of supplemental oxygen or ventilatory support for >48 hours. 
Treatment and Study 
Duration 
This study will consist of a 2-week Treatment Period (last dose Day 8, if 
administered) and a 22-week Follow-up Period, for a total study duration 
of 24 weeks for each subject. 
Study Centers and 
Countries 
This study will be conducted at approximately 20 centers in the United 
States and potentially 6 centers in Mexico; other countries may be added, 
if needed. 


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Study Endpoint(s) 
Primary Endpoint: 
• 
Incidence of mortality by Day 43 
Key Secondary Endpoints: 
• 
Proportion of subjects who survived and were not requiring 
mechanical ventilation on Day 29 
• 
Mechanical ventilation-free days by Day 29 
• 
Time to hospital discharge by Day 43 
Additional Secondary Endpoints: 
• 
Incidence of mortality by Days 15, 22, 29, 85, and 169 
(End-of-Study [EoS]) 
• 
Proportion of subjects who survived and were not requiring 
mechanical ventilation on Days 15, 22, and 43. 
• 
Mechanical ventilation-free days for all subjects by Days 15, 22, 
and 43 
• 
ICU-free days for all subjects by Days 15, 22, 29, and 43. 
• 
Incidence of mechanical ventilation use for all subjects by Days 
15, 22, 29, and 43. 
• 
Incidence of ICU use for all subjects by Days 15, 22, 29, and 43 
• 
Time to death by Day 43 and Day 169 (EoS) 
• 
NEWS assessed daily while hospitalized 
• 
SOFA score, and each of the components, assessed daily while in 
the ICU 
• 
The percentage of subjects reporting each severity rating on the 
7-point ordinal scale, assessed daily while hospitalized and, if 
discharged from hospital, on Days 15, 22, 29, 36, 43, 85, and 169 
(assessed by phone) 
• 
Status on the 7-point ordinal scale, assessed daily while 
hospitalized and, if discharged from hospital, on Days 15, 22, 29, 
36, 43, 85, and 169 (assessed by phone) 
• 
Time to clinical improvement by 2 points on the 7-point ordinal 
scale 
• 
Change from Baseline in SpO2/FiO2, assessed daily while 
hospitalized 
• 
Incidence and duration of oxygen use during the study 
• 
Change from Baseline in viral load as measured by quantitative 
polymerase chain reaction (PCR) test on Days 2, 9, and day-of- 
discharge (DoD) 
• 
Change from Baseline in D-dimer, cardiac troponin I, lactate 
dehydrogenase (LDH), ferritin, and C-reactive protein (CRP) 
• 
Serum gimsilumab concentrations 
• 
Analysis of anti-gimsilumab antibodies (ADAs) 
Safety Endpoints: 
• 
Safety and tolerability, including assessment of clinical safety 
laboratory measurements, physical examinations, vital signs, 


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concomitant medications; cumulative incidence of adverse events 
(AEs), serious adverse events (SAEs), and severe AEs 
Exploratory Endpoints: 
• 
Change from Baseline in the cytokine panel and serum SP-D 
• 
Change from Baseline in LIS (if performed) 
• 
Change from Baseline in chest radiographic assessment (if 
performed) 
• 
Change from Baseline in P/F ratio, if performed 
• 
Incidence and duration of ECMO use 
• 
Change from Baseline in left ventricular ejection fraction (LVEF) 
(when measured) 
• Change from Baseline in estimated glomerular filtration rate 
(eGFR) [Modification of Diet in Renal Disease (MDRD) 
equation], assessed when central clinical safety laboratory 
measurements are collected during hospitalization 


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Inclusion Criteria 
An individual will be eligible for participation in this study only if all 
of the following inclusion criteria are met: 
1. Male or non-pregnant female age ≥18 years 
2. Subject (or legally authorized representative [LAR]) is able and 
willing to provide written or verbal informed consent, which includes 
compliance with study requirements and restrictions listed in the 
consent form. NOTE: If a subject or LAR must be consented verbally, 
the site must have a site policy for verbal consent and the consent must 
be clearly documented in the subject’s chart. 
3. Has documented laboratory-confirmed SARS-CoV-2 infection as 
determined by PCR or other approved clinical testing prior to 
randomization 
4. CRP ≥50 mg/L or serum ferritin ≥1,000 ng/mL. Results from CRP and 
ferritin tests performed within 8 days of randomization are acceptable 
for enrollment. 
5. Radiographic evidence of bilateral infiltrates. Acceptable imaging tests 
(chest X-ray, CT scans) done within 3 days of Day 1 can be used for 
inclusion. 
6. Subject has clinical evidence of lung injury [defined as (1) requiring 
supplemental oxygen ≥4L O2 to attempt to maintain ≥92% SpO2, or 
(2) P/F ratio ≤300 mmHg (can be imputed)], or meets clinical 
classification criteria for ARDS [ARDS Berlin Definition, 2012], 
secondary to COVID-19. 
7. Female subjects must agree to use an approved highly effective birth 
control (BC) method (<1% failure rate per year) throughout the study 
(until completion of the Day 85 Follow-up Visit), unless documented 
to have a reproductive status of non-childbearing potential or is 
postmenopausal: 
• 
Non-childbearing potential defined as pre-menopausal female with 
medical history of bilateral tubal ligation, bilateral oophorectomy 
(removal of the ovaries), or hysterectomy; hysteroscopic 
sterilization, 
• 
Postmenopausal defined as 12 months of spontaneous amenorrhea 
or with follicle stimulating hormone (FSH) confirmation. 
• 
Woman of childbearing potential (WCBP) who is already using an 
established method of highly effective contraception or agrees to 
use one of the allowed BC methods, for at least 28 days prior to 
the start of dosing (as determined by the Investigator Brochure or 
Investigator or designee) to sufficiently minimize the risk of 
pregnancy throughout study participation (until completion of the 
Day 85 Follow-up Visit). 
8. Males who are sexually active must agree to use one of the allowed 
BC methods. Male subjects must also agree to sufficiently minimize 
the risk of pregnancy throughout study participation (until completion 
of the Day 85 Follow-up Visit). 


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Exclusion Criteria 
1. Subject requires norepinephrine at a dose of >0.5 mcg/kg/min, or 
equivalent 
2. Subject has been intubated for >72 hours. Note: in the event of 
extubation and re-intubation, the calculation for the number of hours 
the subject has been intubated begins at the first intubation. 
3. Evidence of life-threatening dysrhythmia (e.g., ventricular tachycardia 
[VT], ventricular fibrillation [VF]), or cardiac arrest on presentation 
4. Evidence of new or preexisting decompensated heart failure. 
5. At the time of screening, subject is anticipated to require ECMO 
6. Absolute neutrophil count <1,000 per mm3 
7. Platelet count <50,000 per mm3 
8. History of known anti-GM-CSF autoantibodies (autoAb) or pulmonary 
alveolar proteinosis. Note: A negative anti-GM-CSF autoAb test result 
is not required at screening. 
9. Severe chronic respiratory disease (e.g., known chronic obstructive 
pulmonary disease [COPD], pulmonary arterial hypertension [PAH], 
idiopathic pulmonary fibrosis [IPF], interstitial lung disease [ILD]) 
requiring supplemental oxygen therapy or mechanical ventilation 
pre-hospitalization (e.g., prior to COVID-19 diagnosis) 
10. Known or suspected active and untreated tuberculosis (TB), human 
immunodeficiency virus (HIV), hepatitis B or C infection 
• 
Results of TB, hepatitis B and C, and HIV tests are not required 
prior to enrollment if there is no suspicion of active infection, as 
per KIN-1901 Guidance on Active Infections Testing. 
11. Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) 
>5 × upper limit of normal (ULN). 
12. eGFR <30 mL/min/1.73m2 (MDRD equation) or requiring 
hemofiltration or dialysis 
13. Use of any immunomodulatory biologic (e.g., anti-IL-1, anti-IL-6R, 
anti-TNF, inhibitors of complement signaling), cell therapies (e.g., 
mesenchymal stem cells), or small molecule Janus kinase [JAK] 
inhibitors within the past 7 days or within five half-lives (whichever is 
longer), or planned use of any of these agents from Screening until 
Day 43 of the study, unless approved by the Medical Monitor. The 
following will be allowed/disallowed: 
• 
Immunomodulatory biologics for COVID-19 treatment are 
excluded and should not be used until Day 43 unless discussed 
with the Medical Monitor. Other non-biologic immunomodulators 
(non-JAK inhibitors), e.g., medicines for previous transplantation, 
or disease modifying anti-rheumatic drugs (DMARDS), and have 
had a stable dose for ≥8 weeks are permitted. 
• 
Subjects who have been treated with convalescent plasma (CP) 
prior to enrollment are eligible if the subject continues to meet all 
inclusion criteria at screening. Ongoing therapy with CP is 
allowable if clinically indicated in the view of the treating 
physician or the Investigator. 
• 
The use of investigational anti-viral treatment (e.g., remdesivir) is 
allowed if the subject continues to meet all inclusion criteria at 
screening. 


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14. Ongoing chronic (≥4 weeks) use of corticosteroids >10 mg/day of 
prednisone or equivalent at the time of randomization. A corticosteroid 
dose that has been tapered to 10 mg or less within 14 days of 
randomization is also prohibited. 
15. Pregnancy and/or breast feeding 
16. Unable to receive invasive or non-invasive ventilatory support 
17. Moribund condition in the opinion of the clinical team 
Database Locks 
The study database will be locked when all subjects complete the Day 43 
Visit, discontinue from the study early, or meet the primary mortality 
endpoint. The second lock will occur when the last subject completes the 
Day 169 EoS visit. 
In addition, there will be 2 database extracts (soft locks) for interim 
analyses, the first of which will be conducted when 60 subjects have been 
treated and have completed through Day 15; the DMC will review the data 
for safety and futility and provide their recommendations. The second 
interim analysis will be conducted when 100 subjects have completed at 
least the Day 29 Visit for non-mortality endpoints and have the data for 
the endpoint of mortality (by Day 43). 


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Statistical Analyses 
Sample Size and Power 
There will be 270 subjects with confirmed COVID-19 and clinical 
evidence of lung injury or ARDS (135 subjects per arm) with 1:1 
randomization. 
The comparisons between the treatment arms will have approximately 
80% power and alpha level 0.05 (two-sided) to demonstrate the significant 
reductions (15% versus 30%) of the primary endpoint between 
gimsilumab versus placebo. 
The study will enroll at least 40%, but no more than 60%, of total subjects 
in each of the two categories of clinical status : ([lung injury/mild ARDS] 
or [moderate/severe ARDS]) at Baseline, which will be used as the 
stratified factor in the randomization. 
Randomization 
The central stratified randomization will be used to assign subjects into 
one of the study treatment arms with an equal randomization ratio (1:1) 
with the stratification factors of subject’s clinical status at Baseline ([lung 
injury/mild ARDS] or [moderate/severe ARDS]) and country. 
Key Analysis Sets 
• The Intent-to-Treat (ITT) Population will include all randomized 
subjects who receive any amount of study drug. The ITT subjects will 
be analyzed according to randomized treatment, irrespective of 
whether or not they have prematurely discontinued. Subjects who 
withdraw from treatment and/or the study early will be followed for 
Day 43 all-cause mortality. All efficacy analyses will be performed 
using the ITT Population. 
• The Safety Population (SP) will include all randomized subjects who 
receive any amount of study drug. The SP will be analyzed according 
to the treatment received. This set will be used for the safety analyses. 
• The Per-Protocol (PP) Population will include all subjects in the ITT 
Population who complete the Day 43 Visit with no major protocol 
violations. The PP Population will be used for supportive analyses of 
the efficacy measurements. 


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Statistical Methods in General 
All statistical analyses will be conducted using SAS, Version 13.1 or later. 
Baseline characteristics will be summarized by treatment arm. For 
continuous measures the mean and standard deviation (SD) will be 
summarized. Categorical variables will be described by the proportion in 
each category. 
Efficacy Analyses 
The primary analysis of the efficacy endpoint (Mortality by Day 43) will 
be performed by using logistic regression [Ge, 2011] with treatment, 
country, and subject’s clinical status at Baseline ([lung injury/mild ARDS] 
or [moderate/severe ARDS]) as covariates. The subjects who meet the 
criteria of endpoint will be summarized by the numbers and percentages of 
the incidence, with odds ratio and its 95% confidence interval (CI) 
presented for gimsilumab versus placebo, and p-value. 
The secondary analysis of the primary endpoint will be conducted by the 
Cox Proportional hazard model on the time to death. The median of the 
time to event from Kaplan-Meier curves will be presented for each 
treatment, and the hazard ratio of gimsilumab versus placebo will be 
presented with 95% CI, and p-value. 
Adjustment of Multiple Comparisons and Interim Analysis 
The interim analysis will be conducted when 60 subjects have been treated 
and have completed through Day 15; the DMC will review the data for 
safety and futility and provide their recommendations. 
The second interim analysis will be conducted when 100 subjects have 
completed at least the Day 29 Visit for non-mortality endpoints and have 
the data for the endpoint of mortality by Day 43. The objectives of the 
second interim analysis will be to stop the study by superiority, futility, or 
perform the sample size re-estimation. For controlling overall two-sided 
alpha of 0.05 overall for the final analysis on the primary endpoint of 
Mortality Day 43, 0.001 of the alpha will be used for the superiority 
comparison during the second interim analysis, and 0.049 will be used for 
the final analysis. The weighted average of two summary measures by 
Cui L, Hung HM, Wang [Cui, 1999] will be used, one based on the data 
collected in the interim analysis, and the other based on the data collected 
after the interim. 
Analyses in General 
All the continuous variables, including the changes from Baseline, will be 
summarized by the treatment with the means, SD, medians and the ranges. 
The Mixed Model with Repeated Measurements (MMRM) /Analysis of 
Covariance (ANCOVA) model with the treatment, country, subject’s 
clinical status at Baseline ([lung injury/mild ARDS] or [moderate/severe 
ARDS]), and visit as the model term, and Baseline value as the covariate 
will be used to test for the significance of the treatment difference. The 
least square means, standard errors, 95% CIs and p-values will be 
presented. 


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All the categorical variables will be summarized by the treatment with the 
numbers and percentages of the subjects, and the treatment difference will 
be tested by using CMH test stratified by 1) country and 2) subject’s 
clinical status at Baseline ([lung injury/mild ARDS] or [moderate/severe 
ARDS]). 
The time to event endpoints will be analyzed by using the Cox 
Proportional Hazard model with the treatment, country, and subject’s 
clinical status at Baseline ([lung injury/mild ARDS] or [moderate/severe 
ARDS]) as the model term. The hazard ratio of gimsilumab versus 
placebo will be presented with 95% CI and p-value from the model. The 
Kaplan-Meier curves of the time to events will be presented for treatments 
on each endpoint. 
Handling of Missing Data 
Sensitivity analyses will be performed for the primary and key secondary 
endpoints by using multiple imputations for the missing data: 
• 
Tipping-point multiple imputation analysis 
Missing data will be imputed for Mortality by Day 43 with all possible 
combinations of Death or Survival in the two arms. The combination 
which alters the conclusion will be defined as the tipping point for 
evaluation on the robustness of the results. 
• 
Imputation differentiating the reasons of missing data from the 
early drop out 
The reasons of the lost to follow-up, SAEs/AEs, and the use of rescue 
medications will be identified, and the percentage of these subjects will be 
summarized by treatment. The data for informative censoring, such as the 
unfavorable or worst outcome, can be used to impute the missing data. 
More details will be pre-specified in the statistical analysis plan (SAP). 
Safety Analyses 
Safety will be assessed based on the SP for AEs, laboratory parameters, 
physical examination, vital signs, and clinical chemistries throughout the 
duration of the study. The safety analyses will include descriptive 
summaries by treatment arm of AEs. The number and percentage of 
participants reporting AEs and SAEs will be presented. Adverse events 
will be categorized by system organ class (SOC) and preferred term (PT) 
and summarized by the number of participants (and percentage) with at 
least 1 event, and the number of events. Adverse events will also be 
summarized by seriousness, grade, and study drug relationship for all 
participants. The continuous variables, including the changes from 
Baseline, will be summarized by descriptive statistics: mean, SD, and the 
range. The categorical variables, such as normal/abnormal will be 
summarized by the numbers and percentages at each visit, and the shift 
table from Baseline to each visit will be presented. 
Timing of Analyses with All Subjects 
The first unblinded analyses will be conducted when the last subject 
completes the Day 43 Visit, discontinues from the study early, or meets 


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the primary mortality endpoint (by Day 43). The second unblinded 
analyses will be conducted when the last subject completes the Day 169 
Follow-up Visit (EoS). 
The DMC will be responsible for closely reviewing the safety data from 
the unblinded interim analysis and for providing their recommendations. 
The detailed objectives and procedures of the interim analyses will be 
described in the DMC Charter. 
Pharmacokinetic, Biomarker, and Immunogenicity 
Data will be summarized by treatment arm. 
Statistical Analysis Plan (SAP) 
A detailed (revised) SAP will be signed and submitted to the agencies 
prior to the interim analysis of 100 subjects. 


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2. 
INTRODUCTION 
 
2.1. 
Study Rationale 
 
2.1.1. 
COVID-19 Background, Clinical Course, and Immunopathogenesis 
 
In December 2019, the city of Wuhan, China experienced an outbreak of coronavirus disease 
2019 (COVID-19), caused by a novel coronavirus, severe acute respiratory syndrome 
coronavirus 2 (SARS-CoV-2). As of March 2020, COVID-19 has become a global pandemic 
[World Health Organization (WHO) COVID-19 Situation Report, 2020], and there are currently 
no approved agents available to treat coronaviruses. 
Although most infections are mild, approximately 20% of COVID-19 patients experience severe 
viral pneumonia that can progress to acute respiratory distress syndrome (ARDS) and death 
[Wu, 2019]. Clinical features of serious cases of COVID-19 resemble infections from severe 
acute respiratory syndrome coronavirus (SARS-CoV), which caused an epidemic in 2002-2003 
[Huang, 2020]. Immunopathological research into SARS-CoV defined three phases of disease: 
(1) fever, cough, and other systemic symptoms accompanied by an increase in viral load, (2) 
severe pneumonia that persists, despite a decline in viral load, due to a hyperactive immune 
response consisting of cytokine storm and significant macrophage/neutrophil lung infiltration, 
(3) pulmonary destruction and death [Lam, 2004; Channappanavar, 2017]. Emerging evidence 
suggests that cytokine storm and aberrant lung inflammation are similarly key features 
contributing to clinical worsening in COVID-19 [Huang, 2020; COVID-19 Investigation Team, 
2020; Kristas, 2020; Mehta, 2020]. Specifically, high concentrations of proinflammatory 
cytokines were found in COVID-19 patients, particularly those who were severely ill 
[Huang, 2020]. The observed cytokine signature was indicative of a T-helper-1 (Th1) cell 
inflammatory response [Huang, 2020], and activation of Th1 cells was found to increase as 
patients progressed to more severe disease [Zhou, 2020]. Analyses of bronchoalveolar lavage 
fluid revealed that severe COVID-19 patients also experienced overwhelming lung infiltration by 
highly inflammatory monocyte-derived macrophages [Liao, 2020]. 
 
2.1.2. 
Rationale for Targeting GM-CSF in COVID-19 
 
Granulocyte macrophage-colony-stimulating factor (GM-CSF), an important hematopoietic 
growth factor and immunomodulatory cytokine, is believed to be a key mediator of cytokine 
storm [Ishii 2016; Sterner, 2019; Turgues, 2018] and to contribute to SARS-CoV-induced ARDS 
[Channappanavar, 2016; Channappanavar, 2017]. GM-CSF was has been identified as a cytokine 
that is upregulated in the serum of COVID-19 patients [Huang, 2020]. Soon after, Zhou and 
colleagues reported that SARS-CoV-2 infection induced activation of immune cells that secreted 
large amounts of GM-CSF [Zhou, 2020]. The percentages of GM-CSF-expressing CD4+ T cells 
(Th1), CD8+ T cells, NK cells, and B cells were significantly higher in the blood of severe 
Intensive Care Unit (ICU)-admitted patients compared with healthy controls. This pan- 
lymphocyte observation was not seen when assessing IL-6 and TNF-α. Further, a 
GM-CSF+IFNγ+CD4+ T cell signature, which is associated with autoimmune encephalomyelitis 
[Stienne, 2020] and arthritis [Piper, 2014], was found in peripheral blood of ICU patients. These 
T cell responses were accompanied by significant upregulation of CD14+CD16+ inflammatory 


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monocytes, and a high percentage of monocytes secreted GM-CSF and IL-6, consistent with 
cytokine release syndrome (CRS) [Barrett, 2016]. The reported immunological changes appeared 
to be more pronounced in ICU-admitted patients versus non-ICU patients. Taken together, these 
results suggest that dysregulated GM-CSF expression from Th1 cells licenses pathogenic 
myeloid cell infiltration into the lung [Zhou, 2020]. These findings are consistent with the 
mechanisms of action of GM-CSF observed in other inflammatory lung conditions [Puljic, 2007; 
Willart, 2012; Shiomi, 2014; Molfino, 2016; Sheih, 2017; Kwon, 2018; Nobs, 2019] and in an 
animal model of SARS-CoV infection [Channappanavar, 2016]. Indeed, administration of 
recombinant GM-CSF (Leukine®) in a clinical setting can induce respiratory symptoms and even 
acute lung injury due to excessive myeloid cell mobilization [Kudlak, 2013]. 
This evidence suggests that GM-CSF stands as a key contributor to and regulator of the cytokine 
storm that characterizes progression to respiratory failure in COVID-19. Therefore, targeting 
GM-CSF represents a promising strategy for curbing immunopathological lung damage while 
buying time for viral clearance. This immunomodulatory strategy is supported by current 
guidelines from the China National Health Commission stating that glucocorticoids, intravenous 
immunoglobulin, and the anti-IL-6R antibody tocilizumab, which is U.S. Food and Drug 
Administration (FDA)-approved for CAR-T-related CRS, may be used to treat severely ill 
COVID-19 patients [Novel Coronavirus Pneumonia Diagnosis and Treatment Plan, 2020]. 
GM-CSF is thought to act upstream and stimulate the expression of IL-6 and other pro- 
inflammatory cytokines during CRS, making a GM-CSF-targeting strategy potentially more 
advantageous for dampening overactive immune responses than other cytokine-targeting 
approaches [Ishii, 2016; Barrett, 2016]. Based on significant preclinical evidence in animal 
models [Sterner, 2019; Tugues, 2018] a Phase 1/2 clinical trial is ongoing to assess the benefit of 
an anti-GM-CSF antibody (lenzilumab) in CAR-T-related CRS, and a Phase 2/3 trial of 
lenzilumab is planned for the treatment of CRS in graft versus host disease [Humanigen, Inc., 
2020]. Interestingly, a randomized, placebo-controlled phase 2 trial demonstrated statistically 
significant efficacy of lenzilumab on pulmonary function in eosinophilic asthmatics, consistent 
with the overall hypothesis that GM-CSF is a critical mediator of lung hyper-inflammation 
[Molfino, 2016]. 
Ultimately, GM-CSF’s master regulatory effect on cytokine storm and lung inflammation 
warrants the clinical investigation of an anti-GM-CSF antibody, gimsilumab (KIN-1901), in 
patients with lung injury or ARDS secondary to COVID-19. Gimsilumab administered 
intravenously or subcutaneously was shown to be well-tolerated in phase 1 clinical trials in 
healthy volunteers and rheumatoid arthritis patients (Studies MORAb-022-001 and 
KIN-1901-1001). Over 1,000 patients have been administered anti-GM-CSF(R) antibodies in 
clinical trials, with acceptable safety profiles seen to date [Hamilton, 2020]. 
 
2.2. 
Dose Rationale 
Gimsilumab will be administered intravenously (IV) on 2 occasions, 400 mg on Day 1 and 
200 mg on Day 8. 
A Phase 1 first-in-man study (MORAB-022-001) was conducted to assess safety, tolerability, 
pharmacokinetics (PK), and pharmacodynamics (PD) of single-dose IV gimsilumab in healthy 
subjects and subjects with rheumatoid arthritis (RA) [Gimsilumab Investigator Brochure, current 
edition]. Doses ranged from 0.0085 to 10 mg/kg in that study, with the highest doses (0.36 mg/kg 


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to 10 mg/kg) administered to subjects with RA. Study MORAB-022-001 showed the PK were 
dose-proportional over the entire dose range, with no differences noted between healthy subjects 
and subjects with RA. Although AEs (headache, nasopharyngitis, flu-like symptoms) were 
encountered more frequently in the gimsilumab group, they were graded mild to moderate and 
were not dose-related. 
Subcutaneous administration of gimsilumab was evaluated in ongoing study KIN-1901-1001. 
Single- and repeat-dose (once weekly for 4 doses) gimsilumab was administered to healthy 
volunteers to evaluate safety and pharmacokinetics. Based on a blinded safety data review on 
26 Feb 2020, gimsilumab was well-tolerated with no serious adverse events (SAEs), the majority 
AEs (67%) were injection site reactions (erythema, tenderness, bruising) [Gimsilumab 
Investigator Brochure, current edition]. 
GM-CSF stimulates increased levels of CD11b on neutrophils, thus inhibition of GM-CSF 
signaling can be measured through suppression of CD11b stimulation index [Sakagami, 2010; 
Nadicksbernd, 2013]. PD measurements with ex vivo stimulation of CD11b from study MORAb- 
022-001 suggested IV doses as low as 0.7 mg/kg caused suppression of CD11b expression, 
demonstrating pharmacologic activity. Observed serum concentrations from the gimsilumab 
first-in-human study suggested serum concentrations of ~20 µg/mL were associated with an 
ACR20 response in subjects with RA and the IC90 determined from the CD11b stimulation 
assay was 25 µg/mL [Gimsilumab Investigator Brochure, current edition]. As there is no 
nonclinical data at this time that can further inform the expected efficacious dose range for 
gimsilumab in the treatment of ARDS, a target trough serum concentration of 20 µg/mL was 
selected for this study. The intent is to maintain a trough concentration above ~20 µg/mL in the 
majority of subjects for the entire 2-week dosing period to maximize the potential to bind 
excessive levels of GM-CSF during ARDS. 
A population PK model of IV gimsilumab was developed from the IV first-in-human study. 
Based on this model, simulations were conducted to a select an appropriate dose regimen. While 
the prior study using IV gimsilumab utilized mg/kg dosing, a ‘flat dose’ regimen (not body 
weight adjusted) was selected for this study to simplify administration in this setting. Simulations 
accounted for a range in subject body weight to select an appropriate flat dose. Using this model, 
a dose of 400 mg on Day 1 results in a median trough serum concentration of 29 µg/mL on Day 
8. Based on the expected variability in exposure and range in subject body weight, the serum 
trough concentration at the lower bound of the 80% prediction interval (i.e., the 10th percentile) 
is expected to be ~20 µg/mL (Figure 2-1), i.e., 90% of subjects are expected to achieve serum 
concentrations above the target. A second dose of gimsilumab 200 mg on Day 8 maintains the 
trough concentration at these levels for an additional week. Based on the duration of ICU time in 
both survivors and non-survivors from a Chinese cohort of ~7 days [Zhou, 2020], two doses, i.e., 
a 14-day treatment period, was considered appropriate for this study. If subjects are discharged 
from the hospital or are no longer in need of supplemental oxygen or ventilatory support for 
>48 hours, the planned Day 8 dose will be omitted. 
The predicted exposure after gimsilumab 400 mg IV on Day 1 (the highest exposure expected 
during the study) is approximately half that observed at 10 mg/kg IV in subjects with RA (Table 
2-1). The expected Cmax at the 90th percentile is also expected to be less than the geometric mean 
Cmax observed previously at 10 mg/kg IV. In addition, the predicted exposure margins after 
400 mg IV compared to the monkey 26-week IV toxicology study is presented in Table 2-1. The 
no-observed-effect level (NOEL) in the monkey was 200 mg/kg IV once weekly; the NOEL was 


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the highest dose tested. The exposures observed in monkeys were at least 40× greater than those 
expected in the current study. Thus, given the observed safety profile and the pharmacologic 
activity at the expected exposures in the current study, gimsilumab 400 mg Day 1 and 200 mg 
Day 8 was selected for the present study. 
Gimsilumab vials are to be diluted in 0.9% saline, the resultant concentration 
is 
similar or less than those demonstrated to be safe in monkey IV toxicology studies. Gimsilumab 
is to be infused over a 
resulting in a rate no higher than 
This rate is similar to the highest rate previously administered to subjects with RA, that was well 
tolerated. 
 
Table 2-1: Predicted Gimsilumab Exposure and Exposure Margins after Gimsilumab 
400 mg IV Compared to Highest IV Dose Studied in Study MORAb-022-001 in 
Humans and the NOEL IV Dose Studied in Cynomolgus Monkeys 
 
Gimsilumab 
Dose 
Median Predicted 
Gimsilumab Exposure 
Predicted Exposure Margin 
(X-fold) Compared to RA 
Patients Gimsilumab 10 
mg/kg IVa 
Predicted Exposure Margin 
(X-fold) Compared to 
Cynomolgus Monkey 200 
mg/kg/week, IVb 
Cmax 
AUC 
Cmax 
AUC 
Cmax 
AUC 
400 mg IV 
128 
µg/mL 
17,860 
µg/mL 
2.1 
2.0 
92 
41 
a. 
Median predicted exposure after planned dose divided by observed geometric mean at 10 mg/kg IV in RA patients 
(Cmax = 267 µg/mL; AUC0-∞ = 35,100 µg.h/mL) 
b. 
Median predicted exposure after planned dose divided by observed mean at 200 mg/kg IV in male and female monkeys at 
Day 176 (gender averaged Cmax = 11,800 µg/mL; AUC0-∞ = 731,000 µg.h/mL) 


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Figure 2-1:
Simulated Serum Gimsilumab PK Profile After Gimsilumab 400 mg IV Day 1
and 200 mg IV Day 8a
a.
Median (line) and 10th and 90th percentiles (shaded area); 20 µg/mL target concentration (dashed)
2.3.
Benefit/Risk Assessment
Summaries of findings from both non-clinical and clinical studies conducted to date can be found 
in the Gimsilumab Investigator Brochure, current edition.
Gimsilumab is a new molecular entity. There are limited data on the therapeutic effect of
gimsilumab in humans, signals of clinical benefit and pharmacodynamic effects were observed 
in subjects with RA treated with single doses of IV gimsilumab ≥0.7 mg/kg and provide a
gimsilumab dose range that has the potential to show clinical benefit in subjects with lung injury 
and ARDS secondary to COVID-19. In healthy subjects, the most frequently reported AE was 
headache. Other reported AEs included nasopharyngitis and flu-like symptoms in subjects 
receiving gimsilumab. For subjects with RA, no AE was reported by more than 1 subject. One 
subject with RA who received gimsilumab 3 mg/kg experienced a SAE of follicular neoplasia of
thyroid/thyroid neoplasm which was considered by the investigator to be mild in severity and not 
related to test article.


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3. 
OBJECTIVES AND ENDPOINTS 
 
OBJECTIVES 
ENDPOINTS 
Primary 
• The primary objective is to evaluate the impact of 
intravenous (IV) treatment with gimsilumab on 
mortality in subjects with lung injury or ARDS 
secondary to COVID-19. 
• Incidence of mortality by Day 43 
Secondary 
Key secondary objectives include the following: 
• 
To assess the effect of gimsilumab on ventilation 
requirements 
• 
To assess the effect of gimsilumab on overall 
duration of hospitalization 
Additional secondary objectives include the following: 
• 
To assess the effect of gimsilumab on the need for 
Intensive Care Unit (ICU) level of care 
• 
To assess the effect of gimsilumab as measured by 
the National Early Warning Score (NEWS) 
• 
To assess the effect of gimsilumab as assessed by 
the Sequential Organ Failure Assessment (SOFA) 
score 
• 
To assess the effect of gimsilumab as measured by 
the 7-point ordinal scale 
• 
To assess the effect of gimsilumab on peripheral 
capillary oxygen saturation / fraction of inspired 
oxygen (SpO2/FiO2) 
• 
To assess the effect of gimsilumab on oxygenation 
requirements 
• 
To assess changes in on-treatment viral load 
• 
To assess the effect of gimsilumab on biomarkers of 
inflammation 
• 
To determine the pharmacokinetic (PK) properties of 
gimsilumab 
• 
To assess the immunogenicity of gimsilumab 
• 
To determine the safety and tolerability of gimsilumab 
Key secondary endpoints include the following: 
• 
Proportion of subjects who survived and were not 
requiring mechanical ventilation on Day 29 
• 
Mechanical ventilation-free days by Day 29 
• 
Time to hospital discharge by Day 43 
Additional secondary endpoints include the following: 
• 
Incidence of mortality by Days 15, 22, 29, 85, and 
169 (End-of-Study [EoS]) 
• 
Proportion of subjects who survived and were not 
requiring mechanical ventilation on Days 15, 22, 
and 43 
• 
Mechanical ventilation-free days for all subjects by 
Days 15, 22, and 43 
• 
ICU-free days for all subjects by Days 15, 22, 29, and 
43 
• 
Incidence of mechanical ventilation use for all 
subjects by Days 15, 22, 29, and 43 
• 
Incidence of ICU use for all subjects by Days 15, 22, 
29, and 43 
• 
Time to death by Day 43 and Day 169 (EoS) 
• 
NEWS assessed daily while hospitalized 
• 
SOFA score, and each of the components, assessed 
daily while in the ICU 
• 
The percentage of subjects reporting each severity 
rating on the 7-point ordinal scale, assessed daily 
while hospitalized and, if discharged from hospital, on 
Days 15, 22, 29, 36, 43, 85, and 169 (assessed by 
phone) 
• 
Status on the 7-point ordinal scale, assessed daily 
while hospitalized and, if discharged from hospital, on 
Days 15, 22, 29, 36, 43, 85, and 169 (assessed by 
phone) 
• 
Time to clinical improvement by 2 points on the 
7-point ordinal scale 
• 
Change from Baseline in SpO2/FiO2, assessed daily 
while hospitalized 
• 
Incidence and duration of oxygen use during the 
study 


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OBJECTIVES 
ENDPOINTS 
• 
Change from Baseline in viral load as measured by 
quantitative polymerase chain reaction (PCR) test on 
Days 2, 9, and day-of-discharge (DoD) 
• 
Change from Baseline in D-dimer, cardiac troponin I, 
lactate dehydrogenase (LDH), ferritin, and C-reactive 
protein (CRP) 
• 
Serum gimsilumab concentrations 
• 
Analysis of anti-gimsilumab antibodies (ADAs) 
Safety endpoints: 
• 
Safety and tolerability, including assessment of 
clinical safety laboratory measurements, physical 
examinations, vital signs, concomitant medications; 
cumulative incidence of adverse events (AEs), 
serious adverse events (SAEs), and severe AEs 
Exploratory 
Exploratory objectives include the following: 
• 
To explore the effect of gimsilumab on serum 
cytokine concentrations and surfactant protein D 
(SP-D) 
• 
To explore the effect of gimsilumab on other 
measurements of lung injury that may be performed 
during standard care (e.g., Lung Injury Score [LIS], 
chest radiography, PaO2/FiO2 [P/F ratio], need for 
extracorporeal membrane oxygenation [ECMO]) 
• 
To explore the effect of gimsilumab on cardiac 
function (if measured) 
• 
To assess the effect of gimsilumab on renal function 
Exploratory endpoints include the following: 
• 
Change from Baseline in the cytokine panel and 
serum SP-D 
• 
Change from Baseline in LIS (if performed) 
• 
Change from Baseline in chest radiographic 
assessment (if performed) 
• 
Change from Baseline in P/F ratio, if performed 
• 
Incidence and duration of ECMO use 
• 
Change from Baseline in left ventricular ejection 
fraction (LVEF) (when measured) 
• 
Change from Baseline in eGFR [Modification of Diet 
in Renal Disease (MDRD) equation], assessed when 
central clinical safety laboratory measurements are 
collected during hospitalization 


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4. 
INVESTIGATIONAL PLAN 
 
4.1. 
Overall Study Design 
This is a randomized, adaptive, double-blind, placebo-controlled study in male and/or female 
subjects who are at risk of developing, or have developed, ARDS consequent to moderate to 
severe COVID-19. 
This study will include subjects with moderate-to-severe disease. There will be 2 treatment arms, 
one receiving blinded gimsilumab, and one receiving blinded placebo. 
Efficacy, safety, tolerability, PK, and PD of gimsilumab will be assessed in hospitalized adult 
subjects diagnosed with COVID-19. 
Randomization will be stratified by country and subject’s clinical status at Baseline: 
• Lung injury/mild ARDS 
• Moderate/severe ARDS 
Clinical classification criteria are defined in Section 9.1. 
 
A schematic of the study design is presented in Figure 4-1. Subjects will be assessed daily while 
hospitalized. Follow-up assessments are planned through Week 24, for a total study duration 
post-randomization of approximately 169 days (24 weeks). Follow-up visits at Days 15, 22, 29, 
36, 43, 85, and 169 will be performed by phone if the subject has been discharged from the 
hospital. All subjects will undergo a series of efficacy, safety, and laboratory assessments as 
detailed in the Schedule of Assessments, Table 7-2. 
 
Figure 4-1: 
Study Schematic 
 
ARDS = acute respiratory distress syndrome; CRP = C-reactive protein; EoS = End of Study; IV = intravenous; ICU = 
Intensive Care Unit; NEWS = National Early Warning Score; SOFA = Sequential Organ Failure Assessment 


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4.2. 
Scientific Rationale for Study Design 
COVID-19 is a newly emerging disease with a clinical spectrum that ranges from asymptomatic 
to severe and potentially lethal. The variability between clinical courses of different individuals 
may make uncontrolled data highly unreliable. Further, the immunopathogenesis of COVID-19 
is currently not well understood, and thus the risk-benefit of immunomodulatory agents in 
COVID-19 has not been established. It is difficult to predict whether altering the immune 
response during an acute infection will have a harmful effect via prevention of viral clearance or 
a beneficial effect via dampening of overactive inflammation. For these reasons, this study will 
be prospective, randomized, double-blinded, and placebo-controlled to minimize bias. 
Preliminary evidence suggests that major deterioration, including progression to lung injury or 
ARDS, occurs within the first 1 to 2 weeks of hospitalization, warranting the 2-week treatment 
period chosen for this study [Huang, 2020; Zhou, 2020]. 
 
The target patient population, patients with lung injury or ARDS secondary to COVID-19, was 
selected based on the putative mechanism of action of the anti-GM-CSF approach in this disease. 
Severely ill COVID-19 patients have significant inflammatory macrophage infiltration into the 
damaged lung as well as cytokine storm syndrome [Liao, 2020; Mehta, 2020]. In inflammatory 
pulmonary conditions, GM-CSF acts to mobilize bone marrow progenitor cells to the lung and 
differentiate them into inflammatory myeloid cells [Kudlak, 2013; Molfino, 2016]. During 
cytokine storm, GM-CSF is thought to induce and perpetuate a “positive feedback” loop with 
other pro-inflammatory cytokines, such as IL-1β, TNF-α, and IL-6, thereby contributing to 
immunopathological consequences [Tugues, 2018; Sterner, 2019; Hamilton, 2020]. Taken 
together, targeting GM-CSF presents an opportunity to both block the damaging macrophage 
lung infiltration and quell the hyper-inflammation characteristic of this particular stage of 
COVID-19. 
 
4.3. 
Treatment Arms and Duration 
Each subject will participate for approximately 24 weeks, with a 2-week Treatment Period (last 
dose on Day 8) and a 22-week Follow-up Period. A summary of the treatment arms is presented 
in Table 4-1. 
 
Table 4-1: Treatment Arms for KIN-1901-2001 
 
Arm 
Randomized Treatment and Population 
N 
Arm 1 
Gimsilumab (400 mg) as a single IV infusion on Day 1 followed by a single 200 mg IV 
infusion on Day 8 
135 
Arm 2 
Placebo (0.9% saline solution) IV infusion on Day 1 and Day 8a 
135 
a. 
The Day 8 dose will be omitted if the subject is discharged from the hospital or is no longer in need of supplemental 
oxygen or ventilatory support for >48 hours. 


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5. 
SUBJECT POPULATION 
 
5.1. 
Type and Number of Subjects 
A sufficient number of subjects will be enrolled to achieve approximately 270 evaluable subjects 
total, with 135 subjects per treatment arm. 
In order to manage the total study enrollment, the Sponsor may suspend screening and/or 
enrolment at any site or study-wide at any time. 
Deviations from inclusion and exclusion criteria are not allowed because they can potentially 
jeopardize the scientific integrity of the study, regulatory acceptability, or subject safety; 
therefore, adherence to the criteria as specified in the protocol is essential. 
 
5.2. 
Inclusion Criteria 
An individual will be eligible for inclusion in this study only if all the following criteria are met. 
1. Male or non-pregnant female age ≥18 years 
2. Subject (or legally authorized representative [LAR]) is able and willing to provide written 
or verbal informed consent, which includes compliance with study requirements and 
restrictions listed in the consent form. NOTE: If a subject or LAR must be consented 
verbally, the site must have a site policy for verbal consent and the consent must be 
clearly documented in the subject’s chart. 
3. Has documented laboratory-confirmed SARS-CoV-2 infection as determined by PCR or 
other approved clinical testing prior to randomization 
4. C-reactive protein ≥50 mg/L or serum ferritin ≥1000 ng/mL. Results from CRP and 
ferritin tests performed within 8 days of randomization are acceptable for enrollment. 
5. Radiographic evidence of bilateral infiltrates. Acceptable imaging tests (chest X-ray, CT 
scans) done within 3 days of Day 1 can be used for inclusion. 
6. Subject has clinical evidence of lung injury [defined as (1) requiring supplemental 
oxygen ≥4L O2 to attempt to maintain ≥92% SpO2, or (2) PaO2/FiO2 ≤300 mmHg (can be 
imputed)] or meets clinical classification criteria for ARDS [ARDS Berlin Definition, 
2012], secondary to COVID-19 
7. Female subjects must agree to use an approved highly effective birth control (BC) 
method (<1% failure rate per year) throughout the study (until completion of the Day 85 
Follow-up Visit), unless documented to have a reproductive status of non-childbearing 
potential or is postmenopausal: 
• Non-childbearing potential defined as pre-menopausal female with medical 
history of bilateral tubal ligation, bilateral oophorectomy (removal of the ovaries), 
or hysterectomy; hysteroscopic sterilization, 
• Postmenopausal defined as 12 months of spontaneous amenorrhea or with follicle 
stimulating hormone (FSH) confirmation. 
• Woman of childbearing potential (WCBP) who is already using an established 
method of highly effective contraception or agrees to use one of the allowed BC 


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methods listed in Section 5.6.1, for at least 28 days prior to the start of dosing (as 
determined by the Investigator Brochure or Investigator or designee) to 
sufficiently minimize the risk of pregnancy throughout study participation (until 
completion of the Day 85 Follow-up Visit). 
8. Males who are sexually active must agree to use one of the allowed BC methods listed in 
Section 5.6.1. Male subjects must also agree to sufficiently minimize the risk of 
pregnancy throughout study participation (until completion of the Day 85 Follow-up 
Visit). 
 
5.3. 
Exclusion Criteria 
An individual will NOT be eligible for inclusion in this study if any of the following criteria 
apply. 
1. Subject requires norepinephrine at a dose of >0.5 mcg/kg/min, or equivalent 
2. Subject has been intubated for >72 hours. Note: in the event of extubation and 
re-intubation, the calculation for the number of hours the subject has been intubated 
begins at the first intubation. 
3. Evidence of life-threatening dysrhythmia (e.g., ventricular tachycardia [VT], ventricular 
fibrillation [VF]) or cardiac arrest on presentation 
4. Evidence of new or preexisting decompensated heart failure 
5. At the time of screening, subject is anticipated to require ECMO 
6. Absolute neutrophil count <1,000 per mm3 
7. Platelet count <50,000 per mm3 
8. History of known anti-GM-CSF autoAb or pulmonary alveolar proteinosis. Note: A 
negative anti-GM-CSF autoAb test result is not required at screening. 
9. Severe chronic respiratory disease (e.g., known chronic obstructive pulmonary disease 
[COPD], pulmonary arterial hypertension [PAH], idiopathic pulmonary fibrosis [IPF], 
interstitial lung disease [ILD]) requiring supplemental oxygen therapy or mechanical 
ventilation pre-hospitalization (e.g., prior to COVID-19 diagnosis) 
10. Known or suspected active and untreated tuberculosis (TB), human immunodeficiency 
virus (HIV), hepatitis B or C infection. 
• Results of TB, hepatitis B and C, and HIV tests are not required prior to enrollment if 
there is no suspicion of active infection, as per KIN-1901 Guidance on Active 
Infections Testing. 
11. Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) >5 × upper limit 
of normal (ULN) 
12. eGFR <30 mL/min/1.73m2 (MDRD equation) or requiring hemofiltration or dialysis 
13. Use of any immunomodulatory biologic (e.g., anti-IL-1, anti-IL-6R, anti-TNF, inhibitors 
of complement signaling), cell therapies (e.g., mesenchymal stem cells), or small 
molecule JAK inhibitors within the past 7 days or within five half-lives (whichever is 
longer), or planned use of any of these agents from Screening until Day 43 of the study, 
unless approved by the Medical Monitor. The following will be allowed/disallowed: 


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• Immunomodulatory biologics for COVID-19 treatment are excluded and should not 
be used until Day 43 unless discussed with the Medical Monitor. Other non-biologic 
immunomodulators (non-JAK inhibitors), e.g., medicines for previous 
transplantation, or disease modifying anti-rheumatic drugs (DMARDS), and have had 
a stable dose for ≥8 weeks are permitted. 
• Subjects who have been treated with convalescent plasma (CP) prior to enrollment 
are eligible if the subject continues to meet all inclusion criteria at screening. Ongoing 
therapy with CP is allowable if clinically indicated in the view of the treating 
physician or the Investigator. 
• The use of investigational anti-viral treatment (e.g., remdesivir) is allowed if the 
subject continues to meet all inclusion criteria at screening. 
14. Ongoing chronic (≥4 weeks) use of corticosteroids >10 mg/day of prednisone or 
equivalent at the time of randomization. A corticosteroid dose that has been tapered to 
10 mg or less within 14 days of randomization is also prohibited. 
15. Pregnancy and/or breast feeding 
16. Unable to receive invasive or non-invasive ventilatory support 
17. Moribund condition in the opinion of the clinical team 
 
5.4. 
Other Eligibility Criteria Considerations 
Individuals who marginally fail to meet eligibility requirements may be rescreened (once), on a 
case-by-case basis, as determined by the Medical Monitor. 
To assess any potential impact on subject eligibility with regard to safety, the Investigator must 
refer to the following document(s) for detailed information regarding warnings, precautions, 
contraindications, AEs, and other significant data pertaining to the investigational product being 
used in this study: 
• Gimsilumab Investigator Brochure, current edition 
 
5.5. 
Screening/Baseline 
Screen failures are defined as subjects who consent to participate in the clinical study but are 
never subsequently randomized. A minimal set of screen failure information is required 
including demography, screen failure details, eligibility criteria, and any SAEs. Screen failure 
data will not be recorded within the Case Report Form (CRF). 
 
5.6. 
Lifestyle and/or Dietary Restrictions 
 
5.6.1. 
Contraception 
 
The potential effects of gimsilumab on embryofetal or postnatal development have not been 
assessed in animals or humans. ICH M2 (R2) defines “highly effective methods of birth control” 
as those, alone or in combination, that result in a low failure rate (<1 pregnancy per 100 women 
in a year). 


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All female and male study subjects must use a highly effective birth control method (<1% failure 
rate per year) until completion of the Day 85 Follow-up Visit, unless they have a reproductive 
status of, sterile, non-childbearing, or postmenopausal (confirmed by FSH). Additionally, female 
partners of eligible male study subjects must use, in parallel, an allowed method of contraception 
Non-childbearing potential is defined as pre-menopausal female with documented bilateral tubal 
ligation, bilateral oophorectomy (removal of the ovaries) or hysterectomy; hysteroscopic 
sterilization. 
Postmenopausal female is defined as 12 consecutive months of spontaneous amenorrhea and 
with FSH confirmation. 
Woman of Childbearing potential (WCBP) are required to use a highly effective BC method 
(<1% failure rate per year): [Hatcher, 2007] 
• Subdermal implant that meets high effectiveness criteria (<1% rate of failure per 
year), stated in the product label 
• Intrauterine device (IUD) or intrauterine system (IUS) that meets high effectiveness 
criteria (<1% rate of failure per year), stated in the product label 
• Oral or injected contraceptives having established use (for at least 30 days); of either 
combined (estrogen- and progestogen) or progestogen alone 
• Male partner with vasectomy and documentation of azoospermia 
• “Double barrier” method, male partner(s) mutual agreement of male condom use in 
combination with: 
o female diaphragm/cervical cap plus spermicide (cream, gel, film, or 
suppository) 
o contraceptive vaginal ring 
o percutaneous contraceptive patches 
Sexually active male subjects must agree to use highly effective birth control (BC) methods. As 
applicable, in parallel to his study participation, his female partner(s) must also use an effective 
method of contraception (listed above). Males allowed to enroll in this study are responsible for 
minimizing the risk of pregnancy (until completion of the Day 85 Follow-up Visit). 
• Vasectomy and documentation of azoospermia 
• Male condom plus female partner use of one of the highly effective contraceptive 
methods listed immediately above, based on the female partner’s childbearing 
potential 
These allowed methods of contraception are only effective when used consistently, correctly and 
in accordance with the Investigator Brochure. The Investigator is responsible for ensuring that all 
study subjects fully understand the importance of this requirement and how to properly use these 
methods of contraception. 


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5.7. 
Withdrawal Criteria 
 
5.7.1. 
Reasons for Withdrawal 
 
An Investigator may discontinue/withdraw a study subject’s participation in the study if any of 
the following criteria apply: 
• Any clinical AE, laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest 
of the subject 
 
• Pregnancy of female subject 
 
• Major protocol violation 
 
• Behavioral and/or administrative reason 
 
• Subject request to discontinue/withdraw consent for any reason. It is important to 
document whether the withdrawal of consent is primarily due to an AE, lack of 
efficacy, or other reason. 
 
• Discontinuation of the study at the request of the Sponsor, regulatory agency, or an 
Institutional Review Board / Independent Ethics Committee 
 
• Liver toxicity where criteria as specified in Section 5.8.1 are met and no compelling 
alternate cause is identified 
 
If a subject meets a withdrawal criterion during treatment, an Early Termination Visit will be 
required. Subjects withdrawn for any reason will not be replaced. 
 
5.7.2. 
Subject Withdrawal Procedures 
 
If a subject is prematurely discontinued from investigational product(s), the Investigator must 
make every effort to perform an Early Termination (ET) Visit per the Schedule of Assessments 
(Table 7-2), and document the primary reason for withdrawal. 
In cases where the subject cannot be reached for phone follow-up visits, the site should attempt 
to contact the subject as soon as possible. The site should also counsel the subject on the 
importance of maintaining the assigned visit schedule and ascertain whether the subject wishes 
to and/or should continue in the study based on previous non-compliance. In cases where the 
subject cannot be reached, the site should make every effort to regain contact with the subject 
(3 documented telephone calls and if necessary a certified letter to the subject’s last known 
mailing address) so that they can appropriately be withdrawn from the study with a primary 
reason of “Lost to Follow-up”. 
Subjects who withdraw from treatment and/or the study early, for any reason, will be followed 
for Day 43 all-cause mortality, whenever possible. 


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5.8. 
Toxicity Management Criteria 
 
5.8.1. 
Liver Chemistry Management Criteria 
 
Liver chemistry criteria have been designed to assure subject safety and evaluate liver event 
etiology (in alignment with the FDA premarketing clinical Drug-induced Liver Injury guidance). 
Timely results of local labs should be used to make the decision to proceed to the second dose. 
Guidance on LFT abnormalities based upon results of LOCAL lab testing: 
1) If a subject has ALT in the normal range prior to study drug administration and develops 
significant elevation >5× ULN after study drug administration, in the absence of a clear 
alternative reason for the change (e.g., hypotension, vasopressor support), this should be 
considered related to study drug and reported as a SAE; procedures described in 
Appendix 2: Liver Safety Required Actions and Follow up Assessments should be 
followed, and the Medical Monitor should be informed. 
2) For subjects with elevated transaminase levels prior to study drug administration who do 
not meet exclusion criterion #11 (alanine aminotransferase [ALT] or aspartate 
aminotransferase [AST] >5× upper limit of normal [ULN]), if after administration of 
study drug the LFTs continue to worsen and no alternate explanation for elevation is 
provided, the following will apply: 
a. If ALT >8× ULN, then this should be reported as a SAE; procedures described in 
Appendix 2: Liver Safety Required Actions and Follow up Assessments will 
be followed, and the Medical Monitor should be informed. If the Investigator is 
considering withholding the second dose of study drug, then a discussion with the 
Medical Monitor is mandatory. Note that subjects with ALT or AST 
abnormalities secondary to multi-organ impairment due to COVID-19 may still 
benefit from the second dose of gimsilumab. 
b. If LFTs are elevated but are not >8× ULN, then daily LFTs (including AST, 
ALT, alkaline phosphatase, and total bilirubin with fractionation) should be 
followed. 
i.  If during follow up ALT or AST increases to >8× ULN, then this should 
be reported as a SAE and then discussed with the Medical Monitor 
concerning the need to withhold the second dose. 
ii. If a subject has AST or ALT 3 to 8× ULN in conjugation with total 
bilirubin >2× ULN or INR >1.5, then this should be reported as a SAE; 
procedures described in Appendix 2: Liver Safety Required Actions 
and Follow up Assessments should be followed. Subjects meeting these 
criteria should not receive a second dose of study drug. 
iii. If during follow up the above stopping criteria are not met and the 
Investigator believes that the subject is suitable to receive a second dose of 
study drug and all eligibility criteria are met for the second dose, then the 
second dose (Day 8) of study drug may be administered. 
3) Any worsening of LFTs that is greater than would be expected due to COVID-19 alone 
that do not rise to the level of an SAE should be reported as an AE. 


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4) A discussion with the Medical Monitor is mandatory prior to withholding the second 
dose of study drug. 
 
5.8.2. 
Individual Stopping Criteria 
 
Infusion of study treatment in an individual subject may be interrupted (and the Day 8 dose held, 
if appropriate) if the subject experiences a treatment-related Grade ≥3 AE or at the discretion of 
the investigator. Under these circumstances, the Medical Monitor must be notified. 
 
5.8.3. 
Study Stopping Criteria 
 
It is understood the safety profile of gimsilumab in the critical care setting of patients with 
impending or established ARDS is not yet understood. Reassuringly the anti-GM-CSF class of 
molecules has been studied in many subjects in multiple Phase 2 trials and to date no specific 
safety signal of concern has been noted to date. In principal, concerns for targeting GM-CSF 
include respiratory tract infection and pulmonary alveolar proteinosis. Hence while the rationale 
for targeting GM-CSF in the setting of severe viral pneumonia with or without ARDS is strong, 
there is concern over AEs and patient safety. 
To ensure subject safety, the sponsor plans a number of measures. An independent Data 
Monitoring Committee (DMC) will be appointed to review unblinded safety and efficacy data on 
an ongoing basis. The Chair of the DMC will issue a Charter outlining the specific plan for 
safety review including both early stopping rules for adverse safety events and also early 
stopping rules for futility, and early stopping rules for efficacy. 
 
5.8.4. 
Other Management Criteria 
 
For an individual study participant, Medical Monitor notification criteria include, but are not 
limited to: 
• 
Relevant severe signs or symptoms, or significant changes in any of the safety 
assessments, that put the safety of the individual at risk (e.g. laboratory tests or vital 
signs, etc.) as judged by the Investigator. 
 
5.9. 
Subject and Study Completion 
A completed subject is 1 who has completed the Treatment Period and the Follow-up Period 
(through the Day 169 End-of-Study [EoS] Follow-up Visit). 
 
6. 
STUDY TREATMENT 
 
6.1. 
Study Treatment 
The term ‘study treatment’ is used throughout the protocol to describe any dose of gimsilumab or 
placebo; study treatments are presented in Table 6-1. 


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Table 6-1: Treatment Descriptions for KIN-1901-2001 
 
Study Treatment 
Product name: 
Gimsilumab 
Placebo 
Formulation description: 
 
0.9% sodium chloride 
Dosage form: 
Vial 
NA 
Unit dose 
strength(s)/Dosage level(s): 
 
 
Route of 
Administration/Duration 
Intravenous infusion on Day 1 and Day 
8 
Intravenous infusion on Day 1 and Day 
8 
Dosing instructions: 
Infuse the entire contents of the IV bag 
via the intravenous route over a 1-hour 
period. Flush the line with 0.9% saline 
to ensure the entire contents is 
administered. 
Infuse the entire contents of the IV bag 
via the intravenous route over a 1-hour 
period ±20 minutes. Flush the line with 
0.9% saline to ensure the entire 
contents is administered. 
Procurement 
Gimsilumab: manufactured for 
Kinevant Sciences GmbH 
Saline: Procured by clinical site 
Saline: Procured by clinical site 
 
6.2. 
Administration of Study Treatments 
Study treatment will be infused intravenously over a period of 
. The start and 
stop time of the infusion will be recorded, including if the infusion had to be stopped or rate 
reduced. Further details are available in the Study Pharmacy Manual. 
Administration of study treatment will be performed by qualified personnel as specified in the 
Schedule of Assessments (Table 7-2). 
 
6.3. 
Randomization / Study Treatment Assignment 
Randomization will occur centrally using an interactive voice or web response system using 
central stratified randomization. Subjects determined to be eligible for enrollment based upon 
screening evaluations will be randomized to receive study treatments according to one of the 
treatments listed in Table 6-2. 
The study will enroll at least 40%, but no more than 60%, of total subjects in each of the two 
categories of clinical status: ([lung injury/mild ARDS] or [moderate/severe ARDS]) at Baseline, 
which will be used as the stratified factor in the randomization. 


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Table 6-2: Randomization Schema for KIN-1901-2001 
 
Arm 
Group 
Ratio 
Treatment Description 
1 
Active Study Drug 
1 
Gimsilumab 400 mg single IV infusion on Day 1 
Gimsilumab 200 mg single IV infusion on Day 8 
2 
Placebo 
1 
Normal saline single IV infusion on Day 1 
Normal saline single IV infusion on Day 8 
 
6.4. 
Blinding 
The study is double-blind. The study pharmacist (and/or qualified pharmacy staff member), and 
the bioanalytical laboratory analysts will be unblinded to study treatment. 
Study treatment will be administered to each subject by blinded qualified personnel at the study 
site. Once diluted in 100 mL 0.9% saline, active gimsilumab and placebo infusion bags are 
indistinguishable. 
The following will apply regarding the unblinding of study treatment: 
• 
The Investigator or treating physician may unblind a subject’s treatment assignment only in 
the case of an emergency OR in the event of a serious medical condition when knowledge 
of the study treatment is essential for the appropriate clinical management or welfare of the 
subject as judged by the Investigator. 
 
• 
Investigators have direct access to the subject’s individual study treatment. 
• 
The Investigator should make every effort to first contact the Medical Monitor or 
appropriate study personnel to discuss options before unblinding the subject’s treatment 
assignment. 
• 
If the Sponsor personnel are not contacted before the unblinding, the Investigator must 
notify the Sponsor as soon as possible after unblinding. 
• 
The date and reason for the unblinding must be fully documented in the CRF. 
• 
The Sponsor or their designee may unblind the treatment assignment for any subject with an 
SAE. If the SAE requires that an expedited regulatory report be sent to one or more 
regulatory agencies, a copy of the report, identifying the subject’s treatment assignment, will 
be sent to Investigators in accordance with local regulations. 
A subject will be withdrawn if the subject’s treatment code is unblinded by the Investigator or 
treating physician. The primary reason for discontinuation (the event or condition which led to 
the unblinding) will be recorded in the CRF. 


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Investigational study treatment clinical supplies will be provided in 
6.5. 
Packaging and Labeling 
 
IV doses of gimsilumab or placebo will be prepared by the site pharmacy, dispensed, and 
administered to subjects by clinic staff at the study site in a container having a label that includes 
at a minimum the study number, subject number, and study treatment name (“gimsilumab or 
placebo”). 
All labels for gimsilumab vials to be distributed will meet all applicable requirements of 
Annex 13 of Good Manufacturing Practices: Manufacture of Investigational Medicinal Products 
(July 2010) and/or other local regulations as applicable. 
 
6.6. 
Preparation/Handling/Storage/Accountability 
Gimsilumab study treatment will be diluted in 100 mL 0.9% saline prior to infusion using aseptic 
technique by qualified personnel per the clinical site standard operating procedures. 
Placebo study treatment will utilize 100 mL 0.9% saline solution with the addition of 4 mL 
(Day 1) or 2 mL (Day 8) sterile 0.9% saline solution using aseptic technique by qualified 
personnel per the clinical site standard operating procedures. 
Refer to the Study Pharmacy Manual for additional details. 
Gimsilumab vials are to be stored at 
and require temperature monitoring. Temperature 
excursions are to be reported to the Sponsor. 
• 
Only subjects enrolled in the study may receive study treatment and only authorized site 
staff may supply or administer study treatment. All study treatments must be stored in a 
secure environmentally controlled and monitored (manual or automated) area in 
accordance with the labelled storage conditions with access limited to authorized site 
staff. 
• 
The Investigator or delegated personnel is responsible for study treatment 
accountability, reconciliation, and record maintenance (i.e. receipt, reconciliation and 
final disposition records). 
• 
Further guidance and information for final disposition of unused study treatment are 
provided in the Study Pharmacy Manual. 
• 
Under normal conditions of handling and administration, study treatment is not 
expected to pose significant safety risks to site staff. In the case of unintentional 
occupational exposure notify the monitor, Medical Monitor and/or the Sponsor Study 
Contact. 
• 
A Material Safety Data Sheet (MSDS) describing occupational hazards and 
recommended handling precautions either will be provided to the Investigator, where 
this is required by local laws, or is available upon request from the Sponsor. 


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6.7. 
Compliance with Study Treatment Administration 
Subjects are dosed in the hospital. They will receive study treatment directly from the 
Investigator or designee, under medical supervision. The date and time of each dose 
administered in the hospital will be recorded in the source documents. The dose of study 
treatment and study subject identification will be confirmed at the time of dosing by a member of 
the study site staff other than the person administering the study treatment. 
 
6.8. 
Treatment of Study Treatment Overdose 
For this study, any single administration of gimsilumab >400 mg will be considered an overdose. 
The Sponsor does not recommend specific treatment for an overdose. There have been no 
previous reports of overdose (accidental or deliberate) with gimsilumab. 
In the event of an overdose the Investigator or treating physician should: 
• contact the Medical Monitor immediately; 
 
• closely monitor the subject for AEs/SAEs and laboratory abnormalities; 
 
• obtain a plasma sample for PK analysis if requested by the Medical Monitor (determined 
on a case-by-case basis); 
 
• document the quantity of the excess dose as well as the duration of the overdosing in the 
CRF. 
 
Decisions regarding dose interruptions or modifications will be made by the Investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the subject. 
 
6.9. 
Concomitant Medications and Non-Drug Therapies 
Best possible medication history for the 30 days prior to enrollment will be collected, and 
include, at a minimum, the drug name (generic or tradename) and start date and stop date (or 
ongoing). 
It would be expected that gimsilumab would reduce the effectiveness of GM-CSFs, such as 
Luekine® (sargramostim), Leucomax® (molgramostim) and Regramostim. No other drug 
interactions are known or expected. 
 
6.9.1. 
Permitted Medications and Non-Drug Therapies 
 
Treatment with convalescent plasma or investigational anti-viral therapies (e.g., remdesivir) will 
be allowed. 
Use of any concomitant medication (including investigational agents) should be recorded in the 
study source records, including the doses administered, dates and times of administration and the 
reason for administration. 


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6.9.2. 
Prohibited Medications and Non-Drug Therapies 
 
Use of tocilizumab or any other immunomodulatory biologic (e.g., anti-IL-1, anti-IL-6R, anti- 
TNF), cell therapies (e.g., mesenchymal stem cells), or small molecules (e.g., JAK inhibitors) is 
prohibited from Screening until Day 43 of the study unless approved by the Medical Monitor. 
 
7. 
STUDY ASSESSMENTS AND PROCEDURES 
Protocol waivers or exemptions are not allowed with the exception of immediate safety concerns. 
Therefore, adherence to the study design requirements, including those specified in the Schedule 
of Assessments (Table 7-2), are essential and required for study conduct. 
This section lists the procedures and parameters of each planned study assessment. The exact 
timing of each assessment is listed in the Schedule of Assessments, (Table 7-2). 
Note: All subjects who are discharged from the hospital will undergo all Day-of-Discharge 
(DoD) Visit assessments. All subjects who discontinue from the study prematurely will undergo 
all Early Termination (ET) Visit assessments, whenever possible. 
Once a subject is discharged from the hospital every effort MUST be made to ensure visit 
timepoints listed on the Schedule of Assessments (Table 7-2) are completed via phone or 
telemed. All visits are required to be completed for every subject unless the subject dies or 
withdraws consent. If a subject is deemed lost to follow-up every effort should be made to check 
vital status records at each visit time point to obtain survival status. Proper follow-up and 
documentation should be completed per GCP/ICH guidelines before deeming a subject lost to 
follow-up. 
The following points must be noted, if assessments are scheduled for the same nominal time, 
THEN the assessments should occur in the following order: 
1. vital signs 
2. blood draws 
Note: The timing of the assessments should allow the blood draw to occur at the exact nominal 
time. 
The Institutional Review Board (IRB)/Independent Ethics Committee (IEC) will be informed of 
any safety issues that require alteration of the safety monitoring scheme or amendment of the 
Informed Consent Form. 
If the subject completes all in hospital assessments, approximately 250 mL of blood will be 
collected over the duration of the study (Table 7-1). 
 
Table 7-1: Estimated Sample Requirements Per Subject 
 
Approximate sample 
volume per collection 
(mL) 
Number of collection 
time points 
Approximate total 
volume collected (mL) 
Clinical laboratory tests 
16.5 
9 
148.5 
Viral screen / Quantiferon® 
11 
1 
11 
Anti-GM-CSF autoAb 
4 
1 
4 
PK blood sampling 
4 
3 
12 
Anti-gimsilumab antibodies 
4 
4 
16 


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Cytokine panel 
8.5 
5 
42.5 
SP-D 
3.5 
4 
14 
FSH (if necessary) 
3.5 
1 
3.5 
Total: 
251.5 


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7.1. 
Schedule of Assessments (Treatment and Follow-up Periods) 
Table 7-2: Schedule of Assessments 
 
Schedule of Assessments: Screening and Treatment Period 
Screen 
Baselinea 
On-Treatment 
Assessments 
(only done if in hospital) 
DoDo / 
ET 
Study Day (± Window) 
-7 to 1 
1 
Days 2 – 14, inclusive 
(All ± 1 day) 
-1 
Week 
0 
0 
1 to 2 
— 
Informed consent and randomization 
X 
Inclusion/Exclusion criteria 
X 
Xb 
Demographic information, medical history, prior medicationsc 
X 
Local QuantiFERON® testd 
X 
Local Viral Screen (HBsAG, HCV RNA/Ag, HIV)d 
X 
Height and Weighte 
X 
Local Urine pregnancy test β-hCG and follicle-stimulating hormone (FSH, women only)f 
X 
Central sample for anti-GM-CSF autoAbd (result not required for determination of eligibility) 
X 
Chest X-ray or chest CT scan (within 3 days of Day 1) 
X 
Local qualitative sample (e.g., nasopharyngeal swab) for PCR SARS-CoV-2 (if not already documented) 
X 
Central quantitative sample (e.g., nasopharyngeal swab) for PCR SARS-CoV-2g 
X 
Days 2 and 9 
X 
Physical examinationh and vital signs (blood pressure, heart rate, respiration rate, and body temperature)i 
X 
X 
Daily, only while hospitalized 
X 
Central clinical laboratory measurements (hematology, blood chemistry [including CRP, ferritin, LDH, 
procalcitonin, troponin I], coagulation [including D-dimer], and urinalysis)j 
X 
X 
Days 4 and 8 
X 
Administration of IV study drugk 
X 
Day 8 
Central PK samples for quantification of gimsilumab serum concentration 
Predose 
Predose on Day 8 
X 
Central samples for cytokine panel 
X 
Days 4 and 8 
X 


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Schedule of Assessments: Screening and Treatment Period 
Screen 
Baselinea 
On-Treatment 
Assessments 
(only done if in hospital) 
DoDo / 
ET 
Study Day (± Window) 
-7 to 1 
1 
Days 2 – 14, inclusive 
(All ± 1 day) 
-1 
Week 
0 
0 
1 to 2 
— 
Central samples for SP-D measurement 
X 
Day 8 
X 
Central sample for immunogenicity (antibodies to gimsilumab) 
X 
X 
7-point Ordinal Scale 
X 
Daily, only while hospitalized 
X 
National Early Warning Score (NEWS) 
X 
Daily, only while hospitalized 
X 
SOFA score 
X 
Daily, only while in ICU 
X 
SpO2/FiO2, and if performed, PaO2/FiO2 (can be imputed) 
X 
X 
Daily, only while hospitalized 
X 
Oxygenation requirements 
X 
X 
Daily, only while hospitalized 
X 
Ventilation requirementsl 
X 
X 
Daily, only while hospitalized 
X 
ECMO requirements 
X 
Daily, only while hospitalized 
X 
Concomitant medications/concurrent proceduresm 
X 
Daily, only while hospitalized 
X 
Adverse event monitoringn 
X 
Daily, only while hospitalized 
X 
β-hCG = beta human chorionic gonadotropin; anti-GM-CSF autoAb = anti-granulocyte macrophage colony- stimulating factor auto-antibody; DoD = Day of Discharge from hospital; ECMO = 
extracorporeal membrane oxygenation; EoS = End-of-Study; ET = early termination; FiO2 = fraction of inspired oxygen; FSH = follicle stimulation hormone; HBsAg = hepatitis B surface 
antigen; HCVAb = hepatitis C virus antibodies; HIV = human immunodeficiency virus; ICU = Intensive Care Unit; IGRA = interferon gamma release assay; IV = intravenous; PCR = polymerase 
chain reaction; PK = pharmacokinetics; PPD = purified protein derivative; PPE = personal protective equipment; SOFA = sequential organ failure assessment; SP-D = serum surfactant protein D; 
SpO2 = peripheral capillary oxygen saturation; TB = tuberculosis 
a. Baseline assessments should be performed prior to study drug administration. Assessments performed within 48 hours of Baseline do not need to be repeated at Baseline. 
b. Verification that no changes affecting eligibility have occurred since Screening will be performed at the Baseline/Day 1 Visit. 
c. Collect medication history from the 30 days leading up to, and including, the time of the Screening Visit, including date of onset of COVID-19 symptoms, prescription medications, over-the- 
counter medications, and herbal supplements/vitamins. 
d. Sample will be collected, but enrollment can continue without receiving results first. HCV testing can be RNA or Ag, only to confirm suspected infection. If a subject is diagnosed with latent TB 
(positive QuantiFERON Gold or PPD), hepatitis B or C, or HIV during the study, the Investigator must discuss this with the medical monitor and a decision will then be made concerning the 
second dose of gimsilumab, if applicable. In the event the QuantiFERON Gold assay is not available, and the site performs a different IGRA such as T Spot, then the alternative IGRA will be 
acceptable for patient screening and enrollment. Enrollment should not be delayed to obtain the QuantiFERON Gold assay in lieu of the IGRA available at the site. If no IGRA test is available, 
PPD can be used. If TB testing and viral serology is missed during screening it must be completed and results received prior to the second dose of study drug. If not completed or unable to 
obtain results further discussion with the medical monitor is required. 


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Schedule of Assessments: Screening and Treatment Period 
Screen 
Baselinea 
On-Treatment 
Assessments 
(only done if in hospital) 
DoDo / 
ET 
Study Day (± Window) 
-7 to 1 
1 
Days 2 – 14, inclusive 
(All ± 1 day) 
-1 
Week 
0 
0 
1 to 2 
— 
e. Height will be assessed only once (at Screening). Estimated height and weight are acceptable if unable to be measured due to patient clinical condition. 
f. The Screening sample can be assessed using local laboratory services for Screening/Eligibility purposes. The local laboratory values must also be documented in the eCRF. 
Note: FSH will be performed to confirm postmenopausal status only in women who have not had 12 months of spontaneous amenorrhea. 
g. When at all possible, if only 1 nostril is swabbed for viral assessments, the same nostril should be used for all subsequent samples. 
h. An abbreviated, targeted physical examination will be performed based on the subject’s clinical status and what the clinic staff feel is appropriate. Note: If a physical examination is performed 
as standard of care by appropriate personnel the same day that consent is signed or the same day of any scheduled study visit, results from that examination may be used if PPE is not 
available or if study site staff consider additional examinations are unwarranted due to already having been performed as standard of care.. 
i. Vital signs will be assessed at all timepoints specified above. On study drug administration days, vital signs will be assessed pre-dose (within 15 minutes) and ± 30 minutes post end of 
infusion. Note: If vital signs measurements are performed as standard of care by appropriate personnel the same day that consent is signed or the same day of any scheduled study visit, 
results from that assessment may be used if PPE is not available or if study site staff consider additional measurements are unwarranted due to already having been performed as standard of 
care.. 
j. ALT, AST, CRP, and Ferritin can be assessed using local laboratory services for Screening The local laboratory values must be documented in the eCRF. 
k. Subjects will receive a single IV infusion of blinded study treatment on Day 1 and Day 8. The Day 8 dose will be omitted if the subject is discharged or is no longer in need of supplemental 
oxygen or ventilatory support for >48 hours. 
l. If subject is receiving mechanical ventilation, the following parameters will be recorded: type of ventilation (CPAP, BiPAP, or intubation), FiO2, SpO2, ventilation rate, pulse, tidal volume, 
positive end-expiratory pressure (PEEP), and airway pressure. 
m. Collect information on concomitant medications and concurrent procedures from the time of informed consent through the EoS Visit (or ET Visit if subject discontinues early), including 
prescription medications, over-the-counter medications, and herbal supplements/vitamins. 
n. Adverse event monitoring will include assessment of treatment-emergent AEs (TEAEs), serious adverse events (SAEs), and severe AEs (Grade 3 or 4 events). 
o. DoD assessments can be performed one day prior to discharge if the subject has been labelled as “ready for discharge.” 
Note: SCREENING LABORATORY ASSESSMENTS: For all screening laboratory assessments, if more than one result is available during the screening period, the most recent value will be 
used as the screening value and for determination of eligibility. 
Note: All subjects who are discharged from the hospital will undergo all Day-of-Discharge (DoD) Visit assessments; daily in-hospital assessments will only need to be performed once on DoD. 
All subjects who discontinue from the study prematurely will undergo all Early Termination (ET) Visit assessments, whenever possible. All subjects who discontinue treatment and/or the study 
early will be followed for Day 43 all-cause mortality. 


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Schedule of Assessments: Follow-up Period 
(Visits will be in-hospital or by phone, if subject has been discharged) 
Study Day (± Window) 
15 
(± 2) 
22 
(± 2) 
29 
(± 2) 
36 
(± 2) 
43a 
(± 2) 
85 
(± 2) 
EoS 
169 
(± 2) 
DoD / 
ET 
Week 
2 
3 
4 
5 
6 
12 
24 
— 
Procedures/Assessments 
SOFA Score 
Daily, only if in ICU, through Day 43 
X 
National Early Warning Score (NEWS) 
Daily, only while hospitalized, through Day 43 
X 
Central samples for cytokine panel 
Hosp 
Hosp 
Central samples for SP-D measurement 
Hosp 
Hosp 
Central sample for immunogenicity (antibodies to gimsilumab) 
Hosp 
Hosp 
Hosp 
Central clinical laboratory measurements (hematology, blood chemistry 
[including CRP, ferritin, LDH, procalcitonin, troponin I], coagulation 
[including D-dimer], and urinalysis)b 
Hosp 
Hosp 
Hosp 
Hosp 
Hosp 
X 
SpO2/FiO2, and if performed, PaO2/FiO2 (can be imputed) 
Daily, only while hospitalized, through Day 43 
X 
Oxygenation requirements 
Daily, only while hospitalized, through Day 43c 
X 
Ventilation requirements 
Daily, only while hospitalized, through Day 43 
X 
ECMO requirements 
Daily, only while hospitalized, through Day 43 
X 
Concomitant medications/concurrent procedures 
Daily, only while hospitalizedd 
X 
X 
X 
Physical examination and vital signs (blood pressure, heart rate, 
respiration rate, and body temperature) 
Hosp 
Hosp 
Hosp 
Hosp 
Hosp 
X 
7-point Ordinal Scale 
Daily, only while hospitalized, through Day 43d 
X 
X 
X 
Adverse event monitoringe 
Daily, only while hospitalizedd 
X 
X 
X 
ECMO = extracorporeal membrane oxygenation; EoS = End-of-Study; FiO2 = fraction of inspired oxygen; Hosp = Assessment to be performed only if subject has not been discharged; ICU = 
Intensive Care Unit; SOFA = sequential organ failure assessment; SP-D = serum surfactant protein D; SpO2 = peripheral capillary oxygen saturation 
a. 
Day 43 will be used for the primary all-cause mortality endpoint. 
b. 
For all on-study laboratory assessments, if central laboratory assessments cannot be collected for any reason, best efforts will be made to record local laboratory data. 
c. 
IF DISCHARGED, will be measured via phone follow-up on Day 15, 22, 29, 36, and 43. 
d. 
IF DISCHARGED, will be measured via phone follow-up on Day 15, 22, 29, 36, 43, 85, and 169. 


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Schedule of Assessments: Follow-up Period 
(Visits will be in-hospital or by phone, if subject has been discharged) 
Study Day (± Window) 
15 
(± 2) 
22 
(± 2) 
29 
(± 2) 
36 
(± 2) 
43a 
(± 2) 
85 
(± 2) 
EoS 
169 
(± 2) 
DoD / 
ET 
Week 
2 
3 
4 
5 
6 
12 
24 
— 
Procedures/Assessments 
e. 
Adverse event monitoring will include assessment of treatment-emergent AEs (TEAEs), serious adverse events (SAEs), and severe AEs (Grade 3 or 4 events) 
Note: Assessments at time points indicated with “Hosp” will only be conducted if the subject has not yet been discharged from the hospital. Assessments indicated with an ‘X’ will be performed 
in-hospital if the subject has not been discharged or via phone if subject has been discharged from the hospital. 
Note: All subjects who are discharged from the hospital will undergo all Day-of-Discharge (DoD) Visit assessments; daily in-hospital assessments will only need to be performed once on DoD. 
All subjects who discontinue from the study prematurely will undergo all Early Termination (ET) Visit assessments, whenever possible. 
All subjects who discontinue treatment and/or the study early will be followed for Day 43 all-cause mortality. 


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7.2. 
Informed Consent 
Documented consent (including regulatory compliant electronic methods) must be obtained from 
each potential subject prior to participating in all study procedures. Consent must be documented 
by the subject’s dated signature or by the subject’s legally acceptable representative’s dated 
signature on a consent form along with the dated signature of the person conducting the consent 
discussion. 
A copy of the signed and dated consent form should be given to the subject before participation 
in the study. 
The initial informed consent form, any subsequent revised written informed consent form and 
any written information provided to the subject must receive the IRB/ERC’s approval/favorable 
opinion in advance of use. The subject or his/her legally acceptable representative should be 
informed in a timely manner if new information becomes available that may be relevant to the 
subject’s willingness to continue participation in the study. The communication of this 
information will be provided and documented via a revised consent form or addendum to the 
original consent form that captures the subject’s dated signature or by the subject’s legally 
acceptable representative’s dated signature. 
Specifics about the study and the study population will be added to the consent form template at 
the protocol level. 
The informed consent will adhere to IRB/ERC requirements, applicable laws and regulations and 
Sponsor requirements. 
 
7.3. 
Inclusion/Exclusion Criteria Eligibility Review 
All inclusion and exclusion criteria will be reviewed by the Investigator or qualified designee at 
the Screening Visit to ensure that the subject qualifies for the study. 
All inclusion criteria must be met and none of the exclusion criteria may apply. No eligibility 
waivers will be granted. 
Subjects found ineligible during review of inclusion/exclusion will not proceed through the 
remaining screening process. 
 
7.4. 
Study Assessments and Procedures 
 
7.4.1. 
Efficacy Assessments 
 
7.4.1.1. 
Measures of clinical support 
 
At each assessment day, the following measure of clinical support should be assessed: 
• Hospitalization 
• Oxygen requirement (via nasal cannula, mask, or high-flow nasal cannula) 
• Non-invasive mechanical ventilation (i.e., CPAP or BiPAP) 


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• Mechanical ventilator requirement (via endotracheal tube or tracheostomy tube) 
• ECMO requirement 
 
7.4.1.2. 
7-Point Ordinal Scale 
 
The ordinal scale is an assessment of the clinical status at the first assessment of a given study 
day [WHO COVID-19 Master Protocol, 2020]. Each day, the worse score for the previous day 
will be recorded (i.e., on Study Day 3, the worse Day 2 score is obtained and recorded as the 
score for Day 2). 
The scale is as follows: 
1. Not hospitalized, no limitations on activities; 
2. Not hospitalized, limitation on activities; 
3. Hospitalized, not requiring supplemental oxygen; 
4. Hospitalized, requiring supplemental oxygen; 
5. Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 
6. Hospitalized, on invasive mechanical ventilation or ECMO; 
7. Death. 
 
7.4.1.3. 
Sequential Organ Failure Assessment (SOFA) 
 
The SOFA score will be assessed daily for subjects while in the ICU. 
 
7.4.1.4. 
National Early Warning Score (NEWS) 
 
The NEW Score has demonstrated an ability to discriminate patients at risk of poor outcomes 
[WHO Master Protocol, 2020]. This score is based on 7 clinical parameters (Figure 7-1). The 
NEW Score is used as an efficacy measure. 
These parameters can be obtained from the hospital chart using the last measurement prior to the 
time of assessment. This is recorded for the day obtained (i.e., on Study Day 3, the Day 3 score is 
obtained and recorded as Day 3). Each parameter and the final score will be recorded. 
This should be evaluated at the first assessment of a given study day. 


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Figure 7-1: 
National Early Warning Score 
 
Level of consciousness = alert (A), and arousable only to voice (V) or pain (P), and unresponsive (U) 
 
7.4.2. 
Safety and Other Assessments 
 
7.4.2.1. 
Physical Examinations 
 
Abbreviated, targeted physical examinations (i.e., assessments of the skin, respiratory, 
cardiovascular system, and abdomen [liver and spleen]), will be performed at time points 
specified in the Schedule of Assessments (Table 7-2) and will be based on the subject’s clinical 
status and what the clinic staff feel is appropriate. 
Height and weight will be measured and recorded at Screening only, if possible. 
Note: If a physical examination is performed as standard of care by appropriate personnel the 
same day that consent is signed or the same day of any scheduled study visit, results from that 
examination may be used if personal protective equipment (PPE) is not available or if study site 
staff consider additional examinations are unwarranted due to already having been performed as 
standard of care. 
 
7.4.2.2. 
Vital Signs 
 
Vital signs including blood pressure, heart rate, respiration rate, and temperature (oral, tympanic, 
or axillary) will be obtained at time points specified in the Schedule of Assessments (Table 7-2). 
The same method for assessing temperature should be used at all visits for each individual 
subject, if possible. 


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Note: If vital signs measurements are performed as standard of care by appropriate personnel the 
same day that consent is signed or the same day of any scheduled study visit, results from that 
examination may be used if PPE is not available or if study site staff consider additional 
measurements are unwarranted due to already having been performed as standard of care. 
 
7.4.2.3. 
Cardiovascular Assessments 
 
7.4.2.3.1. Echocardiograms 
 
Echocardiograms may be performed as standard of care, at the discretion of the Investigator. If 
an echocardiogram is performed, LVEF will be recorded, if assessed. 
 
7.4.2.4. 
Follicle Stimulating Hormone (FSH), Viral Serology, and Tuberculosis 
Assessments 
 
Follicle stimulating hormone (FSH) will be performed at screening, for women only, to confirm 
postmenopausal status in women who have not had 12 months of spontaneous amenorrhea. 
A blood sample will be collected at Screening as specified in the Schedule of Assessments 
(Table 7-2), for viral serology and TB testing, but enrollment can continue without receiving the 
results first. HCV testing can be RNA or Ag, only to confirm suspected infection. If a subject is 
diagnosed with latent TB (positive QuantiFERON Gold or purified protein derivative [PPD]), 
hepatitis B or C, or HIV during the study, the Investigator must discuss this with the medical 
monitor and a decision will then be made concerning the second dose of gimsilumab, if 
applicable. In the event the QuantiFERON Gold assay is not available, and the site performs a 
different IGRA such as T Spot, then the alternative IGRA will be acceptable for patient 
screening and enrollment. Enrollment should not be delayed to obtain the QuantiFERON Gold 
assay in lieu of the IGRA available at the site. If no IGRA test is available, PPD can be used. If 
TB testing and viral serology is missed during screening it must be completed and results 
received prior to the second dose of study drug. If not completed or unable to obtain results 
further discussions with the medical monitor will be required. 
 
7.4.2.5. 
Clinical Safety Laboratory Assessments 
 
All protocol required laboratory assessments must be conducted in accordance with the 
Laboratory Manual, and the Schedule of Assessments (Table 7-2). Laboratory requisition forms 
must be completed, and samples must be clearly labelled with the subject number, protocol 
number, site/center number, and visit date. Details for the preparation and shipment of samples 
will be provided by the laboratory and are detailed in the Laboratory Manual. Reference ranges 
for all safety parameters will be provided to the site by the laboratory responsible for the 
assessments. 
For all on-study laboratory assessments, if central laboratory assessments cannot be collected for 
any reason, best efforts will be made to record local laboratory data. 
If additional non-protocol specified laboratory assessments are performed at the institution’s 
local laboratory and result in a change in subject management or are considered clinically 


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significant by the Investigator (e.g., SAE or AE or dose modification) the results must be 
recorded. 
Hematology, clinical chemistry, coagulation, urinalysis and additional parameters to be tested are 
listed in (Table 7-3). 
 
Table 7-3: List of Clinical Laboratory Analyses 
 
Hematology 
Coagulation 
Platelet Count 
MCV 
Eosinophils 
Prothrombin Time (PT) 
RBC Count 
MCH 
Basophils 
D-dimer 
WBC Count (absolute) 
MCHC 
Activated partial thromboplastin time 
(aPTT) 
Reticulocyte Count 
Neutrophils 
Fibrinogen 
Hemoglobin 
Lymphocytes 
Cardiac Enzymes 
Hematocrit 
Monocytes 
Troponin I 
 
Clinical Chemistry 
BUN 
Total CO2 
AST (SGOT) 
Creatine Kinase 
Creatinine 
Calcium 
ALT (SGPT) 
NT-proBNP 
Glucose 
Ferritin 
Albumin 
FSH (blood) 
(only at screening for 
postmenopausal confirmation) 
Sodium 
C-reactive 
Protein (CRP) 
Alkaline phosphatase 
Potassium 
Lactate 
dehydrogenase 
(LDH) 
Total bilirubin 
Chloride 
Procalcitonin 
Total Protein 
 
Urinalysis 
Glucose 
pH 
Clarity 
Protein 
Blood 
Color 
Ketones 
Nitrite 
Urobilinogen 
Specific gravity 
Leukocytes 
Bilirubin 


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7.4.2.6. 
SARS-CoV-2 Viral Assessments 
 
A local qualitative sample (e.g., nasopharyngeal swab) for PCR SARS-CoV-2 will be collected 
at Screening for determination of eligibility (if not already documented); all other on-study 
samples will be central quantitative samples. 
When at all possible, if only 1 nostril is swabbed for viral assessments, the same nostril should 
be used for all subsequent samples. 
 
7.4.2.7. 
Respiratory Assessments 
 
Safety assessment includes FiO2 and SpO2. If indicated, additional follow up tests may be 
performed at Investigator discretion after consultation with the Medical Monitor. 
If subject is receiving mechanical ventilation, the following parameters will be recorded: type of 
ventilation (high-flow nasal cannula, non-rebreather mask, CPAP, BiPAP, or intubation), FiO2, 
SpO2, ventilation rate, pulse, tidal volume, positive end-expiratory pressure (PEEP), and airway 
pressure. 
Respiratory assessments, when available, will be used to determine the Lung Injury Score (LIS) 
as an exploratory endpoint. The LIS is a composite scoring system including P/F ratio, the level 
of PEEP, the extent of infiltrates on chest X-ray or computerized tomography (CT) scan and 
respiratory static compliance. 
 
7.4.2.8. 
Pharmacokinetic Assessments 
 
Blood samples for PK analysis of serum gimsilumab will be collected at the time points 
indicated in the Schedule of Assessments (Table 7-2). The actual date and time of each blood 
sample collection will be recorded. The time of gimsilumab/placebo dosing on Day 1 will be t=0 
for relative timing of PK samples. 
Processing, storage, and shipping procedures are provided in the Laboratory Manual. 
Serum PK analysis will be performed under the oversight and control of the Sponsor, the details 
of which will be included in the Laboratory Manual. Concentrations of gimsilumab will be 
determined in serum samples using the currently approved bioanalytical methodology. 
 
7.4.2.9. 
Biomarker Assessments 
 
Blood samples for determination of serum cytokines and a safety biomarker SP-D will be 
collected at the time points indicated in the Schedule of Assessments (Table 7-2). The actual date 
and time of each blood sample collection will be recorded. The time of gimsilumab/placebo 
dosing on Day 1 will be t=0 for relative timing of PD samples. 
The cytokine/chemokine panel may include: GM-CSF, G-CSF, IL-1β, IL-2, IL-6, IL-7, IL-8, 
IL-10, IL-15, IL-17A, IL-17A/F, IL-23p19, IFN-γ, TNF-α, IP10 (CXCL10), MCP1 (CCL2), 
MIP1A (CCL3), and CCL17. 
A subset of these cytokines/chemokines will be tested initially, further testing may be performed 
based on results of other study endpoints and emerging scientific information. 


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Concentrations of biomarkers will be determined using qualified or validated assays. 
 
7.4.2.10. 
Immunogenicity Assessments 
 
A single blood sample for the assessment of anti-GM-CSF autoAb will be collected at Screening 
(this result is not required to determine eligibility). 
Blood samples for serum ADA analysis will be collected at the time points indicated in the 
Schedule of Assessments (Table 7-2). The actual date and time of each blood sample collection 
will be recorded. The time of gimsilumab/placebo dosing on Day 1will be t=0 for relative timing 
of ADA samples. 
Processing, storage, and shipping procedures are provided in the Laboratory Manual. 
Serum analysis will be performed under the oversight and control of the Sponsor, the details of 
which will be included in the Laboratory Manual. ADAs will be determined in serum samples 
using the currently approved bioanalytical methodology. 
 
7.4.2.11. 
Safety Monitoring 
 
It is understood the safety profile of gimsilumab in the critical care setting of patients with 
impending or established ARDS is not yet understood. Reassuringly the anti-GM-CSF class of 
molecules has been studied in many subjects in multiple Phase 2 trials [Hamilton, 2020] and to 
date no specific safety signal of concern has been noted to date. In principal concerns for 
targeting GM-CSF include respiratory tract infection and pulmonary alveolar proteinosis. Hence 
while the rationale for targeting GM-CSF in the setting of severe viral pneumonia with or 
without ARDS is strong, there is concern over AEs and patient safety. 
To ensure subject safety, the sponsor will appoint an independent DMC to review unblinded 
safety and efficacy data on an ongoing basis. The Chair of the DMC will issue a Charter 
outlining the specific plan for safety review including both early stopping rules for adverse safety 
events and also early stopping rules for futility, and early stopping rules for efficacy. 
 
8. 
DATA MANAGEMENT 
For this study, subject data will be entered into Sponsor-approved electronic database and 
combined with data provided from other sources in validated datasets then transmitted 
electronically to the Sponsor or designee. 
Management of clinical data will be performed in accordance with applicable Sponsor approved 
standards and data cleaning procedures to ensure the integrity of the data, e.g., re resolving errors 
data queries, and inconsistencies in the data, and datasets in CDISC SDTM/AdaM formats. 
AEs and concomitant medication terms will be coded using the most current versions of the 
Medical Dictionary for Regulatory Activities (MedDRA) and the World Health Organization 
Drug Dictionary Enhanced (WHO-DDE), respectively. 
The Principal Investigator will retain original source documents and the Sponsor will receive 
CRF-required data as electronic datasets. Subject initials will not be collected or transmitted to 
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The detailed Data Management Plan (DMP) will be generated and approved prior to the study 
database lock when all subjects complete the Day 43 Visit, discontinue from the study early, or 
meet the primary endpoint of mortality (by Day 43). 
The study database will be locked when all subjects complete the Day 43 Visit, discontinue from 
the study early, or meet the primary mortality endpoint. The second lock will occur when the last 
subject completes the Day 169 EoS visit. 
In addition, there will be 2 database extracts (soft locks) for interim analyses, the first of which 
will be conducted when 60 subjects have been treated and have completed through Day 15; the 
DMC will review the data for safety and futility and provide their recommendations. The second 
interim analysis will be conducted when 100 subjects have completed at least the Day 29 Visit 
for non-mortality endpoints and have the data for the endpoint of mortality (by Day 43). 
 
9. 
STATISTICAL CONSIDERATIONS AND ANALYSES 
 
9.1. 
Sample Size Determination 
There will be 270 subjects (135 subjects per treatment arm) with 1:1 randomization. 
The comparisons between the treatment arms will have approximately 80% power and two-sided 
alpha level 0.05 to demonstrate the significant reduction of the incidences (15% versus 30%) in 
the primary endpoint between gimsilumab versus placebo. 
The study will enroll at least 40%, but no more than 60%, of total subjects in each of the 
2 categories of clinical status : ([lung injury/mild ARDS] or [moderate/severe ARDS]) at 
Baseline, which will be used as the stratified factor in the randomization. 
Lung injury is defined as (1) requiring supplemental oxygen >4L O2 to maintain >92% SpO2, or 
(2) PaO2/FiO2 ≤300 mmHg (can be imputed). 
ARDS [ARDS Berlin Definition, 2012] is defined as: 
• Bilateral opacities — not fully explained by effusions, lobar/lung collapse, or nodules; 
• Respiratory failure not fully explained by cardiac failure or fluid overload; 
• Need objective assessment (e.g., echocardiography) to exclude hydrostatic edema if no 
risk factor present. 
• ARDS severity categories are defined as: 
o Mild: 200 mmHg, < PaO2/FiO2, ≤300 mmHg with PEEP or CPAP ≥5 cm H2O. 
o Moderate: 100 mmHg, < PaO2/FiO2, ≤200 mmHg with PEEP ≥5 cm H2O. 
o Severe: PaO2/FiO2 ≤100 mmHg with PEEP ≥5 cm H2O. 
 
9.2. 
Randomization 
The central stratified randomization will be used to assign subjects into 1 of the 2 study treatment 
arms with an equal randomization ratio (1:1) with the stratification factors of subject’s clinical 
status at Baseline ([lung injury/mild ARDS] or [moderate/severe ARDS]) and country. 


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Hypotheses 
This is a double-blind, placebo-controlled, randomized trial testing a superiority hypothesis of 
significant reduction of the gimsilumab versus placebo in the percentage of the primary endpoint. 
 
9.3. 
Analysis Endpoints 
 
9.3.1. 
Efficacy Endpoints 
 
Primary endpoint: 
• Incidence of mortality by Day 43 
Key Secondary Endpoints: 
• 
Proportion of subjects who survived and were not requiring mechanical ventilation on 
Day 29 
• 
Mechanical ventilation-free days by Day 29 
• 
Time to hospital discharge by Day 43 
Additional Secondary Endpoints: 
• 
Incidence of mortality by Days 15, 22, 29, 85, and 169 (End-of-Study [EoS]). 
• 
Proportion of subjects who survived and were not requiring mechanical ventilation on Days 
15, 22, and 43. 
• 
Mechanical ventilation-free days for all subjects by Days 15, 22, and 43 
• 
ICU-free days for all subjects by Days 15, 22, 29, and 43. 
• 
Incidence of mechanical ventilation use for all subjects by Days 15, 22, 29, and 43. 
• 
Incidence of ICU use for all subjects by Days 15, 22, 29, and 43 
• 
Time to death by Day 43 and Day 169 (EoS) 
• 
NEWS assessed daily while hospitalized 
• 
SOFA score, and each of the components, assessed daily while in the ICU 
• 
The percentage of subjects reporting each severity rating on the 7-point ordinal scale, 
assessed daily while hospitalized and, if discharged from hospital, on Days 15, 22, 29, 36, 
43, 85, and 169 (assessed by phone) 
• 
Status on the 7-point ordinal scale, assessed daily while hospitalized and, if discharged from 
hospital, on Days 15, 22, 29, 36, 43, 85, and 169 (assessed by phone) 
• 
Time to clinical improvement by 2 points on the 7-point ordinary scale 
• 
Change from Baseline in SpO2/FiO2, assessed daily while hospitalized 
• 
Incidence and duration of oxygen use during the study 
• 
Change from Baseline in viral load as measured by quantitative PCR test on Days 2, 9, and 
DoD 
• 
Change from Baseline in D-dimer, cardiac troponin I, LDH, ferritin, and CRP 
• 
Serum gimsilumab concentrations 


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• 
Analysis of anti-gimsilumab antibodies (ADAs) 
Exploratory Endpoints: 
• 
Change from Baseline in the cytokine panel and SP-D 
• 
Change from Baseline in LIS (if performed) 
• 
Change from Baseline in chest radiographic assessment (if performed) 
• 
Change from Baseline in P/F ratio, if performed 
• 
Incidence and duration of ECMO use 
• 
Change from Baseline in LVEF (when measured) 
• 
Change from Baseline in eGFR (MDRD equation), assessed when central clinical safety 
laboratory measurements are collected during hospitalization 
 
9.3.2. 
Safety Endpoints 
 
Safety and tolerability, including assessment of clinical safety laboratory measurements, physical 
examinations, vital signs, concomitant medications; cumulative incidence of AEs, SAEs, and 
severe AEs. 
 
9.3.3. 
Pharmacokinetic Endpoints 
 
Serum gimsilumab concentration at time points as specified in the Schedule of Assessments 
(Table 7-2). 
 
9.3.4. 
Biomarker Endpoints 
 
Change from Baseline in the cytokine panel and serum SP-D will be measured at time points as 
specified in the Schedule of Assessments (Table 7-2). 
 
9.4. 
Analysis Populations 
Key Analysis Sets 
• The Intent-to-treat (ITT) Population will include all randomized subjects who receive any 
amount of study drug. The ITT subjects will be analyzed according to randomized treatment, 
irrespective of whether or not they have prematurely discontinued. Subjects who withdraw 
from treatment and/or the study will be followed for Day 43 all-cause mortality. All efficacy 
analyses will be performed using the ITT Population. 
• The Safety Population (SP) will include all randomized subjects who receive any amount of 
study drug. The SP will be analyzed according to the treatment received. This set will be used 
for the safety analyses. 
• The per-protocol (PP) Population will include all subjects in the ITT Population who 
complete the Day 43 Visit with no protocol major violations. The PP Population will be used 
for supportive analyses of the efficacy measurements. 


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9.5. 
Statistical Analyses/Methods 
All statistical analyses will be conducted on SAS Version 13.1 or later. 
In general, all the continuous variables, including the changes from Baseline, will be summarized 
by the treatment with the mean, standard deviation (SD), median and the range. The Mixed 
Model with Repeated Measurements (MMRM) /Analysis of Covariance (ANCOVA) model with 
the treatment, country, subject’s clinical status at Baseline ([lung injury/mild ARDS] or 
[moderate/severe ARDS]), and visits as the model term will be used to test for the significance of 
the treatment difference. The least square means, standard errors, 95% CIs and p-values will be 
presented. 
All the categorical variables will be summarized by the treatment with the numbers and 
percentages of the subjects, and the treatment difference, the odds ratio and 95% CI will be 
tested by using logistical model (Ge, 2011) with the Treatment, country, and subject’s clinical 
status at baseline ([lung injury/mild ARDS] or [moderate/severe ARDS]) for binary outcome. 
The CMH test will be used for other categorical outcomes. 
The time to event endpoints will be analyzed by using the Cox Proportional Hazard model with 
the treatment, country , and subject’s clinical status at Baseline ([lung injury/mild ARDS] or 
[moderate/severe ARDS]) as the model term. The hazard ratio of gimsilumab versus placebo will 
be presented with 95% CI and p-value from the model. The Kaplan-Meier curves of the time to 
events will be presented for treatments on each endpoint. 
The sites, which enrolled small number of subjects, will be combined in the statistical models. A 
blinded data review will be conducted for pooling the sites. 
An SAP will be prepared and sent to agencies prior to the interim analysis. 
 
9.5.1. 
Primary Efficacy Analyses 
 
The primary analysis of the primary endpoint will be performed by using the logistical regression 
with the Treatment, country, and subject’s clinical status at Baseline ([lung injury/mild ARDS] 
or [moderate/severe ARDS]). The subjects who died by Day 43 (by Day 169) will be 
summarized by the numbers and percentages, difference of the percentages, the odds ratio and its 
95% CI presented for gimsilumab versus placebo, and p-value. 
The secondary analysis of the primary endpoint will be conducted by using the Cox Proportional 
Hazard model with treatment, country and subject’s clinical status at Baseline ([lung injury/mild 
ARDS] or [moderate/severe ARDS] on the time to death. The median of the time to event from 
Kaplan-Meier curves will be presented for each treatment, and the hazard ratio of the 
gimsilumab dose level versus placebo will be presented with 95% CI, and p-values. 
 
9.5.2. 
Sensitivity Analysis of the Primary Endpoint 
 
Sensitivity analyses will be performed using all randomized subjects and using a multiple 
imputation method, such as the tipping point method, to handle missing data, as described in 
Section 9.5.5. 


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The Per-Protocol (PP) Population will be used for the primary and secondary analysis of the 
primary endpoint as additional supportive analyses. 
 
9.5.3. 
Analysis of the Key and Other Secondary Endpoints 
 
Secondary endpoints will be analyzed as follows: 
• Incidence data (e.g., incidence of new or increased oxygen use) will be summarized as a 
percent with 95% CIs. The logistic regression model with treatment, country, and 
subject’s clinical status at Baseline ([lung injury/mild ARDS] or [moderate/severe 
ARDS]) will be used for the odds ratio of gimsilumab versus placebo, 95% CIs and p- 
values. 
• Change in ordinal scale at specific time points will be summarized by proportions 
(e.g., proportion who have a 1-, 2-, 3-, or 4-point improvement or 1-, 2-, 3-, 4-point 
worsening). The CMH test on combined subject’s clinical status at Baseline ([lung 
injury/mild ARDS] or [moderate/severe ARDS]) will be used for treatment difference. 
The odds ratio of gimsilumab versus placebo, 95% CIs and p-values will be provided. 
• Duration of event free (e.g., mechanical ventilation free days) will be summarized 
according to median days with quartiles. The Wilcoxon rank test will be used for the 
treatment difference. 
• The continuous variables, including the changes from baseline, will be summarized by 
the treatment with the mean, standard deviation (SD), median, and the range. PK 
summaries will include geometric mean and geometric coefficient of variation. The 
Mixed Model with Repeated Measurements (MMRP)/Analysis of Covariance 
(ANCOVA) with the treatment, country, subject’s clinical status at Baseline ([lung 
injury/mild ARDS] or [moderate/severe ARDS]), and visit as the model term, and 
baseline value as the covariate will be used for the treatment difference. The least square 
means, standard errors, 95% CIs and p-values will be presented. 
• The time-to-event endpoints will be summarized with Kaplan Meier curves and 95% 
confidence bounds by the treatment. The Cox Proportional Hazard model with treatment, 
country, and subject’s clinical status at Baseline ([lung injury/mild ARDS] or 
[moderate/severe ARDS]) as model terms will be used. The hazard ratio of gimsilumab 
versus placebo will be presented with 95% CI and p-values. 
 
9.5.4. 
Adjustment of Multiple Comparisons and Interim Analyses 
 
The interim analysis will be conducted when 60 subjects have been treated and have completed 
through Day 15; the DMC will review the data for safety and futility and provide their 
recommendations. 
The second interim analysis will be conducted when 100 subjects have completed at least the 
Day 29 Visit for non-mortality endpoints and have the data for the endpoint of mortality (by 
Day 43). 
The objectives of the second interim analysis will be to stop the study by superiority, futility, or 
perform the sample size re-estimation. For controlling overall two-sided alpha of 0.05 overall for 
the final analysis on the primary endpoint of Mortality Day 43, 0.001 of the alpha will be used 


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for the superiority comparison during the second interim analysis, and 0.049 will be used for the 
final analysis for Day 43. The weighted average of two summary measures by Cui L, Hung HM, 
Wang [Cui, 1999] will be used, one based on the data collected in the interim analysis, and the 
other based on the data collected after the interim. 
 
9.5.5. 
Handling of Missing Data 
 
Sensitivity analyses will be performed for the primary and key secondary endpoints using 
multiple imputations for the missing data: 
• Tipping-point multiple imputation analysis 
Missing data will be imputed for mortality by Day 43 with all possible combinations of death or 
survival in the two arms. The combination which alters the conclusion will be defined as the 
tipping point for evaluation on the robustness of the results. 
• Imputation differentiating the reasons of missing data from the early drop out 
The reasons of the lost to follow-up, SAEs/AEs, and the use of rescue medications will be 
identified, and the percentage of these subjects will be summarized by treatment. The data for 
informative censoring, such as the unfavorable or worst outcome, can be used to impute the 
missing data. 
 
9.5.6. 
Safety Analyses 
 
Safety will be assessed based on the SP for AEs, laboratory parameters, physical examination, 
vital signs, and clinical chemistries throughout the duration of the study. The safety analyses will 
include descriptive summaries by treatment arm of AEs. The number and percentage of 
participants reporting AEs and SAEs will be presented. Adverse events will be categorized by 
system organ class (SOC) and preferred term (PT) and summarized by the number of participants 
(and percentage) with at least 1 event, and the number of events. Adverse events will also be 
summarized by seriousness, grade, and study drug relationship for all participants. The 
continuous variables, including the changes from Baseline, will be summarized by descriptive 
statistics: mean, SD, and the range. The categorical variables, such as normal/abnormal will be 
summarized by the numbers and percentages at each visit, and the shift table from Baseline to 
each visit will be presented. 
 
9.5.7. 
Sub-Group Analyses 
 
Subgroup analyses for the primary outcomes will evaluate the treatment effect across the 
following subgroups: country, subject’s clinical status at Baseline ([lung injury/mild ARDS] or 
[moderate/severe ARDS]), country, age, and sex. A forest plot will display confidence intervals 
across subgroups. Interaction tests will be conducted to determine whether the effect of treatment 
varies by subgroup. 


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9.5.8. 
Timing of Analyses 
 
The first unblinded analysis will be conducted when the last subject completes the Day 43 Visit, 
discontinues the study early, or meets the primary endpoint of mortality (by Day 43). The final 
analysis will be conducted when the last subject completes the Day 169 (EoS) Visit. The first 
interim analysis will be conducted when 60 subjects have been treated and have completed 
through Day 15; the DMC will review the data for safety and futility and provide their 
recommendations. 
The second interim analysis will be conducted when 100 subjects have completed at least the 
Day 29 Visit for non-mortality endpoints and have the data for the endpoint of mortality (by Day 
43). The objectives of the second interim analysis will include the claim of superiority or futility 
to stop the study, or the reassessment of sample size, and/or modifications of the populations. 
The DMC will be responsible for closely reviewing the safety data from the unblinded interim 
analysis and for providing their recommendations. The detailed objectives and procedures, 
including close monitoring of the safety data and the boundaries of futility will be described in 
the SAP and the DMC Charter. 
 
9.5.9. 
Pharmacokinetic, Biomarker, and Immunogenicity Analyses 
 
Serum gimsilumab concentrations will be summarized using descriptive statistics. 
Biomarker analyses will be based on the Safety Population and biomarker (SP-D, 
cytokine/chemokine, anti-GM-CSF autoAb) concentrations will be summarized by treatment 
using descriptive statistics. 
Immunogenicity analysis will be based on the Safety Population and anti-drug antibody data will 
be reported in the format provided by the bioanalytical laboratory. 
Further details will be provided in the SAP. 
 
10. 
ADVERSE EVENTS (AE) AND SERIOUS ADVERSE EVENTS 
(SAES) 
The Investigator or site staff is responsible for detecting, documenting and reporting events that 
meet the definition of an AE or SAE. 
The Investigator is not obligated to actively seek AEs or SAEs in former study participants. 
However, if the Investigator learns of any SAE, including a death, at any time after a subject has 
been discharged from the study, and he/she considers the event reasonably related to the 
investigational product or study participation, the Investigator should promptly notify the 
Sponsor. 
 
10.1. 
Special Consideration for Assessment of Adverse Events 
It is recognized that the patient population in the ICU will experience a number of common 
aberrations in laboratory values, signs and symptoms due to the severity of their underlying 
disease and the impact of standard therapies. These will not necessarily constitute an AE unless 


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they require significant intervention, lead to discontinuation of blinded study drug, or are 
considered to be of concern in the investigator’s clinical judgement. 
Death should be recorded both as a SAE and as the outcome of ONE event, i.e. one event should 
be determined to be the primary cause of death. The 'clinical' AE that resulted in death is the AE 
and the death information supports the clinical AE. 'Death' is not entered as an AE unless the 
cause of death is unknown. In such case the AE term is 'Unspecified fatal event' until the cause 
of the death is known. 
 
10.2. 
Definition of an Adverse Event 
An AE is any untoward medical occurrence in a patient or clinical investigation subject, 
temporally associated with the use of a medicinal product, whether or not considered related to 
the medicinal product. 
Note: 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 a medicinal product. 
Events meeting the definition of an AE include but are not limited to: 
• 
Any clinically significant, new or worsening, abnormal laboratory test results 
(hematology, clinical chemistry, or urinalysis) or findings from other safety assessments 
(e.g., ECGs, radiological scans, vital signs measurements. Clinical significance is 
determined by the medical and scientific judgement of the Investigator. 
• 
Worsening of a chronic or intermittent pre-existing condition including an increase in 
frequency, intensity and/or duration of a condition. 
• 
Signs, symptoms, or the clinical sequelae of a suspected interaction (e.g., with 
medications or food). 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either 
investigational product or a concomitant medication (overdose without the presence of 
an AE are to be reported as a protocol violation). 
• 
New infections occurring on-study, regardless of infection type (i.e., viral, bacterial, 
fungal, etc.) will be reported as AEs. 
Events that do not meet the definition of an AE include: 
• 
Anticipated day-to-day fluctuations of a pre-existing condition(s), (including the 
disease under study), that do not represent a clinically significant exacerbation or 
worsening. 
• 
Abnormal or worsening laboratory, (including imaging) findings or other safety 
findings that are not clinically significant. 
• 
Medical or surgical procedure (e.g., endoscopy, appendectomy). However, the 
condition that leads to the procedure is to be considered a reportable AE. 


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• 
If applicable, the disease/disorder being studied, or expected progression, signs, or 
symptoms of the disease/disorder being studied, unless more severe than expected for 
the subject’s condition. 
• 
Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
 
10.3. 
Definition of a Serious Adverse Event 
An SAE is any untoward medical occurrence that, at any dose: 
• Results in death 
• Is life-threatening 
NOTE: The term 'life-threatening' in the definition of 'serious' refers to an event in which 
the subject was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
• Requires hospitalization or prolongation of existing hospitalization 
NOTE: “Hospitalization” includes admission to the hospital of any duration. 
Complications that occur during hospitalization are AE sand are SAEs if they prolong a 
hospitalization or meets any other serious criteria. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered serious. 
• Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
Baseline is not considered an AE. 
• Results in disability/incapacity 
NOTE: The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. This definition is not intended to include experiences of 
relatively minor medical significance such as uncomplicated headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma (e.g. sprained ankle) which may interfere or 
prevent everyday life functions but do not constitute a substantial disruption. 
• Is a congenital anomaly/birth defect 
• Is an important medical event that may jeopardize the participant or may require medical 
or surgical intervention to prevent one of the outcomes listed above. Examples of such 
events are invasive or malignant cancers, allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency or 
drug abuse. 
 
10.4. 
Time Period and Frequency for Collecting AE and SAE 
Information 
 
• 
AEs will be collected from the start of Study Treatment until the follow-up contact, at 
the timepoints specified in the Schedule of Assessments (Table 7-2). 


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• 
SAEs related to study procedures or investigational product will be collected from the 
time of subject informed consent until the follow-up contact is completed. 
• 
Medical occurrences that begin prior to the start of study treatment but after obtaining 
informed consent may be recorded on the Medical History/Current Medical Conditions 
section of the CRF. 
• 
All SAEs will be recorded and reported to the Sponsor within 24 hours of awareness. 
 
10.5. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and non- 
leading verbal questioning of the subject is the preferred method to inquire about AE occurrence. 
Appropriate questions include: 
• 
“How are you feeling?” 
• 
“Have you had any (other) medical problems since your last visit/contact?” 
• 
“Have you taken any new medicines, other than those provided in this study, since your 
last visit/contact? 
 
10.6. 
Assessing Severity of AEs and SAEs 
Severity describes the intensity of a specific event (as in mild, moderate, or severe myocardial 
infarction); the event itself, however, may be of relatively minor medical significance, such as a 
severe headache. This is not the same as “serious,” which is based on participant/event outcome 
or action taken. The Investigator must determine the severity of each AE according to the 
following criteria. 
 
Criteria for Determining the Grade/Severity of Adverse Event Terms 
 
Grade 
Criteria 
1/Mild 
Asymptomatic or mild symptoms, clinical or diagnostic 
observations only; intervention not indicated 
2/Moderate 
Minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living 
3/Severe or medically significanta 
Not immediately life threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting 
self-care activities of daily living. 
4/Life-threateninga 
Life threatening consequences; urgent intervention 
indicated 
5/Death 
Death related adverse events 
a    Severe AEs include both Grade 3 and Grade 4 AEs. 


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10.7. 
Assessing Causalities of AEs and SAEs 
Regulatory authorities require that both investigator and sponsor assess whether there is a 
reasonable possibility that the study treatment caused each AE. This assessment requires careful 
medical consideration of each event in relationship to the timing of drug administration, the 
presence of other factors which may have caused the event (underlying illness, concomitant 
medication, complications, exposure to other toxins or allergens, environmental factors, etc.), 
and the effects of stopping and/or restarting the study treatment. 
The investigator will assess the causality of each reported AE as follows: 
• 
Probably related: an AE occurring at a reasonable time following administration of a 
drug, where other causes are unlikely, there is evidence to suggest that the drug caused 
the event, and/or where the event recurs after reintroduction of the drug (without other 
explanation for the recurrence). 
• 
Possibly related: an AE occurring at a reasonable time following administration of a 
drug and for which there is a reasonable possibility that the drug caused the event, e.g., 
there is some evidence to suggest a causal relationship. 
• 
Not related: an AE with poor or no relationship to the timing of drug administration, or 
where another cause such as underlying disease, complications, or other medications 
reasonably explains the event, or where the event does not recur after continued 
administration or reintroduction of the drug for an adequate period. 
 
10.8. 
Follow-up of (non-serious) AEs and Serious AEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each subject at 
subsequent visits/contacts. All SAEs, and non-serious AEs, will be followed until resolution, 
until the condition stabilizes, until the event is otherwise explained, or until the subject is lost to 
follow-up. Ongoing AEs may be closed after consultation between the Sponsor and Medical 
Monitor. 
 
10.9. 
Regulatory Reporting Requirements for SAEs 
On discovery, all SAEs should be immediately reported (latest within 24 hours of knowledge of 
 
See Section 6.4 for emergency unblinding service contact information. 
Prompt notification by the Investigator to the Sponsor of SAEs is essential so that legal 
obligations and ethical responsibilities towards the safety of subjects and the safety of a product 
under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and any other 
regulatory agencies about the safety of a product under clinical investigation. The Sponsor will 
comply with country specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRB/IEC and Investigator. 
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Investigator safety reports are prepared for suspected unexpected serious adverse reactions 
according to local regulatory requirements and are forwarded to Investigators as necessary. 
 
11. 
PREGNANCY REPORTING 
• 
All female subjects will be tested for pregnancy prior to dosing. Subjects testing 
positive for pregnancy will be ineligible for study participation. 
• 
Any pregnancy reported between the time of informed consent and completion of the 
Day 85 Follow-up Visit or an Early Termination Visit must be reported to the Sponsor 
within 2 weeks of learning of the pregnancy. 
• 
Female subjects who become pregnant will also be followed to determine the outcome 
of the pregnancy. Information on the status of the mother and child will be provided to 
the Sponsor. Generally, follow-up will be no longer than 6 to 8 weeks following the 
estimated delivery date. Any premature termination of the pregnancy will be reported. 
 
12. 
RESPONSIBILITIES 
 
12.1. 
Principal Investigator Responsibilities 
12.1.1. 
Good Clinical Practice 
 
The Principal Investigator will ensure that this study is conducted in accordance with the 
principles of the “Declaration of Helsinki” (as amended in Edinburgh, Tokyo, Venice, Hong 
Kong, and South Africa), International Conference on Harmonisation (ICH) guidelines, or with 
the laws and regulations of the country in which the research is conducted, whichever affords the 
greater protection to the study subject. For studies conducted under a United States IND, the 
Investigator will ensure that the basic principles of “Good Clinical Practice,” as outlined in 
21 Code of Federal Regulations (CFR 312), subpart D, “Responsibilities of Sponsors and 
Investigators,” 21 CFR, part 50, 1998, and 21 CFR, part 56, 1998, are adhered to. These 
standards are consistent with the requirements of the European Community Directive 
2001/20/EC. 
Since this is a “covered” clinical trial, the Principal Investigator will ensure that 21 CFR, Part 54, 
1998, is adhered to; a “covered” clinical trial is any “study of a drug or device in humans 
submitted in a marketing application or reclassification petition subject to this part that the 
applicant or FDA relies on to establish that the product is effective (including studies that show 
equivalence to an effective product) or that make a significant contribution to the demonstration 
of safety.” This requires that Principal Investigators and all sub-investigators must provide 
documentation of their financial interest or arrangements with the Sponsor, or proprietary 
interests in the drug being studied. This documentation must be provided before participation of 
the Investigator and any sub-investigator. The Principal Investigator and sub-investigator agree 
to notify the Sponsor of any change reportable interests during the study and for one year 
following completion of the study. Study completion is defined as the date that the last subject 
has completed the protocol defined activities. 


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12.1.2. 
Institutional Review Board/Independent Ethics Committee Approval 
 
This protocol and any accompanying material to be provided to the subject (such as 
advertisements, subject information sheets, or descriptions of the study used to obtain informed 
consent) will be submitted by the Investigator to an IRB or IEC. Approval from the IRB or IEC 
must be obtained before starting the study and should be documented in a letter to the 
Investigator specifying the protocol number, protocol version, protocol date, documents 
reviewed, and date on which the committee met and granted the approval. 
Any modifications made to the protocol after receipt of IRB or IEC approval must also be 
submitted to the IRB or IEC for approval before implementation. 
 
12.1.3. 
Informed Consent 
 
The Principal Investigator or designee is responsible for obtaining written informed consent from 
each individual participating in this study after adequate explanation of the aims, methods, 
objectives, and potential hazards of the study and before undertaking any study-related 
procedures. The Investigator must utilize an IRB or IEC-approved consent form for documenting 
written informed consent. Each informed consent will be appropriately signed and dated by the 
subject or the subject’s legally authorized representative and the person obtaining consent. 
 
12.1.4. 
Confidentiality 
 
The Principal Investigator must assure that subjects’ anonymity will be strictly maintained and 
that their identities are protected from unauthorized parties. Only subject number, date of birth, 
and an identification code (i.e., not names) should be recorded on any form or biological sample 
submitted to the Sponsor, IRB or IEC, or laboratory. The Principal Investigator must keep a 
screening log showing codes, names, and addresses for all subjects screened and for all subjects 
enrolled in the trial. 
The Principal Investigator agrees that all information received from the Sponsor, including but 
not limited to the Investigator Brochure, this protocol, CRFs, the investigational new drug, and 
any other study information, remain the sole and exclusive property of the Sponsor during the 
conduct of the study and thereafter. This information is not to be disclosed to any third party 
(except employees or agents directly involved in the conduct of the study or as required by law) 
without prior written consent from the Sponsor. The Investigator further agrees to take all 
reasonable precautions to prevent the disclosure by any employee or agent of the study site to 
any third party or otherwise into the public domain. 
 
12.1.5. 
Study Files and Retention of Records 
 
The Principal Investigator must maintain adequate and accurate records to enable the conduct of 
the study to be fully documented and the study data to be subsequently verified. These 
documents should be classified into at least the following two categories: (1) Investigator’s study 
file, and (2) subject clinical source documents. 


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The Investigator’s study file will contain the protocol/amendments, CRF and query forms, IRB 
or IEC and governmental approval with correspondence, informed consent, drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and correspondence. 
The required source data should include the following for each subject: 
• 
subject identification (name, date of birth, gender); 
• 
documentation that subject meets eligibility criteria, i.e., history, physical examination, 
and confirmation of diagnosis (to support inclusion and exclusion criteria); 
• 
participation in trial (including trial number); 
• 
trial discussed and date of informed consent; 
• 
dates of all visits; 
• 
documentation that protocol specific procedures were performed; 
• 
results of efficacy parameters, as required by the protocol; 
• 
start and end date (including dose regimen) of trial medication (preferably drug 
dispensing and return should be documented as well); 
• 
record of all AEs and other safety parameters (start and end date, and preferably 
including causality and intensity); 
• 
concomitant medication (including start and end date, dose if relevant; dose changes 
should be motivated); 
• 
date of trial completion and reason for early discontinuation, if applicable. 
All clinical study documents must be retained by the Principal Investigator until at least 2 years 
after the last approval of a marketing application in an ICH region (i.e., United States, Europe, or 
Japan) and until there are no pending or contemplated marketing applications in an ICH region; 
or, if no application is filed or if the application is not approved for such indication, until 2 years 
after the investigation is discontinued and regulatory authorities have been notified. The 
Principal Investigator may be required to retain documents longer if required by applicable 
regulatory requirements, by local regulations, or by an agreement with the Sponsor. The 
Investigator must notify the Sponsor before destroying any clinical study records. 
Should the Principal Investigator wish to assign the study records to another party or move them 
to another location, the Sponsor must be notified in advance. 
If the Investigator cannot guarantee this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the Principal Investigator and the 
Sponsor to store these in sealed containers outside of the site so that they can be returned sealed 
to the Investigator in case of a regulatory audit. When source documents are required for the 
continued care of the subject, appropriate copies should be made for storage outside of the site. 
Unused biological samples remaining at the conclusion of this study may be retained in an 
appropriate storage facility by the Sponsor for a period up to 10 years for purposes of this study. 


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12.1.6. 
Electronic Case Report Forms (eCRF) 
 
For each subject enrolled, an eCRF must be completed and signed by the Principal Investigator 
or sub-investigator (as appropriate) within a reasonable time period after data collection. This 
also applies to records for those subjects who fail to complete the study (even during a pre- 
randomization screening period if an eCRF was initiated). If a subject withdraws from the study, 
the reason must be noted on the eCRF. If a subject is withdrawn from the study because of a 
treatment-limiting AE, thorough efforts should be made to clearly document the outcome. 
12.1.7. 
Drug Accountability 
 
The Investigator or designee (i.e., pharmacist) is responsible for ensuring adequate accountability 
of all used and unused investigational medicinal product, placebos, and comparators. This 
includes acknowledgment of receipt of each shipment of study product (quantity and condition), 
subject dispensing records, and returned or destroyed study product. Dispensing records will 
document quantities received from the Sponsor and quantities dispensed to subjects, including 
lot number, date dispensed, subject identifier number, and the initials of the person dispensing 
the medication. 
At study initiation, the monitor will evaluate the site’s standard operating procedure for 
investigational medicinal product disposal/destruction in order to ensure that it complies with the 
Sponsor requirements. Drug may be returned or destroyed on an ongoing basis during the study 
if appropriate. At the end of the study, following final drug inventory reconciliation by the 
monitor, the study site will ship all unused investigational medicinal product supplies to the 
designated depot, according to these procedures. If the site cannot meet the Sponsor’s 
requirements for disposal, arrangements will be made between the site and the Sponsor or its 
representative for destruction or return of unused investigational medicinal product supplies. 
All drug supplies and associated documentation will be periodically reviewed and verified by the 
study monitor over the course of the study. 
 
12.1.8. 
Inspections 
 
The Principal Investigator should understand that source documents for this trial should be made 
available to appropriately qualified personnel from the Sponsor or its representatives, to IRBs or 
IECs, or to regulatory authority or health authority inspectors. 
12.1.9. 
Protocol Compliance 
 
The Principal Investigator is responsible for ensuring the study is conducted in accordance with 
the procedures and evaluations described in this protocol. 
12.2. 
Sponsor Responsibilities 
12.2.1. 
Protocol Modifications 
 
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by the Sponsor. All protocol modifications must be submitted to the IRB or IEC in 


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accordance with local requirements. Approval must be obtained before changes can be 
implemented. 
12.2.2. 
Study Report and Publications 
 
A clinical study report will be prepared and provided to the regulatory agency(ies). The Sponsor 
will ensure that the report meets the standards set out in the ICH Guideline for Structure and 
Content of Clinical Study Reports (ICH E3). Note that an abbreviated report may be prepared in 
certain cases. 
12.3. 
Joint Investigator/Sponsor Responsibilities 
12.3.1. 
Access to Information for Monitoring 
 
In accordance with ICH Good Clinical Practice guidelines, the study monitor must have direct 
access to the Principal Investigator’s source documentation in order to verify the data recorded in 
the CRFs for consistency. 
The monitor is responsible for routine review of the CRFs at regular intervals throughout the 
study to verify adherence to the protocol and the completeness, consistency, and accuracy of the 
data being entered on them. The monitor should have access to any subject records needed to 
verify the entries on the CRFs. The Investigator agrees to cooperate with the monitor to ensure 
that any problems detected in the course of these monitoring visits are resolved. 
12.3.2. 
Access to Information for Auditing or Inspections 
 
Representatives of regulatory authorities or of the Sponsor may conduct inspections or audits of 
the clinical study. If the Principal Investigator is notified of an inspection by a regulatory 
authority the Principal Investigator or designee agrees to notify the Medical Monitor 
immediately. The Principal Investigator agrees to provide to representatives of a regulatory 
agency or the Sponsor access to records, facilities, and personnel for the effective conduct of any 
inspection or audit. 
12.3.3. 
Study Discontinuation 
 
The Sponsor reserves the right to terminate the study at any time. Should this be necessary, the 
Sponsor will arrange discontinuation procedures and notify the appropriate regulatory 
authority(ies), IRBs, and IECs. In terminating the study, the Sponsor and the Principal 
Investigator will assure that adequate consideration is given to the protection of the subjects’ 
interests. 


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Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: The Berlin 
Definition. JAMA. 2012;307(23):2526-33. 
Barrett DM, Singh N, Hofmann T, et al. Interleukin 6 Is Not Made By Chimeric Antigen 
Receptor T Cells and Does Not Impact Their Function. Blood. 2016;128(22):654. 
doi:10.1182/blood.V128.22.654.654. 
Channappanavar R, Fehr AR, Vijay R, et al. Dysregulated type I interferon and inflammatory 
monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host 
Microbe. 2016;19(2):181-193. doi:10.1016/j.chom.2016.01.007. 
Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and 
consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017;39(5):529- 
539. doi:10.1007/s00281-017-0629-x. 
Coronavirus disease (COVID-2019) R&D. Geneva: World Health Organization 
(http://www.who.int/blueprint/priority-diseases/key-action/novel-coronavirus/en/) 
Coronavirus disease 2019 (COVID-19) situation reports. World Health Organization. 
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports Accessed 
March 17, 2020. 
Cui L, Hung HM, Wang SJ. Modification of sample size in group sequential clinical trials. 
Biometrics. 1999;55:853–7. 
Gimsilumab Investigator’s Brochure, Current Edition. 
Ge M, Durham LK, and Meyer DR. Covariate-adjusted difference in proportions from clinical 
trials using logistic regression and weighted risk differences. Drug Information Journal 
2011;45:4 
Hatcher RA, Trussell J, Nelson AL, Cates W Jr, Stewart F, Kowal D, editors. Contraceptive 
Technology. 19th edition. New York: Ardent Media, 2007(a): 24. Table 3-2. 
Hamilton JA. GM-CSF in inflammation. J Exp Med. 2020;217(1)pii:e20190945. 
doi:10.1084/jem.20190945. 
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus 
in Wuhan, China. Lancet. 2020;395(10223):497-506. doi:10.1016/s0140-6736(20)30183-5. 
Ishii K, Shalabi H, Yates B, et al. Tocilizumab-Refractory Cytokine Release Syndrome (CRS) 
Triggered By Chimeric Antigen Receptor (CAR)-Transduced T Cells May Have Distinct 
Cytokine Profiles Compared to Typical CRS. Blood. 2016;128(22):3358. 
doi:10.1182/blood.V128.22.3358.3358. 


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Kristas SK, Ronconi G, Caraffa A, et al. Mast cells contribute to coronavirus-induced 
inflammation: new anti-inflammatory strategy. J Biol Regul Homeost Agents. 2020;34(1). doi: 
10.23812/20-Editorial-Kritas. 
Kwon OC, Lee E, Chang E, et al. IL-17A+GM-CSF+ Neutrophils Are the Major Infiltrating Cells 
in Interstitial Lung Disease in an Autoimmune Arthritis Model. Front Immunol. 2018;9:1544. 
doi:10.3389/fimmu.2018.01544. 
Kudlak K, DeMuro JP, Hanna AF, et al. Acute lung injury following the use of granulocyte- 
macrophage colony-stimulating factor. Int J Crit Illn Inj Sci. 2013;3(4):279-281. 
doi:10.4103/2229-5151.124168. 
Lam CWK, Chan MHM, Wong CK. Severe Acute Respiratory Syndrome: Clinical and 
Laboratory Manifestations. Clin Biochem Rev. 2004;25(2):121-132. 
Liao M, Liu Y, Yuan J, et al. The landscape of lung bronchoalveolar immune cells in COVID-19 
revealed by single-cell RNA sequencing. Pre-Print. 2020. 
https://doi.org/10.1101/2020.02.23.20026690. 
Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and 
immunosuppression. Lancet. 2020. doi:10.1016/S0140-6736(20)30628-0. 
Molfino NA, Kuna P, Leff JA, et al. Phase 2, randomised placebo-controlled trial to evaluate the 
efficacy and safety of an anti-GM-CSF antibody (KB003) in patients with inadequately 
controlled asthma. BMJ Open. 2016;6(1):e007709. doi:10.1136/bmjopen-2015-007709. 
Nobs SP, Kayhan M, Kopf M. GM-CSF intrinsically controls eosinophil accumulation in the 
setting of allergic airway inflammation. J Allergy Clin Immunol. 2019;143(4):1513-1524.e2. 
doi:10.1016/j.jaci.2018.08.044. 
Novel Coronavirus Pneumonia Diagnosis and Treatment Plan (Provisional 7th Edition). China 
Law Translate. https://www.chinalawtranslate.com/en/coronavirus-treatment-plan-7/. Published 
March 10, 2020. Accessed March 15, 2020. 
Pipeline: Humanigen. Humanigen, Inc. https://www.humanigen.com/pipeline. Accessed March 
14, 2020. 
Piper C, Pesenacker AM, Bending D, et al. T Cell Expression of Granulocyte–Macrophage 
Colony-Stimulating Factor in Juvenile Arthritis Is Contingent Upon Th17 Plasticity. Arthritis 
Rheumatol. 2014;66(7):1955-1960. doi:10.1002/art.38647. 
Nadicksbernd J. CD11b expression on granulocytes after induction by granulocyte-macrophase 
colony stimulating factor in EDT whole blood by flow cytometry. PPD Primary Validation 
Summary. 2013. 
Puljic R, Benediktus E, Plater-Zyberk C, et al. Lipopolysaccharide-induced lung inflammation is 
inhibited by neutralization of GM-CSF. Eur J Pharmacol. 2007;557(2-3):230-235. 
doi:10.1016/j.ejphar.2006.11.023. 


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Sakagami T, Suzuki T, Carey B, Chalk C, Trapnell B. A Novel Assay To Measure GM-CSF 
Signaling In Clinical Blood Specimens. Am J Respir Crit Care Med. 2010; 181:A2987. 
Sheih A, Parks WC, Ziegler SF. GM-CSF produced by the airway epithelium is required for 
sensitization to cockroach allergen. Mucosal Immunol. 2017;10(3):705-715. 
doi:10.1038/mi.2016.90. 
Shiomi A, Usui T, Ishikawa Y, et al. GM-CSF but Not IL-17 Is Critical for the Development of 
Severe Interstitial Lung Disease in SKG Mice. J Immunol. 2014;193(2):849-859. 
doi:10.4049/jimmunol.1303255. 
Sterner RM, Sakemura R, Cox MF, et al. GM-CSF inhibition reduces cytokine release syndrome 
and neuroinflammation but enhances CAR-T cell function in xenografts. Blood. 
2019;133(7):697-709. doi:10.1182/blood-2018-10-881722. 
Stienne C, Michieletto MF, Benamar M, et al. Foxo3 Transcription Factor Drives Pathogenic T 
Helper 1 Differentiation by Inducing the Expression of Eomes. Immunity. 2016;45(4):774-787. 
doi:10.1016/j.immuni.2016.09.010. 
The COVID-19 Investigation Team. First 12 patients with coronavirus disease 2019 (COVID- 
19) in the United States. Pre-Print. 2020. https://doi.org/10.1101/2020.03.09.20032896. 
Tugues S, Anorim A, Spath S, et al. Graft-versus-host disease, but not graft-versus-leukemia 
immunity, is mediated by GM-CSF-licensed myeloid cells. Sci Transl Med. 2018;10(469). 
doi:10.1126/scitranslmed.aat8410. 
Willart MAM, Deswarte K, Pouliot P, et al. Interleukin-1α controls allergic sensitization to 
inhaled house dust mite via the epithelial release of GM-CSF and IL-33. J Exp Med. 
2012;209(8):1505-17. doi:10.1084/jem.20112691. 
Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 
2019 (COVID-19) Outbreak in China. JAMA. 2020. doi:10.1001/jama.2020.2648. 
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with 
COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020; 395 (10229): 1054- 
1062. https://doi.org/10.1016/S0140-6736(20)30566-3. 
Zhou Y, Fu B, Zheng X, et al. Aberrant pathogenic GM-CSF+ T cells and inflammatory 
CD14+CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus. 
Pre-Print. 2020. https://doi.org/10.1101/2020.02.12.945576. 


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14. 
APPENDICES 
 
14.1. 
Appendix 1: Abbreviations and Trademarks 
 
Antibody 
Ab 
ADA(s) 
Anti-drug antibodies 
AE(s) 
Adverse event(s) 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of Covariance 
ARDS 
Acute Respiratory Distress Syndrome 
AST 
Aspartate aminotransferase 
AUC 
Area under the concentration-time curve 
BC 
Birth control 
CI 
Confidence interval 
CKD 
Chronic kidney disease 
Cmax 
Maximum concentration 
CMO 
Cochran-Mantel-Haenszel 
CO2 
Carbon dioxide 
COPD 
Chronic obstructive pulmonary disease 
COVID-19 
Coronavirus Disease 2019 
CPAP 
Continuous positive airway pressure 
CPK 
Serum creatine phosphokinase 
CRF 
Case Report Form 
CRP 
C-reactive protein 
CRS 
Cytokine release syndrome 
CT 
Computerized tomography 
DMC 
Data Monitoring Committee 
DMP 
Data Management Plan 
DoD 
Day-of-Discharge (from hospital) 
ECG(s) 
Electrocardiogram(s) 
ECMO 
Extracorporeal membrane oxygenation 
eCRF 
Electronic case report form 
eGFR 
Estimated glomerular filtration rate 
EoS 
End-of-Study 


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ET 
Early Termination 
FDA 
U.S. food and drug administration 
FiO2 
fraction of inspired oxygen 
FSH 
Follicle stimulating hormone 
G-CSF 
Granulocytecolony stimulating factor 
GFR 
Glomerular filtration rate 
GM-CSF 
Granulocyte macrophage-colony stimulating factor 
HBsAg 
Hepatitis B 
HCVAb 
Hepatitis C 
HIV 
Human immunodeficiency virus 
HR 
Heart rate 
ICH 
International Conference on Harmonisation 
ICU 
Intensive Care Unit 
IEC 
Independent ethics committee 
IGRA 
Interferon gamma release assay 
ILD 
Interstitial lung disease 
IPF 
Idiopathic pulmonary fibrosis 
IRB 
Institutional review board 
ITT 
Intent-to-Treat 
IUD 
Intrauterine device 
IUS 
Intrauterine system 
IV 
Intravenous(ly) 
KSG 
Kinevant Sciences GmbH 
KSI 
Kinevant Sciences, Inc. 
LDH 
Lactate dehydrogenase 
LIS 
Lung Injury Score 
LVEF 
Left ventricular ejection fraction 
mAb 
Monoclonal antibody 
MCH 
Mean corpuscular hemoglobin 
MCHC 
Mean corpuscular hemoglobin concentration 
MCV 
Mean corpuscular volume 
MDRD 
Modification of Diet in Renal Disease 
MedDRA 
Medical dictionary for regulatory activities 


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MMRM 
Mixed model with repeated measures 
MSDS 
Material safety data sheet 
NEWS 
National Early Warning Score 
NOEL 
No-observed-effect level 
PAH 
Pulmonary arterial hypertension 
PaO2 
Partial pressure of oxygen 
PCR 
Polymerase chain reaction 
PD 
Pharmacodynamic 
PEEP 
Positive end-expiratory pressure 
P/F 
PaO2/FiO2 ratio 
PK 
Pharmacokinetic 
PP 
Per-Protocol 
PT 
Preferred term 
RA 
Rheumatoid arthritis 
RBC 
Red blood cell 
RR 
Respiration Rate 
SAE(s) 
Serious adverse event(s) 
SAP 
Statistical analysis plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SD 
Standard deviation 
SOC 
System organ class 
SOFA 
Sequential Organ Failure Assessment 
SP 
Safety Population 
SP-D 
Surfactant protein D 
SpO2 
peripheral capillary oxygen saturation 
t1/2 
Elimination half-life 
TB 
Tuberculosis 
Th1 
T-helper-1 
TNF-α 
Tumor Necrosis Factor- alpha 
ULN 
Upper limit or normal 
VF 
Ventricular fibrillation 
VT 
Ventricular tachycardia 
WBC 
White blood cell count 


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WCBP 
Woman of childbearing potential 
WHO 
World Health Organization 
WHO-DDE 
World health organization drug dictionary enhanced 


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14.2. 
Appendix 2: Liver Safety Required Actions and Follow up 
Assessments 
Phase I Liver chemistry stopping criteria have been designed to assure subject safety and to 
evaluate liver event etiology (in alignment with the FDA Drug-induced Liver Injury: 
Premarketing Clinical Evaluation). 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U 
CM174090.pdf 
 
Liver Safety Process 
The procedures listed below are to be followed if a subject has ALT, bilirubin and/or INR 
elevations that meet the definition of an SAE (defined in Section 10.3): 
• 
Notify the Medical Monitor within 24 hours of learning of the abnormality to confirm 
follow-up. 
• 
Complete the liver event case report forms. 
• 
Upon completion of the safety follow-up withdraw the subject from the study unless further 
safety follow-up is required. 
• 
Make every reasonable attempt to have subjects return to the clinic within 24 hours for 
repeat liver chemistries, additional testing, and close monitoring (with specialist or 
hepatology consultation recommended). 
• 
Monitor subjects twice weekly until liver chemistries (ALT, AST, alkaline phosphatase, 
bilirubin) resolve, stabilize or return to within Baseline values. 
• Obtain viral hepatitis serology including: 
• 
Hepatitis A IgM antibody. 
• 
Hepatitis B surface antigen and Hepatitis B Core Antibody (IgM). 
• 
Hepatitis C ribonucleic acid (RNA). 
• 
Cytomegalovirus IgM antibody. 
• 
Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain heterophile 
antibody or monospot testing). 
• 
Hepatitis E IgM antibody. 
• Serum creatine phosphokinase (CPK) and lactate dehydrogenase (LDH). 
• Assess eosinophilia 
• Record the appearance or worsening of clinical symptoms of hepatitis (fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, fever, rash or eosinophilia) on the AE 
CRF. 
• Record use of concomitant medications, acetaminophen, herbal remedies, other over the 
counter medications, or putative hepatotoxins on the Concomitant Medications CRF. 


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• Record alcohol use on the Liver Events CRF. 
• Anti-nuclear antibody, anti-smooth muscle antibody, Type 1 anti-liver kidney microsomal 
antibodies and quantitative total immunoglobulin G (IgG or gamma globulins). 
• Serum acetaminophen adduct HPLC assay (quantifies potential acetaminophen contribution 
to liver injury in subjects with definite or likely acetaminophen use in the preceding week 
[James, 2009]. 
The Liver Imaging and/or Liver Biopsy CRFs are also to be completed if these tests are 
performed. 
 
References 
James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, Davern TJ, Lee WM. 
Pharmacokinetics of Acetaminophen-Adduct in Adults with Acetaminophen Overdose and 
Acute Liver Failure. Drug Metab Dispos 2009; 37:1779-1784. 


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14.3. 
Appendix 3: Summary of Changes for Protocol Amendments 
The original Protocol (Version 1.0) was approved on 22-March-2020, and has been amended 
4 times; Protocol Amendment 1 (Version 2.0) was approved on 05-April-2020, Protocol 
Amendment 2 (Version 3.0) was approved on 06-May-2020, Protocol Amendment 3 
(Version 4.0) was approved on 12-June-2020, and Protocol Amendment 4 (Version 5.0) was 
approved on 17-August-2020. 
Summaries of changes are presented in Table 14-1 for Amendment 1, Table 14-2 for 
Amendment 2, Table 14-3 for Amendment 3, and Table 14-4 for Amendment 4. 
 
Table 14-1: Summary of Changes: Amendment 1 
 
Section(s) Changed 
Description of Changes 
Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
Justification of Changes 
The protocol was amended, prior to implementation, based on feedback 
from the FDA. These changes are summarized below. 
Global change: Version and date 
were updated throughout the entire 
protocol. 
Version 1: 22-March-2020 
Version 2: 05-April-2020 
Contact information for serious 
adverse events was added to the 
administrative information at the 
beginning of the document. 
Monitors listed above (may be contacted during daytime or after-hours). 
On discovery, all SAEs should be immediately reported (latest within 24 
hours of knowledge of the event) to 
Synopsis and Section 3 
Study objectives were revised to identify key secondary objectives and 
clarify secondary and exploratory objectives. 
Primary Objective: 
• 
The primary objective is to evaluate the impact on mortality of 
the intravenous (IV) treatment ofwith gimsilumab on mortality in 
subjects with lung injury or ARDS secondary to COVID-19. 
Key Secondary Objectives: 
• To assess the effect of gimsilumab on ventilation requirements 
• To assess the effect of gimsilumab on the need for Intensive Care 
Unit (ICU) level of care 
• To assess the effect of gimsilumab on overall duration of 
hospitalization 
Additional Secondary efficacy Objectives: 
o Time to an improvement of 1 category from admission on the 
7-point ordinal scale; 
o Subject clinical status on the 7-point ordinal scale; 


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o Mean change from Baseline in ranking on the 7-point ordinal 
scale; 
• Time to hospital discharge (DoD) or to a To assess the effect of 
gimsilumab as measured by the National Early Warning Score 
(NEWS)of ≤4 and maintained for 24 hours, whichever occurs first; 
o Change from Baseline in NEWS (only if hospitalized). 
• To assess the effect of gimsilumab as assessed by the Sequential 
Organ Failure Assessment (SOFA) score 
• To assess the effect of gimsilumab as measured by the 7-point 
ordinal scale 
• To assess the effect of gimsilumab on peripheral capillary oxygen 
saturation / fraction of inspired oxygen (SpO2/FiO2) 
• To assess the effect of gimsilumab on oxygenation requirements 
• To assess changes in on-treatment viral load over time 
• To assess the effect of gimsilumab on biomarkers of inflammation 
• To determine the pharmacokinetic (PK) properties of gimsilumab 
• To assess the immunogenicity of gimsilumab 
• To determine the safety and tolerability of IV gimsilumab 
• To assess immunogenicity in subjects receiving IV gimsilumab. 
• To assess the effects of IV gimsilumab on renal function over time. 
• To assess the pharmacodynamic (PD) effects of IV gimsilumab on 
the following: 
o Duration of need of supplemental oxygenation; 
o Need for mechanical ventilatory support; 
Duration of hospitalization. 
Exploratory Objectives: 
• To explore the laboratory parameterseffect of sepsis during therapy 
including sequential organ failure assessment (SOFA) score ≥2 for 
any organ parameter, white blood cell count (WBC) >12,000 or 
<4,000 per mm3, heart rate (HR) >100 beats/minute, respiration rate 
(RR) >20 breaths/minute. 
• Serum anti GM-CSF autoantibodies, C-reactive protein,gimsilumab 
on serum cytokine concentrations,including GM-CSF, and surfactant 
protein D (SP-D). 
• PercentTo explore the effect of subjects with SARS-CoV-2 detectable 
in oropharyngeal (OP) sample at Days 8, 15, and 29 (if hospitalized), 
and at DoD. 
• To assess the effects of IV gimsilumab on cardiac function over time. 
• Incidence of gimsilumab on other measurements of lung injury that 
may be performed during standard care (e.g., Lung Injury Score 
[LIS], chest radiography, PaO2/FiO2 [P/F ratio], need for 
extracorporeal membrane oxygenation ([ECMO) procedures (if 
applicable).]) 


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• To explore the pharmacokineticseffect of gimsilumab on cardiac 
function (if measured) 
To assess the effect of IVgimsilumab on renal function 
Synopsis and Section 4.3 
Study duration was revised to allow for a longer follow-up period. 
This study will consist of a 2-week Treatment Period (last dose Day 8, if 
administered) and a 422-week Follow-up Period, for a total study duration 
of 624 weeks for each subject. 
Synopsis, Section 3, and Section 
9.3.1 
Endpoints were revised to correspond with the revised objectives. 
Primary Endpoint: 
• Incidence of mortality by Day 43 (End-of-Study [EoS]) 
Key Secondary Endpoints: 
• Incidence and duration of mechanical ventilation use during the study 
• Number of days in the ICU 
• Number of days of inpatient hospitalization 
Additional Secondary Endpoints: 
• Incidence of mortality by Day 15, Day 29, Day 85, and Day29 169 
(End-of-Study [EoS]) 
• NEWS assessed daily while hospitalized 
• SOFA score assessed daily while in the ICU 
• The percentage of subjects reporting each severity rating on the 
7-point ordinal scale (time frame: study duration). The ordinal scale is 
an assessment of the clinical status at the first assessment of a given 
study day. The scale is as follows:, assessed daily while hospitalized 
and, if discharged from hospital, on Days 15, 22, 29, 36, 43, 85, and 
169 (assessed by phone) 
1. Not hospitalized, no limitations on activities; 
2. Not hospitalized, limitation on activities; 
3. Hospitalized, not requiring supplemental oxygen; 
4. Hospitalized, requiring supplemental oxygen; 
5. Hospitalized, on non-invasive ventilation or high-flow oxygen 
devices; 
6. Hospitalized, on invasive mechanical ventilation or ECMO; 
7. Death. 
• Status on the 7-point ordinal scale, assessed daily while hospitalized 
and, if discharged from hospital, on the day of discharge (DoD), and 
on Days 15, 22, 29, 36, 43, 85, and 43 (169 (assessed by phoneif 


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discharged from the hospital).)NEWS assessed daily while 
hospitalized 
• SafetyChange from Baseline in SpO2/FiO2, assessed daily while 
hospitalized 
• Incidence and tolerability, including assessmentduration of 
changesoxygen use during the study 
• Change from Baseline in viral load (as measured by quantitative 
polymerase chain reaction [(PCR]) test), physical examinations, vital 
signs, electrocardiograms (ECGs), clinical safety laboratory 
measurements, local injection site tolerability; concomitant 
medications; cumulative incidence of adverse events (AE)s, serious 
adverse events (SAEs),on Days 2, 9, and severe AEs.day-of- 
discharge (DoD) 
• Change from Baseline in D-dimer, cardiac troponin I, lactate 
dehydrogenase (LDH), ferritin, and C-reactive protein (CRP) 
• Serum gimsilumab concentrations 
• Analysis of anti-gimsilumab antibodies (ADAs) 
• Assessment of change from Baseline to Day 15 (if hospitalized) and 
at DoD in the following parameters: 
o Peripheral capillary oxygen saturation/fraction of inspired oxygen 
(SpO2/FiO2) ratio by day 
o Glomerular filtration rate (GFR), calculated 
• Oxygenation-free days in the first 28 days (to Day 29). 
• Incidence and duration of new or increased oxygen use during the 
study. 
• Ventilator free days in the first 28 days (to Day 29).Incidence and 
duration of new mechanical ventilation use during the study. 
Safety Endpoints: 
• Safety and tolerability, including assessment of clinical safety 
laboratory measurements, physical examinations, vital signs, 
electrocardiograms (ECGs), local injection site tolerability, 
concomitant medications; cumulative incidence of adverse events 
(AEs), serious adverse events (SAEs), and severe AEs 
Exploratory Endpoints: 
• ChangesChange from Baseline in the following biomarkers:cytokine 
panel and serum SP-D, and C-reactive protein (CRP). 
• Serum anti GM-CSF autoantibodiesChange from Baseline in Lung 
Injury Score (LIS) (if performed). 
• Change from Baseline in chest radiographic assessment (if 
performed). 


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• Change from Baseline in P/F ratio, if performed 
• Incidence and duration of ECMO use 
• Serum gimsilumab concentrations. 
• If bronchoalveolar lavage (BAL) is performed as standard of care: 
Change in BAL biomarkers of fibroproliferation (procollagen and 
cytokine panel) and cell count differential (BAL sample will be 
collected and stored for possible future analysis).Change from 
Baseline in left ventricular ejection fraction (LVEF) (when measured). 
• Change from Baseline partial pressure of oxygen (PaO2)/FiO2 
(P/F ratio), if performed 
• Number and percentage of subjects on ECMO. 
• Number of days on ECMO. 
• Number and percentage of subjects successfully removed from 
ECMO.Change from Baseline in estimated glomerular filtration rate 
(eGFR) [Modification of Diet in Renal Disease (MDRD) equation], 
assessed when central clinical safety laboratory measurements are 
collected during hospitalization 
Synopsis and Section 5.2 
Inclusion criteria were revised to reflect feedback from the FDA, including 
a longer Follow-up Period. 
An individual will be eligible for participation in this study only if all 
of the following inclusion criteria are met: 
1. Male or non-pregnant female age 18 to 79 years, inclusive 
2. Subject (or legally authorized representative) is able and willing to 
provide written informed consent, which includes compliance with study 
requirements and restrictions listed in the consent form. 
3. Has laboratory-confirmed SARS-CoV-2 infection as determined by 
PCR or other approved clinical testing <72 hours prior to randomization 
4. SubjectCRP ≥50 mg/L or serum ferritin ≥1,000 ng/mL 
5. Radiographic evidence of bilateral infiltrates 
6. Subject has clinical evidence of lung injury [defined as (1) requiring 
supplemental oxygen >4L O2 to maintain >92% SpO2, or (2) P/F ratio 
≤300 mmHg (can be imputed)], or meets clinical classification criteria for 
ARDS [ARDS Berlin Definition, 2012] or has clinical evidence of lung 
injury,], secondary to COVID-19. 
• 
Lung injury is defined as PaO2/FiO2 ≤300 mmHg, without 
invasive or non-invasive ventilation (or with positive end- 
expiratory pressure [PEEP] or continuous positive airway 
pressure [CPAP] <5 cm H2O). 
• 
ARDS is defined as: 


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o 
Bilateral opacities — not fully explained by effusions, 
lobar/lung collapse, or nodules; 
o 
Respiratory failure not fully explained by cardiac 
failure or fluid overload; 
o 
Need objective assessment (e.g., echocardiography) 
to exclude hydrostatic edema if no risk factor 
present. 
o 
Mild: 200 mm Hg, < PaO2/FiO2, ≤300 mm Hg with 
PEEP or CPAP ≥5 cm H2O. 
o 
Moderate: 100 mm Hg, < PaO2/FiO2, ≤200 mm Hg 
with PEEP ≥5 cm H2O. 
7. Severe: PaO2/FiO2 ≤100 mm Hg with PEEP ≥5 cm H2O.Female 
subjects must agree to use an approved highly effective birth control (BC) 
method (<1% failure rate per year) throughout the study (until completion 
of their EoSthe Day 85 Follow-up Visit), unless documented to have a 
reproductive status of non-childbearing potential or is postmenopausal: 
• 
Non-childbearing potential defined as pre-menopausal female 
with medical history of bilateral tubal ligation, bilateral 
oophorectomy (removal of the ovaries), or hysterectomy; 
hysteroscopic sterilization, 
• 
Postmenopausal defined as 12 months of spontaneous 
amenorrhea; with follicle stimulating hormone (FSH) 
confirmation. 
• 
Woman of childbearing potential (WCBP) who is already using 
an established method of highly effective contraception or 
agrees to use one of the allowed BC methods, for at least 28 
days prior to the start of dosing (as determined by the 
Investigator Brochure or Investigator or designee) to sufficiently 
minimize the risk of pregnancy throughout study participation 
(until completion of their EoSthe Day 85 Follow-up Visit). 
8. Males who are sexually active must agree to use one of the allowed 
BC methods. Male subjects must also agree to sufficiently minimize the 
risk of pregnancy throughout study participation (until completion of their 
EoSthe Day 85 Follow-up Visit). 
Synopsis and Section 5.3 
Exclusion criteria were revised to reflect feedback from the FDA. 
1. Clinical evidence of pneumonia due to bacterial infection or viral (not 
SARS-CoV-2) infection.Clinical Subject requires norepinephrine at a dose 
of >0.5 mcg/kg/min, or equivalent 
2. Subject has been intubated for >72 hours 
3. Evidence of multi-organlife-threatening dysrhythmia (e.g., ventricular 
tachycardia [VT], ventricular fibrillation [VF]), or cardiac arrest on 
presentation 


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4. Evidence of new or preexisting decompensated heart failure. 
5. At the time of screening, subject is anticipated to require ECMO 
6. Absolute neutrophil count <2000 mm3 
7. Platelet count <50,000 mm3 
8. History of known anti-GM-CSF antibodiesautoantibodies (autoAb) or 
pulmonary alveolar proteinosis. 
9. Severe chronic respiratory disease (e.g., known chronic obstructive 
pulmonary disease [COPD], pulmonary arterial hypertension [PAH], 
idiopathic pulmonary fibrosis [IPF], interstitial lung disease [ILD]) requiring 
long-termbaseline oxygen therapy or mechanical ventilation. 
pre-hospitalization 
10. Positive QuantiFERON® test at Screening. 
10. Positive serology forSuspected or confirmed untreated, active 
hepatitis B (HBsAG), hepatitis C (HCVAb), or tuberculosis (TB), human 
immunodeficiency virus (HIV) at Screening), hepatitis B or C infection 
11. Subject meets inclusion criteria but is not expected to be able to be 
managed by the institution personnel with invasive or non-invasive 
ventilatory support.Alanine aminotransferase (ALT) /or Aspartate 
aminotransferase (AST) >5 × upper limit of normal (ULN) 
12. Stage 4 severe chronic kidney disease (CKD, eGFR 
<30 mL/min/1.73m2 (MDRD equation) or requiring hemofiltration or 
dialysis. 
13. Use within the past 60 days, or planned use,Use of any 
investigational drug or any immunomodulatory biologic (e.g., anti-IL-1, 
anti-IL-6R, anti-TNF) within the past 60 days, or planned use of any of 
these agents during the study 
14. Chronic (≥4 weeks) use of corticosteroids >10 mg/day of prednisone 
or equivalent 
15. Pregnancy and/or breast feeding 
16. Anticipated transfer to another hospital which is not a study site 
within 72 hours.Unable to receive invasive or non-invasive ventilatory 
support 
17. Moribund condition as determined byin the opinion of the clinical 
team investigator. 
18. Allergy to any study medication. 
Synopsis and Section 8, Section 
9.5.4, and Section 9.5.8 
Database lock information was update throughout the document to reflect 
longer study duration and database lock timeframes. 
The study database will be locked when all subjects complete the Day 43 
(EoS) Visit, discontinue from the study early, or meet the primary mortality 


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endpoint. The second lock will occur when the last subject completes the 
Day 169 EoS visit. 
In addition, there will be 12 database extractextracts (soft locklocks) for 
interim analysis, analyses, the first of which is towill be performed when 
~40% of plannedconducted when 60 subjects have been treated and 
have completed 7 days of follow-up; the DMC will review the data for 
safety and futility and provide their recommendations. The second interim 
analysis will be conducted when 50% of total subjects are discharged 
from the hospital, complete the Day 43 (EoS) Visit, discontinue the study 
early, or meet the primaryendpoint of mortality endpoint.(by Day 43). 
Synopsis and throughout 
Statistical analysis information regarding analysis sets (Section 9.4), 
adjustments for multiple comparisons (Section 9.5.4), and timing of the 
analyses (Section 9.5.8) was updated to reflect the longer study duration 
and additional interim database lock. 
Key Analysis Sets 
• The Intent-to-Treat (ITT) Population will include all randomized 
subjects who receive any amount of study drug, have a Baseline 
assessment of efficacy endpoint, and at least 1 post-treatment 
assessment of efficacy endpoint. The ITT subjects will be analyzed 
according to randomized treatment, irrespective of whether or not 
they have prematurely discontinued. Subjects who withdraw from 
treatment and/or the study early will be followed for Day 43 all-cause 
mortality. All efficacy analyses will be performed using the ITT 
Population. 
• The Safety Population (SP) will include all randomized subjects who 
receive any amount of study drug. The SP will be analyzed 
according to the treatment received. This set will be used for the 
safety analyses. 
• The Per-Protocol (PP) Population will include all subjects in the ITT 
Population who complete the Day 43 Visit with no major protocol 
violations. The PP Population will be used for supportive analyses of 
the efficacy measurements. 
Adjustment of Multiple Comparisons: There is no need to adjust the 
significance level 0.05 (two-sided) in the analysis since there is only one 
1 primary endpoint and one1 gimsilumab dose level versus placebo. 
However, The interim analysis will be conducted when ~40% of 
planned60 subjects are discharged from the hospital, complete the Day 
43 (EoS) Visit, discontinue the study early, or meet the primary mortality 
endpoint. Therehave been treated and have completed 7 days of follow- 
up; the DMC will bereview the split of alpha 0.05 to be 0.001data for the 


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interim analysis and 0.049 for the final analysis of the primary 
endpointsafety and futility and provide their recommendations. 
The second interim analysis will be conducted when 50% of total subjects 
are discharged from the hospital, complete the Day 43 Visit, discontinue 
the study early, or meet the endpoint of mortality (by Day 43). 
There will be the split of alpha 0.05 to be 0.001 for the 2nd interim analysis 
and 0.049 for the final analysis of the primary endpoint, as the 2nd interim 
analysis may claim for the superior efficacy for the stop of the study early. 
The 3 key secondary endpoints will be analyzed by hierarchical testing 
procedure following the order of the list of endpoints, and each endpoint 
will be analyzed at 0.05 alpha level. 
Timing of Analyses 
The final first unblinded analyses will be conducted when the last subject 
completes the Day 43 (EoS) Visit, discontinues from the study early, or 
meets the primary mortality endpoint (by Day 43). The second unblinded 
analyses will be conducted when the last subject completes the Day 169 
Follow-up Visit (EoS). 
The first interim analysis can be conducted when ~40%will be when 60 
subjects have been treated and have completed 7 days of plannedfollow- 
up; the DMC will review the data for safety and futility and provide their 
recommendations. 
The second interim analysis will be conducted when 50% of total subjects 
are discharged from the hospital, complete the Day 43(EoS) Visit, 
discontinue the study early, or meet the primaryendpoint of mortality 
endpoint. The Data Monitoring Committee (DMC)(by Day 43). The 
objectives of the second interim analysis will include the claim of superior 
efficacy or futility to stop the study, the reassessment of sample size, 
and/or modifications of the populations. 
The DMC will be responsible for this closely reviewing the safety data 
from the unblinded interim analysis and for informing the sponsor about 
the results and the recommendation for the study. providing their 
recommendations. The detailed objectives and procedures of the interim 
analyses will be described in the study protocol,DMC Charter; these can 
be the claim of early stop of the study for superiority, futility, re- 
assessment of the final sample size, and/or the study population. In 
addition, the DMC will review the safety data when 10%, 25%, 50%, and 
75% of planned subjects complete the Day 43 (EoS) Visit. A SAP and 
DMC Charter will be generated with detailed information, including the 
boundaries of the superiority and futility for the interim analysis. 


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Section 4.1 Overall Study Design 
The text and study schematic were revised to reflect the longer Follow-up 
Period. 
Subjects will be assessed daily while hospitalized. Follow-up 
isassessments are planned through Week 6,24, for a total study duration 
post-randomization of approximately 43169 days.Subjects will be asked 
to participate in(24 weeks). Follow-up visits at Days 15, 22, 29, 36, 43, 85 
and 43; these follow-up visits169 will be performed by phone if the subject 
has been discharged from the hospital. 
Section 4.3 Treatment Arms and 
Duration 
The text was revised to reflect longer overall study duration. 
Each subject will participate for approximately 624 weeks, with a 2-week 
Treatment Period (last dose on Day 8) and a 422-week Follow-up Period. 
Synopsis and Section 5.6.1 
Contraception 
The text was revised to update the contraception duration requirements. 
All female and male study subjects must use a highly effective birth 
control method (<1% failure rate per year) throughoutuntil completion of 
the studyDay 85 Follow-up Visit, unless they have a reproductive status 
of, sterile, non-childbearing, or postmenopausal (confirmed by FSH). 
Males allowed to enroll in this study are responsible for minimizing the 
risk of pregnancy (until completion of studythe Day 85 Follow-up Visit). 
Section 5.7.1 Reasons for Withdrawal 
Text was added to specify that withdrawn subjects will not be replaced. 
If a subject meets a withdrawal criterion during treatment, an Early 
Termination Visit will be required. Subjects withdrawn for any reason will 
not be replaced. 
Section 5.7.2 Subject Withdrawal 
Procedures 
Text regarding subject withdrawal procedures was revised. 
Should a In cases where the subject fail to attend the cliniccannot be 
reached for a required study visitphone follow-up visits, the site should 
attempt to contact the subjectand re-schedule the missed visit as soon as 
possible. The site should also counsel the subject on the importance of 
maintaining the assigned visit schedule and ascertain whether the subject 
wishes to and/or should continue in the study based on previous non- 
compliance. In cases where the subject does not return for the 
rescheduled visit or cannot be reachedto reschedule the missed visit, the 
site should make every effort to regain contact with the subject 
(3 documented telephone calls and if necessary a certified letter to the 
subject’s last known mailing address) so that they can appropriately be 
withdrawn from the study with a primary reason of “Lost to Follow-up”. 


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Subjects who withdraw from treatment and/or the study early, for any 
reason, will be followed for Day 43 all-cause mortality, whenever possible. 
Section 5.9 Subject and Study 
Completion 
Text regarding study completion was revised to reflect the longer Follow- 
up Period. 
A completed subject is one1 who has completed the Treatment Period, 
includingand the scheduled Phone Follow-up Assessments (Period 
(through the Day 43;169 End-of-Study [EoS]).] Follow-up Visit). 
Section 6.4 Blinding 
Text regarding study blinding and treatment administration was revised 
for clarification and to add the emergency contact information. 
The study is double-blind. The study pharmacist (and/or qualified 
pharmacy staff member), study treatment administration personnel, and 
the bioanalytical laboratory analysts will be unblinded to study treatment. 
Study treatment will be administered to each subject by blinded qualified 
personnel at the study site. The presentation of the study treatment 
(solution color) will be obscured from the study subject and other study 
personnel using a colored covering or sleeve for the IV bag containing 
study treatment and opaque IV line. Further details will be provided in the 
Study Reference Manual.Once diluted in 100 mL 0.9% saline, active 
gimsilumab and placebo infusion bags are indistinguishable. 
For this study you may contact: 
Section 7 Study Assessments and 
Procedures 
The text and Table 7-1 regarding 
blood sample amount were revised to 
account for the longer study duration. 
The study assessments and procedures were revised to specify the 
follow-up for subjects who are discharged from the hospital and/or 
discontinue from the study early. 
Note: All subjects who are discharged from the hospital will undergo all 
Day-of-Discharge (DoD) Visit assessments. All subjects who discontinue 
from the study prematurely will undergo all Early Termination (ET) Visit 
assessments, whenever possible. 
It is expected that no more than 150If the subject completes all in hospital 
assessments, approximately 250 mL of blood will be collected over the 
duration of the study, including any extra assessments that may be 
required (Table 7-1). 
Section 7.1 Schedule of 
Assessments 
The Schedule of Assessments (Table 7-2) was revised to include 
additional assessments, remove assessments that will not be performed, 
and to accommodate the longer study duration. 


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Table 7-2 now has been split into 2 parts, one for the Treatment Period 
and one for the Follow-up Period. 
Laboratory assessments were clarified for local vs central labs; related 
conduct that is done at the same timepoints was combined (i.e., 
demographic information, medical history, and prior medication); viral 
sample swabs were corrected from oropharyngeal samples to 
nasopharyngeal samples; SOFA score was added; laboratory 
assessments were clarified; footnotes were revised for clarification. 
Section 7.4.1.3 Sequential Organ 
Failure Assessment (SOFA) 
Section was added to include Sequential Organ Failure Assessment 
(SOFA). 
The SOFA score will be assessed daily for patients while in the ICU. 
Section 7.4.2.1 Physical 
Examinations 
Text regarding physical examinations was revised to be more conducive 
to the in-patient hospital conditions. 
An abbreviatedAbbreviated, targeted physical examination will include, at 
a minimum,examinations (i.e., assessments of the skin, respiratory, 
cardiovascular system, and abdomen ([liver and spleen]), will be 
performed at time points specified in the Schedule of Assessments (Table 
7-2) and will be based on the subject’s clinical status and what the clinic 
staff feel is appropriate. 
Height and weight will also be measured and recorded at Screening only, 
if possible. 
Section 7.4.2.2 Vital Signs 
Text regarding vital signs was revised to remove position requirements. 
Vital signs including blood pressure, heart rate, respiration rate, and 
temperature (oral, tympanic, or axillary) will be obtained at time points 
specified in the Schedule of Assessments (Table 7-2after the subject has 
rested quietly in a supine position for 10 minutes.). 
The same method for assessing temperature should be used at all visits 
for each individual subject, if possible. 
Section 7.4.2.3.1 Electrocardiograms 
Section for 12-lead electrocardiograms was removed. 
ECGs will be measured in supine position after at least 5 minutes rest. 
Standard, 12-lead electrocardiograms (ECGs) will be obtained during the 
study using an ECG machine that automatically calculates the heart rate 
and measures PR, QRS, QT, and QTcF intervals. 
Section 7.4.2.4 Clinical Safety 
Laboratory Assessments 
Text was added to clarify sample collection information. 
Table 7-3 was revised to include additional laboratory samples. 


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For all on-study laboratory assessments, if central laboratory 
assessments cannot be collected for any reason, best efforts will be 
made to record local laboratory data. 
NT-proBNP, ferritin, C-reactive protein, lactate dehydrogenase, and 
procalcitonin were added to Table 7-3. 
Section 7.4.2.5: SARS-CoV-2 Viral 
Assessments 
SARS-CoV-2 Viral Assessments section was added to the protocol. 
A local qualitative sample (e.g., nasopharyngeal swab) for PCR 
SARS-CoV-2 will be collected at Screening for determination of eligibility 
(if not already documented); all other on-study samples will be central 
quantitative samples. 
When at all possible, if only 1 nostril is swabbed for viral assessments, 
the same nostril should be used for all subsequent samples. 
Section 7.4.2.6 Respiratory 
Assessments 
Additional examples of ventilation type were added. 
If subject is receiving mechanical ventilation, the following parameters will 
be recorded: type of ventilation (high-flow nasal cannula, non-rebreather 
mask, CPAP, BiPAP, or intubation), FiO2, SpO2, ventilation rate, pulse, 
tidal volume, positive end-expiratory pressure (PEEP), and airway 
pressure. 
Section 7.4.2.8 Biomarker 
Assessments 
Text was revised to include “chemokine” and to remove text regarding 
bronchoalveolar lavage and CRP markers. 
The cytokine/chemokine panel may include: GM-CSF, G-CSF, IL-1β, IL-2, 
IL-6, IL-7 IL-10, IL-15, IL-17A, IL-17A/F, IL-23p19, IFN-γ, TNF-α, IP10 
(CXCL10), MCP1 (CCL2), MIP1A (CCL3), and CCL17. 
A subset of these cytokines/chemokines will be tested initially, further 
testing may be performed based on results of other study endpoints and 
emerging scientific information. 
Concentrations of biomarkers will be determined using qualified or 
validated assays. 
CRP markers are to be determined by the local laboratory (Section ). 
If a bronchoalveolar lavage (BAL) is performed as standard of care, a 
sample will be collected for potential future analysis of select cytokines 
and procollagen. The actual date and time of the sample will be recorded. 
Section 8 Data Management 
The text was revised to reflect the longer study duration and additional 
interim analysis. 
The detailed Data Management Plan (DMP) will be generated and 
approved prior to the start study database lock when all subjects 


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complete the Day 43 Visit, discontinue from the study early, or meet with 
the primary endpoint of enrolling subjects.mortality (by Day 43). 
The study database will be locked when all subjects complete the Visit of 
Day 43 (Day 43 Visit, discontinue from the study early, or meet the 
primary mortality endpoint. The second lock will occur when the last 
subject completes the Day 169 EoS), reach the primary endpoint early, or 
discontinue from the study. visit. 
In addition, there will be 12 database extractextracts (soft locklocks) for 
interim analyses, the first of which will be conducted when 60 subjects 
have been treated and have completed 7 days of follow-up; the DMC will 
review the data for safety and futility and provide their recommendations. 
The second interim analysis, which is towill be performedconducted when 
~4050% of plannedtotal subjects are discharged from the hospital, 
complete the Day 43 (EoS) Visit, discontinue the study early, or meet the 
primaryendpoint of mortality endpoint.(by Day 43). 
Section 9.1 Sample Size 
Determination 
Sample size was updated to include the definitions of lung injury and 
ARDS. 
Lung injury is defined as (1) requiring supplemental oxygen >4L O2 to 
maintain >92% SpO2, or (2) PaO2/FiO2 ≤300 mmHg (can be imputed). 
ARDS [ARDS Berlin Definition, 2012] is defined as: 
• 
Bilateral opacities — not fully explained by effusions, lobar/lung 
collapse, or nodules; 
• 
Respiratory failure not fully explained by cardiac failure or fluid 
overload; 
• 
Need objective assessment (e.g., echocardiography) to exclude 
hydrostatic edema if no risk factor present. 
• 
ARDS severity categories are defined as: 
o Mild: 200 mmHg, < PaO2/FiO2, ≤300 mmHg with PEEP or 
CPAP ≥5 cm H2O. 
o Moderate: 100 mmHg, < PaO2/FiO2, ≤200 mmHg with 
PEEP ≥5 cm H2O. 
o Severe: PaO2/FiO2 ≤100 mmHg with PEEP ≥5 cm H2O. 
Section 9.3.2 Safety Endpoints 
Text regarding safety endpoints was revised to remove viral load, ECGs, 
and local injection site tolerability. 
Safety and tolerability, including assessment of changes from Baseline in 
viral load (PCR test),clinical safety laboratory measurements, physical 
examinations, vital signs,ECGs, clinical safety laboratory measurements, 
local injection site tolerability; concomitant medications; cumulative 
incidence of AEs, SAEs, and severe AEs. 


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Section 9.3.3Pharmacokinetic 
Endpoints 
Text was revised to remove specific timepoints and refer to the Schedule 
of Assessments. 
Serum gimsilumab concentration at time points as specified in the 
Schedule of Assessments (Table 7-2). pre-dose on Day 1 and Day 8. 
Section 9.3.4 Biomarker Endpoints 
“Pharmacodynamic” was replaced with “Biomarker” and serum CRP was 
removed. 
Pharmacodynamic Biomarker Endpoints 
ChangesChange from Baseline in serum CRP,the cytokine, panel and 
serum SP-D concentrations will be measured at time points as specified 
in the Schedule of Assessments (Table 7-2). 
Section 9.5.3 Analysis of the 
Secondary Endpoints 
Section was revised to update the information regarding the continuous 
variables. 
The continuous variables, including the changes from baseline, will be 
summarized by the treatment with the meansmean, standard deviations, 
mediansdeviation (SD), median, and the rangesrange. PK summaries will 
include geometric mean and geometric coefficient of variation. 
Section 9.5.4 Adjustment of Multiple 
Comparisons 
Section was revised to reflect the increased study duration, additional 
interim database lock, and methods for the key secondary endpoints. 
There is no need to adjust the significance level 0.05 (two2-sided) in the 
analysis since there is only one 1 primary endpoint and one 1 gimsilumab 
dose level versus placebo. However, The interim analysis will be 
conducted when ~40%60 subjects have been treated and have 
completed 7 days of plannedfollow-up; the DMC will review the data for 
safety and futility and provide their recommendations. 
The second interim analysis will be conducted when 50% of total subjects 
are discharged from the hospital, complete the Day 43 (EoS) Visit, 
discontinue the study early, or meet the primaryendpoint of mortality 
endpoint.(by Day 43). 
There will be the split of alpha 0.05 to be 0.001 for the 2nd interim analysis 
and 0.049 for the final analysis of the primary endpoint, as the 2nd interim 
analysis may claim for the superior efficacy for the stop of the study early. 
The 3 key secondary endpoints will be analyzed by hierarchical testing 
procedure following the order of the list of endpoints, and each endpoint 
will be analyzed at 0.05 alpha level. 
Section 9.5.8 Timing of Analyses 
Text regarding timing of analyses was revised to reflect the longer study 
duration and the additional interim analysis. 
The final analysesfirst unblinded analysis will be conducted when the last 
subject completes the study at Day 43 (EoS) Visit, meetdiscontinues the 


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study early, or meets the primary endpoint early, or early discontinued 
from the study. of mortality (by Day 43). The final analysis will be 
conducted when the last subject completes the Day 169 (EoS) Visit. 
The first interim analysis can be conducted when ~40% of plannedwill be 
conducted when 60 subjects have been treated and have completed 
7 days of follow-up; the DMC will review the data for safety and futility and 
provide their recommendations. 
The second interim analysis will be conducted when 50% of total subjects 
are discharged from the hospital, complete the Day 43 (EoS) Visit, 
discontinue the study early, or meet the primary mortality endpoint. of 
mortality (by Day 43). The objectives of the second interim analysis will 
include the claim of superior efficacy or futility to stop the study, the 
reassessment of sample size, and/or modifications of the populations. 
The DMC will be responsible for this unblinded analysis and inform the 
sponsor about the results and the recommendation of conducting the 
study, which can be the early stop of the study for the superiority, futility, 
the re-assessment of the sample size, and/or closely reviewing the 
modification of the study population.safety data from the unblinded interim 
analysis and for providing their recommendations. The detailed objectives 
and procedures, including close monitoring of the safety data and the 
boundaries of the interim analysessuperiority or futility will be described in 
the SAP and the DMC Charter.In addition, the DMC will review the safety 
data when 10%, 25%, 50%, and 75% of planned subjects complete the 
Day 43 (EoS) Visit. A DMC Charter will be generated with detailed 
information 
Section 9.5.9 Pharmacokinetic, 
Biomarker, and Immunogenicity 
Analyses 
“Pharmacokinetic, Biomarker, and Immunogenicity Analyses” section was 
added. 
Serum gimsilumab concentrations will be summarized using descriptive 
statistics. 
Biomarker analyses will be based on the Safety Population and biomarker 
(SP-D, cytokine/chemokine, anti-GM-CSF autoAb) concentrations will be 
summarized by treatment using descriptive statistics. 
Immunogenicity analysis will be based on the Safety Population and anti- 
drug antibody data will be reported in the format provided by the 
bioanalytical laboratory. 
Further details will be provided in the SAP. 
Section 10.1 Special Consideration 
for Assessment of Adverse Events 
“Special Consideration for Assessment of Adverse Events” section was 
added. 


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It is recognized that the patient population in the ICU will experience a 
number of common aberrations in laboratory values, signs and symptoms 
due to the severity of their underlying disease and the impact of standard 
therapies. These will not necessarily constitute an AE unless they require 
significant intervention, lead to discontinuation of blinded study drug, or 
are considered to be of concern in the investigator’s clinical judgement. 
Death should not be recorded as an event but should be recorded as the 
outcome of ONE event, i.e. one event should be determined to be the 
primary cause of death. The 'clinical' AE that resulted in death is the 
adverse event and the death information supports the clinical AE. 'Death' 
is not entered as an adverse event unless the cause of death is unknown. 
In such case the AE term is 'Unspecified fatal event' until the cause of the 
death is known. 
Section 10.2 Definition of Adverse 
Events 
Text regarding infections was added for clarification. 
New infections occurring on-study, regardless of infection type (i.e., viral, 
bacterial, fungal, etc.) will be reported as AEs. 
Section 10.9 Regulatory Reporting 
Requirements for SAEs 
Text was added regarding SAE reporting. 
On discovery, all SAEs should be immediately reported (latest within 24 
hours of knowledge of the event) to 
See Section 6.4 for emergency unblinding service contact information. 
Section 11 Pregnancy Reporting 
The text was revised to clarify the follow-up period for pregnancy 
reporting. 
Any pregnancy reported between the time of informed consent and 
completion of the End-of-Study Day 85 Follow-up Visit or an Early 
Termination Visit must be reported to the Sponsor within 2 weeks of 
learning of the pregnancy. 
Section 12.1.7 Drug Accountability 
Text regarding disposal of study drug was revised. 
At the end of the study, following final drug inventory reconciliation by the 
monitor, the study site will dispose of and/or destroy ship all unused 
investigational medicinal product supplies, including empty containers to 
the designated depot, according to these procedures. 
Section 13 References 
References were added. 


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Nadicksbernd J. CD11b expression on granulocytes after induction by 
granulocyte-macrophase colony stimulating factor in EDT whole blood by 
flow cytometry.  PPD Primary Validation Summary. 2013. 
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of 
adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort 
study. The Lancet. 2020; 395 (10229): 1054-1062. 
https://doi.org/10.1016/S0140-6736(20)30566-3. 
Section 14.1: Abbreviations were added to the list of abbreviations, and unused abbreviations were removed from 
the list of abbreviations. 


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Deleted text is indicated as strikethrough, new or moved text is indicated 
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Global change: Synopsis and 
throughout 
Version and date were updated throughout the entire protocol. 
Version 2: 05-April-2020 
Version 3: 06-May-2020 
Global change: Synopsis and 
throughout 
Minor edits, including changing “patient(s)” to “subject(s)” where 
applicable and minor spacing and spelling corrections. 
Medical Contact/Sponsor Information 
Page 
Text referring to Medical Monitoring Plan was deleted because the 
Medical Monitoring Plan is not relevant to the protocol (only relevant to 
Sponsor and CRO). 
See the Medical Monitoring Plan for more details. 
Synopsis, Section 3 Objectives and 
Endpoints, and Section 9.3.1 Efficacy 
Endpoints 
Key secondary endpoints were revised to clarify actual intent of the study, 
as follows: 
• Incidence and duration of subjects who survived and were not on 
mechanical ventilation use on Day 15, Day 22, Day 29, and Day 43 
• Incidence of mechanical ventilation use, and ventilation-free days 
during the study 
• NumberIncidence of ICU use, and ICU-free days induring the 
ICUstudy 
• Number of days of inpatient hospitalization 
Synopsis and Section 5.2 Inclusion 
Criteria 
The following inclusion criteria were revised: 
1. Male or non-pregnant female age ≥18 to 79 years, inclusive 
Justification: to be less restrictive, as sites were having to exclude 
patients who otherwise met all entry criteria. 
3. Has documented laboratory-confirmed SARS-CoV-2 infection as 
determined by PCR or other approved clinical testing prior to 
randomization 
Justification: to clarify the requirement for documentation of disease 
status 
4. CRP ≥50 mg/L or serum ferritin ≥1,000 ng/mL. Results from CRP and 
ferritin tests performed within 8 days of randomization are acceptable for 
enrollment. 
Justification: to clarify the timing window for CRP and ferritin results used 
for entry criteria 
5. Radiographic evidence of bilateral infiltrates. Acceptable imaging tests 
(chest X-ray, CT scans) done within 3 days of Day 1 can be used for 
inclusion. 


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Justification: to clarify the timing window for imaging results used for entry 
criteria 
6. Subject has clinical evidence of lung injury [defined as (1) requiring 
supplemental oxygen >≥4L O2 to attempt to maintain >≥92% SpO2, or (2) 
P/F ratio ≤300 mmHg (can be imputed)], or meets clinical classification 
criteria for ARDS [ARDS Berlin Definition, 2012], secondary to COVID-19. 
Justification: to clarify the intent of the requirements. 
Synopsis and Section 5.3 Exclusion 
Criteria 
The following exclusion criteria were revised: 
6. Absolute neutrophil count <20001000 per mm3 
Justification: limit was corrected to reflect the original intent of the protocol 
7. Platelet count <50,000 per mm3 
Justification: clerical fix 
8. History of known anti-GM-CSF autoantibodies (autoAb) or pulmonary 
alveolar proteinosis. Note: A negative anti-GM-CSF autoAb test result is 
not required at screening. 
Justification: to clarify that the site does not need to wait for the result 
before enrolling the subject into the study. 
9. Severe chronic respiratory disease (e.g., known chronic obstructive 
pulmonary disease [COPD], pulmonary arterial hypertension [PAH], 
idiopathic pulmonary fibrosis [IPF], interstitial lung disease [ILD]) requiring 
baselinesupplemental oxygen therapy or mechanical ventilation 
pre-hospitalization (e.g., prior to COVID-19 diagnosis) 
Justification: “baseline” was removed to avoid confusion with Study 
baseline. 
10. SuspectedKnown or confirmed suspected active and untreated,active 
tuberculosis (TB), human immunodeficiency virus (HIV), hepatitis B or C 
infection 
• 
Results of TB, hepatitis B and C, and HIV tests are not required 
prior to enrollment if there is no suspicion of active infection, as 
per KIN-1901 Guidance on Active Infections Testing. 
Justification: to clarify that the site does not need to wait for the result 
before enrolling the subject into the study as long as there is no suspicion 
or knowledge of active infection. 
18. 13. Use ofinvestigational drug or any immunomodulatory biologic 
(e.g., anti-IL-1, anti-IL-6R, anti-TNF), cell therapies (e.g., 
mesenchymal stem cells), or small molecules (e.g., Janus kinase 
[JAK] inhibitors) within the past 607 days or within five half-lives 
(whichever is longer), or planned use of any of these agents from 


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Screening until Day 43 of the study, unless approved by the Medical 
Monitorduring the study. The following will be allowed: 
• 
Subjects who have been treated with convalescent plasma (CP) 
prior to enrollment are eligible if the subject continues to meet all 
inclusion criteria at screening. 
• 
The use of investigational anti-viral treatment (e.g., remdesivir) is 
allowed if the subject continues to meet all inclusion criteria at 
screening. 
Justification: to further clarify what is allowed and disallowed based on 
emerging standards of care. 
Synopsis and Section 9.5.1 Primary 
Efficacy Analyses 
The following statistical analysis information was revised to clarify which 
statistical models are being used, and to remove hierarchical testing: 
Efficacy Analyses: 
The secondary analysis of the primary endpoint will be conducted by 
using log rank test and/or the Cox Proportional model on the time to event 
of the primary endpoint. The median of the time to event from Kaplan- 
Meier curves will be presented for each treatment, and the hazard ratio of 
gimsilumab versus placebo will be presented with 95% CI, and p-value. 
Adjustment of Multiple Comparisons: 
The 3 key secondary endpoints will be analyzed by hierarchical testing 
procedure following the order of the list of endpoints, and each endpoint 
will be analyzed at 0.05 alpha level. 
Section 5.8 Toxicity Management 
Criteria 
Additional text was added for management of abnormalities in liver 
function tests (LFTs) to specify how the sites should address LFT 
abnormalities to maintain consistency across sites. 
Guidance on LFT abnormalities based upon results of LOCAL lab 
testing: 
1) If a subject has ALT in the normal range prior to study drug 
administration and develops significant elevation >5× ULN after 
study drug administration, in the absence of a clear alternative 
reason for the change (e.g., hypotension, vasopressor support), 
this should be considered related to study drug and reported as 
a SAE; procedures described in Appendix 2: Liver Safety 
Required Actions and Follow up Assessments should be 
followed, and the Medical Monitor should be informed. 
2) For subjects with elevated transaminase levels prior to study 
drug administration who do not meet exclusion criterion #11 
(alanine aminotransferase [ALT] or aspartate 
aminotransferase [AST] >5× upper limit of normal [ULN]), if 
after administration of study drug the LFTs continue to worsen 


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and no alternate explanation for elevation is provided, the 
following will apply: 
a. If ALT >8× ULN, then this should be reported as a 
SAE; procedures described in Appendix 2: Liver 
Safety Required Actions and Follow up 
Assessments will be followed, and the Medical Monitor 
should be informed. If the Investigator is considering 
withholding the second dose of study drug, then a 
discussion with the Medical Monitor is mandatory. Note 
that subjects with ALT or AST abnormalities secondary 
to multi-organ impairment due to COVID-19 may still 
benefit from the second dose of gimsilumab. 
b. If LFTs are elevated but are not >8× ULN, then daily 
LFTs (including AST, ALT, alkaline phosphatase, and 
total bilirubin with fractionation) should be followed. 
i.  If during follow up ALT or AST increases to 
>8× ULN, then this should be reported as a 
SAE and then discussed with the Medical 
Monitor concerning the need to withhold the 
second dose. 
If a subject has AST or ALT 3 to 8× ULN in conjugation with total 
bilirubin >2× ULN or INR >1.5, then this should be reported as a SAE; 
procedures described in Appendix 2The Medical Monitor must be 
notified if a subject meets the following liver chemistry criteria: 
ALT ³5 × the ULN 
ii. : Liver Safety Required Actions and Follow 
up Assessments should be followed. 
Subjects meeting these criteria should not 
receive a second dose of study drug. 
iii. If during follow up the above stopping criteria 
are not met and the Investigator believes that 
the subject is suitable to receive a second 
dose of study drug and all eligibility criteria are 
met for the second dose, then the second 
dose (Day 8) of study drug may be 
administered. 
3) Any worsening of LFTs that is greater than would be expected 
due to COVID-19 alone that do not rise to the level of an SAE 
should be reported as an AE. 
4) A discussion with the Medical Monitor is mandatory prior to 
withholding the second dose of study drug. 


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Section 6.1 Study Treatment 
Unit dose strength/dosage level information was revised for placebo in 
Table 6-1 and in the text; information for placebo was not previously 
included, so it was added for completeness. 
NA / 
of sterile 0.9% sodium chloride added to 100 mL 0.9% 
salinesodium chloride. 
Section 6.6 Preparation/ Handling/ 
Storage/ Accountability 
Placebo mixing information was revised to reflect placebo preparation. 
Placebo study treatment will utilize 100 mL 0.9% saline solution with no 
admixturethe addition of 
(Day 8) sterile 0.9% saline 
solution using aseptic technique by qualified personnel per the clinical site 
standard operating procedures. 
Section 6.9 Concomitant Medications 
and Non-Drug Therapies 
Spelling correction: 
It would be expected that gimsilumab would reduce the effectiveness of 
GM-CSFs, such as Luekine® (sargranostimsargramostim), Leucomax® 
(molgramostim) and Regramostim. No other drug interactions are known 
or expected. 
Section 6.9.1 Permitted Medications 
and Non-Drug Therapies 
Text regarding permitted medications was revised to include prior or 
concomitant use of convalescent plasma and/or anti-viral therapies to 
reflect emerging standards of care. 
Treatment with convalescent plasma or investigational anti-viral therapies 
(e.g., remdesivir) will be allowed. 
Use of any concomitant medication (including investigational agents) 
should be recorded in the study source records, including the doses 
administered, dates and times of administration and the reason for 
administration. 
Section 6.9.2 Prohibited Medications 
and Non-Drug Therapies 
Section was updated to further clarify what is allowed and disallowed 
based on emerging standards of care. 
Use of any investigational drug (i.e., the subject is using the drug as part 
of a clinical trial), tocilizumab or any other immunomodulatory biologic 
(e.g., anti-IL-1, anti-IL-6R, anti-TNF), cell therapies (e.g., mesenchymal 
stem cells), or small molecules (e.g., JAK inhibitors) is prohibited during 
the study, from Screening until Day 43 of the study unless approved by 
the Medical Monitor. 
Section 7.1 Schedule of 
Assessments 
The Schedule of Assessments was revised to clarify study days and 
weeks. Timepoints were clarified for the Follow-up Period. 
Clarifications were added regarding screening laboratory assessments to 
be consistent with revisions to entry criteria as follows: 


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Central sample for anti-GM-CSF autoAbd (result not required for 
determination of eligibility) 
Footnote d: Sample will be collected, but enrollment can continue without 
receiving results first. HCV testing can be RNA or Ag, only to confirm 
suspected infection. If a subject is diagnosed with latent TB (positive 
QuantiFERON Gold or purified protein derivative [PPD]), hepatitis B or C, 
or HIV during the study, the Investigator must discuss this with the 
medical monitor and a decision will then be made concerning the second 
dose of gimsilumab, if applicable. 
Note: SCREENING LABORATORY ASSESSMENTS: For all screening 
laboratory assessments, if more than one result is available during the 
screening period, the most recent value will be used as the screening 
value and for determination of eligibility. 
Section 7.4.2.8 Biomarker 
Assessments 
IL-8 was added to the list of the cytokine/chemokine panel for 
completeness. 
The cytokine/chemokine panel may include: GM-CSF, G-CSF, IL-1β, IL-2, 
IL-6, IL-7, IL-8, IL-10, IL-15, IL-17A, IL-17A/F, IL-23p19, IFN-γ, TNF-α, 
IP10 (CXCL10), MCP1 (CCL2), MIP1A (CCL3), and CCL17. 
Section 9.5.3 Analysis of the 
Secondary Endpoints 
Text regarding time to event endpoints was moved, and other revisions 
were made as follows: 
• The time-to-event endpoints will be summarized with Kaplan Meier 
curves and 95% confidence bounds by the treatment. the Cox 
Hazard Proportional model with treatment, country, and subject’s 
clinical status at Baseline ([lung injury/mild ARDS] or 
[moderate/severe ARDS]) as model terms will be used. The hazard 
ratio of gimsilumab versus placebo will be presented with 95% CI and 
p-values. 
Justification: The time to event endpoints are now at the end of the 
secondary endpoints, so the statistical methods for the analysis is 
also moved to the end. 
• Change in ordinal scale at specific time points will be summarized by 
proportions (e.g., proportion who have a 1-, 2-, 3-, or 4-point 
improvement or 1-, 2-, 3-, 4-point worsening). The CMH test 
controlled by country and subject’s clinical status at Baseline ([lung 
injury/mild ARDS] or [moderate/severe ARDS]) will be used for 
treatment difference. The odds ratio of gimsilumab versus placebo, 
9095% CIs and p-values will be provided. 
Justification: 90% was in error, corrected to 95% 
• Duration of event free (e.g., duration of mechanical ventilation free 
days) will be summarized according to median days with quartiles. 


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as underlined. 
The Wilcoxon rank test will be used for the treatment difference. 
Justification: to remove the bias introduced by death 
• Incidence data (e.g., incidence of new or increased oxygen use) will 
be summarized as a percent with 95% confidence intervals. The 
CMH test controlled by country and subject’s clinical status at 
Baseline ([lung injury/mild ARDS] or [moderate/severe ARDS]) will be 
used for treatment difference. The odds ratio of gimsilumab versus 
placebo, 905% CIs and p-values will be provided. 
Justification: 90% was in error, corrected to 95% 
• The time-to-event endpoints will be summarized with Kaplan Meier 
curves and 95% confidence bounds by the treatment. The log rank 
test and/or the Cox Hazard Proportional model with treatment, 
country, and subject’s clinical status at Baseline ([lung injury/mild 
ARDS] or [moderate/severe ARDS]) as model terms will be used. 
The hazard ratio of gimsilumab versus placebo will be presented with 
95% CI and p-values. 
9.5.4 Adjustment of Multiple 
Comparisons 
Text regarding hierarchical endpoint analyses was deleted as hierarchical 
testing was removed from the study. 
The 3 key secondary endpoints will be analyzed by hierarchical testing 
procedure following the order of the list of endpoints, and each endpoint 
will be analyzed at 0.05 alpha level. 
Section 10.1 Special Consideration 
for Assessment of Adverse Events 
Language was revised to clarify that Death should be considered both an 
SAE and an outcome. 
Death should not be recorded both as an event but should be recordeda 
SAE and as the outcome of ONE event, i.e. one event should be 
determined to be the primary cause of death. 
 
 
Table 14-3: Summary of Changes: Amendment 3 
 
Section(s) Changed 
Description of Changes and Justification 
Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
Global change: Synopsis and 
throughout 
Version and date were updated throughout the entire protocol. 
Version 3: 06-May-2020 
Version 4: 12 June 2020 


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Table 14-3: Summary of Changes: Amendment 3 
 
Section(s) Changed 
Description of Changes and Justification 
Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
Global change: Synopsis and 
throughout 
Minor edits, including formatting, spelling, and grammar corrections. 
Synopsis and Section 3 Objectives 
and Endpoints 
One of the key secondary objectives was moved to additional secondary 
objectives due to changing criteria for ICU level of care during the 
evolution of the current pandemic: 
• To assess the effect of gimsilumab on the need for Intensive Care 
Unit (ICU) level of care 
Synopsis, Section 3 Objectives and 
Endpoints, and Section 9.3.1 Efficacy 
Endpoints 
Key secondary and additional secondary endpoints were revised to clarify 
actual intent of the study, as follows: 
Key secondary endpoints (only those changes are shown): 
• Incidence Proportion of subjects who survived and not on requiring 
mechanical ventilation on Day 15, Day 22, Day 29, and Day 43 
• Mechanical ventilation-free days by Day 29 
• Time to hospital discharge by Day 43 
• 
Incidence of mechanical ventilation use, and ventilation-free days during 
the study 
• 
Incidence of ICU use, and ICU-free days during the study 
• Number of days of inpatient hospitalization 
Additional secondary endpoints (only those changed are shown): 
• Incidence of mortality by Day 15 Day 29, and Day 85, and Day 169 
(End-of-Study [EoS]) 
• 
Proportion of subjects who survived and were not requiring mechanical 
ventilation on Day 15, 22, and 43 
• 
Mechanical ventilation-free days for all subjects by Day 15, 22, and 43 
• 
ICU-free days for all subjects by Day 15, 22, 29, and 43 
• 
Incidence of mechanical ventilation use for all subjects by Day 15, 22, 
29, and 43 
• 
Incidence of ICU use for all subjects by Day 15, 22, 29, and 43 
• Time to death by Day 43 and Day 169 (EoS) 
• 
SOFA score, and each of the components, assessed daily while in the 
ICU 
• 
Time to clinical improvement by 2 points on the 7-point ordinal scale 
Synopsis and Section 9.5.1 Primary 
Efficacy Analyses 
The following statistical analysis information was revised to clarify which 
statistical models are being used, and to remove hierarchical testing: 
Efficacy Analyses: 
The secondary analysis of the primary endpoint will be conducted by 
using log rank test and/or the Cox Proportional model on the time to event 
of the primary endpoint. The median of the time to event from Kaplan- 


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Description of Changes and Justification 
Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
Meier curves will be presented for each treatment, and the hazard ratio of 
gimsilumab versus placebo will be presented with 95% CI, and p-value. 
Adjustment of Multiple Comparisons: 
The 3 key secondary endpoints will be analyzed by hierarchical testing 
procedure following the order of the list of endpoints, and each endpoint 
will be analyzed at 0.05 alpha level. 
Synopsis, Section 8 (Data 
Management), and Section 9 
(Statistical Considerations and 
Analyses section) 
Revisions were made due to FDA feedback and Sponsor decision 
regarding timing of interim analyses, and to reflect that the study is 
currently being conducted in 1 country only. 
Efficacy Analyses: 
The primary analysis of the efficacy endpoint (Mortality by Day 43) will be 
performed by using logistic regression [Ge, 2011] with treatment, site, and 
Cochran-Mantel-Haenszel (CMH) test, controlled by subject’s clinical 
status at Baseline ([lung injury/mild ARDS] or [moderate/severe ARDS]). 
Adjustment of Multiple Comparisons and Interim Analysis: 
The second interim analysis will be conducted when 50% of total 100 
subjects are discharged from the hospital, have completed the Day 2943 
Visit, discontinue the study early, or meet the endpoint of mortality (by 
Day 2943). The objectives of the second interim analysis will be to stop 
the study by futility, or perform the sample size re-estimation. 
There will be the split of alpha 0.05 to be 0.001 for the 2nd interim analysis 
and 0.049 for the final analysis of the primary endpoint, as the 2nd interim 
analysis may claim for the superior efficacy for the stop of the study early. 
For controlling overall two-sided alpha of 0.05 for the final analysis on the 
primary endpoint of Mortality Day 43, the weighted average of two 
summary measures by Cui L, Hung HM, Wang [Cui, 1999] will be used, 
one based on the data collected in the interim analysis, and the other 
based on the data collected after the interim. 
Analyses in General: 
All the categorical variables will be summarized by the treatment with the 
numbers and percentages of the subjects, and the treatment difference 
will be tested by using CMH test stratified by 1) countrysite and 2) 
subject’s clinical status at Baseline ([lung injury/mild ARDS] or 
[moderate/severe ARDS]). 
The time to event endpoints will be analyzed by using the Cox 
Proportional Hazard model with the treatment, subject’s clinical status at 
Baseline ([lung injury/mild ARDS] or [moderate/severe ARDS]), and 
countrysite as the model term. 
Handling of Missing Data 
For the efficacy analyses, the multiple imputation method, including the 
tipping point method, will be used to handle the missing data as the 


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Section(s) Changed 
Description of Changes and Justification 
Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
sensitivity analyses. No imputation will be used for any missing data in 
safety analysis. 
Separate analyses will be performed for the primary and key secondary 
endpoints by using multiple imputations for the missing data: 
• 
Tipping-point multiple imputation analysis 
Missing data will be imputed for Mortality by Day 43 with all possible 
combinations of Death or Survival in the two arms. The combination 
which alters the conclusion will be defined as the tipping point for 
evaluation on the robustness of the results. 
• 
Imputation differentiating the reasons of missing data from the 
early drop out 
The reasons of the lost to follow-up, SAEs/AEs, and the use of rescue 
medications will be identified, and the percentage of these subjects will be 
summarized by treatment. The data for informative censoring, such as the 
unfavorable or worst outcome, can be used to impute the missing data. 
More details will be pre-specified in the statistical analysis plan (SAP). 
Timing of Analyses with All Subjects: 
The first unblinded analyses will be conducted when the last subject 
completes the Day 43 Visit, discontinues from the study early, or meets 
the primary mortality endpoint (by Day 43). The second unblinded 
analyses will be conducted when the last subject completes the Day 169 
Follow-up Visit (EoS). 
In addition, there will be 2 database extracts (soft locks) for interim 
analyses, the first of which will be conducted when 60 subjects have been 
treated and have completed through Day 15; the DMC will review the 
data for safety and futility and provide their recommendations. The 
second interim analysis will be conducted when 50% of total 100 subjects 
who have completed the Day 4329 Visit, discontinue the study early, or 
have met the endpoint of mortality (by Day 4329). 
The first interim analysis will be when 60 subjects have been treated and 
have completed 7 days of follow-up; the DMC will review the data for 
safety and futility and provide their recommendations. 
The second interim analysis will be conducted when 50% of total subjects 
are discharged from the hospital, complete the Day 43 Visit, discontinue 
the study early, or meet the endpoint of mortality (by Day 43). The 
objectives of the second interim analysis will include the claim of superior 
efficacy or futility to stop the study, the reassessment of sample size, 
and/or modifications of the populations. 
The DMC will be responsible for closely reviewing the safety data from 
the unblinded interim analysis and for providing their recommendations. 
The detailed objectives and procedures of the interim analyses will be 


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Section(s) Changed 
Description of Changes and Justification 
Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
described in the DMC Charter. ; these can be the claim of early stop of 
the study for superiority, futility, re-assessment of the final sample size, 
and/or the study population. A SAP and DMC Charter will be generated 
with detailed information, including the boundaries of the superiority and 
futility for the interim analysis. 
Statistical Analysis Plan (SAP): 
A detailed (revised) SAP will be signed and submitted to the agencies 
prior to the interim analysis of 100 subjects. 
Section 7.1 Schedule of 
Assessments 
The Schedule of Assessments was revised to clarify the EoS/Early Term 
assessments. 
Abbreviations were revised, as needed. 
Language was added to footnote d to clarify acceptable testing for TB. 
the event the QuantiFERON Gold assay is not available, and the site 
performs a different IGRA such as T Spot, then the alternative IGRA will 
be acceptable for patient screening and enrollment. Enrollment should not 
be delayed to obtain the QuantiFERON Gold assay in lieu of the IGRA 
available at the site. If no IGRA test is available, PPD can be used. 
Section 7 Study Assessments and 
Procedures 
Language was added to clarify the follow-up conduct for the study. 
Once a subject is discharged from the hospital every effort MUST be 
made to ensure visit timepoints listed on the Schedule of Assessments 
(Table 7-2) are completed via phone or telemed. All visits are required to 
be completed for every subject unless the subject dies or withdraws 
consent. If a subject is deemed lost to follow-up every effort should be 
made to check vital status records at each visit time point to obtain 
survival status. Proper follow-up and documentation should be completed 
per GCP/ICH guidelines before deeming a subject lost to follow-up. 
Section 13 (References) 
New references were added based on text that was added to the 
protocol. 
Appendix 3: Summary of Changes for 
Protocol Amendments (Section 14.3) 
Table 14-3 was added to explain changes made in Protocol 
Amendment 3. 


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Section(s) Changed 
Description of Changes and Justification 
Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
Global change: Synopsis and 
throughout 
Version and date were updated throughout the entire protocol. 
Version 4: 12 June 2020 
Version 5: 17-August-2020 
Global change: Synopsis and 
throughout 
Minor edits, including formatting, spelling, and grammar corrections; 
headers updated throughout. 
Medical Contact/Sponsor Information 
Page 
Secondary Medical Monitor name and contact information was updated to 
reflect staffing change. 
Synopsis, Study Centers and 
Countries 
The synopsis was updated to reflect the addition of another country and to 
revise the planned number of sites in the US and potential number of sites in 
Mexico and to clarify that other countries may be added later. 
The number of study centers and locations where this study will be 
conducted are to be determinedThis study will be conducted at approximately 
20 centers in the United States and potentially 6 centers in Mexico; other 
countries may be added, if needed. 
Synopsis and Section 5.2 Inclusion 
Criteria 
Inclusion criterion #2 was revised to allow for verbal consent to participate 
in the study. Inclusion criterion #7 was revised to clarify that FSH only 
needs to be done to confirm postmenopausal status in women who have 
not had spontaneous amenorrhea for 12 consecutive months. 
2. Subject (or legally authorized representative [LAR]) is able and willing 
to provide written or verbal informed consent, which includes compliance 
with study requirements and restrictions listed in the consent form. NOTE: 
If a subject or LAR must be consented verbally, the site must have a site 
policy for verbal consent and the consent must be clearly documented in 
the subject’s chart. 
7. Postmenopausal defined as 12 months of spontaneous amenorrhea or 
with follicle stimulating hormone (FSH) confirmation. 
Synopsis and Section 5.3 Exclusion 
Criteria 
Exclusion criterion #2 was revised to clarify time of intubation. Exclusion 
criteria #13 and #14 were revised to match the clarification memos that 
were sent to sites prior to this amendment. 
2. Subject has been intubated for >72 hours. Note: in the event of 
extubation and re-intubation, the calculation for the number of hours the 
subject has been intubated begins at the first intubation. 
13. Use of any immunomodulatory biologic (e.g., anti-IL-1, anti-IL-6R, 
anti-TNF, inhibitors of complement signaling), cell therapies (e.g., 
mesenchymal stem cells), or small molecules (e.g., Janus kinase [JAK] 


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Description of Changes and Justification 
Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
inhibitors) within the past 7 days or within five half-lives (whichever is 
longer), or planned use of any of these agents from Screening until 
Day 43 of the study, unless approved by the Medical Monitor. The 
following will be allowed/disallowed: 
• 
Immunomodulatory biologics for COVID-19 treatment are 
excluded and should not be used until Day 43 unless discussed 
with the Medical Monitor. Other non-biologic immunomodulators 
(non-JAK inhibitors), e.g., medicines for previous transplantation, 
or disease modifying anti-rheumatic drugs (DMARDS) and have 
had a stable dose for ≥8 weeks are permitted. 
• 
Subjects who have been treated with convalescent plasma (CP) 
prior to enrollment are eligible if the subject continues to meet all 
inclusion criteria at screening. Ongoing therapy with CP is 
allowable if clinically indicated in the view of the treating 
physician or the Investigator. 
• 
The use of investigational anti-viral treatment (e.g., remdesivir) is 
allowed if the subject continues to meet all inclusion criteria at 
screening. 
14. Ongoing cChronic (≥4 weeks) use of corticosteroids >10 mg/day of 
prednisone or equivalent at the time of randomization. A corticosteroid 
dose that has been tapered to 10 mg or less within 14 days of 
randomization is also prohibited. 
Synopsis, Section 8 (Data 
Management), and Section 9 
(Statistical Considerations and 
Analyses section) 
Revisions were made to reflect that the interim analysis was changed to 
include stop for superiority as well as mortality at day 43 and to add 
country instead of site as a stratification factor since another country was 
added. 
Database Locks: 
The second interim analysis will be conducted when 100 subjects have 
completed at least the Day 29 Visit for non-mortality endpoints, or and 
have met the data for the endpoint of mortality (by Day 2943). 
Efficacy Analyses: 
The primary analysis of the efficacy endpoint (Mortality by Day 43) will be 
performed by using logistic regression [Ge, 2011] with treatment, 
sitecountry, and subject’s clinical status at Baseline ([lung injury/mild 
ARDS] or [moderate/severe ARDS]). 
Adjustment of Multiple Comparisons and Interim Analysis: 
There is no need to adjust the significance level 0.05 (two-sided) in the 
analysis since there is only 1 primary endpoint and 1 gimsilumab dose 
level versus placebo. The interim analysis will be conducted when 60 
subjects have been treated and have completed through Day 15; the 
DMC will review the data for safety and futility and provide their 
recommendations. 


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Section(s) Changed 
Description of Changes and Justification 
Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
The second interim analysis will be conducted when 100 subjects have 
completed at least the Day 29 Visit for non-mortality endpoints, or and 
have met the data for the endpoint of mortality (by Day 2943). The 
objectives of the second interim analysis will be to stop the study by 
superiority, futility, or perform the sample size re-estimation. 
For controlling overall two-sided alpha of 0.05 overall for the final 
analysis on the primary endpoint of Mortality Day 43, 0.001 of the alpha 
will be used for the superiority comparison during the second interim 
analysis, and 0.049 will be used for the final analysis. And tThe weighted 
average of two summary measures by Cui L, Hung HM, Wang [Cui, 1999] 
will be used, one based on the data collected in the interim analysis, and 
the other based on the data collected after the interim. 
Analyses in General: 
All of the continuous variables, including the changes from Baseline, will 
be summarized by the treatment with the means, SD, medians and the 
ranges. The Mixed Model with Repeated Measurements (MMRM) 
/Analysis of Covariance (ANCOVA) model with the treatment, sitecountry, 
subject’s clinical status at Baseline ([lung injury/mild ARDS] or 
[moderate/severe ARDS]), and visit as the model term, and Baseline 
value as the covariate will be used to test for the significance of the 
treatment difference. The least square means, standard errors, 95% CIs 
and p-values will be presented. 
All the categorical variables will be summarized by the treatment with the 
numbers and percentages of the subjects, and the treatment difference 
will be tested by using CMH test stratified by 1) sitecountry and 2) 
subject’s clinical status at Baseline ([lung injury/mild ARDS] or 
[moderate/severe ARDS]). 
The time to event endpoints will be analyzed by using the Cox 
Proportional Hazard model with the treatment, sitecountry, and subject’s 
clinical status at Baseline ([lung injury/mild ARDS] or [moderate/severe 
ARDS]) as the model term. The hazard ratio of gimsilumab versus 
placebo will be presented with 95% CI and p-value from the model. The 
Kaplan-Meier curves of the time to events will be presented for treatments 
on each endpoint. 
Section 4.1 Overall Design 
Text was revised to reflect the addition of another country: 
Randomization will be stratified by sitecountry and subject’s clinical status 
at Baseline 
Sections 2.2 Dose Rationale, 6.1 
Study Treatment, and 6.2 
Administration of Study Treatments 
Table 6-1 was revised to allow a window for the timing of the infusion 
given the clinical care setting. 


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Section(s) Changed 
Description of Changes and Justification 
Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
Infuse the entire contents of the IV bag via the intravenous route over a 
Flush the line with 0.9% saline to ensure the 
entire contents is administered. 
 
Section 7.1 Schedule of 
Assessments 
The Schedule of Assessments footnotes were revised to clarify the 
following: screening serology and TB test results do not need to be 
received prior to enrollment, physical examinations and vital signs 
measurements performed as standard of care may not need to be 
repeated, local laboratory values must be documented in the eCRF, and 
DoD assessments can be performed one day prior to discharge if the 
subject has been labelled as “ready for discharge.”. 
Abbreviations were revised, as needed. 
Section 7.4.2.1 Physical 
Examinations 
Language was added to clarify that physical examinations performed as 
standard of care may not need to be repeated. 
Note: If a physical examination is performed as standard of care by 
appropriate personnel the same day that consent is signed or the same 
day of any scheduled study visit, results from that examination may be 
used if personal protective equipment (PPE) is not available or if study 
site staff consider additional examinations are unwarranted due to already 
having been performed as standard of care. 
Section 7.4.2.2 Vital Signs 
Language was added to clarify that vital signs measurements performed 
as standard of care may not need to be repeated. 
Note: If vital signs measurements are performed as standard of care by 
appropriate personnel the same day that consent is signed or the same 
day of any scheduled study visit, results from that examination may be 
used if PPE is not available or if study site staff consider additional 
measurements are unwarranted due to already having been performed as 
standard of care. 
Section 7.4.2.4 Follicle Stimulating 
Hormone (FSH), Viral Serology, and 
Tuberculosis Assessments 
This section was added to allow for clarifying text to be included in the 
main body of the protocol. 
Follicle stimulating hormone (FSH) will be performed at screening, for 
women only, to confirm postmenopausal status in women who have not 
had 12 months of spontaneous amenorrhea. 
A blood sample will be collected at Screening as specified in the 
Schedule of Assessments (Table 7-2), for viral serology and TB testing, 
but enrollment can continue without receiving the results first. HCV testing 
can be RNA or Ag, only to confirm suspected infection. If a subject is 
diagnosed with latent TB (positive QuantiFERON Gold or purified protein 
derivative [PPD]), hepatitis B or C, or HIV during the study, the 


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Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
Investigator must discuss this with the medical monitor and a decision will 
then be made concerning the second dose of gimsilumab, if applicable. In 
the event the QuantiFERON Gold assay is not available, and the site 
performs a different IGRA such as T Spot, then the alternative IGRA will 
be acceptable for patient screening and enrollment. Enrollment should not 
be delayed to obtain the QuantiFERON Gold assay in lieu of the IGRA 
available at the site. If no IGRA test is available, PPD can be used. If TB 
testing and viral serology is missed during screening it must be completed 
and results received prior to the second dose of study drug. If not 
completed or unable to obtain results further discussions with the medical 
monitor will be required. 
Section 9.2 Randomization 
Text added to reflect the addition of another country. 
The central stratified randomization will be used to assign subjects into 1 
of the 2 study treatment arms with an equal randomization ratio (1:1) with 
the stratification factors of subject’s clinical status at Baseline ([lung 
injury/mild ARDS] or [moderate/severe ARDS]) and country. 
Appendix 3: Summary of Changes for 
Protocol Amendments (Section 14.3) 
Text was revised to reflect the new Amendment. 
The original Protocol (Version 1.0) was approved on 22-March-2020, and 
has been amended 34 times; Protocol Amendment 1 (Version 2.0) was 
approved on 05-April-2020, Protocol Amendment 2 (Version 3.0) was 
approved on 06-May-2020, and Protocol Amendment 3 (Version 4.0) was 
approved on 12-June-2020, and Protocol Amendment 4 (Version 5) was 
approved on 17-August-2020. 
Summaries of changes are presented in Table 14-1 for Amendment 1, 
Table 14-2 for Amendment 2, and Table 14-3 for Amendment 3, and 
Table 14-4 for Amendment 4. 
Table 14-4 was added to explain changes made in Protocol 
Amendment 4. 
 

SAP_001.pdf: 
 
 
 
 
 
Study Number: KIN-1901-2001 
 
 
Study Title: A Multi-Center, Adaptive, Randomized, Double-blind, Placebo-controlled Study to 
Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute 
Respiratory Distress Syndrome (ARDS) Secondary to Coronavirus Disease 2019 (COVID-19) 
 
 
 
Statistical Analysis Plan 
Version 4, 17-November-2020 
NCT04351243 


PAREXEL International 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 1 of 122 
 
 
 
 
 
 
PAREXEL International 
 
 
 
Kinevant 
 
 
 
KIN-1901-2001 
 
 
 
A Multi-Center, Adaptive, Randomized, Double-blind, Placebo-controlled Study to Assess the 
Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute Respiratory Distress 
Syndrome (ARDS) Secondary to Coronavirus Disease 2019 (COVID-19) 
 
 
 
Statistical Analysis Plan 
 
 
 
Version: 4.0 
 
 
 
PAREXEL Project Number: 250621 


PAREXEL International 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 2 of 122 
 
 
 
SPONSOR SIGNATURE PAGE 
 
 
Approved by: 
 
 
 
Date 
 
On Behalf of Kinevant Sciences Inc 
 
 
 
 
 
Date 
 
On Behalf of Kinevant Sciences Inc 
 
 
 
 
 
Date 
 
Kinevant Sciences Inc 


PAREXEL International 
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Statistical Analysis Plan 
Related to: SOP-GDO-WW-019 
Page 3 of 122 
 
 
Author 
 
PAREXEL SIGNATURE PAGE 
 
Signature(s) below confom that the Statistical Analysis Plan was developed in accordance with 
SOP-GDO-WW-019 and that it is approved for release. 
 
This document has been approved and signed electronically on the final page by the 
following: 
 
 
 
Signatory 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date ofla.st signature 


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Statistical Analysis Plan 
Related to: SOP-GDO-WW-019 
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TABLE OF CONTENTS 
1 
INTRODUCTION ..................................................................................................... 10 
2 
STUDY OBJECTIVES ............................................................................................. 11 
2.1 
Primary Objective(s) ............................................................................................. 11 
2.2 
Secondary Objective(s) ......................................................................................... 11 
2.3 
Exploratory Objective(s) ....................................................................................... 11 
3 
INVESTIGATIONAL PLAN ................................................................................... 12 
3.1 
Overall Study Design and Plan ............................................................................. 12 
3.2 
Database locks ....................................................................................................... 13 
3.3 
Determination of Sample Size .............................................................................. 13 
3.4 
Endpoints .............................................................................................................. 14 
3.4.1 
Efficacy Variables ............................................................................................... 14 
3.4.2 
Safety Variables .................................................................................................. 14 
3.5 
Exploratory Variables ........................................................................................... 15 
4 
STATISTICAL METHODS ..................................................................................... 16 
4.1 
Data Quality Assurance ......................................................................................... 16 
4.2 
General Presentation Considerations .................................................................... 16 
4.2.1 
Study Periods ...................................................................................................... 16 
4.2.2 
Study Visits and Windowing .............................................................................. 17 
4.2.3 
Missing dates ...................................................................................................... 18 
4.2.4 
Conventions ........................................................................................................ 18 
4.3 
Software ................................................................................................................ 19 
4.4 
Study Subjects ....................................................................................................... 19 
4.4.1 
Disposition of Subjects ....................................................................................... 19 
4.4.2 
Protocol Deviations ............................................................................................ 19 
4.5 
Analysis Sets ......................................................................................................... 19 
4.6 
Demographic and Other Baseline Characteristics................................................. 20 
4.7 
Prior, Concomitant, and Prohibited Medications and Procedures ........................ 21 
4.8 
Efficacy Evaluation ............................................................................................... 22 
4.8.1 
Analysis and Data Conventions .......................................................................... 22 
4.8.1.1 
Multi-center Study ............................................................................................ 22 
4.8.1.2 
Adjustments for Covariates .............................................................................. 22 
4.8.1.3 
Handling of Dropouts or Missing Data ............................................................ 22 
4.8.1.4 
Multiple Comparisons/Multiplicity .................................................................. 22 
4.8.1.5 
Examination of Subgroups ............................................................................... 23 
4.8.1.6 
Analysis Methods – Multiple imputation ......................................................... 24 
4.8.1.7 
Analysis Methods – Tipping point analysis ..................................................... 26 
4.8.1.8 
Analysis Methods – Final analysis following adaptive sample size increase .. 27 
4.8.1.9 
Analysis Methods – Continuous variables ....................................................... 27 
4.8.1.10 Analysis methods – Count variables ................................................................ 28 
4.8.1.11 Analysis methods – Categorical variables ........................................................ 28 
4.8.1.12 Analysis Methods – Time to event variables ................................................... 28 
4.8.1.13 Analysis Methods - Multi-state competing risks models ................................. 28 
4.8.1.14 By-subject listings ............................................................................................ 30 
4.8.2 
Analysis of the Primary Efficacy Endpoint ........................................................ 30 
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Project Document Effective Date: Date of last signature 


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Related to: SOP-GDO-WW-019 
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4.8.3 
Key Secondary Efficacy Analysis ....................................................................... 32 
4.8.3.1 
Survival and no mechanical ventilation on Day 29 ........................................... 32 
4.8.3.2 
Mechanical ventilation-free days by Day 29 ..................................................... 33 
4.8.3.3 
Time to hospital discharge ............................................................................ 34 
4.8.4 
Other Secondaiy and Exploratory Efficacy Analyses ......................................... 35 
4.9 
Safety Evaluation ................................................................................................... 39 
4.9.1 
Extent of Exposure ............................................................................................... 39 
4.9.2 
Adverse Events .................................................................................................... 39 
4.9.2.1 
AE Summaries by system organ class (SOC) and prefened tenn (PT) ............. 40 
4.9.2.2 
AE of Special Interest (AESI) ........................................................................... 41 
4.9.2.3 
Adverse event listings ........................................................................................ 41 
4.9.3 
Clinical Laboratory Evaluation ........................................................................... 41 
4.9.4 
Vital Signs, Physical Findings and Other Observations Related to Safety .......... 43 
4.9.5 
Independent Data Monitoring Committee ........................................................... 44 
4.10 
Other Analyses ....................................................................................................... 45 
4.10.1 Pha11nacokinetics ............................................................................................... 45 
4.10.2 hnmunogenicity............................................................................................... 45 
4.10.3 Biomarker........................................................................................................ 45 
4.11 
Changes in the Conduct of the Study or Planned Analysis .................................... 46 
5 
INTERIM ANALYSES ............................................................................................. 47 
5.1 
Interim Analysis 1 .................................................................................................... 47 
5.1.1 
Subjects to be included in interim analysis 1 ........................................................ 47 
5.1.2 
Analysis of efficacy endpoints at interim analysis 1 ............................................ 47 
5.1.3 
Futility criteria at interim analysis 1 .................................................................... 47 
5.2 
Interim Analysis 2 .................................................................................................. 47 
5.2.1 
Subjects to be included in interim analysis 2 ....................................................... 48 
5.2.2 
Analysis of efficacy endpoints at interim analysis 2 ............................................ 48 
5.2.3 
Superiority stopping criteria at interim analysis 2 ............................................... 48 
5.2.4 
Futility stopping criteria at interim analysis 2 ...................................................... 48 
5.2.5 
Sample size re-estimation at interim analysis 2 ................................................... 48 
5.2.6 
Interim analysis 2 outcome .................................................................................. 49 
6 
REFERENCES ...................................................................................................... 50 
7 
APPENDICES ....................................................................................................... 51 
7.1 
Schedule of Assessments ....................................................................................... 52 
7.2 
Adverse Events of Special Interest ......................................................................... 56 
 
 
 
 
 
 
 
 
 
 
 
 
 
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REVISION HISTORY 
 
 
Version No. 
Effective Date 
Summary of Change(s) 
0.1 
06Apr2020 
New document 
0.2 
15Apr2020 
Incorporate Parexel internal review comments 
0.3 
19Apr2020 
Incorporate Sponsor statistical review comments 
0.4 
24Apr2020 
Incorporate Sponsor review comments 
0.5 
01May2020 
Incorporate Sponsor review comments 
1.0 
06May2020 
Final version for signature 
1.1 
19Jun2020 
Update to align with Protocol v4.0 (12Jun2020) and to 
address FDA comments on SAP v1.0. Major updates: 
- 
Updates to key secondary endpoints. 
- 
Change missing data imputation method from LOCF 
to tipping point method. 
- 
Use estimand framework to describe primary and key 
secondary efficacy analyses. 
1.2 
21Jun2020 
Incorporate Sponsor statistical review comments 
1.3 
22Jun2020 
Additional details for interim analysis and missing data 
analyses added. 
2.0 
26Jun2020 
Incorporate final Sponsor review comments. Final version for 
signature 
2.1 
20Jul2020 
Incorporate FDA comments on SAP v2. and editorial changes 
to fix minor typographical errors and add clarity. 
2.2 
11Aug2020 
Add superiority boundary for IA2, incorporate Parexel 
internal review comments 
3.0 
12Aug2020 
Incorporate final comments. Final version for signature. 
3.1 
19Oct2020 
Update per IA2 decisions: 
- 
Section 4.7 – Add summaries of any steroid use, any 
dexamethasone use, any other COVID-19 therapies. 
- 
Section 4.8.1.5 – Add new subgroup ‘Baseline 
invasive ventilator use or severe ARDS at baseline’ 
- 
Section 4.8.4 – Amend proposed analyses for 7-point 
ordinal scale to include shift tables and remove odds 
ratios and CMH tests. 
- 
Add section 5.2.6: Interim analysis 2 outcome 
3.2 
30Oct2020 
Incorporate sponsor comments. Add multi-state competing 
risks analysis as supplementary analysis for time to hospital 
discharge and time to clinical improvement (section 4.8.1.13). 
4.0 
13Nov2020 
Incorporate final comments. Final version for signature. 
 
 
 
 
 
 
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LIST OF ABBREVIATIONS 
 
Abbreviation / Acronym 
Definition / Expansion 
 
ADA 
Anti-drng antibodies 
AE 
Adverse event 
AESI 
Adverse events of special interest 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
aPTT 
Activated partial thromboplastin time 
ARDS 
Acute respiratory distress syndrome 
AST 
Aspartate aminotransferase 
BILI 
Total bilirnbin 
BMI 
Body Mass Index 
BP 
Blood pressure 
CI 
Confidence interval 
CMH 
Cochran-Mantel-Haenszel 
CMQ 
Company MedDRA que1y 
COVID-19 
Coronavims disease 2019 
CPAP 
Continuous positive aiiway pressure 
CRP 
C-reactive protein; 
DBP 
Diastolic blood pressure 
DMC 
Data monitoring committee 
DoD 
Day-of-discharge 
DRM 
Data Review Meeting 
EAIR 
Exposure-adjusted incidence rate 
ECMO 
Extraco1poreal membrane oxygenation 
eCRF 
Electronic Case Repo1i Fo1m 
eGFR 
Estimated glomernlar filtration rate 
EoS 
End-of-study 
ET 
Early te1mination 
FAS 
Full analysis set 
FiO2 
Fraction of inspii·ed oxygen 


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Abbreviation / Acronym 
Definition / Expansion 
GM-CSF 
HR 
IA 
ICU 
ITT 
IV 
LDH 
LIS 
LOCF 
LVEF 
MDRD 
MMRP 
MedDRA 
NA 
NEWS 
02 
PEEP 
PIF 
Pa02 
PCR 
P-D 
PK 
pp 
PT 
SAE 
SAP 
SARS-CoV-2 
SBP 
SD 
SMQ 
soc 
Granulocyte macrophage-colony stimulating factor 
Heart rate 
Interim analysis 
Intensive care unit 
Intent-to-ti·eat 
Inti·avenous 
Lactate dehydrogenase 
Lung injmy score 
Last observation caITied fo1ward 
Left venti·icular ejection fraction 
Modification of Diet in Renal Disease 
Mixed model with repeated measures 
Medical Dictionaiy for Regulato1y Activities 
Not available 
National Early Warning Score 
Oxygen 
Positive end-expiratory pressure 
PaOi/Fi02 ratio 
Paiiial pressure of oxygen 
Polymerase chain reaction 
Patient days 
Phannacokinetics 
Per-protocol 
Prefe1Ted Tenn 
Serious adverse event 
Statistical analysis plan 
Severe acute respiratory syndrome corona vims 2 
Systolic blood pressure 
Standard deviation 
Standard MedDRA que1y 
System Organ Class 


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Abbreviation / Acronym 
Definition / Expansion 
SOFA 
SP-D 
SpO2 
TEAE 
TLF 
WHODDE 
Sequential Organ Failure Assessment 
Surfactant protein D 
Peripheral capillary oxygen saturation 
Treatment-emergent adverse event 
Tables, Listings, Figures 
Wodd Health Organization - Dmg Dictionary Enhanced 


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1 
INTRODUCTION 
 
In December 2019, the city of Wuhan, China experienced an outbreak of coronavirus disease 2019 
(COVID-19), caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 
(SARS-CoV-2). As of March 2020, COVID-19 has become a global pandemic, and there are 
currently no approved agents available to treat coronaviruses. SARS-CoV-2 infection often 
induces an overactive immune response that causes significant lung damage, leading to acute 
respiratory distress syndrome (ARDS) and ultimately death. Granulocyte macrophage-colony 
stimulating factor (GM-CSF), a hematopoietic growth factor and immunomodulatory cytokine, is 
believed to have a key driver of cytokine storm and lung hyper-inflammation. Targeting GM-CSF 
using an anti-GM-CSF antibody, gimsilumab (KIN-1901), represents a promising strategy to treat 
patients who have developed lung injury or ARDS secondary to COVID-19. 
 
KIN-1901-2001 is a randomized, double-blind, placebo-controlled study of gimsilumab for the 
treatment of lung injury or ARDS secondary to COVID-19. A total of 270 subjects are planned to 
be treated with IV gimsilumab on day 1 (400mg) and day 8 (200mg) or matching IV placebo (saline 
solution on days 1 and 8). This study consists of a 2-week Treatment Period and a 22-week Follow- 
up Period. 
 
This study will have two database locks, the first when all subjects have completed through Day 
43 or withdraw from the study early or meet the primary mortality endpoint. The second database 
lock will be when the last subject completes the Day 169/End-of-study (EoS) visit. 
 
This statistical analysis plan (SAP) provides a detailed description of the statistical methods and 
analyses to be carried out in support for study KIN-1901-2001. 
 
The following will be collected and not entered into the clinical study database until the database 
is locked: 
 
• Pharmacokinetic data 
• Immunogenicity data 
• Exploratory biomarkers 
 
The analyses described in this SAP are based upon the following study documents: 
 
• Study Protocol, Version 2.0 (April 5, 2020) 
• Study Protocol, Version 5.0 (August17, 2020) 
• KIN-1901-2001 DMC Charter Version 3.1 (July 11, 2020) 
• eCRF (September 29, 2020) 


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2 
STUDY OBJECTIVES 
 
2.1 
Primary Objective(s) 
The primary objective is to evaluate the impact of intravenous (IV) treatment with gimsilumab on 
mortality in subjects with lung injury or ARDS secondary to COVID-19. 
 
2.2 
Secondary Objective(s) 
Key Secondary Objectives: 
 
• To assess the effect of gimsilumab on ventilation requirements 
• To assess the effect of gimsilumab on overall duration of hospitalization 
Additional Secondary Objectives: 
• To assess the effect of gimsilumab on the need for Intensive Care Unit (ICU) level of care 
• To assess the effect of gimsilumab as measured by the National Early Warning Score 
(NEWS) 
• To assess the effect of gimsilumab as assessed by the Sequential Organ Failure Assessment 
(SOFA) score 
• To assess the effect of gimsilumab as measured by the 7-point ordinal scale 
• To assess the effect of gimsilumab on peripheral capillary oxygen saturation / fraction of 
inspired oxygen (SpO2/FiO2) 
• To assess the effect of gimsilumab on oxygenation requirements 
• To assess changes in on-treatment viral load 
• To assess the effect of gimsilumab on biomarkers of inflammation 
• To determine the pharmacokinetic (PK) properties of gimsilumab 
• To assess the immunogenicity of gimsilumab 
• To determine the safety and tolerability of gimsilumab 
 
2.3 
Exploratory Objective(s) 
• To explore the effect of gimsilumab on serum cytokine concentrations and surfactant 
protein D (SP-D) 
• To explore the effect of gimsilumab on other measurements of lung injury that may be 
performed during standard care (e.g., Lung Injury Score [LIS], chest radiography, 
PaO2/FiO2 [P/F ratio], need for extracorporeal membrane oxygenation [ECMO]) 
• To explore the effect of gimsilumab on cardiac function (if measured) 
• To assess the effect of gimsilumab on renal function 


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3 
INVESTIGATIONAL PLAN 
3.1 
Overall Study Design and Plan 
This is a randomized, adaptive, double-blind, placebo-controlled study in male and/or female 
subjects who are at risk of developing, or have developed, ARDS consequent to moderate to severe 
COVID-19. This study will include subjects with moderate-to-severe disease. There will be 2 
treatment aims, one receiving blinded gimsilumab, and one receiving blinded placebo. 
Efficacy, safety, tolerability, phannacokinetics, and phaimacodynamics of gimsilumab will be 
assessed in hospitalized adult subjects diagnosed with COVID-19. Randomization will bestratified 
by: 
• 
Subject's clinical status at Baseline 
o Lung injmy/mild ARDS 
o Moderate/severe ARDS 
 
Lung injmy is defined as (1) requiring supplemental oxygen >4L 02 to maintain >92% SpO2, or 
(2) PaOi/FiO2:S 300 rmnHg (can be imputed). 
 
ARDS is defined (ARDS Definition Task Force 2012) as: 
• 
Bilateral opacities - 
not fully explained by effusions, lobai·/lung collapse, or nodules; 
• 
Respirato1y failme not fully explained by cai·diac failw-e or fluid overload; 
• 
Need objective assessment (e.g., echocai·diography) to exclude hydrostatic edema if no risk 
factor present. 
• 
ARDS severity categories are defined as: 
o Mild: 200 m1nHg, < PaOi/FiO2, :S300 rmnHg with PEEP or CPAP::::5 cm H2O. 
o Moderate: 100 mmHg, < PaOi/FiO2, :S 200 rmnHg with PEEP::::5 cm H2O. 
o Severe: PaOi/FiO2:Sl00 rmnHg with PEEP::::5 cm H2O. 
 
A schematic of the study design is presented in Figure 3-1. Subjects will be assessed daily while 
hospitalized. Follow-up assessments are planned through Week 24, for a total study duration post­ 
randomization of approximately 169 days (24 weeks). Follow-up visits at Days 15, 22, 29, 36, 43, 
85 and 169 will be perfonned by phone if the subject has been discharged from the hospital. All 
subjects will undergo a series of efficacy, safety, and laborato1y assessments as detailed in the 
Schedule of Assessments (Appendix 7.1). 
 
Each subject will pa1ticipate for approximately 24 weeks, with a 2-week Treatment Period (last 
dose on Day 8) and a 22-week Follow-up Period. Treatment Anns for KIN-1901-2001: 
 
Arm 1: Gimsilumab (400 mg) as a single IV infusion on Day 1 followed by a single 200 
mg IV infusion on Day 8* (N=135) 
 
Arm 2: Placebo (0.9% saline solution) IV infusion on Day 1 and Day 8* (N=135) 
 
*The Day 8 dose will be omitted if the subject is discharged from the hospital or is no longer in need ofsupplemental 
oxygen or ventilatory suppo1t for >48 hours. 


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.. 
C: g., 
Gimsilumab arm (N = 135) 
I  I 
I 
·
Ne 
0 
V., 
I 
C: 
I  I 
/I--  
0:: 
Placebo arm (N = 135) 
• Confirmed SARS-CoV-2 
infection 
• Clinical evidence of lung 
Injury or ARDS 
• CRP 250 mg/l or serum 
ferrltln 21,000 ng/ml 
• Mortality at Day 43 
Seoonda!)( Endpoints 
• Ventilation use 
• ICU days 
• Hospital days 
• NEWS and SOFA score 
• lnHammato,y biomarl<ers 
• Virattoad 
• Safety and tolerability 
Prima!)( Endooint 
(If-' 
I 
Screen 
Inclusion Criteria 
169 
43 
15 
8 
1 
-7 
Study Day 
Follow-Up Visits 
(In hospital or by phone) 
Treabnent Period 
(Procedures only done in hospital) 
Screening 
Period 
Asufficient number ofsubjects will be emolled to achieve approximately 270 evaluable subjects total, 
with 135 subjects per treatment aim. There will be two inte1im analyses (IA): 
 
1st IA: For safety and futility when 60 subjects have completed treatment and completed 
through study Day 15 
 
2nd IA: For safety, superiority, and futility when 100 subjects have completed the study Day 
29 Visit (for non-mo1tality endpoints) or have died (mo1tality data) by Day 43 (see Section 
5.2.1 for details). 
The sample size re-estimation will be perfo1med to maintain the 
conditional power of 80% the primary analysis ofM01tality by Day 43. 
 
Figure 3-1: Study Schematic 
 
i 
i 
i 
IV Dose 1 
IV Dose 2 
Primary 
EoS 
(400 mg) 
(200 mg) 
 Endpoint 
Timepoint 
ARDS = acute respirato1y distress syndrnme; CRP = C-reactive prntein; EoS = End of Study; IV = intravenous; ICU = Intensive 
Care Unit; NEWS= National Early Waming Score; SOFA= Sequential Organ Failure Assessment 
 
3.2 
Database locks 
The database will be locked first when all subjects complete the Day 43 Visit, discontinue from 
the study eai·ly, or meet the primary m01tality endpoint. The second lock will occm when the last 
subject completes the Day 169/ EoS visit, discontinue from the study eai·ly, or died up to Day 169. 
Study unblinding will occm at the first database lock. 
All analyses described in this SAP will be perfo1med at the 1st database lock. For the 2nd lock, all 
safety analyses will be perfo1med but efficacy analyses without new data (e.g. assessments only 
collected dming hospitalization if all subjects have been discharged by 1st database lock) may not 
be perfo1med again. 
3.3 
Determination of Sample Size 
There will be 270 subjects (135 subjects per treatment aim) with 1:1 randomization. 
The comparisons between the treatment anns will have approximately 83% power and overall two­ 
sided alpha level 0.05 (the equivalent one-sided overall significance level 0.025 will be used in the 
remainder of this SAP) to demonstrate a statistically significant reduction in mo1tality by Day 43 for 


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Page 14 of 122 
 
 
gimsilumab compared to placebo when assuming tme propo1tions of 15% and 30%, respectively and 
a superiolity / futility inte1im analysis as described in Section 5.2. 
The study will emoll at least 40%, but no more than 60%, of total patients in each of the 2 categories 
of clinical status: ([lung injmy/mild ARDS] or [moderate/severe ARDS]) at Baseline, which will be 
used as the stratified factor in the randomization. 
 
3.4 
Endpoints 
 
3.4.1 Efficacy Variables 
Primary: 
• 
Mo1tality by Day 43 
 
Key Secondary: 
• 
Propo1tion of subjects who survived and not requiring mechanical ventilation on Day 29 
• 
Mechanical ventilation-free days by Day 29 
• 
Time to hospital discharge 
 
Additional Secondary: 
• 
Mortality by Days 15, 22, 29, 85, and 169 (EoS) 
• 
Proportion ofsubjects who survived and were not requiring mechanical ventilation on Days 
15, 22, and 43 
• 
Mechanical ventilation-free days for all subjects by Days 15, 22, and 43. 
• 
ICU-free days for all subjects by Days 15, 22, 29, and 43 
• 
Incidence of mechanical ventilation use for all subjects Days 15, 22, 29, and 43. 
• 
Incidence ofICU use for all subjects Days 15, 22, 29, 43 
• 
Time to death by Day 43 and Day 169 (EoS) 
• 
NEWS assessed daily while hospitalized 
• 
SOFA score and each of the components assessed daily while in the ICU 
• 
Status on the 7-point ordinal scale daily while hospitalized and on Days 15, 22, 29, 36, 43, 
85, and 169 if discharged 
• 
Time to clinical improvement 
• 
Change from Baseline in SpOi/Fi02 assessed daily while hospitalized 
• 
Incidence and duration of oxygen use during the study 
• 
Change from Baseline in viral load as measured by quantitative polymerase chain reaction 
(PCR) test on Days 2, 9, and Day-of-discharge (DoD) 
• 
Change from Baseline in D-dimer, cardiac troponin I, lactate dehydrogenase (LDH), fen-
itin, procalcitonin, and C-reactive protein (CRP) on Days 4, 8, and DoD (and Days 15, 22, 
29, 36, and 43 if hospitalized) 
• 
Se1um gimsilumab concentrations on Days 1, 8, and DoD 
• 
Anti-gimsilumab antibodies (ADAs) on Day 1 and DoD (and Days 15, 29, and 43 if 
hospitalized) 
 
3.4.2 Safety Variables 
• 
Physical examinations 
• 
Vital signs (supine blood pressure [BP] and pulse, oral body temperature, respirato1y rate) 


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• Clinical laboratory tests (hematology, clinical chemistry, and urinalysis parameters) 
• Adverse event (AE) assessments 
• Concomitant medication assessments 
 
The above safety variables will be summarized by Day 43 and Day 169/EoS. 
 
3.5 
Exploratory Variables 
• Change from Baseline in the cytokine panel on Days 4, 8, and DoD (and Days 15 and 29 if 
hospitalized) 
• Change from Baseline in LIS (if performed) daily while hospitalized 
• Change from Baseline in chest radiographic assessment (if performed) 
• Change from Baseline in P/F ratio (if performed) daily while hospitalized 
• Incidence and duration of ECMO use 
• Change from Baseline in left ventricular ejection fraction (LVEF) (when measured) 
• Change from Baseline in eGFR [Modification of Diet in Renal Disease (MDRD) equation], 
assessed when central clinical safety laboratory measurements are collected during 
hospitalization 


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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 
 
4.2.1 Study Periods 
This study has two periods, the treatment period and the follow-up period (Figure 3-1). The follow- 
up period will be divided into two for analysis purposes, the first for follow-up through Day 43 and 
the second for Day 44 through the end-of study. Some assessments will only be done while subjects 
are hospitalized as detailed in the schedule of assessment (Appendix 7.1), because of this some 
endpoints during each period will not be available for all subjects. The hospitalization period will 
contain all assessments during either the treatment period or follow-up period that occur before the 
subject is discharged. The discharge period will cover the time starting the day after hospital 
discharge through the end-of-study. Differences in time at risk will also be taken to account at the 
endpoint level and each endpoint be analyzed using methods appropriate to its planned collection 
pattern. Medical events and medications will be classified into study periods using their start dates. 
The following definitions will be applied: 
Treatment period (Day 1 – Day 15): Starts on first dose date and ends at the earliest of first 
dose date + 14 and end of study date. 
Follow-up period 1 (Day 16 through Day 43): Starts on first dose date + 15 and ends at the 
Day 43 Visit date. 
Follow-up period 2 (Day 44+): Starts on first dose date + 43 and ends at the end of study 
date. 
Overall: Treatment period, follow-up period 1 and follow-up period 2 combined. 
Overall - Hospitalized: Study Day 1 to date of discharge. This period will include all 
assessments that were taken while the subject was hospitalized. 
Overall – After Discharge: Day of discharge through end of study. This period starts at date 
of discharge + 1 and ends at the end of study date. 
Where, 
First dose date: Day 1, date first dose of study drug received. 
End of study date: date of End-of-Study visit (Day 169/ EoS) if subject completes the study 
or date of early withdrawal if subject discontinues early or date of death. 
Date of discharge: date subject is discharged from the hospital. 
Study Day: <Assessment Date> - first dose date + 1 if <Assessment Date> is on or after first 
dose date. <Assessment Date> - first dose date, if <Assessment Date> is before first dose date. 
Study drug: gimsilumab or placebo 
Study treatment: administration of study drug on Day 1 and Day 8 (as required per protocol). 


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4.2.2 Study Visits and Windowing 
Baseline: the last available pre-ti·eatment assessment. All assessments should have time collected. 
If time is not collected and date of assessment is the same as the first dose date, then assessment 
will be assumed to be collected prior to ti·eatment unless schedule of assessments and protocol 
indicate planned collection is always after dosing. 
Day-of-Discharge (DoD): day when subject is discharged from the hospital. 
Early Termination (ET): day when subject withdraws from the study before completion. 
End-of-Study (EoS): the end of study visit is at Day 169 (24 weeks after first dose) for subjects 
who complete the study. 
Study Visits: 
Planned study visits are detailed in Table 4-1 and in the Schedule of Assessments (Appendix 7.1). 
Planned study visits that occur outside of their protocol defined window will be analyzed as 
repo1ied and there will no attempt to coITect visits that fall outside their planned time frame by 
applying analysis visit windows. Unscheduled visits will be assigned to a study visit if they fall 
into the study windows. Unscheduled visits that do not fall into scheduled study visit window will 
be included when classifying endpoints across a period (e.g. maximum value during study period) 
but will not be repo1ied in by visit summaries. 
fu the case of multiple assessments on the same visit the following rnles will apply: 
• 
If more than one assessment occurs during the same nominal visit time window of the 
planned visit, select the record closest to the nominal day for that paiiicular visit day. 
• 
If there ai·e two assessments that are equidistant from the nominal planned visit day, the 
data of the assessment after the scheduled study day will be used. 
• 
If multiple measurements are all taken on the same day the earliest measurement of this 
day will be used. 
Table 4-1: Study Visit Windowing 
Visit 
Study Day/Week 
Window 
Screening 
-7 to 1/0 
None 
Baseline 
1/0 
None 
Day2 
2/1 
+/- 1 day* 
Dav3 
3/1 
+/- 1 day* 
Dav4 
4/1 
+/- 1 day* 
Day5 
5/1 
+/- 1 day* 
Day6 
6/1 
+/- 1 day* 
Dav7 
7/1 
+/- 1 day* 
Dav8 
8/2 
+/- 1 dav* 
Day9 
9/2 
+/- 1 day* 
Dav 10 
10/2 
+/- 1 day* 
Dav 11 
11/2 
+/- 1 dav* 
Day 12 
12/2 
+/- 1 day* 
Dav 13 
13/2 
+/- 1 day* 
Dav 14 
14/2 
+/- 1 day* 
Day 15 
15/2 
+/- 2 day 


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Visit 
Study Dav/Week 
Window 
Dav22 
22/3 
+/- 2 dav 
Day29 
29/4 
+/- 2 day 
Dav36 
36/5 
+/- 2 day 
Dav43 
43/6 
+/- 2 day 
Day85 
85/12 
+/- 2 day 
Dav 169/EoS 
169/24 
+/- 2 day 
*no window will be applied for assessments collected daily during hospitalization per Schedule 
of Assessments (Aooendix 7.1) 
 
4.2.3 Missing dates 
Every effo1t will be made to collect complete dates for all study assessments. The following date 
imputation rnles will be applied for missing or pa1tial dates: 
• 
If month and year available, set start date to latest of (1st of the month,first dose date), if end 
date is complete and imputed strut date > end date, set imputed strut date to end date - 1. 
• 
If year available: Set strut date to Janua1y 1st of year recorded, if end date is complete and 
imputed strut date > end date, set imputed strut date to end date - 1. 
• 
If strut date is completely missing, set to first dose date, if end date is complete and imputed 
strut date > end date, set imputed strut date to end date- 1. 
• 
If any imputed date results in an improbable date (e.g. date occurs in the future, date occurs 
after subject died), set to first dose date. 
 
4.2.4 Conventions 
Continuous data will be summarized in tenns of the mean, standai·d deviation (SD), median, 
minimum, maximum, and number of observations, unless othe1wise stated. Continuous data that 
are expected to be skewed will be presented in tenns of the maximum, upper quaitile, median, 
lower qurutile, minimum, and number of observations. The minimum and maximum will be 
repo1ted to the same number of decimal places as the raw data recorded in the database. The mean, 
median, lower qurutile, and upper quaitile will be repo1ted to one more decimal place than the raw 
data recorded in the database. The SD will be repo1ted to two more decimal places than the raw 
data recorded in the database. In general, the maximum number of decimal places repo1ted shall 
be four for any summary statistic. 
Categorical data will be smnmru·ized in tenns of the number of subjects 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. 
Percenta.ges will be presented to one decimal place. Percenta.ges will not be presented for zero 
counts. Percenta.ges will be calculated using n as the denominator. If sample sizes ai·e 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. 
P-values greater than or equal to 0.001, in general, will be presented to three decimal places. P­ 
values less than 0.001 will be presented as "<0.001". 
Confidence intervals will be presented to one more decimal place than the raw data. 


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4.3 
Software 
All report outputs will be produced using SAS® version 9.4 or a later version in a secure and 
validated environment. 
 
4.4 
Study Subjects 
 
4.4.1 Disposition of Subjects 
A clear accounting of the disposition of all subjects who enter the study will be provided, from 
screening to study completion. 
Summaries will include: 
• 
the number of subjects randomized (full analysis set) 
• 
the number and percentage of subjects treated (with any amount of study drug) 
• 
the number and percentage of subjects entering, withdrawing from study treatment, 
withdrawing from the study and completing each phase of the study by treatment group and 
overall. Withdrawals from the study and from study treatment will also be summarized by 
major reason. (Analysis set: Full Analysis Set) 
By-subject listings of eligibility details, randomization details, visit dates and withdrawal/study 
completion details (including reason for discontinuation and duration of treatment prior to 
discontinuation) will be provided. 
 
4.4.2 Protocol Deviations 
Major protocol deviations are defined as those deviations from the protocol likely to have an impact 
on the perceived efficacy and/or safety of study treatments. The impact of major protocol 
deviations on the efficacy and/or safety results will be investigated by assessing the robustness of 
the study results and conclusions to the choice of analysis set, both including and excluding data 
potentially affected by major protocol deviations. 
Major protocol deviations and any action to be taken regarding the exclusion of subjects or affected 
data from specific analyses are defined in the Protocol Deviation Specification. A summary of the 
number and percentage of subjects with major protocol deviation by treatment group and overall 
and by type of deviation (full analysis set and intent-to-treat analysis set). A by-subject listing of 
major protocol deviations will be provided. 
 
4.5 
Analysis Sets 
The Full Analysis Set (FAS) consists of all subjects randomized regardless of whether they 
received study treatment. Subjects will be summarized and analyzed ‘as randomized’ i.e. by 
randomized treatment group. If a subject is stratified incorrectly, ‘randomized stratum’ will be 
used rather than ‘actual stratum’. Summaries of study disposition, protocol deviations and by- 
subject listings (unless otherwise specified) will be based on the FAS. Efficacy summaries and 
analyses will be based on the FAS. 
The efficacy summaries and analyses will be based on the intent-to-treat (ITT) analysis set, 
which is defined as all randomized subjects who received any amount of study drug. Subjects will 
be summarized and analyzed ‘as randomized’ i.e. by randomized treatment group. If a subject is 
stratified incorrectly, ‘randomized stratum’ will be used rather than ‘actual stratum’. 


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For the primary and key secondary efficacy endpoints, a sensitivity analysis will be performed on 
the per-protocol analysis set to assess the robustness of the study conclusions to the choice of 
analysis set. The per-protocol population is defined as all subjects in the ITT analysis set who 
complete the study with no major protocol deviations. A blinded data review will occur prior to 
the first database lock to decide the subjects being excluded from the per-protocol analysis set. 
The safety summaries and analyses will be based on the safety analysis set. The safety analysis 
set is defined as all randomized subjects who received any amount of study drug. Subjects will be 
summarized and analyzed ‘as treated’ i.e. by actual treatment group. 
PK analyses will be based on the PK analysis set defined as subjects that receive at least one dose 
of gimsilumab and have at least 1 evaluable post-dose pharmacokinetic sample. 
Upon database release, protocol deviation and analysis set outputs will be produced and will be 
sent to Kinevant for review. An analysis set classification meeting will be arranged to discuss the 
outputs and to decide which subjects and/or subject data will be included in the different analysis 
sets. Such decisions will be made prior to unblinding and will be documented and approved by 
Kinevant. 
A summary of the number and percentage of subjects entering and completing each phase of the 
study by treatment group and overall for each analysis set (Analysis set: FAS). 
A by-subject listing of analysis set details including center, subject identifier, inclusion/exclusion 
flag for each analysis set and reason for exclusion from an analysis set. 
 
4.6 
Demographic and Other Baseline Characteristics 
Demographic and other baseline characteristics will be summarized by treatment group and for 
both treatment groups combined (Total) using the ITT analysis set. The summaries provided will 
include the following. 
• 
Demographic variables: 
o Age (continuous and categorical (<65 years; ≥65years)) 
o Sex 
o Race (American Indian or Alaska Native; Asian; Black or African American; Native 
Hawaiian or Other Pacific Islander; White; Other; Multiple) 
o Ethnicity (Hispanic or Latino, Not Hispanic or Latino) 
o Baseline Height 
o Baseline Weight 
o Baseline Body Mass Index (BMI) 
• 
Baseline disease characteristics: 
o Randomization strata (Lung injury/mild ARDS; moderate severe/ARDS) 
o Ventilation status 
o Ventilation type 
o ICU status 
o Oxygenation status 
o Oxygenation type 
o SpO2, FiO2, PaO2, P/F ratio, S/F ratio 
o Baseline ferritin, CRP, d-dimer, cardiac troponin I, LDH 
o Baseline Lung Injury Score 


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o Baseline NEWS Total Score 
o Baseline 7-point Ordinal Scale 
o Baseline SOFA Total Score 
o Baseline anti-GM-CSF autoantibody concentration (continuous and by categories of <5 
µg/mL, ≥5 µg/mL) 
o Days since onset of symptoms 
Medical history will be reported by system organ class and preferred term as coded using the 
Medical Dictionary for Regulatory Activities (MedDRA) Version 23.0 or higher. 
Age will be reported as calculated in the study database at day of informed consent. BMI will be 
calculated from baseline height and weight as weight (kg) / height2 (m2). 
By-subject listings of demographic data and other baseline characteristics (as summarized above) 
will be provided. 
 
4.7 
Prior, Concomitant, and Prohibited Medications and Procedures 
Prior and concomitant medications will be summarized by drug class and preferred medication 
name by treatment group and for both treatment groups combined (Total) using the ITT analysis 
set . Prior and concomitant medications will be summarized separately, concomitant medications 
will also be summarized overall and by study period. WHO DDE March 2020 will be used to 
classify medications. 
Medication start and stop dates will be compared to the date of first dose of study drug to allow 
medications to be classified as either Prior only, both Prior and Concomitant, or Concomitant 
only. Missing or partial start dates will be imputed as described in Section 4.2.3. 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 first dose of study drug will be classified as 
Prior only. If a medication starts before the date of first dose of study drug and stops on or after 
the date of first dose of study drug, then the medication will be classified as both Prior and 
Concomitant. Medications will be classified as Concomitant only if they have a start date on or 
after the date of first dose of study drug. 
Use of tocilizumab or any other immunomodulatory biologic (e.g., anti-IL-1, anti-IL-6R, anti- 
TNF), cell therapies (e.g., mesenchymal stem cells), or small molecules (e.g., JAK inhibitors) is 
prohibited during the study. Additional prohibited medications may also be defined during 
blinded data review prior to general study unblinding. The number and percentages of the 
subjects using such medications will be summarized by treatment groups, and the impact on 
efficacy and safety will be analyzed by subgroup analyses. 
In addition, separate summaries of prior and concomitant steroid use (including the categories 
‘Any Steroid Use’ and ‘Any Dexamethasone Use’) and other COVID-19 therapies will be 
provided. Lists of drugs to include in each of these categories will be provided by a medical 
monitor and the final list will be reviewed and approved prior to general study unblinding. 
 
 
 
By-subject listings of prior, concomitant and prohibited medications will be provided. Listings 
TwPi-lGl aDlOso-WbWe p-0r1o6v-0id7e.ad for any concom
COitNanFtIDpEroNcTeIdAuLres reported. 
Project Document Version No. 4.0 


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4.8 
Efficacy Evaluation 
 
4.8.1 
Analysis and Data Conventions 
4.8.1.1 
Multi-center Study 
The statistical analysis for this multi-center study (with centers quite different in tenns of number 
of subjects per center) will use the pooled set of subjects across all centers. Center will not be used 
as a stratification factor or covariate in the statistical analysis models. 
4.8.1.2 
Adjustments for Covariates 
The primary efficacy analysis will be adjusted by baseline clinical status (lung injmy/mild ARDS 
vs moderate/severe ARDS). Baseline clinical status is a randomization factor and the status as 
repo1ied from the randomization system will be used for all efficacy analyses. 
4.8.1.3 
Handling of Dropouts or Missing Data 
The reason of early study treatment / study discontinuation will be identified, and the percentage 
of these subjects will be smnmarized by treatment group. 
Methodology for multiple imputation and tipping point approaches is described in Section 4.8.1.6 
and Section 4.8.1.7, respectively. 
4.8.1.4 
Multiple Comparisons/Multiplicity 
The one-sided type-I-enor rate (0.025) for the primaiy efficacy endpoint will be adjusted following 
the Haybittle-Peto approach with 0.0005 allocated to the interim analysis and 0.0248 allocated to 
the final analysis. 
For the key secondaiy efficacy endpoints, there is the following serial gate-keeping procedme (also 
known as sequential conditional testing) addressing the multiplicity and controlling the family­ 
wise one-sided type-I-enor probability to 0.025 (equivalent to two-sided 0.05) for the fainily of 
primaiy and key secondary efficacy endpoints: 
• 
Analysis of the primary efficacy endpoint 
Its null hypothesis is tested on one-sided significance level 0.0248 
• 
if the null hypothesis cannot be rejected, the entire testing procedme stops here, i.e., null 
hypotheses for any of the key secondary efficacy endpoints cannot be rejected 
• 
if the null hypothesis can be rejected, the testing procedure continues with the testing of 
key secondaiy efficacy endpoint as described below. 
• 
Analysis of the key secondary efficacy endpoints: 
A. Survival and no mechanical ventilation on Day 29 
Its null hypothesis is tested on one-sided significance level 0.025 
• 
if the null hypothesis is not rejected, the entire testing procedme stops here, i.e., null 
hypotheses for remaining key secondaiy efficacy endpoints cannot be rejected 
• 
if the null hypothesis is rejected, the testing procedme continues with the testing of key 
seconda1y efficacy endpoint as described below. 
B. Mechanical ventilation-free days by Day 29 


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Its null hypothesis is tested on one-sided significance level 0.025 
• 
if the null hypothesis is not rejected, the entire testing procedme stops here, i.e., null 
hypotheses for the remaining key secondary efficacy endpoint cannot be rejected 
• 
if the null hypothesis is rejected, the testing procedme continues with the testing of key 
seconda1y efficacy endpoint as described below. 
C. Time to hospital discharge by Day 43 
Its null hypothesis is tested on one-sided significance level 0.025 
• 
if the null hypothesis is not rejected, the entire testing procedme stops here, i.e., null 
hypotheses for remaining key secondaiy efficacy endpoints cannot be rejected 
• 
if the null hypothesis can be rejected, the testing procedme continues with the testing 
of key secondaiy efficacy endpoint as described below. 
4.8.1.5 Exainination of Subgroups 
The treatment effect for the primaiy, key seconda1y efficacy endpoints, and the 7-point ordinary 
scale will be examined for the following subgroups: 
• 
Site 
• 
Clinical status (lung injmy/mild ARDS vs. moderate/severe ARDS) 
• 
Age (<65 yeai·s6
,   5 yeai·s) 
• 
Sex (Male, Female) 
• 
Body weight (by quaiiiles) 
• 
Race (White, African American, additional groups must represent at least 25% of the 
population if not, will group as 'All Other') 
• 
Ethnicity (Hispanic or Latino, Not Hispanic Latino) 
• 
Invasive ventilator use at baseline (yes, no) 
• 
Baseline invasive ventilator use or severe ARDS at baseline (yes, no) 
• 
Presence of anti-GM-CSF auto antibodies at Screening (<5 µg/mL,5Lg/mL) 
• 
7-point ordinal scale status at baseline 
• 
Received Day 8 study dmg (yes, no) 
• 
Prohibited medications use (yes, no) (see Section 4.7) 
Prohibited medication use will be aligned to time period of endpoint being summai·ized as follows: 
• 
Prohibited medication from Day 1 - Day 43 (Mo1iality by Day 43) 
• 
Prohibited medication from Day 1 - Day 29 (Smvival and no mechanical ventilation by 
Day 29, Mechanical ventilation-free days by Day 29) 
• 
Prohibited medication dming the study (Time to hospital discharge, 7-point ordinal scale) 
Summaries of the primaiy, key secondaiy efficacy vai·iables and the WHO 7-point ordinal scale 
by treatment group and subgroups will be produced. 
Homogeneity of the treatment effect across subgroups may be investigated using graphical and 
analytical methods. An appropriate summa1y of the treatment effect (e.g., risk difference, mean 
difference, hazai·d ratio) and 95% confidence inte1vals will be estimated within each subgroup 


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using the methods described for the main analysis for each endpoint. A forest plot showing these 
estimates and 95% confidence interval within each subgroup and overall will be provided. 
4.8.1.6 Analysis Methods – Multiple imputation 
General approach 
Multiple imputation methods replace each missing primary efficacy endpoint value with a set of 
m=10 plausible values based on a model predicting values for a missing data point based on 
available data, i.e., assuming a Missing at Random (MAR) missingness mechanism. 
This set of values represents the uncertainty about the correct value to be imputed. These complete 
datasets (generated by SAS PROC MI) are then analyzed by relevant statistical procedure (e.g., 
SAS PROC FREQ, SAS PROC LOGISTIC, etc) generating parameter estimates and their standard 
errors, followed by combining those results from these analyses (by using SAS PROC 
MIANALYZE). 
Prediction model 
The prediction model attempts to predict a missing endpoint values (e.g, “death by Day 43” or 
“alive at Day 43” for the binary primary efficacy endpoint) based on available data (variables) that 
may have an influence on that endpoint. 
The proposed prediction model for the binary primary efficacy endpoint is a logistic regression 
model with the following covariates: 
• randomized study treatment: Gimsilumab or placebo 
• baseline clinical status: lung injury/mild ARDS or moderate/severe ARDS 
• country: USA, etc 
• sex: male or female 
• age at baseline (continuous covariate) 
• body weight at baseline (continuous covariate) 
• race (White, African American, additional groups must represent at least 25% of the population 
if not, will group as ‘All Other’) 
• invasive ventilator use at baseline: no or yes 
• anti-GM-CSF auto antibodies at screening: <5 µg/mL or ≥5 µg/mL 
• WHO 7-point ordinal scale status at baseline 
• National Early Warning Score (NEWS) at baseline 
• SpO2 at baseline 
• WHO 7-point ordinal scale status at hospital discharge 
• NEWS at hospital discharge 
• SpO2 at hospital discharge 
• second administration of study treatment: yes or no 
• administration of prohibited treatments (see Section 4.7) during the study: yes or no 


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m
Algorithm for the multiple imputation of missing values 
Within the Bayesian framework, the task of imputing missing values is achieved by drawing 
random values from the posterior predictive disti·ibution of the missing primaiy efficacy endpoint 
data (predicted by the logistic regression prediction model specified above). This posterior 
predictive disti·ibution is a function of the observed data and regression parameters (or function of 
regression parameters). 
As non-monotone missing pattern may be observed, the fully conditional specification (FCS) 
method will be used for dealing with arbiti·aiy non-monotone missing data patterns. The FCS is 
based on an iterative algorithm; at each iteration and for each vai·iable of the prediction model, 
there is a 
• 
prediction step (P-step): the cmTent (iteration) values of the observed and imputed values are 
used to derive the predictive disti·ibution of the missing values 
• 
and an imputation step (I-step): updated imputations ai·e generated by draws from the predictive 
disti·ibution defined by the updated regression model. 
When the last vai·iable in the sequence (e.g., the primaiy efficacy endpoint) has been imputed, the 
algorithm cycles again through each variable, repeating the chain of regression estimation and 
imputation draw steps. These cycles are repeated and finally there will m=IO draws from the 
predictive disti-ibution for each missing primaiy efficacy endpoint value. 
Analyzing multiply imputed datasets 
Individual statistical analysis (as described in Section 4.8.2 and Section 4.8.3) will be perfo1med 
for each of the m=IO imputed complete datasets and the results (point estimates and associated 
standard enors for the study u-eatment effect) will be stored in a single output file. 
Estimation and inference for multiply imputed datasets 
As a final step, the m=IO estimates and associated standai·d enors will be combined as described 
below for making statistical inference. 
Let Qi and Wi denote the point and vai·iance estimates for the study ti·eatment effect from the i-th 
imputed complete data set, i=l, 2,...,m. Then the point estimate for the study ti·eatment effect from 
multiple imputations, Q, is the average of them imputed complete datasets estimates: 
 
Let W denote the average of the m ("within-imputation") variance estimates 
 
W
-   =-lim  W- - 
l 
i=l 
and B the estimated ("between-imputation") variance of the point estimates 
B
-   =-1- Im  cQ- i--Q)2 • 
m-1  
i=l 


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Then the total variance V of the multiple imputation estimate Q for the study treatment effect is 
estimated as 
v = W + (1 + m-1) • B. 
Q and Vwill be used for testing null hypotheses stated in Section 4.8.2 and Section 4.8.3 and 
constructing two-sided 95% Cis for the study ti·eatment effects: 
• 
test statistic 
Q 
t=- 
Jv 
is approximately disti-ibuted as a I-distribution with degrees of :freedom equal to 
- 
2 
DFM1 =(m-1)(1+ (1+:l)·B) 
• and the two-sided 95% CI for the study ti·eatment effect is calculated as 
(Q -  Jv'to.975,DFMI, Q + Jv'to.975,DFMI). 
Where relevant, the exponential function will be used for ti·ansfonning point estimates and CI 
limits from the log scale to the original scale. 
4.8.1.7 Analysis Methods - Tipping point analysis 
Graphical displays, based on the "tipping-point" analysis inti·oduced by Yan 2009 and not 
requiring the MAR assumption, will be used to visualize the results of a two-dimensional set of 
sensitivity analyses using different imputations for missing binaiy endpoint values (e.g., either 
"death by Day 43" or "alive at Day 43" for the primaiy efficacy endpoint) for compai·ison of 
the two study t:I'eatments. All possible combinations of imputations of missing binaiy 
endpoint values in the gimsilumab and placebo group will be evaluated by the statistical method 
described in Section 4.8.2 and Section 4.8.3, with study ti·eatment as the only factor. 
Figure 4-1 below is an example graphic taken from Campbell 2011 with 8 missing endpoint values 
in the "Treatment Group" (one can impute Oto 8 successes) and 11 missing endpoint values in the 
"Cont:I'ol group" (one can impute O to 11 successes), leading to a mati·ix of 108 (= 9 times 12) 
combinations to be tested. For the example displayed in Figure 4-1, 10 combinations close to the 
upper left upper comer "worst case" (all missing values in the "Cont:I'ol Group" were imputed as 
successes and all missing value in the "Treatment Group" were imputed as failures) did not lead 
to a significant test result (rejection of the null hypothesis). 


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a 
C) 
Figure 4-1 Example for a tipping point analysis summary display 
 
Tipping-Point Analysis 
for the Primary Effectiveness Endpoint 
 
s: 
u, 
n 
Si? 
VI 
VI 
CD 
VI :s 
3· 
3: 
ii" (D 
3
00· 
CD 
3· V 
0 
0:, 
[ 
N 
C) 
 
C 
 
 
0 
2 
4 
6 
8 
"Successes" In Missing in Treatment Group 
"Enhanced tipping-point displays" (Liublinska 2014) will be provided as compact summaries of 
conclusions drawn from different alternative assumptions. 
4.8.1.8 Analysis Methods - Final analysis following adaptive sample size increase 
If the sample size has been increased at interim analysis 2 (see Section 5.2.5), then the final 
analysis of the primaiy efficacy endpoint (mo1iality by Day 43) and key secondaiy 
endpoints will be perfo1med by using a weighted average of the two one-sided test statistics Z1 
and Z2 based on data from subjects in stage 1 and stage 2 sepai·ately, respectively. 
The test statistic ZcHw (maintaining the type-l-eITor probability restricted to one-sided 0.0248 
(primaiy endpoint) or 0.025 (key seconda1y endpoints) per Cui/Hung/Wang 1999) for the final 
analysis will be 
ZcHw = W1• Z1 + W2•   Z2 
and the pre-specified weights are 
w1 = .ffe.with n1 denoting the number of subjects in the FAS for stage 1 
w2 = j27   n1  where 270 -  n1 represents the number of subjects in the FAS for stage 2. 
4.8.1.9 Analysis Methods - Continuous vai·iables 
All continuous outcomes will be sUffilnai·ized using descriptive statistics by treatment group and 
visit. For each outcome only planned visits as detailed in the schedule of assessments (Appendix 
7.1) will be summarized. 
C


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4.8.1.10 Analysis methods - Count variables 
For number of event-free days (mechanical ventilation free days, ICU-free days) the median, 1st 
quaiiile and 3rd qua1iile will be presented by treatment. A Wilcoxon rank sum test will be used to 
evaluate the difference between treatment groups. 
4.8.1.11 Analysis methods - Categorical vai·iables 
For bina1y endpoints the number and propo1iion in each treatment group will be presented along 
with the common risk difference with 95% CI (gimsilumab - placebo) as estimated using the 
Mantel-Haenszel method. Baseline clinical status will be used as stratification factor. A Cochran­ 
Mantel-Haenszel (CMH) test may be used to test for a treatment effect. 
Binaiy primaiy and key secondaiy endpoints will also be evaluated with common risk difference 
obtained from logistic regression (following Ge et al 2011) with covariates study treatment and 
baseline clinical status 
Other categorical outcomes will be evaluated using CMH tests stratified for baseline clinical status. 
4.8.1.12 Analysis Methods - Time to event variables 
Time to event analyses will be perfonned using Kaplan-Meier method and a log-rank test stratified 
by baseline clinical status will be used to evaluate the treatment effect (gimsilumab vs. placebo). 
The total number of subjects with an event, the total number censored, reasons for censoring, and 
Kaplan-Meier estimates with associated 95% Cis for survival probabilities at Days 15, 29, 43, 85, 
169 as well as 25th percentile, median, and 75% percentile (if available) survival time and 95% Cis 
will be presented bytreatment group. Survival plots or cumulative incidence plots as specified for 
each time to event endpoint will be presented by treatment and by randomization strata (baseline 
clinical sta.tus) and treatment. If one of the baseline clinical sta.tus categories have fewer than 10 
events overall, Kaplan-Meier estimates will only be presented overall. 
A propo1iional hazard model stratified by baseline clinical sta.tus (if there are sufficient events in 
each stratum) will be used to estimate the hazai·d ratio and associated 95% CI of gimsilumab vs. 
placebo. 
4.8.1.13 Analysis Methods - Multi-state competing risks models 
For time to hospital discharge and time to clinical improvement a supplementaiy analysis using a 
multi-stat competing risks model will be perfo1med (Beyersmann, Allignol, Schumacher 2012). 
Multi-state competing risks model 
For each subject, a multi-state stochastic process (Xd)tkO is considered where Xd denotes the state a 
subject is in at the end of day d, 1 :S d '.S 43 (43 is the final day of the planned observation period 
Three states are defined as follows: 
[Baseline]       baseline state 
[Improvement] improvement state (assumed as an absorbing state as further transitions ai·e not 
considered here) 
[Death] 
death state (absorbing state) 


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Improvement 
Baseline 
Death 
All subjects staii in the initial state [Baseline] at time of randomization, d=O,     i.e., Xo       =[Baseline]. 
If subject recovers but dies (afte1wai·ds) on the same day d, then that subject's state Xd will be set 
to xd =[Death]. 
States and possible transitions between states are illustrated by Figure 1 below. 
Figure 1 
Competing risks model 
 
 
 
 
 
 
 
 
A transition probability from state [Baseline] at day d     (0   d 
42) to state [m]        at daye,  d        e 
43, 
is defined as: 
P[Baseline)[m](d, e) = P(Xe = [m]IXd = [Baseline]) 
Subjects stay in state [Baseline] as long as none of the competing events have occuned; the 
competing risks process moves out of the [Baseline] state at day TD, defined as 
TD= min{d > OIXd* [Baseline]} 
and is called the transition day; state Xm is the type of transition. 
The competing risks process is subject to right-censoring (assumed to be independent of the 
transition processes) when a subject's follow-up was terminated while the subject was still in state 
[Baseline]: 
• 
either prematurely prior to the end of Day 43 
• 
or when reaching the planned end of observation period at end of Day 43. 
The hazai·d functions for transitions from state [Baseline] to state [Improvement] or to state 
[Death], respectively, ai·e assumed to detennine the stochastic behavior of the competing risks 
process; these hazai·d functions differ bystudy treatment group. 
The transition-specific cumulative incidence functions over the 43 days observation period are 
defined as Pk,c(D :::; d,Xv = [m]), where [m] can be state [Improvement] or state [Death], k 
denotes the stratum and c the study treatment (gimsilumab or placebo) will be derived from non­ 
parametric Nelson-Aalen estimators for cumulative hazai·d functions. 
 
Stratified transition-specific proportional hazards models 


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The transition-specific proportional hazards model stratified for factors used in the randomization 
and its assumptions are illustrated by: 
ℎ[Baseline],[𝑚𝑚] (𝑑𝑑, x𝑗𝑗𝑗𝑗 , β[Baseline],[𝑚𝑚]) = ℎ[Baseline],[𝑚𝑚];0𝑘𝑘(𝑑𝑑) ∙ exp (𝑥𝑥𝑗𝑗𝑗𝑗   ∙ β[Baseline],[𝑚𝑚]) 
h[Baseline],[m](.) transition-specific hazard functions as a function of days (relative to date of 
randomization), the subject’s stratum and study treatment (gimsilumab or 
placebo), and unknown hazard ratio 
h[Baseline],[m];0k(d)      unspecified transition-specific hazard function for placebo subjects in stratum 
k at day d; transition-specific hazard functions for placebo are allowed to vary 
across strata without any restrictions 
xjk 
study treatment indicator for subject j in stratum k, coded as 0 for placebo, 1 for 
gimsilumab 
h[Baseline],[m]: 
vector of unknown transition-specific log hazard ratios for study treatment; 
assumed to be common across strata, allowed to differ by transition. 
Estimation of transition-specific hazard ratios will be performed by maximizing partial likelihood 
functions; two-sided 95% confidence intervals will be provided. 
4.8.1.14 By-subject listings 
All derived efficacy endpoints and the raw data points used to derive them will be listed by subject. 
 
4.8.2 Analysis of the Primary Efficacy Endpoint 
Clinical question of interest: Does gimsilumab reduce mortality (up to Day 43) in subjects with 
lung injury or ARDS secondary to COVID-19 in comparison to placebo? 
Intercurrent events (may occur between randomization and Day 43), not mutually exclusive: 
• IE1: subject’s withdrawal from the study prior to Day 43 
• IE2: subject lost to follow-up prior to Day 43 
• IE3: subject did not receive any dose of study treatment 
Attributes of Estimand 1 (following a treatment policy strategy) 
A. Patient population: as defined by protocol eligibility criteria and treated 
B. Treatment conditions: 
• condition of interest: randomized to gimsilumab and treated 
• alternative/control condition: randomized to placebo and treated 
C. Endpoint: subject’s death by Day 43 
D. Population-level summary: estimated incidence probability for death up to Day 43 (in each 
treatment group separately) 
Main estimator for Estimand 1: common mortality risk difference (for death up to Day 43) across 
both strata defined by baseline clinical status used in the stratified randomization 
• Intercurrent events IE1 and IE2 will be disregarded for the inclusion of subjects in the 
statistical analysis, IE3 restricts the inclusion of subjects to those who received at least one 
dose of study treatment. Hence, the main estimator for Estimand 1 will be based on the ITT 
analysis set. 


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• 
For subjects with missing primaiy endpoint data resulting from !El and IE2, a multiple 
imputation approach (details see Section 4.8.1.6) assuming MAR will be used. The set of 
complete (imputed) datasets will be analyzed as 2x2 frequency tables strntified by baseline 
clinical status obtaining Mantel-Haenszel common risk difference estimates and respective 
standard enors for those datasets. These results will then appropriately combined (see 
Section 4.8.1.6) to obtain point estimate and CI for the common risk difference as well as 
for a one-sided p-value for testing the null hypothesis of a common mo1iality risk 
difference 
0. 
Sensitivity estimators for Estimand 1 (also based on the ITT analysis set): 
• 
Two-dimensional tipping point analysis vaiying the missing primaiy endpoint data in the 
two study treatment aims (see Section 4.8.1.7) not assuming MAR 
• 
Common mo1iality risk difference (for death up to Day 43) obtained from logistic 
regression (following Ge et al 2011) with covai·iates study treatment and baseline clinical 
status (and multiple imputation approach described in Section 4.8.1.6 assuming MAR). 
Supplementaiy   analysis: Overall smvival   will be analyzed   using   time to   event methods 
as described in Section 4.8.1.12. Time to death is defined as the time from randomization to 
death in days (date of death - randomization date + 1). Subjects without a recorded death will be 
censored at their last date known alive (completion date if they were followed through Day 169 
or at their early discontinuation date if they withdrew early or at their date of last assessment if 
they ai·e alive and ongoing in study at time of analysis; last date known alive - randomization 
date +J). 
Eugpl fuantluly5 Secondaiy) analysis: Main estimator analysis will be repeated for mo1iality by 
 
 
Attributes of Estimand 2 (following a composite policy strategy) 
A. Patient population: as defined by protocol eligibility criteria and treated 
B. Treatment conditions: 
• 
condition of interest: randomized to gimsilumab and treated 
• 
alternative/control condition: randomized to placebo and treated 
C. Endpoint: subject's death by Day 43 or subject withdrawn from the study prior to Day 43 
or subject got lost to follow-up prior to Day 43 
D. Population-level summaiy: estimated incidence probability for death by Day 43 or study 
withdrawal prior to Day 43 or lost to follow-up prior to Day 43 (in each treatment group 
sepai·ately) 
Main estimator for Estimand 2: common risk difference across both strata defined by baseline 
clinical status used in the stratified randomization 
• !El and IE2 are pait of the composite endpoint, so these two!Es will be disregarded for the 
inclusion ofsubjects in the statistical analysis, IE3 restricts the inclusion ofsubjects to those 
who received at least one dose of study treatment. Hence, the main estimator for Estimand 
2 will be based on the ITT analysis set and none of the subjects have a missing composite 
endpoint value. 


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Sensitivity estimators for Estimand 2 (also based on the ITT analysis set): 
• 
Common risk difference obtained from logistic regression (following Ge et al 2011) with 
covariates study treatment and baseline clinical status 
Supplementaiy analysis: time to death or withdrawal or lost to follow-up will be analyzed using 
time to event methods as described in Section 4.8.1.12. Time to death or withdrawal is defined as 
the time from randomization to death or withdrawal in days (date of death/withdrawal - 
randomization date + 1). Subjects without a recorded death or withdrawal will be censored at their 
last date known alive in the study (completion date if they were followed through Day 169 or 
othe1wise at their date of last assessment; last date known alive in the study - randomization date 
+]). 
 
4.8.3 Key Secondary Efficacy Analysis 
4.8.3.1 Survival and no mechanical ventilation on Day 29 
Clinical question of interest: Does gimsilumab reduce mechanical ventilation on Day 29 and 
m01iality up to Day 29 in subjects with lung injury or ARDS secondary to COVID-19 m 
comparison to placebo? 
futercmTent events (may occur between randomization and Day 29), not mutually exclusive: 
• 
IEl: subject's discharge from the hospital prior to Day 29 
• 
IE2: subject's withdrawal from the study prior to Day 29 
• 
IE3: subject lost to follow-up prior to Day 29 
• 
IE4: subject did not receive any dose of study treatment 
Attributes of Estimand 2-1 (following a composite policy strategy) 
A. Patient population: as defmed by protocol eligibility criteria and treated 
B. Treatment conditions: 
• 
condition of interest: randomized to gimsilumab and treated 
• 
alternative/control condition: randomized to placebo and treated 
C. Endpoint: subject is alive and not on mechanical ventilation on Day 29 or discharged prior 
to Day29 
D. Population-level summaiy: estimated probability of being alive and not on mechanical 
ventilation on Day 29 (in each treatment group separately) 
Main estimator for Estimand 2-1: common risk difference across both strata defmed by baseline 
clinical status used in the stratified randomization 
• 
futercmTent events IEl is included in the endpoint definition: subjects dischai·ged alive 
prior to Day 29 (IEl) are considered successes for this endpoint as it is assumed that 
mechanical ventilation is no longer necessaiy for subjects who have been discharged from 
the hospital. 
• 
futercmTent events IE2 and IE3 will be disregarded for the inclusion of subjects in the 
statistical analysis; IE4 restricts the inclusion of subjects to those who received at least one 
dose of study treatment. Hence, the main estimator for Estimand 2-1 will be based on the 
ITT analysis set. 


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• 
For subjects with missing primaiy endpoint data resulting from IE2 and IE3, a multiple 
imputation approach (details see Section 4.8.1.6) assuming MAR will be used. The set of 
complete (imputed) datasets will be analyzed as 2x2 frequency tables strntified by baseline 
clinical status obtaining Mantel-Haenszel common risk difference estimates and respective 
standard enors for those datasets. These results will then appropriately combined (see 
Section 4.8.1.6) to obtain point estimate and confidence interval (CI) for the common risk 
difference as well as for a one-sided p-value for testing the null hypothesis of a common 
risk difference 
0. 
Sensitivity estimators for Estimand 2-1: 
• 
Two-dimensional tipping point analysis vaiying the missing primaiy endpoint data in the 
two study treatment aims (see Section 4.8.1.7) 
• 
Common response probability difference obtained from logistic regression (following Ge 
et al 2011) with covai·iates study ti·eatment and baseline clinical status (and multiple 
imputation approach described in Section 4.8.1.6). 
Supplementaiy (Secondaiy) analysis: Main estimator analysis will be repeated for probability of 
being alive and not on mechanical ventilation on Days 15, 22, and 43. 
4.8.3.2 Mechanical ventilation-free days by Day 29 
Clinical question of interest: Does gimsilumab increase the number of mechanical ventilation-free 
days up to Day 29 in subjects with lung injmy or ARDS secondaiy to COVID-19 in comparison 
to placebo? 
Intercmrent events (may occm between randomization and Day 29), not mutually exclusive: 
• 
!El: subject's death prior to Day 29 
• 
IE2: subject discharge (alive) from the hospital prior to Day 29 
• 
IE3: subject's withdrawal from the study prior to Day 29 and prior to hospital discharge 
• 
IE4: subject did not receive any dose of study ti·eatment 
Attributes of Estimand 2-2 (following a composite policy strategy) 
A. Patient population: as defined by protocol eligibility criteria and ti·eated 
B. Treatment conditions: 
• 
condition of interest: randomized to gimsilumab and ti·eated 
• 
altemative/conti·ol condition: randomized to placebo and ti·eated 
C. Endpoint: subject's number of mechanical ventilation-free days by Day 29 
D. Population-level summaiy: median number of days not on mechanical ventilation by Day 
29 (in each ti·eatment group separately) 
Main estimator for Estimand 2-2: difference of medians for number of days not on mechanical 
ventilation by Day 29. 
• 
Mechanical ventilation status (yes/no) will be assessed daily while subjects remain 
hospitalized up to and including their date of dischai·ge. 
• 
For a subject who died prior to Day 29 (IEl), the number of mechanical ventilation-free 
days up to Day 29 will be set to 0. 


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• For a subject alive at Day 29 and hospitalized at least up to Day 29, the number of 
mechanical ventilation-free days up to Day 29 is the sum of days with mechanical 
ventilation status of ‘no’ from Day 1 through Day 29. 
• For a subject discharged from hospital alive prior to study day 29 (IE2), the number of 
mechanical ventilation-free days up to Day 29 is the sum of 
(1) the number of days with mechanical ventilation status of ‘no’ from Day 1 to date of 
hospital discharge and 
(2) the number of days from their date of discharge through their Day 29 visit (Day 29 visit 
date – date of discharge), assuming that a subject is not mechanically ventilated after 
hospital discharge. 
• For a subject who withdrew from the study prior to Day 29 and prior hospital discharge 
(IE3), the number for mechanical ventilation-free days will be the sum of days with 
mechanical ventilation status of ‘no’ from Day 1 through the day of study withdrawal. 
• Intercurrent event IE3 will be disregarded for the inclusion of subjects in the statistical 
analysis; IE4 restricts the inclusion of subjects to those who received at least one dose of 
study treatment. Hence, the main estimator for Estimand 2-2 will be based on the ITT 
analysis set. 
The number of mechanical ventilation-free days will be analyzed by a Wilcoxon rank sum test 
stratified by baseline clinical status to obtain a one-sided p-value for testing the null hypothesis of 
equal or more favorable distribution for placebo compared to gimsilumab. 
 
Supplementary (Secondary) analyses: Main estimator analysis will be repeated for mechanical 
ventilation-free days by Days 15, 22, and 43. 
4.8.3.3 Time to hospital discharge 
Clinical question of interest: Does treatment with gimsilumab result in a shorter overall duration 
of hospitalization in subjects with lung injury or ARDS secondary to COVID-19 in comparison to 
placebo? 
 
Intercurrent events : 
• IE1: subject’s death prior to hospital discharge 
• IE2: subject’s withdrawal from the study prior to hospital discharge 
• IE3: subject did not receive any dose of study treatment 
Attributes of Estimand 2-3 (following a composite policy strategy) 
A. Patient population: as defined by protocol eligibility criteria and treated 
B. Treatment conditions: 
• condition of interest: randomized to gimsilumab and treated 
• alternative/control condition: randomized to placebo and treated 
C. Endpoint: subject’s time to hospital discharge 
D. Population-level summary: median time to hospital discharge (in each treatment group 
separately) 


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Main estimator for Estimand 2-3: hazard ratio across combined strnta defined by baseline clinical 
status used in the stratified randomization (see Section 4.8.1.12 for details) 
• 
Time to hospital discharge is the time in the hospital after randomization in days (Table 4- 
- 
• ilthle case that a subject is still hospitalized at time of analysis they will be censored at 
their date of last assessment in the data cut. 
• 
Subjects who die before leaving the hospital (IEl) will be considered failures (did not 
achieve hospital discharge) and will continue to contribute to the risk pool through the end 
of the analysis period, that is they will be censored at the date of data cut. 
• 
ill the case that a subject withdraws from the study before leaving the hospital (IE3), they 
will be censored at their discontinuation date, respectively. 
• 
IE3 restricts the inclusion of subjects to those who received at least one dose of study 
treatment. Hence, the main estimator for Estimand 2-3will be based on the ITT analysis set. 
Sensitivity estimator: Analyses for main estimator will be repeated using a modified definition of 
time to hospital discharge where subjects who died (IEl) are censored at time of death. Table 4-2 
provides endpoint derivation details. 
 
Table 4-2: Time to hospital discharge definitions 
 
Subjects status at time of 
analysis: 
Main estimator * 
Sensitivity estimator* 
Event date 
Censored 
(yes/no) 
Event date 
Censored 
(yes/no) 
Alive, discharged from hospital 
Date of 
discharge 
No 
Date of 
discharge 
No 
Alive, still hospitalized 
Date oflast 
assessment 
Yes 
Date oflast 
assessment 
Yes 
Early withdrawal from study 
before discharged from hospital 
(IE2) 
Date of early 
withdrawal 
Yes 
Date of early 
withdrawal 
Yes 
Lost to follow-up before 
discharged from hospital (IE3) 
Date oflast 
assessment 
Yes 
Date oflast 
assessment 
Yes 
Died (IEl) 
Date of data cut 
Yes 
Date of death 
Yes 
*Time to hospital dischar e will be repo1ted in davs and defined as event date - randomization date + 1. 
 
Supplementa1y analysis: A multi-state competing risks model will be perfo1med as described in 
Section 4.8.1.13 replacing the improvement state by hospital discharge. 
 
4.8.4 Other Secondary and Exploratory Efficacy Analyses 
Other secondary and explorato1y endpoints will be analyzed according to the type of endpoint as 
described below. If data are sparse for any of the exploratory endpoints, summaries may be limited 
to descriptive statistics of available data or listings only as appropriate. 
ICU-free davs bv Davs 15, 22, 29 and 43 
This endpoint will be defined and analyzed similarly to mechanical ventilation-free days (Section 
4.8.3.2). ICU status (yes/no) will be assessed daily while subjects remain hospitalized up to and 


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including their date of discharge. For subjects who are alive at the time of analysis and remain 
hospitalized the number of days with ICU status of ‘no’ from day of first dose through their Day 
15 (22/29/43) visit will be summed. For subjects who are alive at time of analysis visit but have 
been discharged prior to study Day 15 (22/29/43), the total number of ICU-free days will be the 
sum of (1) the number of days with ICU status of ‘no’ will be summed through their date of 
discharge and (2) the number of days from their date of discharge through their Day 15 (22/29/43) 
visit (Day 15 (22/29/43) visit date – date of discharge). For subjects who died at time of analysis 
the number of ICU-free days will be set to 0. For subjects with missing data due to early study 
withdrawal prior to hospital discharge, the number for ICU-free days will be the sum of days with 
ICU status of ‘no’ from Day 1 through the day of study withdrawal. The median, 1st quartile, and 
3rd quartile of the number of ICU-free days will be presented for each treatment group. A Wilcoxon 
rank sum test will be used to test the null hypothesis that there is no difference in number of ICU- 
free days between gimsilumab and placebo (Section 4.8.1.10). 
Incidence of mechanical ventilation use Overall and by Days 15, 22, 29 and 43 
This endpoint will be evaluated for all subjects, no matter if the subject was on or not on a 
mechanical ventilator at the time of the randomization. Mechanical ventilation use by Day 15 
(22/29/43) will be defined as ‘Yes’ if subject is alive and was on mechanical ventilation on or prior 
to Day 15 (22/29/43). As ventilation status is only collected while subject remains in the hospital, 
subjects who were discharged before Day 15 (22/29/43) and are still alive will be considered not 
be on mechanical ventilation. Subjects missing data due to death, early study withdrawal, or lost 
to follow-up prior to Day 15 (22/29/43) will be considered ‘on mechanical ventilation’. 
The number and percentage of subjects achieving this endpoint will be summarized by treatment 
group. In addition, the common mechanical ventilation use risk difference across both strata 
defined by baseline clinical status used in the stratified randomization with 95% CI will be 
reported. 
Among subjects with mechanical ventilation, median, 25th percentile and 75th percentile (with 95% 
confidence intervals) estimated using Kaplan-Meier method will be used to summarize duration of 
mechanical ventilation and time to first mechanical ventilation. Duration of mechanical ventilation 
will be summarized for subjects on mechanical ventilation separately for ventilation starting at 
baseline and ventilation starting post-baseline. Duration of mechanical ventilation will only be 
derived for subjects who are removed from ventilation (end date of ventilation – start date of 
ventilation + 1) or who died while still on ventilation (date of death – start date of ventilation + 1). 
Time to first mechanical ventilation will be summarized only for subjects starting mechanical 
ventilation post-baseline and is defined as time from randomization to first date of mechanical 
ventilation for subjects who started ventilation post-baseline. 
Incidence of ICU use by Days 15, 22, 29 and 43 
Incidence of ICU use will be defined and analyzed similarly to incidence of mechanical ventilation 
use using the daily assessments of ICU status taken while subjects are hospitalized. 
NEWS and SOFA scores 
Standard descriptive statistics (mean, standard deviation, median, minimum, maximum) will be 
used to summarize each of these scores by treatment group and visit. NEWS and SOFA (total and 
component scores) scores will be assessed daily while subject is hospitalized. Plots of mean score 


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(with standard error bars) by treatment group over time may be produced. SOFA component scores 
are respiratory score, cardiovascular score, liver score, renal score, coagulation score, and 
neurologic score. 
Figure 4-2: National Early Warning Score (NEWS) 
7- point ordinal scale 
The 7-point ordinal scale is as follows: 
1. Not hospitalized, no limitations on activities; 
2. Not hospitalized, limitation on activities; 
3. Hospitalized, not requiring supplemental oxygen; 
4. Hospitalized, requiring supplemental oxygen; 
5. Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 
6. Hospitalized, on invasive mechanical ventilation or ECMO; 
7. Death. 
The 7-point ordinal scale represents the worst status on the day prior to the visit, that is, assessment 
collected on Day 2 is reported for Baseline (Day 1), assessment collected on Day 3 is reported for 
Day 2, etc. As data is not expected to be reported the day after a subject’s death, hence a score of 
7/”Death” will be imputed on the date of death for analysis purposes. No visit windowing will be 
applied. For example, for subjects who were discharged from the hospital prior to Day 15 their 
results from follow-up visit Day 15 are reported on Day 14 regardless of actual study day result 
was recorded for. 
The percentage of subjects reporting each severity rating (1-7) of the 7-point ordinal scale and shift 
from baseline category will be reported for all study days (Daily while hospitalized and then on 
Days 15, 22, 29, 35, 43, 85, and 169/EoS). The percentage of subjects with change in ordinal scale 
at these time points will also be summarized for each of the following: 
• 1-point improvement from baseline 
• 2-point improvement from baseline 


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• 3-point improvement from baseline 
• ≥4-point improvement from baseline 
• No change from baseline 
• 1-point worsening from baseline 
• 2-point worsening from baseline 
• 3-point worsening from baseline 
• 4-point worsening from baseline 
Shift tables comparing score at baseline to last assessment available for each subject will be created 
overall and by subgroup. 
Stacked bar plots by treatment group and visit (Baseline, Days 7, 14, 21, 28, 35, 42, 84 and 168) 
will be produced for 7-point scale results and change from baseline (excluding baseline visit). 
Time to first clinical improvement 
Time to first clinical improvement is defined as the earliest of (1) first time the 7-point 
ordinal scale shows a 2-point decrease from the baseline score or (2) discharge from the hospital 
(date of first clinical improvement - first dose date + 1) for subjects who achieved clinical 
improvement and are still alive at time of analysis. Subjects who did not achieve a 2-point 
reduction and are still alive at time of analysis will be censored at their date of last assessment. 
Subjects who died will be treated as failures (did not achieve clinical improvement) and will 
continue to contribute to the risk pool through the end of the analysis period, that is they will be 
censored at the date of data cut. Kaplan-Meier method will be used to estimate the median time 
to clinical improvement (Section 4.8.1.12) and a cumulative incidence plot will be provided. 
Supplementary analysis: A multi-state competing risks model will be performed as described in 
Section 4.8.1.13 replacing the improvement state by first clinical improvement (earliest of 2- 
point decrease from baseline in 7-point ordinal scale score or hospital discharge). 
Oxygen-free days during hospitalization 
Oxygen use status (yes/no) will be assessed daily while subjects remain hospitalized up to and 
including their date of discharge. For subjects who are alive at the time of analysis and remain 
hospitalized the number of days with oxygen status of ‘no’ from day of randomization through 
their Day 15 (22/29/43) visit will be summed. For subjects who died at time of analysis the 
number of Oxygen-free days during the hospitalization will be set to 0. Descriptive statistics by 
treatment group and a treatment group comparison of number of days not oxygen by Day 15 
(22/29/43) using a Wilcoxon rank sum test as described in Section 4.8.1.10. 
Incidence of ECMO use and duration 
The number and percentage of subjects using ECMO while on study will be summarized by 
treatment. For subjects who used ECMO the duration in days will be summarized using 
descriptive statistics. 
Change from baseline in respiratory outcomes, select laboratory test results, COVID-19 viral load, 
and LVEF 
Respiratory outcomes include the secondary endpoint SpO2/FiO2 and the exploratory endpoints 
lung injury score (LIS), and PaO2/FiO2. Laboratory test endpoints include D-dimer, cardiac 
troponin I, lactate dehydrogenase (LDH), ferritin, procalcitonin, and C-reactive protein (CRP) as 


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seconda1y endpoints. COVID-19 viral load as measured by quantitative PCR is a secondaiy 
endpoint. and LVEF is an optional cardiovascular assessment and explorato1y endpoint. 
Standard descriptive statistics (mean, standai·d deviation, median, minimum, maximum) will be 
used to summarize each outcome and it's change from baseline bytreatment group and visit. Only 
scheduled visits as described in the schedule of assessments (Appendix 7.1) will be included for 
each endpoint. 
For select endpoints, mean (with standard enor bars) results and change from baseline may be 
plotted over time by treatment group. 
Explorato1y endpoints (LIS, PaO2/FiO2, LVEF) will only be summarized by visit if at least 20% 
of subjects have at least one non-missing assessment, othe1wise only by-subject listings will be 
provided for these endpoints. Chest radiographic results will be provided in a by-subject listing. 
 
4.9 
Safety Evaluation 
All safety summaries and analyses will be based upon the safety analysis set as defined in 
Section 4.5. Safety analyses summarized by study period will be analyzed separately for 
each of the following periods as defined in Section 4.2.1: 
 
• 
Overall 
• 
Treatment Period (Day 1 -Day 15) 
• 
Follow-up Period 1 (Day 16-Day 43) 
• 
Follow-up Period 2 (Day 44 +) 
• 
Overall-Hospitalized (Day 1 through DoD) 
• 
Overall -  After Discharge (DoD +) 
 
Note: only subjects who were on study in a given period will be included in the analysis for that 
period (e.g. if a subject withdraws from study or dies before Day 43 they will contribute to the 
denominator for summaries in the Overall, Treatment Period, and Follow-up Period 1 periods, but 
not in summaries of Follow-up Period 2). 
 
4.9.1 Extent of Exposure 
 
The number and percent of subjects that were dosed at each planned dose (Day 1 and Day 8) will 
be presented by treatment group. The number and percent of dose inte1n1ptions will also be 
summarized by treatment group. The daily dose at days 1 and 8 and cumulative dose will be 
presented by treatment group using descriptive statistics. A by-subject listing of exposure data will 
be provided. 
 
4.9.2 Adverse Events 
 
Adverse events will be coded using the Medical Dictionaiy for Regulatory Activities (MedDRA) 
Version 23.0 or higher. 


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Treatment-emergent adverse events will be tabulated and are defined as those adverse events that 
either staii or worsen in severity on or after the date/time of first dose of study treatment and 
through the end of safety follow-up period. 
 
Where dates are missing or paiiially missing, adverse events will be classified as treatment 
emergent and into study periods using imputed dates as described in Section 4.2.3. 
 
An overall summaiy table of treatment-emergent AEs (TEAEs) will be provided with the number 
and percentage of patients (incidence) repo1iing an event along with the total number of events 
presented for the following categories: 
• 
All TEAEs (all grades and grades 3-5) 
• 
Study dmg-related TEAEs (all grades and grades 3-5) 
• 
Serious TEAEs 
• 
Study dmg-related SAEs 
• 
Fatal TEAEs 
• 
TEAEs leading to study diug discontinuation 
• 
Each AESI (see Section 4.9.2.2) 
 
4.9.2.1 AE Summaries bysystem organ class (SOC) and prefened te1m (PT) 
 
The incidence and total number of events for the following will be sUilllllai·ized by SOC and PT: 
• 
All TEAEs 
• 
Study dmg-related TEAEs 
• 
TEAEs by maximum severity 
• 
Study dmg-related TEAEs by maximum severity 
• 
Grade 3 or higher TEAEs 
• 
Study dmg-related grade 3 or higher TEAEs 
• 
Serious TEAEs 
• 
Dmg-related SAEs 
• 
Fatal Serious TEAEs 
• 
TEAEs leading to study diug discontinuation 
• 
Each AESI (see Section 4.9.2.2) 
 
Adverse events will be summarized by treatment overall and by study period. Adverse event 
summaries will be ordered by decreasing frequency for SOC, and PT within SOC, in the 
gimsilumab treatment group, and then similai·ly by decreasing frequency in the placebo treatment 
group, and then alphabetically for SOC, and PT within SOC. 
 
For each subject and each adverse event, the worst severity recorded will be attributed and used in 
the by-severity summaries. Similarly, the worst causality (most related to treatment) will be 
attributed and used in the by-causality summaries. If severity or causality is missing, the worst 
case will be assumed. 


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4.9.2.2 AE of Special Interest (AESI) 
AESI will be defined using standard MedDRA queries (SMQ). See Appendix 7.3 for a complete 
list of terms. The following TEAEs are of special interest: 
 
Adverse Event of Special Interest 
Include all terms (Narrow and Broad) from SMQs 
Clinically severe or life-threatening 
onset of new infections (besides 
COVID-19) 
Infective Pneumonia 
Opportunistic Infections 
Note: include only events with severity of ‘Severe’ or 
‘Life-threatening’, exclude PTs ‘Coronavirus 
infection’ ‘Coronavirus test positive’ 
Neutropenia, Thrombocytopenia, and 
Leukopenia 
Hematopoietic Cytopenia 
Injection related reactions 
Hypersensitivity Reaction 
Drug Reaction 
Anaphylactic reaction 
Transaminitis 
Hepatic Disorders- Drug related hepatic disorder 
Pulmonary alveolar proteinosis 
Interstitial Lung Disease 
4.9.2.3 Adverse event listings 
By-subject listings of all adverse events (including non-treatment-emergent events) will be 
provided. This listing will be presented by treatment group and will include center, subject 
identifier, age, sex, race, adverse event (SOC, PT, and verbatim term), date of onset, date of 
resolution, study period, hospitalization status, duration, severity, seriousness, action taken, 
outcome and causality. The following listings will be provided: 
 
• 
All adverse events 
• 
All drug-related adverse events 
• 
All grade 3-5 adverse events 
• 
All serious adverse events 
• 
All fatal adverse events 
• 
All adverse events leading to discontinuation of study treatment 
• 
All adverse events of special interest 
 
4.9.3 Clinical Laboratory Evaluation 
 
The following laboratory parameters will be summarized by treatment group and visit for each 
study period using appropriate descriptive statistics. 
 
Hematology 
Chemistry 
Coagulation 
Hemoglobin 
BUN 
Prothrombin time 


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(ALT
Hematocrit 
Creatinine 
Activated pa1iial 
 
 
 
Eosinophils 
Alanine aminotransferase 
pH 
Basophils 
Aspaiiate aminotransferase 
Blood 
 
 
 
 
For by-visit summai·ies, visit windows as described in Section 4.2.2 will be used. In the case 
more than one result is collected for the same visit date the eai·liest result will be 
presented. For summaries across visits (e.g. maximum post-baseline value), scheduled, 
unscheduled and repeat assessments will be considered. 
 
Abnonnal laborato1y results ai·e defined as any result outside the nonnal range (either below the 
lower limit of the nonnal range or above the upper limit of the nonnal range) at any visit 
 
The following will be summai·ized: 
 
• 
A summa1y of each laboratory pai·ameter result and change from baseline by treatment group 
and visit 
• 
A summa1y of the number and percentage of subjects experiencing low, nonnal or high values 
at baseline and worst post-baseline result, by laborato1y paraineter and treatment group (shift 
table). Worst will be defined for both low and high abnonnalities for each pai·ameter (i.e. each 
paraineter will be presented twice, once where low abno1malities ai·e worst and once where 
high abno1malities ai·e worst). 
• 
A summary of the number and percentage of subjects experiencing at least one post-baseline 
laboratory abno1malities, by laboratory paraineter and treatment group. Both low and high 
abnonnalities will be repo1ied for each parameter. 
• 
A summaiy of the number and percentage of subjects experiencing clinically significant 
laboratory abno1malities, by laborato1y pai·ameter, treatment group and visit and at any post­ 
baseline visit 
 
Clinically significant laboratory abno1malities include laborato1y results of special interest and 
markers of potential liver injmy. 
thromboplastin time (aPTT) 
Platelets 
Glucose 
Fibrinogen 
Red blood cells 
Sodium 
Urinalysis 
White bloods cells 
Potassium 
Glucose 
Neutrophils 
Chloride 
Protein 
Lymphocytes 
Total CO2 
Ketones 
Monocytes 
Calcium 
Specific gravity 
(AST) 
Reticulocyte Count 
Albumin 
Nitrite 
MCV 
Alkaline phosphatase (ALP) 
Leukocytes 
MCH 
Total bilirnbin (BILI) 
Clai·ity 
MCHC 
Total protein 
Creatine Kinase 
NT-proBNP 
Color 
Urobilinogen 
Bilirnbin 


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Laboratory results of special interest: 
 
• Hemoglobin < 8 g/dL or decrease > 2 g/dL from baseline 
• Leukocytes < 4 x 103/µL 
• Neutrophils < 1.0 x 103/µL 
• Platelets < 30 x 103/µL 
 
Assessment of Liver Injury: 
• ALT > 3x upper limit of normal (ULN) 
• ALT > 5x ULN 
• ALT > 10x ULN 
• AST > 3x ULN 
• AST > 5x ULN 
• AST> 10x ULN 
• ALP > 1.5x ULN 
• BILI > 2x ULN 
• ALT > 3x ULN and BILI > 2x ULN at the same visit 
• AST > 3x ULN and BILI > 2x ULN at the same visit 
• ALT or AST >3x ULN and BILI > 2x ULN at the same visit 
• ALT > 3x ULN and BILI > 2x ULN and ALP < 2x ULN at the same visit 
• AST > 3x ULN and BILI > 2x ULN and ALP < 2x ULN at the same visit 
• ALT or AST >3x ULN and BILI > 2x ULN and ALP < 2x ULN at the same visit 
 
By-subject listings of all laboratory data will be provided by treatment group, with abnormal values 
highlighted, and including center, subject identifier, age, sex, race, weight and visit. Laboratory 
reference ranges will also be listed. 
 
Laboratory values (hematology, chemistry, coagulation/cardiac, and urinalysis) will be listed by 
subject and study time point including changes from baseline (with the exception of urinalysis). 
All values outside the clinical reference ranges will be flagged in the data listings. The abnormal 
values will be flagged with ‘L’ for values below the lower limit of the clinical reference range and 
‘H’ for values above the upper limit of the clinical reference range and included in the listings. 
Listings of abnormal or clinically significant results may be provided. 
 
4.9.4 Vital Signs, Physical Findings and Other Observations Related to Safety 
 
The following vital sign parameters including change from baseline will be summarized by 
treatment group and visit for each study period.: 
 
• Heart rate (HR: bpm) 
• Respiratory rate (breaths per minute) 
• Diastolic blood pressure (DBP; mmHg) 
• Systolic blood pressure (SBP; mmHg) 


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• 
Body temperature (C) 
 
fu addition, a summary of the number and percentage of patients meeting the following abno1mal 
vital sign criteria by visit and at any time during each study period: 
 
• 
HR > 110 beats per minute 
• 
HR > 20 beats per minute change from baseline 
• 
DBP 90 mmHg 
• 
DBP < 60 mmHg 
• 
DBP >20 mmHg change from baseline 
• 
SBP 
160 mmHg 
• 
SBP < 90 mmHg 
• 
SBP > 30 mmHg change from baseline 
 
By-subject listings of vital sign parameters and physical examination results will be provided. 
 
4.9.5 Independent Data Monitoring Committee 
An independent Data Monitoring Committee (DMC) will meet regularly while the study is ongoing 
and will be responsible for inte1preting the results of both interim analyses. 
Programs for analysis datasets and tables, listings, and figures (TLFs) for the DMC will be created 
by the blinded statistical team (biostatisticians and statistical programmers) using dummy 
randomization. These programs will be passed to the unblinded statistical team who will apply the 
trne randomization. Blinded and unblinded directories will be maintained and access to the 
unblinded directory will be restricted to the unblinded team member until general study unblinding. 
All TLFs (planned and ad hoc) created for the DMC will be developed following the guidelines 
defined in this SAP as appropriate. 
Further details can be found in section 2and in the DMC Charter. 
Table 4-3: Scheduled DMC Meetings 
Meetin!!: 
Timin!!: 
ReviewTvoe 
1st Data Review 
Meeting 
After 10% of planned subjects are randomized, 
after 6 days of follow up post-first dose day, 
DMC will review the unblinded data for safety 
and change from baseline in clinically 
meaningful parameters such as change from 
baseline in hypoxemia measurements and the 7- 
point ordinal scale. 
Safety 
futerim Analysis 1 
Meeting 
After 22% of planned subjects have been treated 
and have completed 7 days of follow-up (i.e., 
completed the Day 15 Visit), the DMC will 
review unblinded accumulated data for safety 
and futility, including an analysis of whether 
any changes in measures of hypoxemia or 
oxygen saturation (e.g., SpOi/FiO2, PaO2/FiO2, 
Safety/ Futility/ Change in 
oxygenation 


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Meetine: 
Timine: 
Review Type 
or SpO2 on room air) are clinically meaningful. 
The DMC may recommend a pause in 
emolhnent at this time. 
futerim Analysis 2 
Meeting 
After 100 subjects completed the Day 29 Visit 
or died by Day 43 (Section 5.2.1), the DMC 
will review unblinded accumulated data. 
Safety/ Superiority/Futility/ 
Sample Size Re-Estimation 
2nd Data Review 
Meeting (if 
needed) 
After 75% of planned subjects* are discharged 
from the hospital, complete the Day 43 Visit, 
discontinue the study early, or meet the primaiy 
mortality endpoint (by Day 43), the DMC will 
review unblinded accumulated data. 
Safety 
 
 
4.10 Other Analyses 
 
4.10.1 Pharmacokinetics 
Sernm gimsilumab concentrations will be summarized (including geometric mean, CV%, and 95% 
confidence interval for post-baseline timepoints) at Baseline (pre-dose), Day 8 (pre-dose) and 
DoD/ET using descriptive statistics for the PK population. A scatter plot of individual 
concentrations (overlaid) versus actual time of sampling (relative to Day 1 dose) will be provided 
(conditioned on subjects receiving Day 1 or Day 1 and Day 8 dosesofstudy chug). Phannacokinetic 
data analysis will not be perfonned until after database lock as it is potentially unblinding. 
 
Population PK analysis, if conducted, will be described in a separate analysis plan and report. 
 
4.10.2 Immunogenicity 
Sernm anti-chug antibody (ADA) data will be summarized by visit and treatment for the safety 
analysis set (note, this analysis is distinct from the anti-GM-CSF auto-antibody test at 
Screening). 
The following will be summai·ized: 
• 
ADA positive at baseline 
• 
ADA negative post baseline 
• 
ADA positive post baseline (regai·dless of baseline; hnmunogenicity rate) 
• 
ADA positive post baseline (but negative at baseline) 
Assessment of ADA incidence and Day 8 pre-dose sernm gimsilumab concentrntion will be 
descriptively summarized by: 
• 
ADA positive on any day 
• 
ADA positive on Day 15 
 
4.10.3 Biomarker 
Actual and change from baseline senun cytokines and safety biomarker SP-D results will be 
summarized by ti·eatment at Baseline (pre-dose), Day 4, Day 8, and DoD/ET using descriptive 
statistics for the safety analysis set. Summary plots of actual and change from baseline sernm 
cytokines will be provided, where time=0 will be: 


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• Study Day 1 
• Day of onset of symptoms 
By-subject listings of biomarker results will be provided. Biomarker data analysis will not be 
performed until after database lock as it is potentially unblinding. Additional exploratory analyses 
may be performed. 
 
4.11 Changes in the Conduct of the Study or Planned Analysis 
SAP v3.0 incorporates changes to Interim Analysis 2 to include stopping criteria for 
superiority (Section 5.2.3) and to amend the stopping criteria for inferiority to use Mortality 
by Day 43 instead of Mortality by Day 29 (Section 5.2.4). SAP was updated before planned 
amendments to include these changes in the protocol and DMC Charter were finalized. 


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5 
INTERIM ANALYSES 
See also Section 4.9.5 for infonnation on the DMC interim analyses. Please note the 
distinction between "DMC data review" and "DMC interim analysis". 
 
5.1 
Interim Analysis 1 
Objectives of interim analysis 1 (!Al) are for the DMC to 
• 
review unblinded safety data 
• 
check efficacy for futility 
 
5.1.1 Subjects to be included in interim analysis 1 
Trigger date for !Al: 60 subjects ti-eated completed the Day 15 Visit or died 
Subjects to be included in !Al: All subjects in the ITT analysis set randomized and treated at least 
15 days prior to the !Al trigger date 
 
5.1.2 Analysis of efficacy endpoints at interim analysis 1 
• 
Mortality up to Day 15: treatment effect estimated using CMH test strntified by baseline 
clinical status, odds ratio and 95% CI estimated using logistic regression model with 
treatment and baseline clinical status and independent variables. 
• 
Overall survival: treatment effect estimated using logrank test, median, 25th percentile, 75th 
percentile smvival times in days, and by ti·eatment surivival cmve as estimated using 
Kaplan-Meier methods. 
• 
Alive and no mechanical ventilation on Day 15: ti·eatment effect estimated using CMH test 
sti·atified by baseline clinical status, odds ratio and 95% CI estimated using logistic 
regression model with ti·eatment and baseline clinical status and independent variables. 
• 
Time to hospital discharge: ti·eatment effect estimated using logrank test, median, 25th 
percentile, 75th percentile smvival times in days, and by ti·eatment surivival cmve as 
estimated using Kaplan-Meier methods. 
• 
Time to first 2-point improvement on 7-point ordinal scale: ti·eatment effect estimated using 
logrank test, median, 25th percentile, 75th percentile smvival times in days, and by ti·eatment 
surivival cmve as estimated using Kaplan-Meier methods. 
 
5.1.3 Futility criteria at interim analysis 1 
No fonnal futility criteria were set. DMC met on June 19, 2020 and agreed that the study could 
continue without modification. 
 
5.2 
Interim Analysis 2 
Objectives of interim analysis 2 (IA2) are for the DMC to 
• 
review unblinded safety data 
• 
check efficacy superiority stopping criteria 
• 
check efficacy futility stopping criteria 
• 
assess, if applicable, a sample size re-estimation based on the primary efficacy endpoint. 


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5.2.1 Subjects to be included in interim analysis 2 
Trigger date for IA2: 100 subjects completed at least the Day 29 Visit (non-mortality data by Day 
29) or died (mo1iality data by Day 43). 
All subjects in the ITT analysis set randomized (and treated) at least 29 days prior to the IA2 trigger 
date and safety and efficacy data collected through the IA2 trigger date for these subjects will be 
included in the interim analysis. 
Superiority analysis, futility analysis, and sample size re-estimation on the primaiy endpoint, 
Mo1iality by Day 43, will be based on subjects randomized (and treated) at least 43 days prior to 
the IA2 trigger date. Confnmation of survival status by Day 43 will consist of review of death date 
and eai·ly study withdrawal date by a clinical research associate and dates confmned by source data 
verification. If no death date is available site personnel should confinn whether or not the subject 
was still alive on Day 43. 
 
5.2.2 Analysis of efficacy endpoints at interim analysis 2 
The following efficacy endpoints will be analyzed at IA2: 
• 
Mortality up to Day 43 as Estimand 1 described in Section 4.8.2 
• 
Composite key secondaiy endpoint "Survival and no mechanical ventilation on Day 29" as 
described in Section 4.8.3.1. 
 
5.2.3 Superiority stopping criteria at interim analysis 2 
The DMC may recommend stopping the study for superiority if the following condition is met: 
D. Robust and compelling benefit of gimsilumab compai·ed to placebo on mo1iality up to Day 
43, i.e., one-sided p-value < 0.0005. 
 
5.2.4 Futility stopping criteria at interim analysis 2 
The DMC may recommend stopping the study for futility, if at least one of the following conditions 
ai·e met (relevant analysis specifications follow Section 5.2.1 and Section 5.2.2): 
• 
No benefit of gimsilumab compared to placebo on m01iality up to Day 43, i.e., estimated 
treatment risk difference 0 and one-sided p-value 0.5. 
• 
No benefit of gimsilumab compared to placebo on composite "survival and no mechnical 
ventilation on Day 29", i.e., estimated treatment response difference:::;0 and one-sided p­ 
value 0.5. 
5.2.5 Sample size re-estimation at interim analysis 2 
If the study is neither stopped for superiority nor futility at IA2, the sample size will be re-assed 
by the following procedure for the primaiy efficacy endpoint mo1iality by Day 43: 
(A) The conditional power given the estimated common risk difference at IA2 will be calculated 
by 
• using the estimated common risk difference and its standai·d enor at IA2 (Estimand 1 
described in Section 4.8.2) 
• assuming the cunent trend observed up to IA2 (stage 1) as hue disti·ibution pai·ameters 
for the remaining paii of the study (stage 2) 
• keeping the total sample size as 270 subjects. 


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(B) If the conditional power is ≥ 0.8 (80%), then the initial sample size can be kept. 
(C) If the conditional power is < 0.8 (80%), then the sample size may be increased, so that 
• the conditional power calculated with the increased sample size is 0.8 (80%) for the final 
analysis combining the test statistics from first and second stage with pre-specified 
weights (Cui/Hung/Wang 1999) to maintain the type-I-error probability restricted to 
0.025 one-sided; the two pre-specified weights are 
 
 
𝑤𝑤
1 
27
0 
= √ 
𝑛𝑛1   with𝑛𝑛 
denoting the number of subjects in the FAS for stage 1, i.e., subjects 
randomized at least 43 days prior to the IA2 trigger date 
 
 
270−𝑛𝑛 
𝑤𝑤2 = √ 270 
where 270 − 𝑛𝑛1 represents the number of subjects in the FAS for stage 2, 
i.e., subjects randomized 42 days prior to the IA2 trigger date or later 
• but not increasing the maximum allowed total sample size of 400 subjects. 
(D) In order not disclosing too much information to sponsor and investigators, only the 
following categories for the total sample size can be recommended: 
• 270 subjects (i.e., no increase of the initial sample size) 
• 300 subjects 
• 330 subjects 
• 360 subjects 
• 400 subjects (i.e., the maximum allowed total sample size). 
5.2.6 Interim analysis 2 outcome 
 
The DMC met on Aug 26th, 2020 to review results from interim analysis 2. After the meeting ad 
hoc analyses were requested to review efficacy endpoints by select subgroups and to perform some 
additional analyses on mechanical ventilation-free days. These analyses are documented in KIN- 
1901-2001 PXL250621 Additional Statistical Analysis V1.0.docx. Per sponsor decision, enrollment 
was stopped early with the intention of completing the study as planned for the 227 (84%) of 
subjects randomized on or before October 12, 2020. For planning purposes the ad hoc analyses 
were repeated using a data cut-off date of September 28, 2020 including all subjects randomized 
as of the cut-off date. 
1
1


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6 
REFERENCES 
ARDS Definition Task Force. Ranieri VM, Rubenfield GD, Thompson BT, Ferguson ND, Caldwell E, 
Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: The Berlin Definition. JAMA. 
2012;307(23):2526-33 
Beyersmann J, Allignol A, Schumacher M. Competing Risks and Multistate Models with R. Springer; 
2012. 
Cui L, Hung HMJ, Wang S-J. Modification of sample size in group sequential clinical trials. Biometric 
1999;55:853-857 
Ge M, et al. Covariate-adjusted difference in proportions from clinical trials using logistic regression 
and weighted risk differences. Drug Information Journal 2011;45:481-493 
Liublinska V, Rubin DB. Sensitivity analysis for a partially missing binary outcome in a two-arm 
randomized clinical trial. Statistics in Medicine 2014;33:4170-4185 
Yan X, Lee S, Li N. Missing data handling methods in medical device clinical trials. Journal of 
Biopharmaceutical Statistics 2009;19:1085-1098 


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7 
APPENDICES 


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7.1 
Schedule of Assessments 
 


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K.inevant 
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Statistical Analysis Plan 
 
7.2 
Adverse Events of Special Interest 
 
Infective pneumonia (SMQ) 
Scope 
Group 
PT 
PT Code 
NaITow 
A 
Actinomycotic pulmonary infection 
10000628 
NaITow 
A 
Acute pulmonary histoplasmosis 
10001027 
NaITow 
A 
Atypical mycobacterial pneumonia 
10071075 
NaITow 
A 
Atypical pneumonia 
10003757 
NaITow 
A 
Blastomycosis 
10005098 
NaITow 
A 
Bronchopulmonary aspergillosis 
10006473 
NaITow 
A 
Burkholderia cepacia complex infection 
10069657 
NaITow 
A 
Burkholderia pseudomallei infection 
10069748 
NaITow 
A 
Candida pneumonia 
10053158 
NaITow 
A 
Chlamydia! infection 
10061041 
NaITow 
A 
Chronic pulmonary histoplasmosis 
10009115 
NaITow 
A 
Coccidioidomycosis 
10009825 
NaITow 
A 
Embolic oneumonia 
10065680 
NaITow 
A 
Enterobacter pneumonia 
10054218 
NaITow 
A 
Haemophilus infection 
10061190 
NaITow 
A 
HaemoITha!lic pneumonia 
10077933 
NaITow 
A 
Hantavirns pulmonary infection 
10019143 
NaITow 
A 
Herpes simplex pneumonia 
10065046 
NaITow 
A 
Histoplasmosis 
10020141 
NaITow 
A 
fufectious pleural effusion 
10071699 
NaITow 
A 
Lung abscess 
10025028 
NaITow 
A 
Miliaiy pneumonia 
10055088 
NaITow 
A 
Pai·acancerouspneumonia 
10080986 
NaITow 
A 
Pai·asitic pneumonia 
10078883 
NaITow 
A 
Pleural infection 
10061351 
NaITow 
A 
Pleural infection bacterial 
10067334 
NaITow 
A 
Pleurisy viral 
10052761 
NaITow 
A 
Pneumocystis iirovecii pneumonia 
10073755 
NaITow 
A 
Pneumonia 
10035664 
NaITow 
A 
Pneumonia acinetobacter 
10079866 
NaITow 
A 
Pneumonia adenoviral 
10035665 
NaITow 
A 
Pneumonia anthrax 
10035667 
NaITow 
A 
Pneumonia bacterial 
10060946 
NaITow 
A 
Pneumonia blastomyces 
10035671 
NaITow 
A 
Pneumonia bordetella 
10035672 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 57 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Narrow 
A 
Pneumonia chlamydial 
10035673 
Narrow 
A 
Pneumonia cryptococcal 
10067565 
Narrow 
A 
Pneumonia cytomegaloviral 
10035676 
Narrow 
A 
Pneumonia escherichia 
10035699 
Narrow 
A 
Pneumonia fungal 
10061354 
Narrow 
A 
Pneumonia haemophilus 
10035702 
Narrow 
A 
Pneumonia helminthic 
10065246 
Narrow 
A 
Pneumonia herpes viral 
10035703 
Narrow 
A 
Pneumonia influenzal 
10035714 
Narrow 
A 
Pneumonia klebsiella 
10035717 
Narrow 
A 
Pneumonia legionella 
10035718 
Narrow 
A 
Pneumonia measles 
10035722 
Narrow 
A 
Pneumonia moraxella 
10035723 
Narrow 
A 
Pneumonia mycoplasmal 
10035724 
Narrow 
A 
Pneumonia necrotising 
10055672 
Narrow 
A 
Pneumonia parainfluenzae viral 
10035727 
Narrow 
A 
Pneumonia pneumococcal 
10035728 
Narrow 
A 
Pneumonia proteus 
10079867 
Narrow 
A 
Pneumonia pseudomonal 
10035731 
Narrow 
A 
Pneumonia respiratory syncytial viral 
10035732 
Narrow 
A 
Pneumonia salmonella 
10035733 
Narrow 
A 
Pneumonia serratia 
10079868 
Narrow 
A 
Pneumonia staphylococcal 
10035734 
Narrow 
A 
Pneumonia streptococcal 
10035735 
Narrow 
A 
Pneumonia toxoplasmal 
10067566 
Narrow 
A 
Pneumonia tularaemia 
10035736 
Narrow 
A 
Pneumonia viral 
10035737 
Narrow 
A 
Pneumonic plague 
10053026 
Narrow 
A 
Post procedural pneumonia 
10066590 
Narrow 
A 
Pulmonary echinococciasis 
10037374 
Narrow 
A 
Pulmonary mucormycosis 
10078354 
Narrow 
A 
Pulmonary mycosis 
10037422 
Narrow 
A 
Pulmonary nocardiosis 
10080435 
Narrow 
A 
Pulmonary paracoccidioidomycosis 
10080468 
Narrow 
A 
Pulmonary sepsis 
10051739 
Narrow 
A 
Pulmonary sporotrichosis 
10080480 
Narrow 
A 
Pulmonary syphilis 
10037434 
Narrow 
A 
Pulmonary trichosporonosis 
10068184 
Narrow 
A 
Pulmonary tuberculosis 
10037440 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 58 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Narrow 
A 
Pyopneumothorax 
10057102 
Narrow 
A 
Septic pulmonary embolism 
10083093 
Narrow 
A 
Tuberculosis 
10044755 
Narrow 
A 
Tuberculous pleurisy 
10045104 
Narrow 
A 
Varicella zoster pneumonia 
10074254 
Broad 
A 
Acinetobacter infection 
10051894 
Broad 
A 
Acinetobacter test positive 
10069962 
Broad 
A 
Adenovirus infection 
10060931 
Broad 
A 
Adenovirus test positive 
10070369 
Broad 
A 
Aspergillus infection 
10074171 
Broad 
A 
Aspergillus test positive 
10070448 
Broad 
A 
Aspiration tracheal abnormal 
10003531 
Broad 
A 
Atelectasis 
10003598 
Broad 
A 
Atypical mycobacterial infection 
10061663 
Broad 
A 
Atypical mycobacterial lower respiratory tract 
infection 
10075026 
Broad 
A 
Auscultation 
10076270 
Broad 
A 
Avian influenza 
10064097 
Broad 
A 
Bacterial test positive 
10059421 
Broad 
A 
Bronchopneumopathy 
10053582 
Broad 
A 
Burkholderia test positive 
10069960 
Broad 
A 
Carbon dioxide abnormal 
10064156 
Broad 
A 
Carbon dioxide increased 
10007225 
Broad 
A 
Chest X-ray abnormal 
10008499 
Broad 
A 
Chlamydia test positive 
10070159 
Broad 
A 
Coxiella test positive 
10070194 
Broad 
A 
Crepitations 
10011376 
Broad 
A 
Cryptococcosis 
10011490 
Broad 
A 
Culture throat positive 
10011634 
Broad 
A 
Disseminated aspergillosis 
10080492 
Broad 
A 
Disseminated blastomycosis 
10080477 
Broad 
A 
Disseminated coccidioidomycosis 
10080474 
Broad 
A 
Disseminated mucormycosis 
10073239 
Broad 
A 
Disseminated paracoccidioidomycosis 
10080478 
Broad 
A 
Disseminated sporotrichosis 
10080491 
Broad 
A 
Disseminated tuberculosis 
10013453 
Broad 
A 
Egobronchophony 
10056744 
Broad 
A 
Empyema 
10014568 
Broad 
A 
Enterobacter infection 
10051910 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 59 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
A 
Enterobacter test positive 
10070023 
Broad 
A 
Escherichia infection 
10061126 
Broad 
A 
Escherichia test positive 
10070090 
Broad 
A 
Francisella test positive 
10070097 
Broad 
A 
Fungal test positive 
10059423 
Broad 
A 
H1N1 influenza 
10069767 
Broad 
A 
H2N2 influenza 
10077909 
Broad 
A 
H3N2 influenza 
10081286 
Broad 
A 
Haemophilus test positive 
10070100 
Broad 
A 
Haemoptysis 
10018964 
Broad 
A 
Hantavirus test positive 
10070212 
Broad 
A 
Human metapneumovirus test positive 
10072859 
Broad 
A 
Hypoventilation 
10021133 
Broad 
A 
Hypoxia 
10021143 
Broad 
A 
Increased bronchial secretion 
10062530 
Broad 
A 
Influenza 
10022000 
Broad 
A 
Influenza A virus test positive 
10070215 
Broad 
A 
Influenza virus test positive 
10070717 
Broad 
A 
Klebsiella infection 
10061259 
Broad 
A 
Klebsiella test positive 
10070091 
Broad 
A 
Legionella infection 
10061266 
Broad 
A 
Legionella test positive 
10070092 
Broad 
A 
Lower respiratory tract congestion 
10075565 
Broad 
A 
Lower respiratory tract herpes infection 
10077390 
Broad 
A 
Lower respiratory tract infection 
10024968 
Broad 
A 
Lower respiratory tract infection bacterial 
10063890 
Broad 
A 
Lower respiratory tract infection fungal 
10065187 
Broad 
A 
Lower respiratory tract infection viral 
10065188 
Broad 
A 
Lung consolidation 
10025080 
Broad 
A 
Lung infiltration 
10025102 
Broad 
A 
Lung opacity 
10081792 
Broad 
A 
Metapneumovirus infection 
10066226 
Broad 
A 
Middle East respiratory syndrome 
10075271 
Broad 
A 
Moraxella infection 
10062204 
Broad 
A 
Moraxella test positive 
10070095 
Broad 
A 
Mucormycosis 
10028098 
Broad 
A 
Mycobacterial infection 
10062207 
Broad 
A 
Mycobacterium test positive 
10070323 
Broad 
A 
Mycoplasma infection 
10061300 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 60 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
A 
Mycoplasma test positive 
10070160 
Broad 
A 
Nocardiosis 
10029444 
Broad 
A 
Organising pneumonia 
10067472 
Broad 
A 
Oxygen saturation abnormal 
10033317 
Broad 
A 
Oxygen saturation decreased 
10033318 
Broad 
A 
Paracoccidioides infection 
10061906 
Broad 
A 
PCO2 abnormal 
10058982 
Broad 
A 
PCO2 decreased 
10034181 
Broad 
A 
Percussion test abnormal 
10051721 
Broad 
A 
Pleural effusion 
10035598 
Broad 
A 
Pleural rub 
10035615 
Broad 
A 
Pleuritic pain 
10035623 
Broad 
A 
Pneumococcal bacteraemia 
10058859 
Broad 
A 
Pneumococcal infection 
10061353 
Broad 
A 
Pneumococcal sepsis 
10054047 
Broad 
A 
Pneumocystis test positive 
10070454 
Broad 
A 
Pneumovirus test positive 
10070345 
Broad 
A 
PO2 abnormal 
10062087 
Broad 
A 
PO2 decreased 
10035768 
Broad 
A 
Productive cough 
10036790 
Broad 
A 
Proteus infection 
10061470 
Broad 
A 
Proteus test positive 
10070134 
Broad 
A 
Pseudomonas infection 
10061471 
Broad 
A 
Pseudomonas test positive 
10070135 
Broad 
A 
Psittacosis 
10037151 
Broad 
A 
Pulmonary congestion 
10037368 
Broad 
A 
Pulmonary imaging procedure abnormal 
10082582 
Broad 
A 
Pulmonary tuberculoma 
10066927 
Broad 
A 
Q fever 
10037688 
Broad 
A 
Rales 
10037833 
Broad 
A 
Respiratory tract infection 
10062352 
Broad 
A 
Respiratory tract infection bacterial 
10060693 
Broad 
A 
Respiratory tract infection fungal 
10060692 
Broad 
A 
Respiratory tract infection viral 
10062106 
Broad 
A 
Rhonchi 
10039109 
Broad 
A 
Serratia infection 
10061512 
Broad 
A 
Serratia test positive 
10070128 
Broad 
A 
Severe acute respiratory syndrome 
10061982 
Broad 
A 
Sporotrichosis 
10041736 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date oflast signature 
Page 61 of 122 
 
 
K.inevant 
KIN-1901-2001 
 
Statistical Analysis Plan 
Broad 
A 
Sputum abnonnal 
10060991 
Broad 
A 
Sputum culture positive 
10051612 
Broad 
A 
Sputum discoloured 
10041807 
Broad 
A 
Sputum pmulent 
10050090 
Broad 
A 
Staphylococcal infection 
10058080 
Broad 
A 
Staphylococcus test positive 
10070052 
Broad 
A 
Sti·eptococcal infection 
10061372 
Broad 
A 
Sti·eptococcus test positive 
10070055 
Broad 
A 
Tachypnoea 
10043089 
Broad 
A 
Tularaemia 
10045146 
Broad 
A 
Use of accessory respirato1y muscles 
10069555 
Broad 
A 
Venous oxygen saturation abno1mal 
10068428 
Broad 
A 
Venous oxygen saturation decreased 
10068427 
 
 
Opportunistic infections (SMQ) 
Scope 
Group 
PT 
PT Code 
NaITow 
A 
Acid fast bacilli infection 
10054204 
NaITow 
A 
Acinetobacter sepsis 
10083897 
NaITow 
A 
Acute oulmonarv histoolasmosis 
10001027 
NaITow 
A 
Adenoviral haemonhagic cystitis 
10057373 
NaITow 
A 
Adrenal gland tuberculosis 
10001358 
NaITow 
A 
Altemaria infection 
10054207 
NaITow 
A 
Amoebic brain abscess 
10001984 
NaITow 
A 
Amoebic lung abscess 
10001990 
NaITow 
A 
Althritis fungal 
10060966 
NaITow 
A 
Aspergillosis oral 
10003489 
NaITow 
A 
Asoergillus infection 
10074171 
NaITow 
A 
Atypical mycobacterial infection 
10061663 
NaITow 
A 
Atypical mycobacterial lower respirato1y ti·act 
infection 
10075026 
NaITow 
A 
Atypical mycobacterial lvmphadenitis 
10003755 
NaITow 
A 
Atypical mycobacterial pneumonia 
10071075 
NaITow 
A 
Atypical mycobacterium pericarditis 
10055036 
NaITow 
A 
Bacillaiy angiomatosis 
10003971 
NaITow 
A 
Biliary ti-act infection cryptosporidial 
10067319 
NaITow 
A 
Biliary ti-act infection fungal 
10065203 
NaITow 
A 
BK vims infection 
10055181 
NaITow 
A 
Blastocystis infection 
10005092 
NaITow 
A 
Blastomycosis 
10005098 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 62 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Narrow 
A 
Bone tuberculosis 
10056377 
Narrow 
A 
Borderline leprosy 
10006029 
Narrow 
A 
Bovine tuberculosis 
10006049 
Narrow 
A 
Bronchitis fungal 
10061737 
Narrow 
A 
Bronchopulmonary aspergillosis 
10006473 
Narrow 
A 
Burkholderia cepacia complex sepsis 
10069684 
Narrow 
A 
Burkholderia gladioli infection 
10073030 
Narrow 
A 
Burkholderia pseudomallei infection 
10069748 
Narrow 
A 
Candida endophthalmitis 
10059449 
Narrow 
A 
Candida osteomyelitis 
10064699 
Narrow 
A 
Candida pneumonia 
10053158 
Narrow 
A 
Candida retinitis 
10068612 
Narrow 
A 
Candida sepsis 
10053166 
Narrow 
A 
Capnocytophaga infection 
10061738 
Narrow 
A 
Capnocytophaga sepsis 
10081740 
Narrow 
A 
Central nervous system fungal infection 
10072805 
Narrow 
A 
Central nervous system viral infection 
10061037 
Narrow 
A 
Cerebral aspergillosis 
10051597 
Narrow 
A 
Cerebral fungal infection 
10049657 
Narrow 
A 
Cerebral toxoplasmosis 
10057854 
Narrow 
A 
Chromoblastomycosis 
10008803 
Narrow 
A 
Chronic pulmonary histoplasmosis 
10009115 
Narrow 
A 
Coccidioides encephalitis 
10054214 
Narrow 
A 
Coccidioidomycosis 
10009825 
Narrow 
A 
Colitis herpes 
10051782 
Narrow 
A 
Conjunctivitis tuberculous 
10010754 
Narrow 
A 
Cryptococcal cutaneous infection 
10054216 
Narrow 
A 
Cryptococcal fungaemia 
10067112 
Narrow 
A 
Cryptococcosis 
10011490 
Narrow 
A 
Cryptosporidiosis infection 
10011502 
Narrow 
A 
Cutaneous coccidioidomycosis 
10068747 
Narrow 
A 
Cutaneous tuberculosis 
10011684 
Narrow 
A 
Cytomegalovirus chorioretinitis 
10048843 
Narrow 
A 
Cytomegalovirus colitis 
10048983 
Narrow 
A 
Cytomegalovirus duodenitis 
10049014 
Narrow 
A 
Cytomegalovirus enteritis 
10049074 
Narrow 
A 
Cytomegalovirus enterocolitis 
10049015 
Narrow 
A 
Cytomegalovirus gastritis 
10049016 
Narrow 
A 
Cytomegalovirus gastroenteritis 
10051349 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 63 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Narrow 
A 
Cytomegalovirus gastrointestinal infection 
10052817 
Narrow 
A 
Cytomegalovirus gastrointestinal ulcer 
10075619 
Narrow 
A 
Cytomegalovirus hepatitis 
10011830 
Narrow 
A 
Cytomegalovirus infection 
10011831 
Narrow 
A 
Cytomegalovirus infection reactivation 
10058666 
Narrow 
A 
Cytomegalovirus mononucleosis 
10011834 
Narrow 
A 
Cytomegalovirus mucocutaneous ulcer 
10065036 
Narrow 
A 
Cytomegalovirus myelomeningoradiculitis 
10065621 
Narrow 
A 
Cytomegalovirus myocarditis 
10056261 
Narrow 
A 
Cytomegalovirus oesophagitis 
10049018 
Narrow 
A 
Cytomegalovirus pancreatitis 
10049566 
Narrow 
A 
Cytomegalovirus pericarditis 
10056721 
Narrow 
A 
Cytomegalovirus syndrome 
10056262 
Narrow 
A 
Cytomegalovirus urinary tract infection 
10051350 
Narrow 
A 
Cytomegalovirus viraemia 
10058854 
Narrow 
A 
Disseminated aspergillosis 
10080492 
Narrow 
A 
Disseminated blastomycosis 
10080477 
Narrow 
A 
Disseminated coccidioidomycosis 
10080474 
Narrow 
A 
Disseminated cryptococcosis 
10013439 
Narrow 
A 
Disseminated cytomegaloviral infection 
10049075 
Narrow 
A 
Disseminated leishmaniasis 
10013444 
Narrow 
A 
Disseminated mucormycosis 
10073239 
Narrow 
A 
Disseminated mycobacterium avium complex 
infection 
10069662 
Narrow 
A 
Disseminated paracoccidioidomycosis 
10080478 
Narrow 
A 
Disseminated sporotrichosis 
10080491 
Narrow 
A 
Disseminated strongyloidiasis 
10080496 
Narrow 
A 
Disseminated toxoplasmosis 
10083434 
Narrow 
A 
Disseminated trichosporonosis 
10068185 
Narrow 
A 
Disseminated tuberculosis 
10013453 
Narrow 
A 
Disseminated varicella zoster vaccine virus infection 
10076667 
Narrow 
A 
Ear tuberculosis 
10014027 
Narrow 
A 
Encephalitis cytomegalovirus 
10014586 
Narrow 
A 
Encephalitis fungal 
10065170 
Narrow 
A 
Endocarditis candida 
10014669 
Narrow 
A 
Endocarditis histoplasma 
10014676 
Narrow 
A 
Endocarditis Q fever 
10014682 
Narrow 
A 
Enterocolitis fungal 
10065205 
Narrow 
A 
Epididymitis blastomyces 
10015001 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 64 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Narrow 
A 
Epididymitis tuberculous 
10015004 
Narrow 
A 
Epstein-Barr virus associated lymphoproliferative 
disorder 
10068349 
Narrow 
A 
Epstein-Barr virus infection reactivation 
10015109 
Narrow 
A 
Exserohilum infection 
10073244 
Narrow 
A 
Extrapulmonary tuberculosis 
10064445 
Narrow 
A 
Eye infection toxoplasmal 
10015939 
Narrow 
A 
Female genital tract tuberculosis 
10061150 
Narrow 
A 
Flavobacterium infection 
10054222 
Narrow 
A 
Fournier's gangrene 
10017068 
Narrow 
A 
Fungaemia 
10017523 
Narrow 
A 
Fungal abscess central nervous system 
10017524 
Narrow 
A 
Fungal cystitis 
10017525 
Narrow 
A 
Fungal endocarditis 
10017529 
Narrow 
A 
Fungal labyrinthitis 
10065174 
Narrow 
A 
Fungal oesophagitis 
10049656 
Narrow 
A 
Fungal peritonitis 
10061138 
Narrow 
A 
Fungal retinitis 
10068613 
Narrow 
A 
Fungal rhinitis 
10065182 
Narrow 
A 
Fungal sepsis 
10058872 
Narrow 
A 
Fungal tracheitis 
10069508 
Narrow 
A 
Fusarium infection 
10051919 
Narrow 
A 
Gastritis fungal 
10061972 
Narrow 
A 
Gastritis herpes 
10051784 
Narrow 
A 
Gastroenteritis cryptococcal 
10011485 
Narrow 
A 
Gastroenteritis cryptosporidial 
10017899 
Narrow 
A 
Gastrointestinal fungal infection 
10049479 
Narrow 
A 
Gastrointestinal mucormycosis 
10082721 
Narrow 
A 
Hepatic candidiasis 
10049653 
Narrow 
A 
Hepatic infection fungal 
10065217 
Narrow 
A 
Hepatosplenic candidiasis 
10051590 
Narrow 
A 
Herpes oesophagitis 
10052330 
Narrow 
A 
Herpes ophthalmic 
10062004 
Narrow 
A 
Herpes pharyngitis 
10066888 
Narrow 
A 
Herpes sepsis 
10058876 
Narrow 
A 
Herpes simplex colitis 
10074239 
Narrow 
A 
Herpes simplex encephalitis 
10019953 
Narrow 
A 
Herpes simplex gastritis 
10074240 
Narrow 
A 
Herpes simplex hepatitis 
10067389 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 65 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Narrow 
A 
Herpes simplex meningitis 
10019956 
Narrow 
A 
Herpes simplex meningoencephalitis 
10074247 
Narrow 
A 
Herpes simplex meningomyelitis 
10074250 
Narrow 
A 
Herpes simplex necrotising retinopathy 
10074252 
Narrow 
A 
Herpes simplex oesophagitis 
10074242 
Narrow 
A 
Herpes simplex otitis externa 
10019959 
Narrow 
A 
Herpes simplex pharyngitis 
10074244 
Narrow 
A 
Herpes simplex pneumonia 
10065046 
Narrow 
A 
Herpes simplex sepsis 
10074246 
Narrow 
A 
Herpes simplex visceral 
10019963 
Narrow 
A 
Herpes zoster cutaneous disseminated 
10074297 
Narrow 
A 
Herpes zoster disseminated 
10065038 
Narrow 
A 
Herpes zoster infection neurological 
10061208 
Narrow 
A 
Herpes zoster meningitis 
10074259 
Narrow 
A 
Herpes zoster meningoencephalitis 
10074248 
Narrow 
A 
Herpes zoster meningomyelitis 
10074251 
Narrow 
A 
Herpes zoster necrotising retinopathy 
10074253 
Narrow 
A 
Herpes zoster oticus 
10063491 
Narrow 
A 
Herpes zoster pharyngitis 
10074245 
Narrow 
A 
Histoplasmosis 
10020141 
Narrow 
A 
Histoplasmosis cutaneous 
10049142 
Narrow 
A 
Histoplasmosis disseminated 
10020144 
Narrow 
A 
Human herpesvirus 6 encephalitis 
10081897 
Narrow 
A 
Human herpesvirus 6 infection reactivation 
10066845 
Narrow 
A 
Human herpesvirus 8 infection 
10066435 
Narrow 
A 
Immune reconstitution inflammatory syndrome 
associated tuberculosis 
10072797 
Narrow 
A 
Indeterminate leprosy 
10021700 
Narrow 
A 
Infection in an immunocompromised host 
10021818 
Narrow 
A 
Infection susceptibility increased 
10021866 
Narrow 
A 
Intestinal tuberculosis 
10075268 
Narrow 
A 
Isosporiasis 
10023076 
Narrow 
A 
JC virus CSF test positive 
10078957 
Narrow 
A 
JC virus granule cell neuronopathy 
10074361 
Narrow 
A 
JC virus infection 
10023163 
Narrow 
A 
Joint tuberculosis 
10056367 
Narrow 
A 
Kaposi's sarcoma 
10023284 
Narrow 
A 
Kaposi's sarcoma AIDS related 
10023286 
Narrow 
A 
Kaposi's varicelliform eruption 
10051891 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 66 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Narrow 
A 
Laryngitis fungal 
10067321 
Narrow 
A 
Lepromatous leprosy 
10024227 
Narrow 
A 
Leprosy 
10024229 
Narrow 
A 
Listeria encephalitis 
10054116 
Narrow 
A 
Listeria sepsis 
10063085 
Narrow 
A 
Listeriosis 
10024641 
Narrow 
A 
Lower respiratory tract infection fungal 
10065187 
Narrow 
A 
Lupus vulgaris 
10025143 
Narrow 
A 
Lymph node tuberculosis 
10025183 
Narrow 
A 
Lymphadenitis fungal 
10065208 
Narrow 
A 
Male genital tract tuberculosis 
10061234 
Narrow 
A 
Mastitis fungal 
10065211 
Narrow 
A 
Meningitis aspergillus 
10073245 
Narrow 
A 
Meningitis candida 
10027205 
Narrow 
A 
Meningitis coccidioides 
10027207 
Narrow 
A 
Meningitis cryptococcal 
10027209 
Narrow 
A 
Meningitis exserohilum 
10073246 
Narrow 
A 
Meningitis fungal 
10027236 
Narrow 
A 
Meningitis herpes 
10027242 
Narrow 
A 
Meningitis histoplasma 
10027243 
Narrow 
A 
Meningitis listeria 
10027248 
Narrow 
A 
Meningitis toxoplasmal 
10048848 
Narrow 
A 
Meningitis tuberculous 
10027259 
Narrow 
A 
Meningoencephalitis herpetic 
10027285 
Narrow 
A 
Meningomyelitis herpes 
10074249 
Narrow 
A 
Methylobacterium infection 
10070983 
Narrow 
A 
Microsporidia infection 
10053982 
Narrow 
A 
Miliary pneumonia 
10055088 
Narrow 
A 
Mucormycosis 
10028098 
Narrow 
A 
Mycetoma mycotic 
10028426 
Narrow 
A 
Mycobacterial infection 
10062207 
Narrow 
A 
Mycobacterial peritonitis 
10073514 
Narrow 
A 
Mycobacterium abscessus infection 
10064789 
Narrow 
A 
Mycobacterium avium complex immune restoration 
disease 
10058449 
Narrow 
A 
Mycobacterium avium complex infection 
10058806 
Narrow 
A 
Mycobacterium chelonae infection 
10071401 
Narrow 
A 
Mycobacterium fortuitum infection 
10049659 
Narrow 
A 
Mycobacterium kansasii infection 
10028447 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 67 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Narrow 
A 
Mycobacterium marinum infection 
10028452 
Narrow 
A 
Mycobacterium ulcerans infection 
10066289 
Narrow 
A 
Mycotic endophthalmitis 
10063202 
Narrow 
A 
Myocarditis mycotic 
10059026 
Narrow 
A 
Myocarditis toxoplasmal 
10028617 
Narrow 
A 
Necrotising fasciitis fungal 
10052892 
Narrow 
A 
Necrotising herpetic retinopathy 
10065119 
Narrow 
A 
Neurocryptococcosis 
10068368 
Narrow 
A 
Nocardia sepsis 
10064952 
Narrow 
A 
Nocardiosis 
10029444 
Narrow 
A 
Oesophageal candidiasis 
10030154 
Narrow 
A 
Oesophageal tuberculosis 
10030200 
Narrow 
A 
Ophthalmic herpes simplex 
10073938 
Narrow 
A 
Ophthalmic herpes zoster 
10030865 
Narrow 
A 
Opportunistic infection 
10030901 
Narrow 
A 
Oral tuberculosis 
10076879 
Narrow 
A 
Oro-pharyngeal aspergillosis 
10053029 
Narrow 
A 
Osteomyelitis blastomyces 
10031255 
Narrow 
A 
Osteomyelitis fungal 
10065239 
Narrow 
A 
Otitis media fungal 
10065175 
Narrow 
A 
Pancreatitis fungal 
10065190 
Narrow 
A 
Paracoccidioides infection 
10061906 
Narrow 
A 
Parvovirus B19 infection reactivation 
10076281 
Narrow 
A 
Penicillium infection 
10078580 
Narrow 
A 
Pericarditis fungal 
10065220 
Narrow 
A 
Pericarditis histoplasma 
10034489 
Narrow 
A 
Pericarditis tuberculous 
10055069 
Narrow 
A 
Peritoneal candidiasis 
10056562 
Narrow 
A 
Peritoneal tuberculosis 
10053583 
Narrow 
A 
Phaeohyphomycosis 
10080815 
Narrow 
A 
Pneumocystis jirovecii infection 
10073756 
Narrow 
A 
Pneumocystis jirovecii pneumonia 
10073755 
Narrow 
A 
Pneumonia blastomyces 
10035671 
Narrow 
A 
Pneumonia cryptococcal 
10067565 
Narrow 
A 
Pneumonia cytomegaloviral 
10035676 
Narrow 
A 
Pneumonia fungal 
10061354 
Narrow 
A 
Pneumonia herpes viral 
10035703 
Narrow 
A 
Pneumonia legionella 
10035718 
Narrow 
A 
Pneumonia toxoplasmal 
10067566 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 68 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Narrow 
A 
Polyomavirus viraemia 
10083628 
Narrow 
A 
Polyomavirus-associated nephropathy 
10065381 
Narrow 
A 
Proctitis herpes 
10036780 
Narrow 
A 
Progressive multifocal leukoencephalopathy 
10036807 
Narrow 
A 
Progressive vaccinia 
10069582 
Narrow 
A 
Prostatitis tuberculous 
10064743 
Narrow 
A 
Protothecosis 
10081250 
Narrow 
A 
Pseudallescheria infection 
10061919 
Narrow 
A 
Pseudallescheria sepsis 
10058973 
Narrow 
A 
Pseudomonas aeruginosa meningitis 
10074185 
Narrow 
A 
Pulmonary mucormycosis 
10078354 
Narrow 
A 
Pulmonary mycosis 
10037422 
Narrow 
A 
Pulmonary trichosporonosis 
10068184 
Narrow 
A 
Pulmonary tuberculoma 
10066927 
Narrow 
A 
Pulmonary tuberculosis 
10037440 
Narrow 
A 
Pyelonephritis fungal 
10065214 
Narrow 
A 
Renal tuberculosis 
10038534 
Narrow 
A 
Respiratory tract infection fungal 
10060692 
Narrow 
A 
Retinitis histoplasma 
10038912 
Narrow 
A 
Retinitis viral 
10038915 
Narrow 
A 
Rhinocerebral mucormycosis 
10076959 
Narrow 
A 
Rhodococcus infection 
10065041 
Narrow 
A 
Salpingitis tuberculous 
10039463 
Narrow 
A 
Scedosporium infection 
10059045 
Narrow 
A 
Septic arthritis staphylococcal 
10040063 
Narrow 
A 
Sinusitis aspergillus 
10051016 
Narrow 
A 
Sinusitis fungal 
10058678 
Narrow 
A 
Sphingomonas paucimobilis bacteraemia 
10081563 
Narrow 
A 
Sphingomonas paucimobilis infection 
10069639 
Narrow 
A 
Spleen tuberculosis 
10041640 
Narrow 
A 
Splenic candidiasis 
10051725 
Narrow 
A 
Splenic infection fungal 
10065194 
Narrow 
A 
Stenotrophomonas infection 
10054138 
Narrow 
A 
Stenotrophomonas sepsis 
10054137 
Narrow 
A 
Superinfection fungal 
10066984 
Narrow 
A 
Superinfection mycobacterial 
10075381 
Narrow 
A 
Systemic candida 
10042938 
Narrow 
A 
Systemic mycosis 
10052366 
Narrow 
A 
Thyroid tuberculosis 
10043774 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 69 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Narrow 
A 
Tonsillitis fungal 
10065236 
Narrow 
A 
Toxoplasmosis 
10044272 
Narrow 
A 
Tuberculoid leprosy 
10044729 
Narrow 
A 
Tuberculoma of central nervous system 
10052883 
Narrow 
A 
Tuberculosis 
10044755 
Narrow 
A 
Tuberculosis bladder 
10044758 
Narrow 
A 
Tuberculosis gastrointestinal 
10061390 
Narrow 
A 
Tuberculosis liver 
10058120 
Narrow 
A 
Tuberculosis of central nervous system 
10061391 
Narrow 
A 
Tuberculosis of eye 
10044819 
Narrow 
A 
Tuberculosis of genitourinary system 
10044828 
Narrow 
A 
Tuberculosis of intrathoracic lymph nodes 
10044846 
Narrow 
A 
Tuberculosis of peripheral lymph nodes 
10044965 
Narrow 
A 
Tuberculosis ureter 
10045026 
Narrow 
A 
Tuberculous abscess central nervous system 
10052884 
Narrow 
A 
Tuberculous endometritis 
10071559 
Narrow 
A 
Tuberculous laryngitis 
10045072 
Narrow 
A 
Tuberculous pleurisy 
10045104 
Narrow 
A 
Tuberculous tenosynovitis 
10059161 
Narrow 
A 
Upper respiratory fungal infection 
10062219 
Narrow 
A 
Urinary tract infection fungal 
10049059 
Narrow 
A 
Varicella zoster gastritis 
10074241 
Narrow 
A 
Varicella zoster oesophagitis 
10074243 
Narrow 
A 
Varicella zoster pneumonia 
10074254 
Narrow 
A 
Varicella zoster sepsis 
10074298 
Broad 
A 
Abdominal sepsis 
10058040 
Broad 
A 
Abscess fungal 
10065330 
Broad 
A 
Acanthamoeba infection 
10061618 
Broad 
A 
Achromobacter infection 
10082866 
Broad 
A 
Acinetobacter bacteraemia 
10064965 
Broad 
A 
Acinetobacter infection 
10051894 
Broad 
A 
Actinomyces test positive 
10069956 
Broad 
A 
Actinomycosis 
10000620 
Broad 
A 
Actinomycotic abdominal infection 
10000621 
Broad 
A 
Actinomycotic pulmonary infection 
10000628 
Broad 
A 
Actinomycotic skin infection 
10000629 
Broad 
A 
Acute haemorrhagic conjunctivitis 
10067817 
Broad 
A 
Acute hepatitis B 
10059193 
Broad 
A 
Acute hepatitis C 
10065051 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 70 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
A 
Adenoviral conjunctivitis 
10001257 
Broad 
A 
Adenoviral encephalitis 
10080441 
Broad 
A 
Adenoviral hepatitis 
10056885 
Broad 
A 
Adenoviral upper respiratory infection 
10001260 
Broad 
A 
Adenovirus encephalomyeloradiculitis 
10079668 
Broad 
A 
Adenovirus infection 
10060931 
Broad 
A 
Adenovirus test positive 
10070369 
Broad 
A 
Aeromonas infection 
10054205 
Broad 
A 
Aeromonas test positive 
10069957 
Broad 
A 
African trypanosomiasis 
10001461 
Broad 
A 
Alcaligenes infection 
10068911 
Broad 
A 
Allergic bronchopulmonary mycosis 
10082909 
Broad 
A 
Allescheriosis 
10001754 
Broad 
A 
Alpha haemolytic streptococcal infection 
10054265 
Broad 
A 
Alphavirus test positive 
10070370 
Broad 
A 
American trypanosomiasis 
10001935 
Broad 
A 
Amoeba test positive 
10072431 
Broad 
A 
Amoebiasis 
10001980 
Broad 
A 
Amoebic colitis 
10001985 
Broad 
A 
Amoebic dysentery 
10001986 
Broad 
A 
Amoebic skin ulcer 
10001992 
Broad 
A 
Anal candidiasis 
10002140 
Broad 
A 
Anal fungal infection 
10068556 
Broad 
A 
Angina gangrenous 
10002379 
Broad 
A 
Angiostrongylus infection 
10069517 
Broad 
A 
Anogenital warts 
10059313 
Broad 
A 
Anorectal human papilloma virus infection 
10073941 
Broad 
A 
Anthrax sepsis 
10058873 
Broad 
A 
Anti-JC virus antibody index 
10075613 
Broad 
A 
Arbovirus test positive 
10070371 
Broad 
A 
Arenavirus test positive 
10070376 
Broad 
A 
Arthritis salmonella 
10003271 
Broad 
A 
Aspergilloma 
10003487 
Broad 
A 
Aspergillus test positive 
10070448 
Broad 
A 
Atypical mycobacterium test positive 
10070326 
Broad 
A 
Atypical pneumonia 
10003757 
Broad 
A 
Avian influenza 
10064097 
Broad 
A 
Babesiosis 
10003965 
Broad 
A 
Bacteraemia 
10003997 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 71 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
A 
Bacterial sepsis 
10053840 
Broad 
A 
Bacterial test positive 
10059421 
Broad 
A 
Balamuthia infection 
10069523 
Broad 
A 
Balanitis candida 
10004074 
Broad 
A 
Bartonella test positive 
10070157 
Broad 
A 
Bartonellosis 
10004145 
Broad 
A 
Beta haemolytic streptococcal infection 
10052100 
Broad 
A 
Biliary sepsis 
10057847 
Broad 
A 
BK polyomavirus test positive 
10070355 
Broad 
A 
Bladder candidiasis 
10058523 
Broad 
A 
Blood beta-D-glucan abnormal 
10051795 
Broad 
A 
Blood beta-D-glucan increased 
10051793 
Broad 
A 
Blood beta-D-glucan positive 
10083491 
Broad 
A 
Blood culture positive 
10005488 
Broad 
A 
Body tinea 
10005913 
Broad 
A 
Botryomycosis 
10072055 
Broad 
A 
Bronchitis haemophilus 
10006460 
Broad 
A 
Bronchopulmonary aspergillosis allergic 
10006474 
Broad 
A 
Brucella sepsis 
10054210 
Broad 
A 
Brucella test positive 
10070021 
Broad 
A 
Bullous impetigo 
10006563 
Broad 
A 
Burkholderia cepacia complex infection 
10069657 
Broad 
A 
Burkholderia infection 
10073031 
Broad 
A 
Burkholderia mallei infection 
10069747 
Broad 
A 
Burkholderia test positive 
10069960 
Broad 
A 
Bursitis infective staphylococcal 
10048894 
Broad 
A 
Buschke-Lowenstein's tumour 
10059427 
Broad 
A 
Campylobacter sepsis 
10070681 
Broad 
A 
Campylobacter test positive 
10070025 
Broad 
A 
Candida cervicitis 
10071209 
Broad 
A 
Candida infection 
10074170 
Broad 
A 
Candida test positive 
10070451 
Broad 
A 
Capnocytophaga test positive 
10070026 
Broad 
A 
Cat scratch disease 
10007729 
Broad 
A 
Catheter bacteraemia 
10062957 
Broad 
A 
Cellulitis enterococcal 
10007904 
Broad 
A 
Cellulitis pasteurella 
10007919 
Broad 
A 
Cellulitis staphylococcal 
10007921 
Broad 
A 
Cellulitis streptococcal 
10007922 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 72 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
A 
Cerebral malaria 
10063094 
Broad 
A 
Cervicitis human papilloma virus 
10051800 
Broad 
A 
Cervicitis streptococcal 
10067236 
Broad 
A 
Cervix warts 
10063815 
Broad 
A 
Chancroid 
10008392 
Broad 
A 
Chlamydia test positive 
10070159 
Broad 
A 
Choriomeningitis lymphocytic 
10008761 
Broad 
A 
Choroid tubercles 
10008779 
Broad 
A 
Chronic active Epstein-Barr virus infection 
10082848 
Broad 
A 
Chronic hepatitis B 
10008910 
Broad 
A 
Chronic hepatitis C 
10008912 
Broad 
A 
Citrobacter infection 
10051904 
Broad 
A 
Citrobacter sepsis 
10054213 
Broad 
A 
Citrobacter test positive 
10069963 
Broad 
A 
Clostridial sepsis 
10078496 
Broad 
A 
Clostridium bacteraemia 
10058852 
Broad 
A 
Clostridium colitis 
10058305 
Broad 
A 
Clostridium difficile colitis 
10009657 
Broad 
A 
Clostridium difficile infection 
10054236 
Broad 
A 
Clostridium test positive 
10070027 
Broad 
A 
Coronavirus infection 
10051905 
Broad 
A 
Coronavirus test positive 
10070255 
Broad 
A 
Corynebacterium infection 
10061092 
Broad 
A 
Corynebacterium sepsis 
10057767 
Broad 
A 
Corynebacterium test positive 
10070028 
Broad 
A 
Coxiella infection 
10053187 
Broad 
A 
Coxiella test positive 
10070194 
Broad 
A 
Coxsackie viral disease of the newborn 
10011260 
Broad 
A 
Creutzfeldt-Jakob disease 
10011384 
Broad 
A 
Cronobacter bacteraemia 
10069854 
Broad 
A 
Cronobacter infection 
10069855 
Broad 
A 
Cronobacter necrotising enterocolitis 
10069939 
Broad 
A 
Cryptococcus test positive 
10070455 
Broad 
A 
CSF measles antibody positive 
10061795 
Broad 
A 
Cutaneous anthrax 
10011660 
Broad 
A 
Cutaneous mucormycosis 
10082722 
Broad 
A 
Cutaneous sporotrichosis 
10011676 
Broad 
A 
Cyclosporidium infection 
10061802 
Broad 
A 
Cystitis escherichia 
10011790 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 73 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
A 
Cystitis klebsiella 
10011797 
Broad 
A 
Cystitis pseudomonal 
10011799 
Broad 
A 
Cytomegalovirus immunisation 
10072247 
Broad 
A 
Cytomegalovirus test positive 
10051620 
Broad 
A 
Delftia acidovorans infection 
10081339 
Broad 
A 
Deltaretrovirus test positive 
10070346 
Broad 
A 
Dengue fever 
10012310 
Broad 
A 
Device related sepsis 
10069802 
Broad 
A 
Ear infection fungal 
10068630 
Broad 
A 
Eczema herpeticum 
10014197 
Broad 
A 
Encephalitis australia 
10014583 
Broad 
A 
Encephalitis california 
10014584 
Broad 
A 
Encephalitis eastern equine 
10014587 
Broad 
A 
Encephalitis enteroviral 
10063946 
Broad 
A 
Encephalitis influenzal 
10058094 
Broad 
A 
Encephalitis Japanese B 
10014596 
Broad 
A 
Encephalitis meningococcal 
10014597 
Broad 
A 
Encephalitis mumps 
10014598 
Broad 
A 
Encephalitis post varicella 
10014603 
Broad 
A 
Encephalitis protozoal 
10061118 
Broad 
A 
Encephalitis rickettsial 
10061119 
Broad 
A 
Encephalitis venezuelan equine 
10014611 
Broad 
A 
Encephalitis viral 
10014612 
Broad 
A 
Encephalitis western equine 
10014614 
Broad 
A 
Encephalomyelitis rubella 
10014622 
Broad 
A 
Endocarditis enterococcal 
10014671 
Broad 
A 
Endocarditis haemophilus 
10014675 
Broad 
A 
Endocarditis pseudomonal 
10067336 
Broad 
A 
Endocarditis staphylococcal 
10014684 
Broad 
A 
Endocarditis viral 
10061837 
Broad 
A 
Enterobacter bacteraemia 
10058857 
Broad 
A 
Enterobacter infection 
10051910 
Broad 
A 
Enterobacter pneumonia 
10054218 
Broad 
A 
Enterobacter sepsis 
10054219 
Broad 
A 
Enterobacter test positive 
10070023 
Broad 
A 
Enterobacter tracheobronchitis 
10054220 
Broad 
A 
Enterococcal bacteraemia 
10014885 
Broad 
A 
Enterococcal infection 
10061124 
Broad 
A 
Enterococcal sepsis 
10054221 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 74 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
A 
Enterococcus test positive 
10070024 
Broad 
A 
Enterocolitis viral 
10061841 
Broad 
A 
Enterovirus test positive 
10070386 
Broad 
A 
Epiglottitis haemophilus 
10015031 
Broad 
A 
Epstein-Barr viraemia 
10065110 
Broad 
A 
Epstein-Barr virus antibody positive 
10052324 
Broad 
A 
Epstein-Barr virus antigen positive 
10052363 
Broad 
A 
Epstein-Barr virus associated lymphoma 
10071441 
Broad 
A 
Epstein-Barr virus infection 
10015108 
Broad 
A 
Epstein-Barr virus test positive 
10064545 
Broad 
A 
Erysipelas 
10015145 
Broad 
A 
Erythema induratum 
10015213 
Broad 
A 
Escherichia bacteraemia 
10054258 
Broad 
A 
Escherichia infection 
10061126 
Broad 
A 
Escherichia sepsis 
10015296 
Broad 
A 
Escherichia test positive 
10070090 
Broad 
A 
Escherichia urinary tract infection 
10052238 
Broad 
A 
Escherichia vaginitis 
10054259 
Broad 
A 
Exanthema subitum 
10015586 
Broad 
A 
Exserohilum test positive 
10073243 
Broad 
A 
Eye infection fungal 
10015933 
Broad 
A 
Eye infection staphylococcal 
10015937 
Broad 
A 
Eye infection viral 
10015940 
Broad 
A 
Flavivirus test positive 
10070211 
Broad 
A 
Flavobacterium test positive 
10070007 
Broad 
A 
Fungal infection 
10017533 
Broad 
A 
Fungal paronychia 
10017540 
Broad 
A 
Fungal test positive 
10059423 
Broad 
A 
Gastric ulcer helicobacter 
10051348 
Broad 
A 
Gastroenteritis adenovirus 
10017889 
Broad 
A 
Gastroenteritis aeromonas 
10017891 
Broad 
A 
Gastroenteritis Escherichia coli 
10017903 
Broad 
A 
Gastroenteritis pseudomonas 
10017911 
Broad 
A 
Gastroenteritis salmonella 
10017914 
Broad 
A 
Gastroenteritis staphylococcal 
10017916 
Broad 
A 
Gastroenteritis vibrio 
10017917 
Broad 
A 
Gastrointestinal anthrax 
10017931 
Broad 
A 
Gastrointestinal candidiasis 
10017938 
Broad 
A 
Genital candidiasis 
10018143 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 75 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
A 
Genital herpes 
10018150 
Broad 
A 
Genital herpes simplex 
10073931 
Broad 
A 
Genital herpes zoster 
10072210 
Broad 
A 
Genital infection fungal 
10061180 
Broad 
A 
Geotrichum infection 
10056660 
Broad 
A 
Group B streptococcus neonatal sepsis 
10053588 
Broad 
A 
H1N1 influenza 
10069767 
Broad 
A 
Haemophilus bacteraemia 
10058922 
Broad 
A 
Haemophilus infection 
10061190 
Broad 
A 
Haemophilus sepsis 
10058875 
Broad 
A 
Haemophilus test positive 
10070100 
Broad 
A 
Helicobacter gastritis 
10054272 
Broad 
A 
Helicobacter infection 
10054263 
Broad 
A 
Helicobacter sepsis 
10054264 
Broad 
A 
Helicobacter test positive 
10070101 
Broad 
A 
Hepatitis A antibody abnormal 
10019722 
Broad 
A 
Hepatitis A antibody positive 
10019725 
Broad 
A 
Hepatitis A antigen positive 
10058751 
Broad 
A 
Hepatitis A virus test positive 
10070216 
Broad 
A 
Hepatitis B 
10019731 
Broad 
A 
Hepatitis B antibody abnormal 
10019733 
Broad 
A 
Hepatitis B antibody positive 
10019736 
Broad 
A 
Hepatitis B antigen positive 
10063411 
Broad 
A 
Hepatitis B core antibody positive 
10071344 
Broad 
A 
Hepatitis B core antigen positive 
10052328 
Broad 
A 
Hepatitis B DNA assay positive 
10060047 
Broad 
A 
Hepatitis B DNA increased 
10068379 
Broad 
A 
Hepatitis B e antibody positive 
10071348 
Broad 
A 
Hepatitis B e antigen positive 
10052329 
Broad 
A 
Hepatitis B surface antibody positive 
10071346 
Broad 
A 
Hepatitis B surface antigen positive 
10019742 
Broad 
A 
Hepatitis B virus test positive 
10070217 
Broad 
A 
Hepatitis C 
10019744 
Broad 
A 
Hepatitis C antibody positive 
10019747 
Broad 
A 
Hepatitis C core antibody positive 
10077052 
Broad 
A 
Hepatitis C RNA increased 
10068377 
Broad 
A 
Hepatitis C RNA positive 
10019750 
Broad 
A 
Hepatitis C virus test positive 
10070218 
Broad 
A 
Hepatitis D 
10019762 


PAREXEL International 
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CONFIDENTIAL 
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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
A 
Hepatitis D antibody positive 
10059528 
Broad 
A 
Hepatitis D antigen positive 
10058436 
Broad 
A 
Hepatitis D RNA positive 
10059540 
Broad 
A 
Hepatitis D virus test positive 
10070626 
Broad 
A 
Hepatitis E antibody positive 
10057985 
Broad 
A 
Hepatitis E antigen positive 
10060049 
Broad 
A 
Hepatitis E virus test positive 
10070220 
Broad 
A 
Hepatitis infectious mononucleosis 
10019781 
Broad 
A 
Hepatitis non-A non-B 
10019786 
Broad 
A 
Hepatitis non-A non-B non-C 
10019787 
Broad 
A 
Hepatitis syphilitic 
10019794 
Broad 
A 
Hepatitis toxoplasmal 
10019798 
Broad 
A 
Hepatitis viral test positive 
10072748 
Broad 
A 
Herpes dermatitis 
10062639 
Broad 
A 
Herpes gestationis 
10019939 
Broad 
A 
Herpes simplex 
10019948 
Broad 
A 
Herpes simplex test positive 
10077969 
Broad 
A 
Herpes simplex virus conjunctivitis neonatal 
10049458 
Broad 
A 
Herpes virus infection 
10019973 
Broad 
A 
Herpes zoster 
10019974 
Broad 
A 
Human anaplasmosis 
10071038 
Broad 
A 
Human ehrlichiosis 
10020429 
Broad 
A 
Human herpes virus 6 serology positive 
10060827 
Broad 
A 
Human herpes virus 8 test positive 
10071210 
Broad 
A 
Human herpesvirus 6 infection 
10020431 
Broad 
A 
Human herpesvirus 7 infection 
10063571 
Broad 
A 
Human metapneumovirus test positive 
10072859 
Broad 
A 
Human papilloma virus test positive 
10064328 
Broad 
A 
Human polyomavirus infection 
10057366 
Broad 
A 
Immune reconstitution inflammatory syndrome 
10065042 
Broad 
A 
Infectious thyroiditis 
10071250 
Broad 
A 
Infective aneurysm 
10058017 
Broad 
A 
Influenza 
10022000 
Broad 
A 
Influenza A virus test positive 
10070215 
Broad 
A 
Influenza B virus test positive 
10070208 
Broad 
A 
Influenza C virus test positive 
10070209 
Broad 
A 
Influenza virus test positive 
10070717 
Broad 
A 
Interferon gamma release assay positive 
10072866 
Broad 
A 
JC polyomavirus test positive 
10070356 


PAREXEL International 
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CONFIDENTIAL 
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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
A 
Keratitis fungal 
10062353 
Broad 
A 
Keratitis viral 
10062029 
Broad 
A 
Klebsiella bacteraemia 
10058856 
Broad 
A 
Klebsiella infection 
10061259 
Broad 
A 
Klebsiella sepsis 
10054160 
Broad 
A 
Klebsiella test positive 
10070091 
Broad 
A 
Lactobacillus infection 
10062031 
Broad 
A 
Legionella infection 
10061266 
Broad 
A 
Legionella test positive 
10070092 
Broad 
A 
Leishmaniasis 
10024198 
Broad 
A 
Leptotrichia infection 
10070981 
Broad 
A 
Leuconostoc infection 
10070982 
Broad 
A 
Listeria test positive 
10070094 
Broad 
A 
Lower respiratory tract infection viral 
10065188 
Broad 
A 
Malaria 
10025487 
Broad 
A 
Malaria antibody test positive 
10070881 
Broad 
A 
Malarial myocarditis 
10054123 
Broad 
A 
Meningitis cronobacter 
10069856 
Broad 
A 
Meningitis enterococcal 
10027232 
Broad 
A 
Meningitis haemophilus 
10027241 
Broad 
A 
Meningitis meningococcal 
10027249 
Broad 
A 
Meningitis pneumococcal 
10027253 
Broad 
A 
Meningitis salmonella 
10027254 
Broad 
A 
Meningitis staphylococcal 
10027255 
Broad 
A 
Meningitis streptococcal 
10027256 
Broad 
A 
Meningitis trypanosomal 
10027258 
Broad 
A 
Meningoencephalitis herpes simplex neonatal 
10053586 
Broad 
A 
Meningoencephalitis viral 
10074672 
Broad 
A 
Metapneumovirus infection 
10066226 
Broad 
A 
Micrococcal sepsis 
10054162 
Broad 
A 
Micrococcus infection 
10054120 
Broad 
A 
Micrococcus test positive 
10070001 
Broad 
A 
Microsporum infection 
10054121 
Broad 
A 
Middle East respiratory syndrome 
10075271 
Broad 
A 
Morganella infection 
10054876 
Broad 
A 
Mucocutaneous candidiasis 
10028080 
Broad 
A 
Mumps antibody test positive 
10059644 
Broad 
A 
Murray Valley encephalitis 
10053981 
Broad 
A 
Mycobacterium leprae test positive 
10070324 


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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
A 
Mycobacterium test positive 
10070323 
Broad 
A 
Mycobacterium tuberculosis complex test positive 
10070325 
Broad 
A 
Mycotic corneal ulcer 
10028518 
Broad 
A 
Mycotoxicosis 
10028520 
Broad 
A 
Myocarditis septic 
10028615 
Broad 
A 
Nail candida 
10028688 
Broad 
A 
Nasal candidiasis 
10050345 
Broad 
A 
Nasal herpes 
10074936 
Broad 
A 
Necrotising fasciitis staphylococcal 
10028887 
Broad 
A 
Necrotising fasciitis streptococcal 
10028888 
Broad 
A 
Neisseria test positive 
10070096 
Broad 
A 
Neonatal candida infection 
10028924 
Broad 
A 
Neonatal infective mastitis 
10028950 
Broad 
A 
Neonatal mucocutaneous herpes simplex 
10053587 
Broad 
A 
Neutropenic infection 
10059482 
Broad 
A 
Neutropenic sepsis 
10049151 
Broad 
A 
Nocardia test positive 
10070131 
Broad 
A 
Onychomycosis 
10030338 
Broad 
A 
Oral candidiasis 
10030963 
Broad 
A 
Oral fungal infection 
10061324 
Broad 
A 
Oral hairy leukoplakia 
10030979 
Broad 
A 
Oral herpes 
10067152 
Broad 
A 
Organic dust toxic syndrome 
10075078 
Broad 
A 
Oropharyngeal candidiasis 
10050346 
Broad 
A 
Oropharyngitis fungal 
10061891 
Broad 
A 
Orthopox virus infection 
10069586 
Broad 
A 
Orthopoxvirus test positive 
10070349 
Broad 
A 
Osteomyelitis salmonella 
10031262 
Broad 
A 
Otitis externa candida 
10033076 
Broad 
A 
Otitis media haemophilus 
10067322 
Broad 
A 
Paediatric autoimmune neuropsychiatric disorders 
associated with streptococcal infection 
10072147 
Broad 
A 
Pantoea agglomerans infection 
10070020 
Broad 
A 
Pantoea agglomerans test positive 
10070019 
Broad 
A 
Papilloma viral infection 
10061331 
Broad 
A 
Parainfluenzae viral laryngotracheobronchitis 
10033797 
Broad 
A 
Parainfluenzae virus infection 
10061907 
Broad 
A 
Parasitic encephalitis 
10069588 
Broad 
A 
Parechovirus infection 
10071449 


PAREXEL International 
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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
A 
Pasteurella test positive 
10070132 
Broad 
A 
Peliosis hepatis 
10034229 
Broad 
A 
Pelvic sepsis 
10059070 
Broad 
A 
Penile wart 
10034325 
Broad 
A 
Peptostreptococcus infection 
10054124 
Broad 
A 
Peptostreptococcus test positive 
10070003 
Broad 
A 
Perianal streptococcal infection 
10068921 
Broad 
A 
Perinatal HBV infection 
10075233 
Broad 
A 
Periporitis staphylogenes 
10064163 
Broad 
A 
Peritonitis pneumococcal 
10034681 
Broad 
A 
Pharyngeal abscess 
10067781 
Broad 
A 
Pharyngoconjunctival fever of children 
10034843 
Broad 
A 
Plasmodium falciparum infection 
10035500 
Broad 
A 
Plasmodium malariae infection 
10035501 
Broad 
A 
Plasmodium ovale infection 
10035502 
Broad 
A 
Plasmodium vivax infection 
10035503 
Broad 
A 
Pneumococcal bacteraemia 
10058859 
Broad 
A 
Pneumococcal infection 
10061353 
Broad 
A 
Pneumococcal sepsis 
10054047 
Broad 
A 
Pneumocystis test positive 
10070454 
Broad 
A 
Pneumonia adenoviral 
10035665 
Broad 
A 
Pneumonia anthrax 
10035667 
Broad 
A 
Pneumonia escherichia 
10035699 
Broad 
A 
Pneumonia haemophilus 
10035702 
Broad 
A 
Pneumonia influenzal 
10035714 
Broad 
A 
Pneumonia klebsiella 
10035717 
Broad 
A 
Pneumonia parainfluenzae viral 
10035727 
Broad 
A 
Pneumonia pneumococcal 
10035728 
Broad 
A 
Pneumonia pseudomonal 
10035731 
Broad 
A 
Pneumonia respiratory syncytial viral 
10035732 
Broad 
A 
Pneumonia salmonella 
10035733 
Broad 
A 
Pneumonia staphylococcal 
10035734 
Broad 
A 
Pneumonia streptococcal 
10035735 
Broad 
A 
Polyomavirus test positive 
10070342 
Broad 
A 
Pontiac fever 
10054161 
Broad 
A 
Porphyromonas infection 
10061914 
Broad 
A 
Porphyromonas test positive 
10070133 
Broad 
A 
Post streptococcal glomerulonephritis 
10036303 
Broad 
A 
Post transplant lymphoproliferative disorder 
10051358 


PAREXEL International 
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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
A 
Presumed ocular histoplasmosis syndrome 
10063664 
Broad 
A 
Prion agent test positive 
10070343 
Broad 
A 
Proctitis fungal 
10063201 
Broad 
A 
Proctitis monilial 
10036781 
Broad 
A 
Prostatitis Escherichia coli 
10067320 
Broad 
A 
Pseudomonal bacteraemia 
10058923 
Broad 
A 
Pseudomonal sepsis 
10058877 
Broad 
A 
Pseudomonas bronchitis 
10067024 
Broad 
A 
Pseudomonas infection 
10061471 
Broad 
A 
Pseudomonas peritonitis 
10082669 
Broad 
A 
Pseudomonas test positive 
10070135 
Broad 
A 
Pulmonary sepsis 
10051739 
Broad 
A 
Pyoderma streptococcal 
10037637 
Broad 
A 
Pythium insidiosum infection 
10074264 
Broad 
A 
Q fever 
10037688 
Broad 
A 
Raoultella ornithinolytica infection 
10070087 
Broad 
A 
Respiratory moniliasis 
10038705 
Broad 
A 
Respiratory syncytial virus bronchiolitis 
10038718 
Broad 
A 
Respiratory syncytial virus bronchitis 
10069811 
Broad 
A 
Respiratory syncytial virus infection 
10061603 
Broad 
A 
Respiratory syncytial virus test positive 
10068563 
Broad 
A 
Retroviral rebound syndrome 
10065989 
Broad 
A 
Rhodococcus test positive 
10070005 
Broad 
A 
Roseolovirus test positive 
10070213 
Broad 
A 
Rubella antibody positive 
10039258 
Broad 
A 
Salmonella bacteraemia 
10058924 
Broad 
A 
Salmonella sepsis 
10058878 
Broad 
A 
Salmonella test positive 
10070127 
Broad 
A 
Salmonellosis 
10039447 
Broad 
A 
Scarlet fever 
10039587 
Broad 
A 
Sepsis 
10040047 
Broad 
A 
Sepsis neonatal 
10040049 
Broad 
A 
Sepsis pasteurella 
10040051 
Broad 
A 
Sepsis syndrome 
10053879 
Broad 
A 
Septic arthritis haemophilus 
10040059 
Broad 
A 
Septic arthritis streptobacillus 
10040064 
Broad 
A 
Septic arthritis streptococcal 
10067323 
Broad 
A 
Septic coagulopathy 
10083159 
Broad 
A 
Septic embolus 
10040067 


PAREXEL International 
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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
A 
Septic necrosis 
10052762 
Broad 
A 
Septic phlebitis 
10056518 
Broad 
A 
Septic pulmonary embolism 
10083093 
Broad 
A 
Septic shock 
10040070 
Broad 
A 
Serratia bacteraemia 
10058921 
Broad 
A 
Serratia infection 
10061512 
Broad 
A 
Serratia sepsis 
10058879 
Broad 
A 
Serratia test positive 
10070128 
Broad 
A 
Severe acute respiratory syndrome 
10061982 
Broad 
A 
Severe invasive streptococcal infection 
10072839 
Broad 
A 
Shewanella algae bacteraemia 
10076437 
Broad 
A 
Shigella infection 
10054178 
Broad 
A 
Shigella test positive 
10070129 
Broad 
A 
Silicotuberculosis 
10068876 
Broad 
A 
Skin candida 
10054152 
Broad 
A 
Sporotrichosis 
10041736 
Broad 
A 
Spotted fever rickettsia test positive 
10070196 
Broad 
A 
St. Louis encephalitis 
10041896 
Broad 
A 
Staphylococcal abscess 
10041917 
Broad 
A 
Staphylococcal bacteraemia 
10051017 
Broad 
A 
Staphylococcal impetigo 
10041923 
Broad 
A 
Staphylococcal infection 
10058080 
Broad 
A 
Staphylococcal mediastinitis 
10066410 
Broad 
A 
Staphylococcal osteomyelitis 
10064250 
Broad 
A 
Staphylococcal scalded skin syndrome 
10041929 
Broad 
A 
Staphylococcal sepsis 
10056430 
Broad 
A 
Staphylococcal skin infection 
10066409 
Broad 
A 
Staphylococcal toxaemia 
10041932 
Broad 
A 
Staphylococcus test positive 
10070052 
Broad 
A 
Stenotrophomonas test positive 
10070006 
Broad 
A 
Stoma site candida 
10059052 
Broad 
A 
Stomatococcal infection 
10068385 
Broad 
A 
Stomatococcus test positive 
10070008 
Broad 
A 
Streptobacillary fever 
10042175 
Broad 
A 
Streptobacillus infection 
10062118 
Broad 
A 
Streptobacillus test positive 
10070054 
Broad 
A 
Streptococcal abscess 
10042176 
Broad 
A 
Streptococcal bacteraemia 
10051018 
Broad 
A 
Streptococcal endocarditis 
10073742 


PAREXEL International 
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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
A 
Streptococcal impetigo 
10042178 
Broad 
A 
Streptococcal infection 
10061372 
Broad 
A 
Streptococcal sepsis 
10048960 
Broad 
A 
Streptococcal urinary tract infection 
10070300 
Broad 
A 
Streptococcus test positive 
10070055 
Broad 
A 
Streptokinase antibody increased 
10053797 
Broad 
A 
Strongyloidiasis 
10042254 
Broad 
A 
Subacute sclerosing panencephalitis 
10042297 
Broad 
A 
Syphilis 
10062120 
Broad 
A 
Systemic inflammatory response syndrome 
10051379 
Broad 
A 
Thrombophlebitis septic 
10043593 
Broad 
A 
Tick-borne viral encephalitis 
10043847 
Broad 
A 
Torulopsis infection 
10053188 
Broad 
A 
Toxic shock syndrome staphylococcal 
10044250 
Broad 
A 
Toxic shock syndrome streptococcal 
10044251 
Broad 
A 
Toxoplasma serology positive 
10056278 
Broad 
A 
Toxoplasmosis prophylaxis 
10066653 
Broad 
A 
Treponema test positive 
10070158 
Broad 
A 
Trichophytic granuloma 
10053419 
Broad 
A 
Trichosporon infection 
10053461 
Broad 
A 
Trypanosoma serology positive 
10063055 
Broad 
A 
Trypanosomiasis 
10044707 
Broad 
A 
Tuberculid 
10044725 
Broad 
A 
Tuberculin test false negative 
10074840 
Broad 
A 
Tuberculin test false positive 
10064057 
Broad 
A 
Tuberculin test positive 
10044728 
Broad 
A 
Typhus rickettsia test positive 
10070193 
Broad 
A 
Urinary tract candidiasis 
10083162 
Broad 
A 
Urinary tract infection enterococcal 
10046572 
Broad 
A 
Urinary tract infection pseudomonal 
10062279 
Broad 
A 
Urinary tract infection staphylococcal 
10062280 
Broad 
A 
Urogenital infection fungal 
10065582 
Broad 
A 
Urosepsis 
10048709 
Broad 
A 
Variant Creutzfeldt-Jakob disease 
10064199 
Broad 
A 
Varicella 
10046980 
Broad 
A 
Varicella post vaccine 
10063522 
Broad 
A 
Varicella virus test positive 
10070214 
Broad 
A 
Varicella zoster virus infection 
10075611 
Broad 
A 
Vibrio test positive 
10070161 


PAREXEL International 
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K.inevant 
KIN-1901-2001 
 
Statistical Analysis Plan 
Broad 
A 
Viraemia 
10058874 
Broad 
A 
Viral myelitis 
10071763 
Broad 
A 
Viral myocarditis 
10047470 
Broad 
A 
Viral oesophagi.tis 
10060190 
Broad 
A 
Viral pericarditis 
10047472 
Broad 
A 
Viral sepsis 
10071362 
Broad 
A 
Viral test positive 
10059424 
Broad 
A 
Viral uveitis 
10071005 
Broad 
A 
Vulvovaginal candidiasis 
10047784 
Broad 
A 
Vulvovaginal human papilloma vims infection 
10066416 
Broad 
A 
West Nile viral infection 
10057293 
Broad 
A 
West Nile vims test positive 
10068812 
Broad 
A 
Wound infection fungal 
10065242 
Broad 
A 
Wound infection pseudomonas 
10059444 
Broad 
A 
Wound infection staphylococcal 
10059442 
Broad 
A 
Wound sepsis 
10058041 
Broad 
A 
Yersinia.sepsis 
10072902 
Broad 
A 
Yersinia test positive 
10070162 
 
 
 
 
Haematopoietic cytopenias (SMQ) 
Scope 
Group 
PT 
PT Code 
Haematopoietic cytopenias affecting more than one type of blood cell (SMQ) 
NaITow 
A 
Aplastic anaemia 
10002967 
NaITow 
A 
Autoimmune aolastic anaemia 
10071576 
NaITow 
A 
Bicytopenia 
10058956 
NaITow 
A 
Bone maiTow failure 
10065553 
NaITow 
A 
Cytopenia 
10066274 
NaITow 
A 
Febrile bone mairnw aplasia 
10053213 
NaITow 
A 
Full blood count decreased 
10017413 
NaITow 
A 
Gelatinous transfonnation of the bone marrow 
10078097 
NaITow 
A 
Immune-mediated pancytopenia 
10083004 
NaITow 
A 
Pancytopenia 
10033661 
NaITow 
A 
Panmyelopathy 
10050026 
Broad 
A 
Aspiration bone maITow abnonnal 
10003506 
Broad 
A 
Biopsy bone maiTow abno1mal 
10004738 
Broad 
A 
Blood count abno1mal 
10064198 
Broad 
A 
Blood disorder 
10061590 
Broad 
A 
Bone maiTow disorder 
10061729 


PAREXEL International 
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K.inevant 
KIN-1901-2001 
 
Statistical Analysis Plan 
Broad 
A 
Bone maiTow infiltrntion 
10075173 
Broad 
A 
Bone maiTow mvelo!Zram abnonnal 
10057528 
Broad 
A 
Bone maiTow necrosis 
10058822 
Broad 
A 
Bone maiTow toxicity 
10051779 
Broad 
A 
Congenital aplastic anaemia 
10053138 
Broad 
A 
Haematotoxicitv 
10061188 
Broad 
A 
Myelodysplastic syndrome 
10028533 
Broad 
A 
Myelodysplastic syndrome trnnsfonnation 
10067387 
Broad 
A 
Mvelofibrosis 
10028537 
Broad 
A 
Mveloid metaplasia 
10028561 
Broad 
A 
Plasmablast count decreased 
10058774 
Broad 
A 
Primary myelofibrosis 
10077161 
Broad 
A 
Scan bone maITow abnonnal 
10053504 
Haematopoietic erythropenia (SMQ) 
NaITow 
A 
Anaemia macrocytic 
10002064 
NaITow 
A 
Aplasia pure red cell 
10002965 
NaITow 
A 
Aplastic anaemia 
10002967 
NaITow 
A 
Ervthroblast count decreased 
10058505 
NaITow 
A 
Erythroid maturation aITest 
10015279 
NaITow 
A 
Erythropenia 
10015287 
NaITow 
A 
Hypoplastic anaemia 
10021074 
NaITow 
A 
Microcvtic anaemia 
10027538 
NaITow 
A 
Proerythroblast count decreased 
10060229 
NaITow 
A 
Red blood cell count decreased 
10038153 
NaITow 
A 
Reticulocvte count decreased 
10038790 
NaITow 
A 
Reticulocytopenia 
10038795 
Broad 
A 
Anaemia 
10002034 
Broad 
A 
Anaemia neonatal 
10002068 
Broad 
A 
Ervthroblast count abnormal 
10058508 
Broad 
A 
Ervthropoiesis abnonnal 
10049467 
Broad 
A 
Foetal anaemia 
10077577 
Broad 
A 
Haematocrit abnonnal 
10049221 
Broad 
A 
Haematocrit decreased 
10018838 
Broad 
A 
Haemo1Zlobin abnonnal 
10018879 
Broad 
A 
Haemoglobin decreased 
10018884 
Broad 
A 
Leukoerythroblastic anaemia 
10053199 
Broad 
A 
Nonnochromic anaemia 
10029782 
Broad 
A 
Nonnochromic n01mocvtic anaemia 
10029783 
Broad 
A 
Nonnocytic anaemia 
10029784 


PAREXEL International 
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K.inevant 
KIN-1901-2001 
 
Statistical Analysis Plan 
Broad 
A 
Proervthroblast count abno1mal 
10060227 
Broad 
A 
Red blood cell count abno1mal 
10038151 
Broad 
A 
Reticulocyte count abnormal 
10038788 
Broad 
A 
Reticulocyte percentage decreased 
10059921 
Haematopoietic leukopenia (SMQ) 
NaITow 
A 
A1zranulocvtosis 
10001507 
NaITow 
A 
Band neutrophil count decreased 
10057950 
NaITow 
A 
Band neutrophil percentage decreased 
10059130 
NaITow 
A 
Basophil count decreased 
10004167 
NaITow 
A 
Basophilopenia 
10075813 
NaITow 
A 
B-lymphocyte count decreased 
10051313 
NaITow 
A 
Cyclic neutropenia 
10053176 
NaITow 
A 
Eosinopenia 
10014940 
NaITow 
A 
Eosinophil count decreased 
10014943 
NaITow 
A 
Febrile neutropenia 
10016288 
NaITow 
A 
Granulocyte count decreased 
10018681 
NaITow 
A 
Granulocvtes maturation anest 
10050443 
NaITow 
A 
Granulocytopenia 
10018687 
NaITow 
A 
Idiopathic neutropenia 
10051645 
NaITow 
A 
Leukopenia 
10024384 
NaITow 
A 
Lymphocvte count decreased 
10025256 
NaITow 
A 
Lvmohooenia 
10025327 
NaITow 
A 
Metamyelocyte count decreased 
10050984 
NaITow 
A 
Monoblast count decreased 
10058772 
NaITow 
A 
Monocvte count decreased 
10027878 
NaITow 
A 
Monocytopenia 
10027905 
NaITow 
A 
Myeloblast count decreased 
10050961 
NaITow 
A 
Myelocyte count decreased 
10050986 
NaITow 
A 
Neutropenia 
10029354 
NaITow 
A 
Neutropenic infection 
10059482 
NaITow 
A 
Neutropenic sepsis 
10049151 
NaITow 
A 
Neutrophil count decreased 
10029366 
NaITow 
A 
Promvelocvte count decreased 
10050987 
NaITow 
A 
Pure white cell aolasia 
10068043 
NaITow 
A 
Radiation leukopenia 
10067354 
NaITow 
A 
T-lymphocyte count decreased 
10051318 
NaITow 
A 
White blood cell count decreased 
10047942 
Broad 
A 
Basophil count abno1mal 
10060978 
Broad 
A 
Basophil percentage decreased 
10052219 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 86 of 122 
 
 
K.inevant 
KIN-1901-2001 
 
Statistical Analysis Plan 
Broad 
A 
B-lvmphocvte abno1malities 
10053775 
Broad 
A 
B-lvmphocvte count abnonnal 
10078589 
Broad 
A 
Differential white blood cell count abnonnal 
10012785 
Broad 
A 
Eosinophil count abno1mal 
10061125 
Broad 
A 
Eosinophil percentage decreased 
10052221 
Broad 
A 
Full blood count abnonnal 
10017412 
Broad 
A 
Granulocytes abno1mal 
10018685 
Broad 
A 
Granulocytopenia neonatal 
10018688 
Broad 
A 
Leukopenia neonatal 
10050504 
Broad 
A 
Lymphocvte count abnormal 
10025252 
Broad 
A 
Lymphocyte percentage abno1mal 
10063337 
Broad 
A 
Lymphocyte percentage decreased 
10052231 
Broad 
A 
Lymphocytopenia neonatal 
10025279 
Broad 
A 
Monocvte count abno1mal 
10061293 
Broad 
A 
Monocyte percentage decreased 
10052229 
Broad 
A 
Mononuclear cell count decreased 
10082036 
Broad 
A 
Mveloblast percentage decreased 
10052225 
Broad 
A 
Mvelocvte percentage decreased 
10052227 
Broad 
A 
Myeloid maturation aiTest 
10028560 
Broad 
A 
Neutropenia neonatal 
10029358 
Broad 
A 
Neutrophil count abno1mal 
10061313 
Broad 
A 
Neutrophil percentage decreased 
10052223 
Broad 
A 
Plasma cell disorder 
10062081 
Broad 
A 
Plasma cells absent 
10035230 
Broad 
A 
T-lvmphocvte count abno1mal 
10057284 
Broad 
A 
White blood cell analysis abno1mal 
10073323 
Broad 
A 
White blood cell count abno1mal 
10047940 
Broad 
A 
White blood cell disorder 
10061414 
Haematopoietic thrombocytopenia (SMQ) 
NaITow 
A 
Acquired amegakarvocvtic thrombocytopenia 
10076747 
NaITow 
A 
Megakaryocytes decreased 
10027119 
NaITow 
A 
Platelet count decreased 
10035528 
NaITow 
A 
Platelet maturation aiTest 
10035537 
NaITow 
A 
Platelet production decreased 
10035540 
NaITow 
A 
Platelet toxicity 
10059440 
NaITow 
A 
Thrombocytopenia 
10043554 
Broad 
A 
Megakarvocvtes abnonnal 
10027118 
Broad 
A 
Platelet count abno1mal 
10035526 
Broad 
A 
Platelet disorder 
10035532 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 87 of 122 
 
 
K.inevant 
KIN-1901-2001 
 
Statistical Analysis Plan 
Broad 
A 
Plateletcrit abnonnal 
10064785 
Broad 
A 
Plateletcrit decreased 
10064784 
Broad 
A 
Thrombocytopenia neonatal 
10043557 
 
Hypersensitivity (SMQ) 
Scope 
Group 
PT 
PT Code 
NaITow 
A 
Acquired Cl inhibitor deficiency 
10081035 
NaITow 
A 
Acute generalised exanthematous pustulosis 
10048799 
NaITow 
A 
Administrntion related reaction 
10069773 
NaITow 
A 
Administrntion site de1matitis 
10075096 
NaITow 
A 
Administration site eczema 
10075099 
NaITow 
A 
Administration site hypersensitivity 
10075102 
NaITow 
A 
Administration site rash 
10071156 
NaITow 
A 
Administration site recall reaction 
10075964 
NaITow 
A 
Administration site urticaria 
10075109 
NaITow 
A 
Administration site vasculitis 
10075969 
NaITow 
A 
Allergic bronchitis 
10052613 
NaITow 
A 
Allergic colitis 
10059447 
NaITow 
A 
Allergic cough 
10053779 
NaITow 
A 
Allergic cystitis 
10051394 
NaITow 
A 
Allergic eosinophilia 
10075185 
NaITow 
A 
Allergic gastroenteritis 
10075308 
NaITow 
A 
Allergic hepatitis 
10071198 
NaITow 
A 
Allergic keratitis 
10057380 
NaITow 
A 
Allergic oedema 
10060934 
NaITow 
A 
Allergic otitis extema 
10075072 
NaITow 
A 
Allergic otitis media 
10061557 
NaITow 
A 
Allergic pharyngitis 
10050639 
NaITow 
A 
Allergic reaction to excipient 
10078853 
NaITow 
A 
Allergic resoiratory disease 
10063532 
NaITow 
A 
Allergic respiratory symptom 
10063527 
NaITow 
A 
Allergic sinusitis 
10049153 
NaITow 
A 
Allergic stomatitis 
10079554 
NaITow 
A 
Allergic transfusion reaction 
10066173 
NaITow 
A 
Allergy aleit test positive 
10075479 
NaITow 
A 
Allenrv test positive 
10056352 
NaITow 
A 
Allernv to immunoglobulin therapy 
10074079 
NaITow 
A 
Allergy to sur!rical sutures 
10077279 
NaITow 
A 
Allergy to vaccine 
10055048 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 88 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Narrow 
A 
Anal eczema 
10078682 
Narrow 
A 
Anaphylactic reaction 
10002198 
Narrow 
A 
Anaphylactic shock 
10002199 
Narrow 
A 
Anaphylactic transfusion reaction 
10067113 
Narrow 
A 
Anaphylactoid reaction 
10002216 
Narrow 
A 
Anaphylactoid shock 
10063119 
Narrow 
A 
Anaphylaxis treatment 
10002222 
Narrow 
A 
Angioedema 
10002424 
Narrow 
A 
Antiallergic therapy 
10064059 
Narrow 
A 
Antiendomysial antibody positive 
10065514 
Narrow 
A 
Anti-neutrophil cytoplasmic antibody positive 
vasculitis 
10050894 
Narrow 
A 
Application site dermatitis 
10003036 
Narrow 
A 
Application site eczema 
10050099 
Narrow 
A 
Application site hypersensitivity 
10063683 
Narrow 
A 
Application site rash 
10003054 
Narrow 
A 
Application site recall reaction 
10076024 
Narrow 
A 
Application site urticaria 
10050104 
Narrow 
A 
Application site vasculitis 
10076027 
Narrow 
A 
Arthritis allergic 
10061430 
Narrow 
A 
Aspirin-exacerbated respiratory disease 
10075084 
Narrow 
A 
Atopic cough 
10081492 
Narrow 
A 
Atopy 
10003645 
Narrow 
A 
Blepharitis allergic 
10005149 
Narrow 
A 
Blood immunoglobulin E abnormal 
10005589 
Narrow 
A 
Blood immunoglobulin E increased 
10005591 
Narrow 
A 
Bromoderma 
10006404 
Narrow 
A 
Bronchospasm 
10006482 
Narrow 
A 
Bullous haemorrhagic dermatosis 
10083809 
Narrow 
A 
Catheter site dermatitis 
10073992 
Narrow 
A 
Catheter site eczema 
10073995 
Narrow 
A 
Catheter site hypersensitivity 
10073998 
Narrow 
A 
Catheter site rash 
10052271 
Narrow 
A 
Catheter site urticaria 
10052272 
Narrow 
A 
Catheter site vasculitis 
10074014 
Narrow 
A 
Chronic eosinophilic rhinosinusitis 
10071399 
Narrow 
A 
Chronic hyperplastic eosinophilic sinusitis 
10071380 
Narrow 
A 
Circulatory collapse 
10009192 
Narrow 
A 
Circumoral oedema 
10052250 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 89 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Narrow 
A 
Circumoral swelling 
10081703 
Narrow 
A 
Conjunctival oedema 
10010726 
Narrow 
A 
Conjunctivitis allergic 
10010744 
Narrow 
A 
Contact stomatitis 
10067510 
Narrow 
A 
Contrast media allergy 
10066973 
Narrow 
A 
Contrast media reaction 
10010836 
Narrow 
A 
Corneal oedema 
10011033 
Narrow 
A 
Cutaneous vasculitis 
10011686 
Narrow 
A 
Dennie-Morgan fold 
10062918 
Narrow 
A 
Dermatitis 
10012431 
Narrow 
A 
Dermatitis acneiform 
10012432 
Narrow 
A 
Dermatitis allergic 
10012434 
Narrow 
A 
Dermatitis atopic 
10012438 
Narrow 
A 
Dermatitis bullous 
10012441 
Narrow 
A 
Dermatitis contact 
10012442 
Narrow 
A 
Dermatitis exfoliative 
10012455 
Narrow 
A 
Dermatitis exfoliative generalised 
10012456 
Narrow 
A 
Dermatitis herpetiformis 
10012468 
Narrow 
A 
Dermatitis infected 
10012470 
Narrow 
A 
Dermatitis psoriasiform 
10058675 
Narrow 
A 
Device allergy 
10072867 
Narrow 
A 
Dialysis membrane reaction 
10076665 
Narrow 
A 
Distributive shock 
10070559 
Narrow 
A 
Documented hypersensitivity to administered product 10076470 
Narrow 
A 
Drug eruption 
10013687 
Narrow 
A 
Drug hypersensitivity 
10013700 
Narrow 
A 
Drug provocation test 
10074350 
Narrow 
A 
Drug reaction with eosinophilia and systemic 
symptoms 
10073508 
Narrow 
A 
Eczema 
10014184 
Narrow 
A 
Eczema infantile 
10014198 
Narrow 
A 
Eczema nummular 
10014201 
Narrow 
A 
Eczema vaccinatum 
10066042 
Narrow 
A 
Eczema vesicular 
10058681 
Narrow 
A 
Eczema weeping 
10055182 
Narrow 
A 
Encephalitis allergic 
10056387 
Narrow 
A 
Encephalopathy allergic 
10014627 
Narrow 
A 
Eosinophilic granulomatosis with polyangiitis 
10078117 
Narrow 
A 
Epidermal necrosis 
10059284 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 90 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Narrow 
A 
Epidermolysis 
10053177 
Narrow 
A 
Epidermolysis bullosa 
10014989 
Narrow 
A 
Epiglottic oedema 
10015029 
Narrow 
A 
Erythema multiforme 
10015218 
Narrow 
A 
Erythema nodosum 
10015226 
Narrow 
A 
Exfoliative rash 
10064579 
Narrow 
A 
Eye allergy 
10015907 
Narrow 
A 
Eye oedema 
10052139 
Narrow 
A 
Eye swelling 
10015967 
Narrow 
A 
Eyelid oedema 
10015993 
Narrow 
A 
Face oedema 
10016029 
Narrow 
A 
Fixed eruption 
10016741 
Narrow 
A 
Giant papillary conjunctivitis 
10018258 
Narrow 
A 
Gingival oedema 
10049305 
Narrow 
A 
Gingival swelling 
10018291 
Narrow 
A 
Gleich's syndrome 
10066837 
Narrow 
A 
Haemorrhagic urticaria 
10059499 
Narrow 
A 
Hand dermatitis 
10058898 
Narrow 
A 
Henoch-Schonlein purpura 
10019617 
Narrow 
A 
Henoch-Schonlein purpura nephritis 
10069440 
Narrow 
A 
Heparin-induced thrombocytopenia 
10062506 
Narrow 
A 
Hereditary angioedema 
10019860 
Narrow 
A 
Hereditary angioedema with C1 esterase inhibitor 
deficiency 
10080955 
Narrow 
A 
Hypersensitivity 
10020751 
Narrow 
A 
Hypersensitivity myocarditis 
10081004 
Narrow 
A 
Hypersensitivity pneumonitis 
10081988 
Narrow 
A 
Hypersensitivity vasculitis 
10020764 
Narrow 
A 
Idiopathic urticaria 
10021247 
Narrow 
A 
Immediate post-injection reaction 
10067142 
Narrow 
A 
Immune thrombocytopenia 
10083842 
Narrow 
A 
Immune tolerance induction 
10070581 
Narrow 
A 
Implant site dermatitis 
10063855 
Narrow 
A 
Implant site hypersensitivity 
10063858 
Narrow 
A 
Implant site rash 
10063786 
Narrow 
A 
Implant site urticaria 
10063787 
Narrow 
A 
Incision site dermatitis 
10073168 
Narrow 
A 
Incision site rash 
10073411 
Narrow 
A 
Infusion related hypersensitivity reaction 
10082742 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 91 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Narrow 
A 
Infusion related reaction 
10051792 
Narrow 
A 
Infusion site dermatitis 
10065458 
Narrow 
A 
Infusion site eczema 
10074850 
Narrow 
A 
Infusion site hypersensitivity 
10065471 
Narrow 
A 
Infusion site rash 
10059830 
Narrow 
A 
Infusion site recall reaction 
10076085 
Narrow 
A 
Infusion site urticaria 
10065490 
Narrow 
A 
Infusion site vasculitis 
10074851 
Narrow 
A 
Injection related reaction 
10071152 
Narrow 
A 
Injection site dermatitis 
10022056 
Narrow 
A 
Injection site eczema 
10066221 
Narrow 
A 
Injection site hypersensitivity 
10022071 
Narrow 
A 
Injection site rash 
10022094 
Narrow 
A 
Injection site recall reaction 
10066797 
Narrow 
A 
Injection site urticaria 
10022107 
Narrow 
A 
Injection site vasculitis 
10067995 
Narrow 
A 
Instillation site hypersensitivity 
10073612 
Narrow 
A 
Instillation site rash 
10073622 
Narrow 
A 
Instillation site urticaria 
10073627 
Narrow 
A 
Interstitial granulomatous dermatitis 
10067972 
Narrow 
A 
Intestinal angioedema 
10076229 
Narrow 
A 
Iodine allergy 
10052098 
Narrow 
A 
Kaposi's varicelliform eruption 
10051891 
Narrow 
A 
Kounis syndrome 
10069167 
Narrow 
A 
Laryngeal oedema 
10023845 
Narrow 
A 
Laryngitis allergic 
10064866 
Narrow 
A 
Laryngospasm 
10023891 
Narrow 
A 
Laryngotracheal oedema 
10023893 
Narrow 
A 
Limbal swelling 
10070492 
Narrow 
A 
Lip oedema 
10024558 
Narrow 
A 
Lip swelling 
10024570 
Narrow 
A 
Mast cell degranulation present 
10076606 
Narrow 
A 
Medical device site dermatitis 
10075572 
Narrow 
A 
Medical device site eczema 
10075575 
Narrow 
A 
Medical device site hypersensitivity 
10075579 
Narrow 
A 
Medical device site rash 
10075585 
Narrow 
A 
Medical device site recall reaction 
10076140 
Narrow 
A 
Medical device site urticaria 
10075588 
Narrow 
A 
Mouth swelling 
10075203 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 92 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Narrow 
A 
Mucocutaneous rash 
10056671 
Narrow 
A 
Multiple allergies 
10028164 
Narrow 
A 
Nephritis allergic 
10029120 
Narrow 
A 
Nikolsky's sign 
10029415 
Narrow 
A 
Nodular rash 
10075807 
Narrow 
A 
Nutritional supplement allergy 
10084049 
Narrow 
A 
Oculomucocutaneous syndrome 
10030081 
Narrow 
A 
Oculorespiratory syndrome 
10067317 
Narrow 
A 
Oedema mouth 
10030110 
Narrow 
A 
Oral allergy syndrome 
10068355 
Narrow 
A 
Oropharyngeal blistering 
10067950 
Narrow 
A 
Oropharyngeal oedema 
10078783 
Narrow 
A 
Oropharyngeal spasm 
10031111 
Narrow 
A 
Oropharyngeal swelling 
10031118 
Narrow 
A 
Palatal oedema 
10056998 
Narrow 
A 
Palatal swelling 
10074403 
Narrow 
A 
Palisaded neutrophilic granulomatous dermatitis 
10068809 
Narrow 
A 
Palpable purpura 
10056872 
Narrow 
A 
Pathergy reaction 
10074332 
Narrow 
A 
Perioral dermatitis 
10034541 
Narrow 
A 
Periorbital oedema 
10034545 
Narrow 
A 
Periorbital swelling 
10056647 
Narrow 
A 
Pharyngeal oedema 
10034829 
Narrow 
A 
Pharyngeal swelling 
10082270 
Narrow 
A 
Procedural shock 
10080894 
Narrow 
A 
Pruritus allergic 
10063438 
Narrow 
A 
Radioallergosorbent test positive 
10037789 
Narrow 
A 
Rash 
10037844 
Narrow 
A 
Rash erythematous 
10037855 
Narrow 
A 
Rash follicular 
10037857 
Narrow 
A 
Rash macular 
10037867 
Narrow 
A 
Rash maculo-papular 
10037868 
Narrow 
A 
Rash maculovesicular 
10050004 
Narrow 
A 
Rash morbilliform 
10037870 
Narrow 
A 
Rash neonatal 
10037871 
Narrow 
A 
Rash papulosquamous 
10037879 
Narrow 
A 
Rash pruritic 
10037884 
Narrow 
A 
Rash pustular 
10037888 
Narrow 
A 
Rash rubelliform 
10057984 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 93 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Narrow 
A 
Rash scarlatiniform 
10037890 
Narrow 
A 
Rash vesicular 
10037898 
Narrow 
A 
Reaction to azo-dyes 
10037973 
Narrow 
A 
Reaction to colouring 
10037974 
Narrow 
A 
Reaction to excipient 
10079925 
Narrow 
A 
Reaction to food additive 
10037977 
Narrow 
A 
Reaction to preservatives 
10064788 
Narrow 
A 
Red man syndrome 
10038192 
Narrow 
A 
Rhinitis allergic 
10039085 
Narrow 
A 
Scleral oedema 
10057431 
Narrow 
A 
Scleritis allergic 
10051126 
Narrow 
A 
Scrotal dermatitis 
10083260 
Narrow 
A 
Scrotal oedema 
10039755 
Narrow 
A 
Serum sickness 
10040400 
Narrow 
A 
Serum sickness-like reaction 
10040402 
Narrow 
A 
Shock 
10040560 
Narrow 
A 
Shock symptom 
10040581 
Narrow 
A 
SJS-TEN overlap 
10083164 
Narrow 
A 
Skin necrosis 
10040893 
Narrow 
A 
Skin reaction 
10040914 
Narrow 
A 
Skin test positive 
10040934 
Narrow 
A 
Solar urticaria 
10041307 
Narrow 
A 
Solvent sensitivity 
10041316 
Narrow 
A 
Stevens-Johnson syndrome 
10042033 
Narrow 
A 
Stoma site hypersensitivity 
10074509 
Narrow 
A 
Stoma site rash 
10059071 
Narrow 
A 
Swelling face 
10042682 
Narrow 
A 
Swelling of eyelid 
10042690 
Narrow 
A 
Swollen tongue 
10042727 
Narrow 
A 
Symmetrical drug-related intertriginous and flexural 
exanthema 
10078325 
Narrow 
A 
Therapeutic product cross-reactivity 
10079645 
Narrow 
A 
Tongue oedema 
10043967 
Narrow 
A 
Toxic epidermal necrolysis 
10044223 
Narrow 
A 
Toxic skin eruption 
10057970 
Narrow 
A 
Tracheal oedema 
10044296 
Narrow 
A 
Type I hypersensitivity 
10045240 
Narrow 
A 
Type II hypersensitivity 
10054000 
Narrow 
A 
Type III immune complex mediated reaction 
10053614 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 94 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Narrow 
A 
Type IV hypersensitivity reaction 
10053613 
Narrow 
A 
Urticaria 
10046735 
Narrow 
A 
Urticaria cholinergic 
10046740 
Narrow 
A 
Urticaria chronic 
10052568 
Narrow 
A 
Urticaria contact 
10046742 
Narrow 
A 
Urticaria papular 
10046750 
Narrow 
A 
Urticaria physical 
10046751 
Narrow 
A 
Urticaria pigmentosa 
10046752 
Narrow 
A 
Urticaria vesiculosa 
10046755 
Narrow 
A 
Urticarial dermatitis 
10082290 
Narrow 
A 
Urticarial vasculitis 
10048820 
Narrow 
A 
Vaccination site dermatitis 
10069477 
Narrow 
A 
Vaccination site eczema 
10076161 
Narrow 
A 
Vaccination site exfoliation 
10069489 
Narrow 
A 
Vaccination site hypersensitivity 
10068880 
Narrow 
A 
Vaccination site rash 
10069482 
Narrow 
A 
Vaccination site recall reaction 
10076188 
Narrow 
A 
Vaccination site urticaria 
10069622 
Narrow 
A 
Vaccination site vasculitis 
10076191 
Narrow 
A 
Vaccination site vesicles 
10069623 
Narrow 
A 
Vaginal ulceration 
10046943 
Narrow 
A 
Vasculitic rash 
10047111 
Narrow 
A 
Vernal keratoconjunctivitis 
10081000 
Narrow 
A 
Vessel puncture site rash 
10077117 
Narrow 
A 
Vessel puncture site vesicles 
10077813 
Narrow 
A 
Vulval eczema 
10066273 
Narrow 
A 
Vulval ulceration 
10047768 
Narrow 
A 
Vulvovaginal rash 
10071588 
Narrow 
A 
Vulvovaginal ulceration 
10050181 
Narrow 
A 
Vulvovaginitis allergic 
10080783 
Broad 
A 
Acute respiratory failure 
10001053 
Broad 
A 
Administration site photosensitivity reaction 
10075961 
Broad 
A 
Airway remodelling 
10075289 
Broad 
A 
Allergy to chemicals 
10061626 
Broad 
A 
Allergy to fermented products 
10054929 
Broad 
A 
Alpha tumour necrosis factor increased 
10059982 
Broad 
A 
Alveolitis 
10001889 
Broad 
A 
Antibody test abnormal 
10061425 
Broad 
A 
Antibody test positive 
10061427 


PAREXEL International 
TP-GDO-WW-016-07.a 
Effective Date: 30 Jan 19 
Related to: SOP-GDO-WW-019 
CONFIDENTIAL 
Project Document Version No. 4.0 
Project Document Effective Date: Date of last signature 
Page 95 of 122 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
A 
Anti-insulin antibody increased 
10053815 
Broad 
A 
Anti-insulin antibody positive 
10053814 
Broad 
A 
Anti-insulin receptor antibody increased 
10068226 
Broad 
A 
Anti-insulin receptor antibody positive 
10068225 
Broad 
A 
Application site photosensitivity reaction 
10058730 
Broad 
A 
Asthma 
10003553 
Broad 
A 
Asthma late onset 
10003559 
Broad 
A 
Asthma-chronic obstructive pulmonary disease 
overlap syndrome 
10077005 
Broad 
A 
Asthmatic crisis 
10064823 
Broad 
A 
Auricular swelling 
10003800 
Broad 
A 
Blister 
10005191 
Broad 
A 
Blister rupture 
10073385 
Broad 
A 
Blood immunoglobulin A abnormal 
10005584 
Broad 
A 
Blood immunoglobulin A increased 
10005586 
Broad 
A 
Blood immunoglobulin D increased 
10063244 
Broad 
A 
Blood immunoglobulin G abnormal 
10005594 
Broad 
A 
Blood immunoglobulin G increased 
10005596 
Broad 
A 
Blood immunoglobulin M abnormal 
10005599 
Broad 
A 
Blood immunoglobulin M increased 
10005601 
Broad 
A 
Bronchial hyperreactivity 
10066091 
Broad 
A 
Bronchial oedema 
10056695 
Broad 
A 
Bullous impetigo 
10006563 
Broad 
A 
Caffeine allergy 
10074895 
Broad 
A 
Capillaritis 
10068406 
Broad 
A 
Charcot-Leyden crystals 
10008413 
Broad 
A 
Cheilitis 
10008417 
Broad 
A 
Childhood asthma 
10081274 
Broad 
A 
Choking 
10008589 
Broad 
A 
Choking sensation 
10008590 
Broad 
A 
Complement factor C1 decreased 
10051552 
Broad 
A 
Complement factor C2 decreased 
10051555 
Broad 
A 
Complement factor C3 decreased 
10050981 
Broad 
A 
Complement factor C4 decreased 
10050983 
Broad 
A 
Complement factor decreased 
10061048 
Broad 
A 
Conjunctivitis 
10010741 
Broad 
A 
Corneal exfoliation 
10064489 
Broad 
A 
Cough variant asthma 
10063076 
Broad 
A 
Cytokine release syndrome 
10052015 


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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
A 
Cytokine storm 
10050685 
Broad 
A 
Ear swelling 
10014025 
Broad 
A 
Eosinophil count abnormal 
10061125 
Broad 
A 
Eosinophil count increased 
10014945 
Broad 
A 
Eosinophil percentage abnormal 
10058133 
Broad 
A 
Eosinophil percentage increased 
10052222 
Broad 
A 
Eosinophilia 
10014950 
Broad 
A 
Eosinophilia myalgia syndrome 
10014952 
Broad 
A 
Eosinophilic bronchitis 
10065563 
Broad 
A 
Eosinophilic oesophagitis 
10064212 
Broad 
A 
Eosinophilic pneumonia 
10014962 
Broad 
A 
Eosinophilic pneumonia acute 
10052832 
Broad 
A 
Eosinophilic pneumonia chronic 
10052833 
Broad 
A 
Erythema 
10015150 
Broad 
A 
Flushing 
10016825 
Broad 
A 
Gastrointestinal oedema 
10058061 
Broad 
A 
Generalised oedema 
10018092 
Broad 
A 
Genital rash 
10018175 
Broad 
A 
Genital swelling 
10067639 
Broad 
A 
Haemolytic transfusion reaction 
10067122 
Broad 
A 
HLA marker study positive 
10067937 
Broad 
A 
Human anti-hamster antibody increased 
10082107 
Broad 
A 
Human anti-hamster antibody positive 
10082109 
Broad 
A 
Immune complex level increased 
10064650 
Broad 
A 
Immunoglobulins abnormal 
10021497 
Broad 
A 
Immunoglobulins increased 
10021500 
Broad 
A 
Immunology test abnormal 
10061214 
Broad 
A 
Implant site photosensitivity 
10073415 
Broad 
A 
Infusion site photosensitivity reaction 
10065486 
Broad 
A 
Injection site panniculitis 
10083040 
Broad 
A 
Injection site photosensitivity reaction 
10053396 
Broad 
A 
Interstitial lung disease 
10022611 
Broad 
A 
Laryngeal dyspnoea 
10052390 
Broad 
A 
Laryngeal obstruction 
10059639 
Broad 
A 
Leukotriene increased 
10064663 
Broad 
A 
Lip exfoliation 
10064482 
Broad 
A 
Localised oedema 
10048961 
Broad 
A 
Macrophage inflammatory protein-1 alpha increased 
10083049 
Broad 
A 
Mechanical urticaria 
10068773 


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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
A 
Medical device site photosensitivity reaction 
10076137 
Broad 
A 
Mesenteric panniculitis 
10063031 
Broad 
A 
Monocyte chemotactic protein-2 increased 
10083043 
Broad 
A 
Mouth ulceration 
10028034 
Broad 
A 
Mucocutaneous ulceration 
10028084 
Broad 
A 
Mucosa vesicle 
10028103 
Broad 
A 
Mucosal erosion 
10061297 
Broad 
A 
Mucosal exfoliation 
10064486 
Broad 
A 
Mucosal necrosis 
10067993 
Broad 
A 
Mucosal ulceration 
10028124 
Broad 
A 
Nasal crease 
10078581 
Broad 
A 
Necrotising panniculitis 
10062579 
Broad 
A 
Neurodermatitis 
10029263 
Broad 
A 
Neutralising antibodies positive 
10064980 
Broad 
A 
Noninfective conjunctivitis 
10074701 
Broad 
A 
Non-neutralising antibodies positive 
10064982 
Broad 
A 
Occupational asthma 
10070836 
Broad 
A 
Occupational dermatitis 
10030012 
Broad 
A 
Oedema mucosal 
10030111 
Broad 
A 
Oral mucosal exfoliation 
10064487 
Broad 
A 
Orbital oedema 
10031051 
Broad 
A 
Panniculitis 
10033675 
Broad 
A 
Penile exfoliation 
10064485 
Broad 
A 
Penile oedema 
10066774 
Broad 
A 
Penile rash 
10082571 
Broad 
A 
Penile swelling 
10034319 
Broad 
A 
Perineal rash 
10075364 
Broad 
A 
Perivascular dermatitis 
10064986 
Broad 
A 
Photosensitivity reaction 
10034972 
Broad 
A 
Pneumonitis 
10035742 
Broad 
A 
Prurigo 
10037083 
Broad 
A 
Pruritus 
10037087 
Broad 
A 
Pulmonary eosinophilia 
10037382 
Broad 
A 
Reactive airways dysfunction syndrome 
10070832 
Broad 
A 
Respiratory arrest 
10038669 
Broad 
A 
Respiratory distress 
10038687 
Broad 
A 
Respiratory failure 
10038695 
Broad 
A 
Respiratory tract oedema 
10070774 
Broad 
A 
Reversible airways obstruction 
10062109 


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K.inevant 
KIN-1901-2001 
 
Statistical Analysis Plan 
Broad 
A 
Rhinitis perennial 
10039094 
Broad 
A 
Scrotal exfoliation 
10081178 
Broad 
A 
Scrotal swelling 
10039759 
Broad 
A 
Seasonal allergy 
10048908 
Broad 
A 
Septal panniculitis 
10056876 
Broad 
A 
Skin erosion 
10040840 
Broad 
A 
Skin exfoliation 
10040844 
Broad 
A 
Skin oedema 
10058679 
Broad 
A 
Skin swelling 
10053262 
Broad 
A 
Sneezing 
10041232 
Broad 
A 
Status asthmaticus 
10041961 
Broad 
A 
Stomatitis 
10042128 
Broad 
A 
Streptokinase antibody increased 
10053797 
Broad 
A 
Stridor 
10042241 
Broad 
A 
Suffocation feeling 
10042444 
Broad 
A 
Sunscreen sensitivity 
10083629 
Broad 
A 
Throat tightness 
10043528 
Broad 
A 
Tongue exfoliation 
10064488 
Broad 
A 
Tracheal obstmction 
10044291 
Broad 
A 
Tracheostomy 
10044320 
Broad 
A 
Transplantation associated food allergy 
10075008 
Broad 
A 
Uooer ai1wav obstruction 
10067775 
Broad 
A 
Vaccination site photosensitivity reaction 
10076186 
Broad 
A 
Vaginal oedema 
10063818 
Broad 
A 
Visceral oedema 
10065768 
Broad 
A 
Vulval oedema 
10047763 
Broad 
A 
Vulvovaginal exfoliation 
10083435 
Broad 
A 
Vulvovaginal swelling 
10071211 
Broad 
A 
Wheezing 
10047924 
 
 
Drug reaction with eosinophilia and systemic symptoms syndrome (SMQ) 
Scope 
Group 
PT 
PT Code 
NaITow 
A 
Dmg reaction with eosinophilia and systemic 
symptoms 
10073508 
NaITow 
A 
Pseudolymphoma 
10037127 
Broad 
B 
Acute generalised exanthematous pustulosis 
10048799 
Broad 
B 
Acute hepatic failure 
10000804 
Broad 
B 
Acute interstitial pneumonitis 
10066728 
Broad 
B 
Acute kidney inimv 
10069339 


PAREXEL International 
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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
B 
Acute respiratory distress syndrome 
10001052 
Broad 
B 
Adenovirus reactivation 
10083326 
Broad 
B 
Alanine aminotransferase abnormal 
10001547 
Broad 
B 
Alanine aminotransferase increased 
10001551 
Broad 
B 
Allergic hepatitis 
10071198 
Broad 
B 
Allergic oedema 
10060934 
Broad 
B 
Allergic pharyngitis 
10050639 
Broad 
B 
Allergic stomatitis 
10079554 
Broad 
B 
Alveolitis 
10001889 
Broad 
B 
Amylase increased 
10002016 
Broad 
B 
Anal blister 
10082677 
Broad 
B 
Angioedema 
10002424 
Broad 
B 
Anuria 
10002847 
Broad 
B 
Ascites 
10003445 
Broad 
B 
Aspartate aminotransferase abnormal 
10003477 
Broad 
B 
Aspartate aminotransferase increased 
10003481 
Broad 
B 
Autoimmune blistering disease 
10083961 
Broad 
B 
Autoimmune colitis 
10075761 
Broad 
B 
Autoimmune hepatitis 
10003827 
Broad 
B 
Autoimmune myocarditis 
10064539 
Broad 
B 
Autoimmune myositis 
10082418 
Broad 
B 
Autoimmune thyroiditis 
10049046 
Broad 
B 
Bilirubin conjugated abnormal 
10067718 
Broad 
B 
Bilirubin conjugated increased 
10004685 
Broad 
B 
Bilirubin urine 
10053113 
Broad 
B 
Bilirubinuria 
10004710 
Broad 
B 
Biopsy liver abnormal 
10004792 
Broad 
B 
Blood alkaline phosphatase abnormal 
10059571 
Broad 
B 
Blood alkaline phosphatase increased 
10059570 
Broad 
B 
Blood bilirubin abnormal 
10058477 
Broad 
B 
Blood bilirubin increased 
10005364 
Broad 
B 
Blood bilirubin unconjugated increased 
10005370 
Broad 
B 
Blood creatine abnormal 
10005462 
Broad 
B 
Blood creatine increased 
10005464 
Broad 
B 
Blood creatinine abnormal 
10005481 
Broad 
B 
Blood creatinine increased 
10005483 
Broad 
B 
Blood lactate dehydrogenase increased 
10005630 
Broad 
B 
Blood urea abnormal 
10005846 
Broad 
B 
Blood urea increased 
10005851 
 


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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
B 
Blood urea nitrogen/creatinine ratio increased 
10050760 
Broad 
B 
Bullous haemorrhagic dermatosis 
10083809 
Broad 
B 
Carditis 
10062746 
Broad 
B 
Cholestasis 
10008635 
Broad 
B 
Cholestatic liver injury 
10067969 
Broad 
B 
Cholestatic pruritus 
10064190 
Broad 
B 
Chromaturia 
10008796 
Broad 
B 
Chronic active Epstein-Barr virus infection 
10082848 
Broad 
B 
Chronic autoimmune glomerulonephritis 
10073016 
Broad 
B 
Circumoral oedema 
10052250 
Broad 
B 
Coma hepatic 
10010075 
Broad 
B 
Conjunctival hyperaemia 
10051625 
Broad 
B 
Conjunctival oedema 
10010726 
Broad 
B 
Creatinine renal clearance abnormal 
10068447 
Broad 
B 
Creatinine renal clearance decreased 
10011372 
Broad 
B 
Cutaneous vasculitis 
10011686 
Broad 
B 
Cytomegalovirus infection 
10011831 
Broad 
B 
Cytomegalovirus infection reactivation 
10058666 
Broad 
B 
Cytomegalovirus test positive 
10051620 
Broad 
B 
Dermatitis 
10012431 
Broad 
B 
Dermatitis allergic 
10012434 
Broad 
B 
Dermatitis bullous 
10012441 
Broad 
B 
Dermatitis exfoliative 
10012455 
Broad 
B 
Dermatitis exfoliative generalised 
10012456 
Broad 
B 
Dermatosis 
10048768 
Broad 
B 
Dialysis 
10061105 
Broad 
B 
Drug eruption 
10013687 
Broad 
B 
Drug hypersensitivity 
10013700 
Broad 
B 
Drug-induced liver injury 
10072268 
Broad 
B 
Encephalitis 
10014581 
Broad 
B 
Encephalitis allergic 
10056387 
Broad 
B 
Encephalopathy 
10014625 
Broad 
B 
Endocarditis 
10014665 
Broad 
B 
Eosinophilia myalgia syndrome 
10014952 
Broad 
B 
Eosinophilic bronchitis 
10065563 
Broad 
B 
Eosinophilic colitis 
10057271 
Broad 
B 
Eosinophilic cystitis 
10056246 
Broad 
B 
Eosinophilic fasciitis 
10014954 


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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
B 
Eosinophilic gastritis 
10083619 
Broad 
B 
Eosinophilic myocarditis 
10014961 
Broad 
B 
Eosinophilic oesophagitis 
10064212 
Broad 
B 
Eosinophilic otitis media 
10081430 
Broad 
B 
Eosinophilic pleural effusion 
10080148 
Broad 
B 
Eosinophilic pneumonia 
10014962 
Broad 
B 
Eosinophilic pneumonia acute 
10052832 
Broad 
B 
Eosinophilic pneumonia chronic 
10052833 
Broad 
B 
Eosinophilic pustulosis 
10049172 
Broad 
B 
Eosinophils urine present 
10058363 
Broad 
B 
Epidermal necrosis 
10059284 
Broad 
B 
Epidermolysis 
10053177 
Broad 
B 
Epidermolysis bullosa 
10014989 
Broad 
B 
Epstein-Barr virus antibody positive 
10052324 
Broad 
B 
Epstein-Barr virus infection 
10015108 
Broad 
B 
Epstein-Barr virus infection reactivation 
10015109 
Broad 
B 
Erythema 
10015150 
Broad 
B 
Erythema annulare 
10015153 
Broad 
B 
Erythema multiforme 
10015218 
Broad 
B 
Erythrodermic atopic dermatitis 
10082985 
Broad 
B 
Exfoliative rash 
10064579 
Broad 
B 
Eye oedema 
10052139 
Broad 
B 
Eye swelling 
10015967 
Broad 
B 
Eyelid exfoliation 
10064580 
Broad 
B 
Eyelid oedema 
10015993 
Broad 
B 
Face oedema 
10016029 
Broad 
B 
Fibrillary glomerulonephritis 
10068279 
Broad 
B 
Gamma-glutamyltransferase abnormal 
10017688 
Broad 
B 
Gamma-glutamyltransferase increased 
10017693 
Broad 
B 
Genital blister 
10074995 
Broad 
B 
Giant cell myocarditis 
10083635 
Broad 
B 
Glomerular filtration rate abnormal 
10018356 
Broad 
B 
Glomerular filtration rate decreased 
10018358 
Broad 
B 
Glomerulonephritis 
10018364 
Broad 
B 
Glomerulonephritis acute 
10018366 
Broad 
B 
Glomerulonephritis chronic 
10018367 
Broad 
B 
Glomerulonephritis membranoproliferative 
10018370 
Broad 
B 
Glomerulonephritis membranous 
10018372 


PAREXEL International 
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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
B 
Glomerulonephritis minimal lesion 
10018374 
Broad 
B 
Glomerulonephritis proliferative 
10018376 
Broad 
B 
Glomerulonephritis rapidly progressive 
10018378 
Broad 
B 
Glossitis 
10018386 
Broad 
B 
Haematuria 
10018867 
Broad 
B 
Haemodialysis 
10018875 
Broad 
B 
Hepatic encephalopathy 
10019660 
Broad 
B 
Hepatic enzyme abnormal 
10062685 
Broad 
B 
Hepatic enzyme increased 
10060795 
Broad 
B 
Hepatic failure 
10019663 
Broad 
B 
Hepatic function abnormal 
10019670 
Broad 
B 
Hepatic infiltration eosinophilic 
10064668 
Broad 
B 
Hepatic necrosis 
10019692 
Broad 
B 
Hepatitis 
10019717 
Broad 
B 
Hepatitis acute 
10019727 
Broad 
B 
Hepatitis cholestatic 
10019754 
Broad 
B 
Hepatitis fulminant 
10019772 
Broad 
B 
Hepatitis toxic 
10019795 
Broad 
B 
Hepatocellular injury 
10019837 
Broad 
B 
Hepatomegaly 
10019842 
Broad 
B 
Hepatorenal failure 
10019845 
Broad 
B 
Hepatorenal syndrome 
10019846 
Broad 
B 
Hepatosplenomegaly 
10019847 
Broad 
B 
Hepatotoxicity 
10019851 
Broad 
B 
Herpes simplex reactivation 
10080137 
Broad 
B 
Herpes zoster reactivation 
10080516 
Broad 
B 
Human herpes virus 6 serology positive 
10060827 
Broad 
B 
Human herpesvirus 6 infection 
10020431 
Broad 
B 
Human herpesvirus 6 infection reactivation 
10066845 
Broad 
B 
Hyperammonaemia 
10020575 
Broad 
B 
Hyperamylasaemia 
10062770 
Broad 
B 
Hyperbilirubinaemia 
10020578 
Broad 
B 
Hypercholia 
10051924 
Broad 
B 
Hypercreatininaemia 
10062747 
Broad 
B 
Hyperlipasaemia 
10067725 
Broad 
B 
Hyperphosphatasaemia 
10060851 
Broad 
B 
Hypersensitivity 
10020751 
Broad 
B 
Hypersensitivity myocarditis 
10081004 


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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
B 
Hypersensitivity pneumonitis 
10081988 
Broad 
B 
Hypertransaminasaemia 
10068237 
Broad 
B 
Immune effector cell-associated neurotoxicity 
syndrome 
10083347 
Broad 
B 
Immune-mediated arthritis 
10083155 
Broad 
B 
Immune-mediated cholangitis 
10083406 
Broad 
B 
Immune-mediated dermatitis 
10083156 
Broad 
B 
Immune-mediated encephalitis 
10083074 
Broad 
B 
Immune-mediated enterocolitis 
10078961 
Broad 
B 
Immune-mediated hepatic disorder 
10083521 
Broad 
B 
Immune-mediated hepatitis 
10078962 
Broad 
B 
Immune-mediated hyperthyroidism 
10083517 
Broad 
B 
Immune-mediated hypothyroidism 
10083075 
Broad 
B 
Immune-mediated myocarditis 
10082606 
Broad 
B 
Immune-mediated myositis 
10083073 
Broad 
B 
Immune-mediated nephritis 
10083070 
Broad 
B 
Immune-mediated pancreatitis 
10083072 
Broad 
B 
Immune-mediated pneumonitis 
10082452 
Broad 
B 
Immune-mediated renal disorder 
10083522 
Broad 
B 
Immune-mediated thyroiditis 
10083071 
Broad 
B 
Immune-mediated uveitis 
10083069 
Broad 
B 
Immunotactoid glomerulonephritis 
10067871 
Broad 
B 
Interstitial lung disease 
10022611 
Broad 
B 
Intestinal angioedema 
10076229 
Broad 
B 
Ischaemic skin ulcer 
10077408 
Broad 
B 
Jaundice 
10023126 
Broad 
B 
Jaundice cholestatic 
10023129 
Broad 
B 
Jaundice hepatocellular 
10023136 
Broad 
B 
Lip erosion 
10051992 
Broad 
B 
Lip exfoliation 
10064482 
Broad 
B 
Lip oedema 
10024558 
Broad 
B 
Lip swelling 
10024570 
Broad 
B 
Lip ulceration 
10024572 
Broad 
B 
Lipase abnormal 
10054821 
Broad 
B 
Lipase increased 
10024574 
Broad 
B 
Liver disorder 
10024670 
Broad 
B 
Liver function test abnormal 
10024690 
Broad 
B 
Liver injury 
10067125 
Broad 
B 
Liver palpable 
10075895 


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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
B 
Liver scan abnormal 
10061947 
Broad 
B 
Liver transplant 
10024714 
Broad 
B 
Localised oedema 
10048961 
Broad 
B 
Lung infiltration 
10025102 
Broad 
B 
Macule 
10025421 
Broad 
B 
Membranous-like glomerulopathy with masked IgG- 
kappa deposits 
10083098 
Broad 
B 
Meningitis 
10027199 
Broad 
B 
Mixed liver injury 
10066758 
Broad 
B 
Mouth ulceration 
10028034 
Broad 
B 
Mucocutaneous rash 
10056671 
Broad 
B 
Mucocutaneous ulceration 
10028084 
Broad 
B 
Mucosal erosion 
10061297 
Broad 
B 
Mucosal exfoliation 
10064486 
Broad 
B 
Mucosal necrosis 
10067993 
Broad 
B 
Mucosal ulceration 
10028124 
Broad 
B 
Multi-organ disorder 
10058092 
Broad 
B 
Multiple organ dysfunction syndrome 
10077361 
Broad 
B 
Myocarditis 
10028606 
Broad 
B 
Myopathy 
10028641 
Broad 
B 
Myopathy toxic 
10028648 
Broad 
B 
Myositis 
10028653 
Broad 
B 
Nasal mucosal blistering 
10082185 
Broad 
B 
Nephritic syndrome 
10065673 
Broad 
B 
Nephritis 
10029117 
Broad 
B 
Nephritis allergic 
10029120 
Broad 
B 
Nephropathy toxic 
10029155 
Broad 
B 
Nephrotic syndrome 
10029164 
Broad 
B 
Nikolsky's sign 
10029415 
Broad 
B 
Ocular icterus 
10058117 
Broad 
B 
Oedema mouth 
10030110 
Broad 
B 
Oedema mucosal 
10030111 
Broad 
B 
Oliguria 
10030302 
Broad 
B 
Oral lichenoid reaction 
10083833 
Broad 
B 
Oral macule 
10083314 
Broad 
B 
Oral mucosa erosion 
10064594 
Broad 
B 
Oral mucosal blistering 
10030995 
Broad 
B 
Oral mucosal eruption 
10030997 
Broad 
B 
Oral mucosal erythema 
10067418 


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Page   105   of 
 
 
Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
B 
Oral mucosal exfoliation 
10064487 
Broad 
B 
Oral papule 
10031010 
Broad 
B 
Oral purpura 
10083533 
Broad 
B 
Oral pustule 
10056674 
Broad 
B 
Orbital oedema 
10031051 
Broad 
B 
Oropharyngeal blistering 
10067950 
Broad 
B 
Oropharyngeal swelling 
10031118 
Broad 
B 
Palpable purpura 
10056872 
Broad 
B 
Pancreatic enzymes increased 
10061900 
Broad 
B 
Pancreatitis 
10033645 
Broad 
B 
Pancreatitis acute 
10033647 
Broad 
B 
Papule 
10033733 
Broad 
B 
Parvovirus B19 infection reactivation 
10076281 
Broad 
B 
Pemphigoid 
10034277 
Broad 
B 
Pemphigus 
10034280 
Broad 
B 
Penile blister 
10052898 
Broad 
B 
Pericardial effusion 
10034474 
Broad 
B 
Pericarditis 
10034484 
Broad 
B 
Perioral dermatitis 
10034541 
Broad 
B 
Periorbital oedema 
10034545 
Broad 
B 
Periorbital swelling 
10056647 
Broad 
B 
Peritoneal dialysis 
10034660 
Broad 
B 
Perivascular dermatitis 
10064986 
Broad 
B 
Pharyngeal oedema 
10034829 
Broad 
B 
Pharyngeal swelling 
10082270 
Broad 
B 
Pharyngeal ulceration 
10034834 
Broad 
B 
Pharyngitis 
10034835 
Broad 
B 
Pleural effusion 
10035598 
Broad 
B 
Pleuropericarditis 
10059361 
Broad 
B 
Pneumonia 
10035664 
Broad 
B 
Pneumonitis 
10035742 
Broad 
B 
Polymyositis 
10036102 
Broad 
B 
Polyserositis 
10036141 
Broad 
B 
Post streptococcal glomerulonephritis 
10036303 
Broad 
B 
PRIDE syndrome 
10082958 
Broad 
B 
Protein urine present 
10053123 
Broad 
B 
Proteinuria 
10037032 
Broad 
B 
Pruritus 
10037087 


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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
B 
Pruritus allergic 
10063438 
Broad 
B 
Pulmonary eosinophilia 
10037382 
Broad 
B 
Purpura 
10037549 
Broad 
B 
Pustule 
10037578 
Broad 
B 
Rash 
10037844 
Broad 
B 
Rash erythematous 
10037855 
Broad 
B 
Rash follicular 
10037857 
Broad 
B 
Rash macular 
10037867 
Broad 
B 
Rash maculo-papular 
10037868 
Broad 
B 
Rash maculovesicular 
10050004 
Broad 
B 
Rash morbilliform 
10037870 
Broad 
B 
Rash papular 
10037876 
Broad 
B 
Rash papulosquamous 
10037879 
Broad 
B 
Rash pruritic 
10037884 
Broad 
B 
Rash pustular 
10037888 
Broad 
B 
Rash rubelliform 
10057984 
Broad 
B 
Rash scarlatiniform 
10037890 
Broad 
B 
Rash vesicular 
10037898 
Broad 
B 
Red blood cells urine positive 
10038182 
Broad 
B 
Renal disorder 
10038428 
Broad 
B 
Renal failure 
10038435 
Broad 
B 
Renal function test abnormal 
10061480 
Broad 
B 
Renal impairment 
10062237 
Broad 
B 
Renal tubular disorder 
10038537 
Broad 
B 
Renal tubular dysfunction 
10050335 
Broad 
B 
Renal tubular necrosis 
10038540 
Broad 
B 
Respiratory distress 
10038687 
Broad 
B 
Scrotal dermatitis 
10083260 
Broad 
B 
Serum sickness-like reaction 
10040402 
Broad 
B 
SJS-TEN overlap 
10083164 
Broad 
B 
Skin erosion 
10040840 
Broad 
B 
Skin exfoliation 
10040844 
Broad 
B 
Skin lesion 
10040882 
Broad 
B 
Skin necrosis 
10040893 
Broad 
B 
Skin oedema 
10058679 
Broad 
B 
Skin reaction 
10040914 
Broad 
B 
Skin swelling 
10053262 
Broad 
B 
Skin ulcer 
10040943 


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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
B 
Stevens-Johnson syndrome 
10042033 
Broad 
B 
Stomatitis 
10042128 
Broad 
B 
Stomatitis necrotising 
10042135 
Broad 
B 
Subacute hepatic failure 
10056956 
Broad 
B 
Sunscreen sensitivity 
10083629 
Broad 
B 
Swelling face 
10042682 
Broad 
B 
Swelling of eyelid 
10042690 
Broad 
B 
Swollen tongue 
10042727 
Broad 
B 
Symmetrical drug-related intertriginous and flexural 
exanthema 
10078325 
Broad 
B 
Target skin lesion 
10081998 
Broad 
B 
Therapeutic product cross-reactivity 
10079645 
Broad 
B 
Thyroiditis 
10043778 
Broad 
B 
Thyroiditis acute 
10043780 
Broad 
B 
Tongue exfoliation 
10064488 
Broad 
B 
Tongue necrosis 
10067360 
Broad 
B 
Tongue oedema 
10043967 
Broad 
B 
Tongue ulceration 
10043991 
Broad 
B 
Tonsillitis 
10044008 
Broad 
B 
Toxic epidermal necrolysis 
10044223 
Broad 
B 
Toxic skin eruption 
10057970 
Broad 
B 
Transaminases abnormal 
10062688 
Broad 
B 
Transaminases increased 
10054889 
Broad 
B 
Tubulointerstitial nephritis 
10048302 
Broad 
B 
Type IV hypersensitivity reaction 
10053613 
Broad 
B 
Urea renal clearance decreased 
10046358 
Broad 
B 
Urine bilirubin increased 
10050792 
Broad 
B 
Urine output decreased 
10059895 
Broad 
B 
Urobilinogen urine increased 
10070479 
Broad 
B 
Urticaria 
10046735 
Broad 
B 
Urticaria papular 
10046750 
Broad 
B 
Urticaria vesiculosa 
10046755 
Broad 
B 
Urticarial dermatitis 
10082290 
Broad 
B 
Vaginal mucosal blistering 
10048904 
Broad 
B 
Vasculitic rash 
10047111 
Broad 
B 
Yellow skin 
10048245 
Broad 
C 
Body temperature increased 
10005911 
Broad 
C 
Hyperpyrexia 
10020741 
Broad 
C 
Hyperthermia 
10020843 


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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
C 
Masked fever 
10079681 
Broad 
C 
Pyrexia 
10037660 
Broad 
D 
Abdominal lymphadenopathy 
10073485 
Broad 
D 
Dermatopathic lymphadenopathy 
10074339 
Broad 
D 
Hilar lymphadenopathy 
10020094 
Broad 
D 
Lymph node pain 
10025182 
Broad 
D 
Lymph node palpable 
10057470 
Broad 
D 
Lymphadenitis 
10025188 
Broad 
D 
Lymphadenopathy 
10025197 
Broad 
D 
Lymphadenopathy mediastinal 
10025205 
Broad 
D 
Paratracheal lymphadenopathy 
10033969 
Broad 
D 
Persistent generalised lymphadenopathy 
10049025 
Broad 
D 
Retroperitoneal lymphadenopathy 
10067015 
Broad 
E 
Autoimmune heparin-induced thrombocytopenia 
10083812 
Broad 
E 
Blood immunoglobulin E increased 
10005591 
Broad 
E 
B-lymphocyte count decreased 
10051313 
Broad 
E 
Cytopenia 
10066274 
Broad 
E 
Eosinophil count abnormal 
10061125 
Broad 
E 
Eosinophil count increased 
10014945 
Broad 
E 
Eosinophil percentage abnormal 
10058133 
Broad 
E 
Eosinophil percentage increased 
10052222 
Broad 
E 
Eosinophilia 
10014950 
Broad 
E 
Hypereosinophilic syndrome 
10048643 
Broad 
E 
Hypogammaglobulinaemia 
10020983 
Broad 
E 
Immune thrombocytopenia 
10083842 
Broad 
E 
Immune-mediated pancytopenia 
10083004 
Broad 
E 
Leukocytosis 
10024378 
Broad 
E 
Leukopenia 
10024384 
Broad 
E 
Lymphocyte count abnormal 
10025252 
Broad 
E 
Lymphocyte count decreased 
10025256 
Broad 
E 
Lymphocyte count increased 
10025258 
Broad 
E 
Lymphocyte morphology abnormal 
10062047 
Broad 
E 
Lymphocyte percentage abnormal 
10063337 
Broad 
E 
Lymphocyte percentage decreased 
10052231 
Broad 
E 
Lymphocyte percentage increased 
10052232 
Broad 
E 
Lymphocyte stimulation test positive 
10060760 
Broad 
E 
Lymphocyte transformation test positive 
10057771 
Broad 
E 
Lymphocytic infiltration 
10062049 


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K.inevant 
KIN-1901-2001 
 
Statistical Analysis Plan 
Broad 
E 
Lymphocvtosis 
10025280 
Broad 
E 
Lymphopenia 
10025327 
Broad 
E 
Monocyte count abno1mal 
10061293 
Broad 
E 
Monocyte count increased 
10027880 
Broad 
E 
Monocvte percentage abno1mal 
10067238 
Broad 
E 
Monocvte percentage increased 
10052230 
Broad 
E 
Monocytosis 
10027906 
Broad 
E 
Mononuclear cell count increased 
10082032 
Broad 
E 
Mononucleosis syndrome 
10027924 
Broad 
E 
Natural killer cell count decreased 
10068497 
Broad 
E 
Neutropenia 
10029354 
Broad 
E 
Neutrophil count abno1mal 
10061313 
Broad 
E 
Neutrophil count decreased 
10029366 
Broad 
E 
Neutrophil count increased 
10029368 
Broad 
E 
Neutrophil percentage decreased 
10052223 
Broad 
E 
Neutrophil percentage increased 
10052224 
Broad 
E 
Neutrophilia 
10029379 
Broad 
E 
Pancytopenia 
10033661 
Broad 
E 
Platelet count decreased 
10035528 
Broad 
E 
Splenomegaly 
10041660 
Broad 
E 
Thrombocytopenia 
10043554 
Broad 
E 
White blood cell count abno1mal 
10047940 
Broad 
E 
White blood cell count decreased 
10047942 
Broad 
E 
White blood cell count increased 
10047943 
 
Anaphylactic reaction (SMQ) 
Scope 
Group 
PT 
PT Code 
NaITow 
A 
Anaphylactic reaction 
10002198 
NaITow 
A 
Anaphylactic shock 
10002199 
NaITow 
A 
Anaohvlactic transfusion reaction 
10067113 
NaITow 
A 
Anaphylactoid reaction 
10002216 
NaITow 
A 
Anaphylactoid shock 
10063119 
NaITow 
A 
Circulatory collapse 
10009192 
NaITow 
A 
Dialysis membrane reaction 
10076665 
NaITow 
A 
Kounis syndrome 
10069167 
NaITow 
A 
Procedural shock 
10080894 
NaITow 
A 
Shock 
10040560 
NaITow 
A 
Shock svmotom 
10040581 
NaITow 
A 
Type I hypersensitivity 
10045240 


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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
B 
Acute respiratory failure 
10001053 
Broad 
B 
Asthma 
10003553 
Broad 
B 
Bronchial oedema 
10056695 
Broad 
B 
Bronchospasm 
10006482 
Broad 
B 
Cardio-respiratory distress 
10049874 
Broad 
B 
Chest discomfort 
10008469 
Broad 
B 
Choking 
10008589 
Broad 
B 
Choking sensation 
10008590 
Broad 
B 
Circumoral oedema 
10052250 
Broad 
B 
Cough 
10011224 
Broad 
B 
Cough variant asthma 
10063076 
Broad 
B 
Cyanosis 
10011703 
Broad 
B 
Dyspnoea 
10013968 
Broad 
B 
Hyperventilation 
10020910 
Broad 
B 
Irregular breathing 
10076213 
Broad 
B 
Laryngeal dyspnoea 
10052390 
Broad 
B 
Laryngeal oedema 
10023845 
Broad 
B 
Laryngospasm 
10023891 
Broad 
B 
Laryngotracheal oedema 
10023893 
Broad 
B 
Mouth swelling 
10075203 
Broad 
B 
Nasal obstruction 
10028748 
Broad 
B 
Oedema mouth 
10030110 
Broad 
B 
Oropharyngeal oedema 
10078783 
Broad 
B 
Oropharyngeal spasm 
10031111 
Broad 
B 
Oropharyngeal swelling 
10031118 
Broad 
B 
Pharyngeal oedema 
10034829 
Broad 
B 
Pharyngeal swelling 
10082270 
Broad 
B 
Respiratory arrest 
10038669 
Broad 
B 
Respiratory distress 
10038687 
Broad 
B 
Respiratory failure 
10038695 
Broad 
B 
Reversible airways obstruction 
10062109 
Broad 
B 
Sensation of foreign body 
10061549 
Broad 
B 
Sneezing 
10041232 
Broad 
B 
Stridor 
10042241 
Broad 
B 
Swollen tongue 
10042727 
Broad 
B 
Tachypnoea 
10043089 
Broad 
B 
Throat tightness 
10043528 
Broad 
B 
Tongue oedema 
10043967 


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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
B 
Tracheal obstruction 
10044291 
Broad 
B 
Tracheal oedema 
10044296 
Broad 
B 
Upper airway obstruction 
10067775 
Broad 
B 
Wheezing 
10047924 
Broad 
C 
Acquired C1 inhibitor deficiency 
10081035 
Broad 
C 
Allergic oedema 
10060934 
Broad 
C 
Angioedema 
10002424 
Broad 
C 
Circumoral swelling 
10081703 
Broad 
C 
Erythema 
10015150 
Broad 
C 
Eye oedema 
10052139 
Broad 
C 
Eye pruritus 
10052140 
Broad 
C 
Eye swelling 
10015967 
Broad 
C 
Eyelid oedema 
10015993 
Broad 
C 
Face oedema 
10016029 
Broad 
C 
Flushing 
10016825 
Broad 
C 
Hereditary angioedema with C1 esterase inhibitor 
deficiency 
10080955 
Broad 
C 
Injection site urticaria 
10022107 
Broad 
C 
Lip oedema 
10024558 
Broad 
C 
Lip swelling 
10024570 
Broad 
C 
Nodular rash 
10075807 
Broad 
C 
Ocular hyperaemia 
10030041 
Broad 
C 
Oedema 
10030095 
Broad 
C 
Oedema blister 
10080039 
Broad 
C 
Periorbital oedema 
10034545 
Broad 
C 
Periorbital swelling 
10056647 
Broad 
C 
Pruritus 
10037087 
Broad 
C 
Pruritus allergic 
10063438 
Broad 
C 
Rash 
10037844 
Broad 
C 
Rash erythematous 
10037855 
Broad 
C 
Rash pruritic 
10037884 
Broad 
C 
Skin swelling 
10053262 
Broad 
C 
Swelling 
10042674 
Broad 
C 
Swelling face 
10042682 
Broad 
C 
Swelling of eyelid 
10042690 
Broad 
C 
Urticaria 
10046735 
Broad 
C 
Urticaria papular 
10046750 
Broad 
D 
Blood pressure decreased 
10005734 
Broad 
D 
Blood pressure diastolic decreased 
10005737 


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K.inevant 
KIN-1901-2001 
 
Statistical Analysis Plan 
Broad 
D 
Blood pressure systolic decreased 
10005758 
Broad 
D 
Cardiacmest 
10007515 
Broad 
D 
Cardio-respiratory anest 
10007617 
Broad 
D 
Cardiovascular insufficiency 
10065929 
Broad 
D 
Diastolic hypotension 
10066077 
Broad 
D 
Hypotension 
10021097 
Broad 
D 
Hypotensive crisis 
10083659 
Broad 
D 
Post procedural hypotension 
10084013 
 
Drue related hepatic disorders - comprehensive search (SMQ) 
Scope 
Group 
Pr ferred Term 
PT Code 
Cholestasis and _jaundice of hepatic orhdn (SMQ) 
Nanow 
A 
Bilirnbin excretion disorder 
10061009 
Nanow 
A 
Cholaemia 
10048611 
Nanow 
A 
Cholestasis 
10008635 
Nanow 
A 
Cholestatic liver iniury 
10067969 
Nanow 
A 
Cholestatic prnritus 
10064190 
Nanow 
A 
Drng-induced liver iniurv 
10072268 
Nanow 
A 
Hepatitis cholestatic 
10019754 
Nanow 
A 
Hyperbilirnbinaemia 
10020578 
Nanow 
A 
Icterns index increased 
10021209 
Nanow 
A 
Jaundice 
10023126 
Nanow 
A 
Jaundice cholestatic 
10023129 
Nanow 
A 
Jaundice hepatocellular 
10023136 
Nanow 
A 
Mixed liver iniury 
10066758 
Nanow 
A 
Ocular icterns 
10058117 
Nanow 
A 
Parenteral nutrition associated liver disease 
10074151 
Broad 
A 
Deficiency of bile secretion 
10071634 
Broad 
A 
Yellow skin 
10048245 
Dru!!: related heoatic disorders - severe events onlv (SMO) 
Nanow 
A 
Acquired hepatocerebral degeneration 
10080860 
Nanow 
A 
Acute hepatic failure 
10000804 
Nanow 
A 
Acute on chronic liver failure 
10077305 
Nanow 
A 
Acute yellow liver atrophy 
10070815 
Nanow 
A 
Ascites 
10003445 
Nanow 
A 
Asterixis 
10003547 
Nanow 
A 
Bacterascites 
10068547 
Nanow 
A 
Biliarv cinhosis 
10004659 
Nanow 
A 
Biliary fibrosis 
10004664 


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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Narrow 
A 
Cardiohepatic syndrome 
10082480 
Narrow 
A 
Cholestatic liver injury 
10067969 
Narrow 
A 
Chronic hepatic failure 
10057573 
Narrow 
A 
Coma hepatic 
10010075 
Narrow 
A 
Cryptogenic cirrhosis 
10063075 
Narrow 
A 
Diabetic hepatopathy 
10071265 
Narrow 
A 
Drug-induced liver injury 
10072268 
Narrow 
A 
Duodenal varices 
10051010 
Narrow 
A 
Gallbladder varices 
10072319 
Narrow 
A 
Gastric variceal injection 
10076237 
Narrow 
A 
Gastric variceal ligation 
10076238 
Narrow 
A 
Gastric varices 
10051012 
Narrow 
A 
Gastric varices haemorrhage 
10057572 
Narrow 
A 
Gastrooesophageal variceal haemorrhage prophylaxis 
10066597 
Narrow 
A 
Hepatectomy 
10061997 
Narrow 
A 
Hepatic atrophy 
10019637 
Narrow 
A 
Hepatic calcification 
10065274 
Narrow 
A 
Hepatic cirrhosis 
10019641 
Narrow 
A 
Hepatic encephalopathy 
10019660 
Narrow 
A 
Hepatic encephalopathy prophylaxis 
10066599 
Narrow 
A 
Hepatic failure 
10019663 
Narrow 
A 
Hepatic fibrosis 
10019668 
Narrow 
A 
Hepatic hydrothorax 
10067365 
Narrow 
A 
Hepatic infiltration eosinophilic 
10064668 
Narrow 
A 
Hepatic lesion 
10061998 
Narrow 
A 
Hepatic necrosis 
10019692 
Narrow 
A 
Hepatic steato-fibrosis 
10077215 
Narrow 
A 
Hepatic steatosis 
10019708 
Narrow 
A 
Hepatitis fulminant 
10019772 
Narrow 
A 
Hepatobiliary disease 
10062000 
Narrow 
A 
Hepatocellular foamy cell syndrome 
10053244 
Narrow 
A 
Hepatocellular injury 
10019837 
Narrow 
A 
Hepatopulmonary syndrome 
10052274 
Narrow 
A 
Hepatorenal failure 
10019845 
Narrow 
A 
Hepatorenal syndrome 
10019846 
Narrow 
A 
Hepatotoxicity 
10019851 
Narrow 
A 
Immune-mediated cholangitis 
10083406 
Narrow 
A 
Immune-mediated hepatic disorder 
10083521 


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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Narrow 
A 
Intestinal varices 
10071502 
Narrow 
A 
Intestinal varices haemorrhage 
10078058 
Narrow 
A 
Liver dialysis 
10076640 
Narrow 
A 
Liver disorder 
10024670 
Narrow 
A 
Liver injury 
10067125 
Narrow 
A 
Liver operation 
10062040 
Narrow 
A 
Liver transplant 
10024714 
Narrow 
A 
Lupoid hepatic cirrhosis 
10025129 
Narrow 
A 
Minimal hepatic encephalopathy 
10076204 
Narrow 
A 
Mixed liver injury 
10066758 
Narrow 
A 
Nodular regenerative hyperplasia 
10051081 
Narrow 
A 
Nonalcoholic fatty liver disease 
10082249 
Narrow 
A 
Non-alcoholic steatohepatitis 
10053219 
Narrow 
A 
Non-cirrhotic portal hypertension 
10077259 
Narrow 
A 
Oedema due to hepatic disease 
10049631 
Narrow 
A 
Oesophageal varices haemorrhage 
10030210 
Narrow 
A 
Peripancreatic varices 
10073215 
Narrow 
A 
Portal fibrosis 
10074726 
Narrow 
A 
Portal hypertension 
10036200 
Narrow 
A 
Portal hypertensive colopathy 
10079446 
Narrow 
A 
Portal hypertensive enteropathy 
10068923 
Narrow 
A 
Portal hypertensive gastropathy 
10050897 
Narrow 
A 
Portal vein cavernous transformation 
10073979 
Narrow 
A 
Portal vein dilatation 
10073209 
Narrow 
A 
Portopulmonary hypertension 
10067281 
Narrow 
A 
Primary biliary cholangitis 
10080429 
Narrow 
A 
Regenerative siderotic hepatic nodule 
10080679 
Narrow 
A 
Renal and liver transplant 
10052279 
Narrow 
A 
Retrograde portal vein flow 
10067338 
Narrow 
A 
Reye's syndrome 
10039012 
Narrow 
A 
Reynold's syndrome 
10070953 
Narrow 
A 
Splenic varices 
10067823 
Narrow 
A 
Splenic varices haemorrhage 
10068662 
Narrow 
A 
Steatohepatitis 
10076331 
Narrow 
A 
Subacute hepatic failure 
10056956 
Narrow 
A 
Sugiura procedure 
10083010 
Narrow 
A 
Varices oesophageal 
10056091 
Narrow 
A 
Varicose veins of abdominal wall 
10072284 


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K.inevant 
KIN-1901-2001 
 
Statistical Analysis Plan 
NaITow 
A 
White nioole si!lll 
10078438 
Broad 
A 
Anorectal varices 
10068924 
Broad 
A 
Anorectal varices haemonhage 
10068925 
Broad 
A 
Complications of transplanted liver 
10010186 
Broad 
A 
Hepatic perfusion disorder 
10083840 
Broad 
A 
fucreased liver stiffness 
10082444 
Broad 
A 
futrahepatic portal hepatic venous fistula 
10072629 
Broad 
A 
Liver and pancreas ti·ansplant rejection 
10051603 
Broad 
A 
Liver transplant failure 
10083175 
Broad 
A 
Liver transplant reiection 
10024715 
Broad 
A 
Multivisceral transplantation 
10082450 
Broad 
A 
Peritoneovenous shunt 
10052716 
Broad 
A 
Po1tal shunt 
10036204 
Broad 
A 
Po1tal shunt procedure 
10077479 
Broad 
A 
Small-for-size liver syndrome 
10069380 
Broad 
A 
Spider naevus 
10041519 
Broad 
A 
Splenic aiterv embolisation 
10083795 
Broad 
A 
Splenorenal shunt 
10041661 
Broad 
A 
Splenorenal shunt procedure 
10077281 
Broad 
A 
Spontaneous inti·ahepatic po1tosysteinic venous shunt 
10076239 
Broad 
A 
Stomal varices 
10075186 
Heoatitis. non-infectious (SMO) 
NaITow 
A 
Acute graft versus host disease in liver 
10066263 
NaITow 
A 
Allergic hepatitis 
10071198 
NaITow 
A 
Alloimmune hepatitis 
10080576 
NaITow 
A 
Autoimmune hepatitis 
10003827 
NaITow 
A 
Chronic graft versus host disease in liver 
10072160 
NaITow 
A 
Chronic hepatitis 
10008909 
NaITow 
A 
Graft versus host disease in liver 
10064676 
NaITow 
A 
Hepatitis 
10019717 
NaITow 
A 
Hepatitis acute 
10019727 
NaITow 
A 
Hepatitis cholestatic 
10019754 
NaITow 
A 
Hepatitis chronic active 
10019755 
NaITow 
A 
Hepatitis chronic persistent 
10019759 
NaITow 
A 
Hepatitis fulininant 
10019772 
NaITow 
A 
Hepatitis toxic 
10019795 
NaITow 
A 
Immune-mediated hepatitis 
10078962 
NaITow 
A 
Ischaeinic hepatitis 
10023025 


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K.inevant 
KIN-1901-2001 
 
Statistical Analysis Plan 
NaITow 
A 
Lupus hepatitis 
10067737 
NaITow 
A 
Non-alcoholic steatohepatitis 
10053219 
NaITow 
A 
Radiation hepatitis 
10051015 
NaITow 
A 
Steatohepatitis 
10076331 
Broad 
A 
Granulomatous liver disease 
10018704 
Broad 
A 
Liver sarcoidosis 
10068664 
Broad 
A 
Portal trnct inflammation 
10075331 
Liver neoplasms, benie.n (incl cysts and polyps) (SMQ) 
NaITow 
A 
Beni!ffihepatic neoplasm 
10004269 
NaITow 
A 
Beni!ffihepatobiliarv neoplasm 
10077922 
NaITow 
A 
Focal nodular hyperplasia 
10052285 
NaITow 
A 
Haemangioma of liver 
10018821 
NaITow 
A 
HaemoITha!lic hepatic cyst 
10067796 
NaITow 
A 
Hepatic adenoma 
10019629 
NaITow 
A 
Hepatic cyst 
10019646 
NaITow 
A 
Hepatic cyst rnptured 
10053973 
NaITow 
A 
Hepatic haemangioma rnpture 
10054885 
NaITow 
A 
Hepatic hama1toma 
10079685 
NaITow 
A 
Hepatobiliaiy cyst 
10079889 
Liver neoplasms, malie.nant and unspecified (SMQ) 
Liver malie.nant tumours (SMQ) 
NaITow 
A 
Cholangiosai·coma 
10077861 
NaITow 
A 
Hepatic an!liosarcoma 
10067388 
NaITow 
A 
Hepatic cancer 
10073069 
NaITow 
A 
Hepatic cancer metastatic 
10055110 
NaITow 
A 
Hepatic cancer recuITent 
10073070 
NaITow 
A 
Hepatic cancer stage I 
10059318 
NaITow 
A 
Hepatic cancer stage II 
10059319 
NaITow 
A 
Hepatic cancer stage III 
10059324 
NaITow 
A 
Hepatic cancer stage IV 
10059325 
NaITow 
A 
Hepatobiliaiy cancer 
10073073 
NaITow 
A 
Hepatobiliarv cancer in situ 
10073074 
NaITow 
A 
Hepatoblastoma 
10062001 
NaITow 
A 
Heoatoblastoma recmTent 
10019823 
NaITow 
A 
Hepatocellulai·cai·cinoma 
10073071 
NaITow 
A 
Liver cai·cinoma rnptured 
10050842 
NaITow 
A 
Mixed hepatocellular cholangiocarcinoma 
10027761 
Broad 
A 
Liver ablation 
10074766 


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K.inevant 
KIN-1901-2001 
 
Statistical Analysis Plan 
Liver tumours of unspecified malie:nancv (SMQ) 
NaITow 
A 
Hepatic neoplasm 
10019695 
NaITow 
A 
Hepatobiliaiy neoplasm 
10061203 
Liver related investieations, siens and symptoms (SMQ) 
NaITow 
A 
Alanine aminotransferase abno1mal 
10001547 
NaITow 
A 
Alanine aminotransferase increased 
10001551 
NaITow 
A 
Ammonia abnonnal 
10001942 
NaITow 
A 
Ammonia increased 
10001946 
NaITow 
A 
Ascites 
10003445 
NaITow 
A 
Aspartate aminotransferase abnonnal 
10003477 
NaITow 
A 
Aspartate aminotransferase increased 
10003481 
NaITow 
A 
ASTIALT ratio abno1mal 
10082832 
NaITow 
A 
Bacterascites 
10068547 
NaITow 
A 
Bile output abno1mal 
10051344 
NaITow 
A 
Bile output decreased 
10051343 
NaITow 
A 
Biliai·y ascites 
10074150 
NaITow 
A 
Bilirnbin conjugated abnonnal 
10067718 
NaITow 
A 
Bilirnbin conjugated increased 
10004685 
NaITow 
A 
Bilirnbin urine present 
10077356 
NaITow 
A 
Biopsy liver abnonnal 
10004792 
NaITow 
A 
Blood bilirnbin abno1mal 
10058477 
NaITow 
A 
Blood bilirnbin increased 
10005364 
NaITow 
A 
Blood bilirnbin unconjugated increased 
10005370 
NaITow 
A 
Bromosulphthalein test abno1mal 
10006408 
NaITow 
A 
Child-Pugh-Turcotte score abno1mal 
10077020 
NaITow 
A 
Child-Pugh-Turcotte score increased 
10068287 
NaITow 
A 
Computerised tomogram liver abno1mal 
10078360 
NaITow 
A 
Congestive hepatopathy 
10084058 
NaITow 
A 
Foetor hepaticus 
10052554 
NaITow 
A 
Galactose elimination capacity test abnonnal 
10059710 
NaITow 
A 
Galactose elimination capacity test decreased 
10059712 
NaITow 
A 
Gamma-glutamvltransferase abn01mal 
10017688 
NaITow 
A 
Gamma-glutamvltransferase increased 
10017693 
NaITow 
A 
Guanase increased 
10051333 
NaITow 
A 
Hepaplastin abno1mal 
10019621 
NaITow 
A 
Hepaplastin decreased 
10019622 
NaITow 
A 
Hepatic aiterv flow decreased 
10068997 
NaITow 
A 
Hepatic enzyme abno1mal 
10062685 


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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Narrow 
A 
Hepatic enzyme decreased 
10060794 
Narrow 
A 
Hepatic enzyme increased 
10060795 
Narrow 
A 
Hepatic function abnormal 
10019670 
Narrow 
A 
Hepatic hydrothorax 
10067365 
Narrow 
A 
Hepatic hypertrophy 
10076254 
Narrow 
A 
Hepatic mass 
10057110 
Narrow 
A 
Hepatic pain 
10019705 
Narrow 
A 
Hepatic sequestration 
10066244 
Narrow 
A 
Hepatic vascular resistance increased 
10068358 
Narrow 
A 
Hepatic venous pressure gradient abnormal 
10083172 
Narrow 
A 
Hepatic venous pressure gradient increased 
10083171 
Narrow 
A 
Hepatobiliary scan abnormal 
10066195 
Narrow 
A 
Hepatomegaly 
10019842 
Narrow 
A 
Hepatosplenomegaly 
10019847 
Narrow 
A 
Hyperammonaemia 
10020575 
Narrow 
A 
Hyperbilirubinaemia 
10020578 
Narrow 
A 
Hypercholia 
10051924 
Narrow 
A 
Hypertransaminasaemia 
10068237 
Narrow 
A 
Kayser-Fleischer ring 
10023321 
Narrow 
A 
Liver function test abnormal 
10024690 
Narrow 
A 
Liver function test decreased 
10077677 
Narrow 
A 
Liver function test increased 
10077692 
Narrow 
A 
Liver induration 
10052550 
Narrow 
A 
Liver palpable 
10075895 
Narrow 
A 
Liver scan abnormal 
10061947 
Narrow 
A 
Liver tenderness 
10024712 
Narrow 
A 
Magnetic resonance imaging liver abnormal 
10083123 
Narrow 
A 
Magnetic resonance proton density fat fraction 
measurement 
10082443 
Narrow 
A 
Mitochondrial aspartate aminotransferase increased 
10064712 
Narrow 
A 
Molar ratio of total branched-chain amino acid to 
tyrosine 
10066869 
Narrow 
A 
Oedema due to hepatic disease 
10049631 
Narrow 
A 
Perihepatic discomfort 
10054125 
Narrow 
A 
Retrograde portal vein flow 
10067338 
Narrow 
A 
Total bile acids increased 
10064558 
Narrow 
A 
Transaminases abnormal 
10062688 
Narrow 
A 
Transaminases increased 
10054889 
Narrow 
A 
Ultrasound liver abnormal 
10045428 


PAREXEL International 
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K.inevant 
KIN-1901-2001 
 
Statistical Analysis Plan 
NaITow 
A 
Urine bilirnbin increased 
10050792 
NaITow 
A 
White nioole si!lll 
10078438 
NaITow 
A 
X-ray hepatobiliary abno1mal 
10056536 
Broad 
A 
5'nucleotidase increased 
10000028 
Broad 
A 
Blood alkaline phosphatase abnonnal 
10059571 
Broad 
A 
Blood alkaline phosphatase increased 
10059570 
Broad 
A 
Blood cholinesterase abno1mal 
10005429 
Broad 
A 
Blood cholinesterase decreased 
10005430 
Broad 
A 
Deficiency of bile secretion 
10071634 
Broad 
A 
Glutamate dehydrogenase increased 
10049483 
Broad 
A 
Glycocholic acid increased 
10080824 
Broad 
A 
HaemoIThamc ascites 
10059766 
Broad 
A 
Hepatic fibrosis marker abno1mal 
10074084 
Broad 
A 
Hepatic fibrosis marker increased 
10074413 
Broad 
A 
Hepatic lymphocytic infiltration 
10079686 
Broad 
A 
Hypoalbuminaeinia 
10020942 
Broad 
A 
Leucine aminopeptidase increased 
10024275 
Broad 
A 
Liver iron concentration abno1mal 
10074352 
Broad 
A 
Liver iron concentration increased 
10074354 
Broad 
A 
Liver opacity 
10084071 
Broad 
A 
Model for end stage liver disease score abno1mal 
10077291 
Broad 
A 
Model for end stage liver disease score increased 
10077292 
Broad 
A 
Peripoital oedema 
10068821 
Broad 
A 
Peritoneal fluid protein abno1mal 
10069000 
Broad 
A 
Peritoneal fluid protein decreased 
10068999 
Broad 
A 
Peritoneal fluid protein increased 
10068998 
Broad 
A 
Pneumobilia 
10066004 
Broad 
A 
Portal vein flow decreased 
10067337 
Broad 
A 
Po1tal vein pressme increased 
10064936 
Broad 
A 
Retinol binding protein decreased 
10048473 
Broad 
A 
Urobilinogen mine decreased 
10070480 
Broad 
A 
Urobilinogen mine increased 
10070479 
Liver-related coae:ulation and bleedine: disturbances (SMQ) 
NaITow 
A 
Acauired antithrombin III deficiency 
10074561 
NaITow 
A 
Acquired factor IX deficiency 
10082747 
NaITow 
A 
Acquired factor VIII deficiency 
10082745 
NaITow 
A 
Acauired factor XI deficiency 
10082746 
NaITow 
A 
Acauired protein S deficiency 
10068370 


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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Narrow 
A 
Anti factor X activity abnormal 
10077670 
Narrow 
A 
Anti factor X activity decreased 
10077674 
Narrow 
A 
Anti factor X activity increased 
10077671 
Narrow 
A 
Antithrombin III decreased 
10049547 
Narrow 
A 
Blood fibrinogen abnormal 
10005518 
Narrow 
A 
Blood fibrinogen decreased 
10005520 
Narrow 
A 
Blood thrombin abnormal 
10005818 
Narrow 
A 
Blood thrombin decreased 
10005820 
Narrow 
A 
Blood thromboplastin abnormal 
10005824 
Narrow 
A 
Blood thromboplastin decreased 
10005826 
Narrow 
A 
Coagulation factor decreased 
10009736 
Narrow 
A 
Coagulation factor IX level abnormal 
10061770 
Narrow 
A 
Coagulation factor IX level decreased 
10009746 
Narrow 
A 
Coagulation factor V level abnormal 
10061771 
Narrow 
A 
Coagulation factor V level decreased 
10009754 
Narrow 
A 
Coagulation factor VII level abnormal 
10061772 
Narrow 
A 
Coagulation factor VII level decreased 
10009761 
Narrow 
A 
Coagulation factor X level abnormal 
10061774 
Narrow 
A 
Coagulation factor X level decreased 
10009775 
Narrow 
A 
Hyperfibrinolysis 
10074737 
Narrow 
A 
Hypocoagulable state 
10020973 
Narrow 
A 
Hypofibrinogenaemia 
10051125 
Narrow 
A 
Hypoprothrombinaemia 
10021085 
Narrow 
A 
Hypothrombinaemia 
10058517 
Narrow 
A 
Hypothromboplastinaemia 
10058518 
Narrow 
A 
International normalised ratio abnormal 
10022592 
Narrow 
A 
International normalised ratio increased 
10022595 
Narrow 
A 
Protein C decreased 
10037005 
Narrow 
A 
Protein S abnormal 
10051736 
Narrow 
A 
Protein S decreased 
10051120 
Narrow 
A 
Prothrombin level abnormal 
10037048 
Narrow 
A 
Prothrombin level decreased 
10037050 
Narrow 
A 
Prothrombin time abnormal 
10037057 
Narrow 
A 
Prothrombin time prolonged 
10037063 
Narrow 
A 
Prothrombin time ratio abnormal 
10061918 
Narrow 
A 
Prothrombin time ratio increased 
10037068 
Narrow 
A 
Thrombin time abnormal 
10051319 
Narrow 
A 
Thrombin time prolonged 
10051390 
 


PAREXEL International 
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K.inevant 
KIN-1901-2001 
Statistical Analysis Plan 
 
Interstitial lung disease (SMQ) 
Scope 
Group 
PT 
PT Code 
NaITow 
A 
Acute interstitial pneumonitis 
10066728 
NaITow 
A 
Alveolar lung disease 
10073344 
NaITow 
A 
Alveolar proteinosis 
10001881 
NaITow 
A 
Alveolitis 
10001889 
NaITow 
A 
Alveolitis necrotising 
10050343 
NaITow 
A 
Autoimmune lung disease 
10080701 
NaITow 
A 
Bronchiolitis 
10006448 
NaITow 
A 
Combined pulmonary fibrosis and emphysema 
10076515 
NaITow 
A 
Diffuse alveolar damage 
10060902 
NaITow 
A 
Eosinophilia myalgia syndrome 
10014952 
NaITow 
A 
Eosinophilic izranulomatosis with polyan!Ziitis 
10078117 
NaITow 
A 
Eosinophilic pneumonia 
10014962 
NaITow 
A 
Eosinoohilic oneumonia acute 
10052832 
NaITow 
A 
Eosinophilic pneumonia chronic 
10052833 
NaITow 
A 
Hypersensitivity pneumonitis 
10081988 
NaITow 
A 
Idiopathic interstitial pneumonia 
10078268 
NaITow 
A 
Idiopathic pneumonia syndrome 
10063725 
NaITow 
A 
Idiopathic pulmonary fibrosis 
10021240 
NaITow 
A 
Immune-mediated pneumonitis 
10082452 
NaITow 
A 
Interstitial lung disease 
10022611 
NaITow 
A 
Lung infiltration 
10025102 
NaITow 
A 
Lung opacity 
10081792 
NaITow 
A 
Necrotising bronchiolitis 
10070831 
NaITow 
A 
Obliterative bronchiolitis 
10029888 
NaITow 
A 
Pneumonitis 
10035742 
NaITow 
A 
Progressive massive fibrosis 
10036805 
NaITow 
A 
Pulmonary fibrosis 
10037383 
NaITow 
A 
Pulmonary necrosis 
10058824 
NaITow 
A 
Pulmonary radiation injury 
10061473 
NaITow 
A 
Pulmonary toxicity 
10061924 
NaITow 
A 
Pulmonary vasculitis 
10037457 
NaITow 
A 
Radiation alveolitis 
10037754 
NaITow 
A 
Radiation fibrosis - lung 
10037758 
NaITow 
A 
Radiation pneumonitis 
10037765 
NaITow 
A 
Small aiiways disease 
10080547 
NaITow 
A 
Transfusion-related acute lung injury 
10052235 


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Kinevant 
KIN-1901-2001 
Statistical Analysis Plan 
Broad 
A 
Acute lung injury 
10069351 
Broad 
A 
Acute respiratory distress syndrome 
10001052 
Broad 
A 
Airway remodelling 
10075289 
Broad 
A 
Allergic eosinophilia 
10075185 
Broad 
A 
Antisynthetase syndrome 
10068801 
Broad 
A 
Biopsy lung abnormal 
10004795 
Broad 
A 
Complications of transplanted lung 
10010187 
Broad 
A 
Cystic lung disease 
10078811 
Broad 
A 
Goodpasture's syndrome 
10018620 
Broad 
A 
Granulomatosis with polyangiitis 
10072579 
Broad 
A 
Granulomatous pneumonitis 
10069152 
Broad 
A 
Langerhans' cell histiocytosis 
10069698 
Broad 
A 
Lung induration 
10057261 
Broad 
A 
Lung transplant rejection 
10051604 
Broad 
A 
Lupus pneumonitis 
10057481 
Broad 
A 
Lymphangioleiomyomatosis 
10049459 
Broad 
A 
Organising pneumonia 
10067472 
Broad 
A 
Pneumonitis chemical 
10035745 
Broad 
A 
Polyarteritis nodosa 
10036024 
Broad 
A 
Pulmonary alveolar haemorrhage 
10037313 
Broad 
A 
Pulmonary eosinophilia 
10037382 
Broad 
A 
Pulmonary granuloma 
10037391 
Broad 
A 
Pulmonary haemosiderosis 
10037396 
Broad 
A 
Pulmonary renal syndrome 
10068513 
Broad 
A 
Pulmonary sarcoidosis 
10037430 
Broad 
A 
Restrictive pulmonary disease 
10048667 
Broad 
A 
Rheumatoid lung 
10039081 
Broad 
A 
Sarcoidosis 
10039486 
Broad 
A 
Systemic sclerosis pulmonary 
10042954 
Broad 
A 
Toxic oil syndrome 
10051222 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
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