A Phase 1, Open Label, Dose-escalation Study of the Safety and Pharmacokinetics of a Combination of Two Anti-SARS-CoV-2 mAbs (C144-LS and C135-LS) in Healthy Volunteers
Phase: PHASE1
Conditions: Covid19
Sponsor: Rockefeller University

The Rockefeller University 
 
IND: 150929 
February 4, 2021 
 
PROTOCOL: RUCOV1 
CONFIDENTIAL 
1 
A phase 1 study of the safety and pharmacokinetics of a combination of two anti-SARS-CoV-2 
mAbs (C144-LS and C135-LS) in healthy volunteers (Protocol Number: RUCOV1) 
 
 
 
 
 
 
 
IND Sponsor: 
The Rockefeller University 
IND # 150929 
 
DAIDS-ES ID 38798 
 
Principal Investigator/Protocol Chair: 
Christian Gaebler MD 
 
Version: 
2.1 
 
Version Date: 
February 4, 2021 
 
 
 
 
 
 
 
 
 
 
 
 
Confidentiality Statement 
This document is confidential and is to be distributed for review only to investigators, potential 
investigators, consultants, study staff, and applicable independent ethics committees or institutional 
review boards. The contents of this document shall not be disclosed to others without written 
authorization from The Rockefeller University, unless it is necessary to obtain informed consent from 
potential study participants. 
 
Statement of Compliance 
The clinical trial will be conducted in compliance with the protocol, with the International Conference 
on Harmonization Good Clinical Practice E6 (R2) (ICH-GCP), and with 45 CFR 46 and 21 CFR 50, 
56 and 312. All protocol investigators have completed Protection of Human Subjects Training. 
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The Rockefeller University 
 
IND: 150929 
February 4, 2021 
 
PROTOCOL: RUCOV1 
CONFIDENTIAL 
2 
Signature Page 1 
 
 
The signature below constitutes the approval of this protocol and the attachments, and provides the 
necessary assurances that this trial will be conducted according to all stipulations of the protocol, 
including all statements regarding confidentiality, and according to local legal and regulatory 
requirements and applicable U.S. federal regulations and ICH guidelines. 
 
The Lead Principal Investigator (Protocol Chair) should sign Signature Page 1. A copy of this 
Signature Page 1 should be filed with the holder of the Regulatory documents and a copy should be 
maintained at the site. 
 
 
Principal Investigator: _______________________________________________ 
Print/Type 
 
Signed: ______________________________      Date:  ____________________ 
Name/Title 
 
 
 
 
 
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The Rockefeller University 
 
IND: 150929 
February 4, 2021 
 
PROTOCOL: RUCOV1 
CONFIDENTIAL 
3 
Signature Page 2 
 
 
The signature below constitutes the approval of this protocol and the attachments, and provides the 
necessary assurances that this trial will be conducted according to all stipulations of the protocol, 
including all statements regarding confidentiality, and according to local legal and regulatory 
requirements and applicable U.S. federal regulations and ICH guidelines. 
 
The Investigator(s) of Record (signature(s) on 1572) from each participating clinical site should sign 
the Signature Page 2 as appropriate. This Signature Page 2 should be maintained at each site. 
 
 
Investigator of Record: _______________________________________________ 
Print/Type 
Signed: _________________________________  Date: ______________________ 
Name/Title 
 
Investigator of Record: _______________________________________________ 
Print/Type 
Signed: ________________________________   Date: ______________________ 
Name/Title 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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The Rockefeller University 
 
IND: 150929 
February 4, 2021 
 
PROTOCOL: RUCOV1 
CONFIDENTIAL 
4 
Table of Contents 
1 Key Roles ........................................................................................................................................14 
1.1 
Study Site and associated Institutions ................................................................................. 14 
1.2 
Study Personnel .................................................................................................................. 15 
1.3 
External Personnel .............................................................................................................. 16 
1.4 
Statistician: .......................................................................................................................... 16 
2 LAY SUMMARY ..........................................................................................................................17 
3 Objectives and Rationale .................................................................................................................17 
3.1 
Background ......................................................................................................................... 17 
3.2 
Preclinical Characterization ................................................................................................ 20 
3.2.1 
Identification of C135 and C144 and in vitro characterization ................................. 20 
3.2.2 
In vitro characterization of C135 and C144 ............................................................... 21 
3.2.3 
In vitro characterization of C135-LS and C144-LS .................................................... 23 
3.2.4 
In vivo characterization of C135-LS and C144-LS ..................................................... 23 
3.2.5 
Toxicology studies ....................................................................................................... 28 
3.3 
Clinical experience .............................................................................................................. 28 
3.3.1 
Anti-SARS-CoV-2 antibodies to treat or prevent infections ....................................... 28 
3.3.2 
Fc-modified antibodies to enhance binding to the FcRn receptor ............................. 29 
3.4 
Hypothesis........................................................................................................................... 30 
3.5 
Study Objectives ................................................................................................................. 30 
3.6 
Study Outcomes .................................................................................................................. 30 
Primary Outcomes: ......................................................................................................................... 30 
4 Study Design ...................................................................................................................................31 
4.1 
Dose Selection and Dose Escalation Plan ........................................................................... 32 
Part A - Dose escalation phase ........................................................................................................ 33 
Part B – Randomized, double-blinded phase .................................................................................. 34 
4.2 
End of the clinical trial ........................................................................................................ 35 
5 Study Population .............................................................................................................................35 
5.1 
Inclusion Criteria: ............................................................................................................... 35 
5.2 
Exclusion Criteria: .............................................................................................................. 36 
6 Methods and Procedures .................................................................................................................36 
6.1 
Screening Procedure and Study Visits ................................................................................ 36 
6.1.1 
Pre-Screening ............................................................................................................. 37 
6.1.2 
Screening Visit ............................................................................................................ 37 
6.1.3 
Pre-administration Visit.............................................................................................. 37 
6.1.4 
C144-LS and C135-LS Administration Visit ............................................................... 37 
6.1.5 
Post- C144-LS and C135-LS Administration Visits .................................................... 39 
6.1.6 
Final Visit/Early termination Visit.............................................................................. 39 
6.1.7 
Discontinuation of study drug infusions and/or participant withdrawal from study.. 39 
6.1.8 
Unblinding (Group S3) ............................................................................................... 41 
6.2 
Study Procedures ................................................................................................................ 41 
6.2.1 
Consent Procedure...................................................................................................... 41 
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The Rockefeller University 
 
IND: 150929 
February 4, 2021 
 
PROTOCOL: RUCOV1 
CONFIDENTIAL 
5 
6.2.2 
Study Assignment ........................................................................................................ 41 
6.2.3 
C144-LS and C135-LS Administration Procedure ..................................................... 42 
6.2.4 
Medical History and Physical Examination ............................................................... 43 
6.2.5 
Monitoring for cytokine release associated adverse events and treatment of cytokine 
release syndrome ........................................................................................................................ 43 
6.2.6 
SARS-CoV-2 Infection ................................................................................................. 44 
6.2.7 
SARS-CoV-2 Vaccination ............................................................................................ 44 
6.2.8 
Other COVID-19 Considerations ............................................................................... 44 
6.2.9 
Family Planning Counseling ...................................................................................... 45 
6.2.10 
Safety Assessments ...................................................................................................... 45 
6.2.11 
Blood Collection, Storage and Shipment .................................................................... 46 
6.2.12 
Routine Laboratory Parameters ................................................................................. 46 
6.2.13 
Pharmacokinetics and Immunogenicity Assessments ................................................. 47 
6.2.14 
Other Laboratory Assessments ................................................................................... 47 
6.2.15 
Compensation ............................................................................................................. 48 
7 Investigational Product ....................................................................................................................48 
7.1 
Regimen .............................................................................................................................. 48 
7.2 
Study Product Formulation and Preparation ....................................................................... 48 
7.3 
Dispensing and Handling of Investigational Product: ........................................................ 50 
7.4 
Accountability and Disposal of Used and Unused Investigational Product ....................... 50 
7.5 
Concomitant Medications and Procedures .......................................................................... 50 
7.6 
Permitted Medications and Procedures ............................................................................... 50 
7.7 
Prohibited Medications and Procedures .............................................................................. 51 
7.8 
Precautionary Medications and Procedures ........................................................................ 51 
7.9 
Required Medications ......................................................................................................... 51 
7.10 
Rescue Medications ............................................................................................................ 51 
8 Data Analysis ..................................................................................................................................51 
8.1 
Analysis of Safety, PK and Antiretroviral effects .............................................................. 52 
8.2 
Sample Size Considerations ................................................................................................ 53 
9 Data and Sample Storage ................................................................................................................53 
10 Recruitment and Advertising ...........................................................................................................54 
11 Potential Benefits to Participants ....................................................................................................54 
12 Potential risks to the participant including to the fetus ...................................................................54 
13 Procedures to minimize risk ............................................................................................................55 
14 Data and Safety Monitoring Plan ....................................................................................................57 
14.1 
Safety Monitoring Committee ............................................................................................ 57 
14.2 
Monitoring .......................................................................................................................... 59 
14.3 
Adverse Event Definition and Classification ...................................................................... 60 
14.4 
Reporting Adverse Events .................................................................................................. 60 
14.5 
Reporting Unanticipated AEs ............................................................................................. 60 
14.6 
Clinical Laboratory Improvement Amendment/Clinical Laboratory Evaluation Program 
(CLIA/CLEP) .................................................................................................................................. 61 
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The Rockefeller University 
 
IND: 150929 
February 4, 2021 
 
PROTOCOL: RUCOV1 
CONFIDENTIAL 
6 
14.7 
Toxicity Management and Stopping Rules ......................................................................... 61 
14.8 
Other Disease Events .......................................................................................................... 62 
15 Clinical Trial Registration ...............................................................................................................62 
16 Bibliography ....................................................................................................................................63 
 
 
Table of Figures 
Figure 1. In vitro neutralizing activity of selected anti-SARS-CoV-2 antibodies ...............................21 
Figure 2. SARS-CoV-2 antibody combinations suppress the selection of antibody resistance ..........22 
Figure 3. Antibody combinations synergize to increase in vivo potency. ...........................................24 
Figure 4. Evaluation of C144-LS and C135-LS for prophylactic and therapeutic efficacy against 
SARS-CoV-2 infection in Hamsters ...................................................................................25 
Figure 5. C144-LS and C135-LS for prophylaxis against SARS-CoV-2 infection in macaques ........26 
Figure 6. C144-LS and C135-LS for therapy of SARS-CoV-2 infection in macaques .......................27 
Figure 7. Schedule of Study Visits and Sample Collection .................................................................32 
Figure 8. Dose Escalation Scheme.......................................................................................................35 
 
 
Table of Tables 
Table 1. Study Groups .................................................................................................................. 31 
 
 
 
 
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The Rockefeller University 
 
IND: 150929 
February 4, 2021 
 
PROTOCOL: RUCOV1 
CONFIDENTIAL 
7 
List of Abbreviations 
 
Ab 
Antibody 
ACE 
Angiotensin Converting Enzyme 
ADA 
Anti-drug Antibodies 
AE 
Adverse Event/Adverse Experience 
ANOVA 
Analysis of Variance 
AUC 
Area Under the Curve 
bNAbs 
Broadly Neutralizing Antibodies 
CD4 
T-cell Surface Glycoprotein CD4 
CFR 
Code of Federal Regulations 
cGMP 
Current Good Manufacturing Practices 
CONSORT 
Consolidated Standards of Reporting Trials 
CHO 
Chinese Hamster Ovary 
CL/F 
Clearance 
COVID-19 
Coronavirus Disease 2019 
Cmax 
Maximum Concentration Of A Drug In The Body After Dosing 
CRF  
Case Report Form 
CRSO  
Clinical Research Support Office 
CTSA  
Clinical and Translational Science Award 
CCTS  
Center for Clinical and Translational Science 
DAIDS 
Division Of Acquired Immunodeficiency Syndrome 
DLT 
Dose Limiting Toxicity 
DMID 
Division of Microbiology and Infectious Diseases 
DNA 
Deoxyribonucleic Acid 
DSMB  
Data and Safety Monitoring Board 
ELISA 
Enzyme-Linked Immunosorbent Assay 
FDA  
Food and Drug Administration 
FWA  
Federal-Wide Assurance 
GCP  
Good Clinical Practice 
HAHA 
Human Anti-Human Antibody 
HIPAA  
Health Insurance Portability and Accountability Act 
hu-mice 
Humanized Mice 
IC50 
Half Maximal Inhibitory Concentration 
ICF  
Informed Consent Form 
ICH  
International Conference on Harmonization 
I.M.  
Intramuscularly 
IND  
Investigational New Drug 
IP 
Investigational Product 
IRB  
Institutional Review Board 
I.V.  
Intravenously 
mAb 
Monoclonal antibody 
MCB 
Master Cell Bank 
MFI 
Mean Fluorescence Intensity 
mg/mL 
Milligram Per Millileter 
MTD 
Maximum tolerated dose 
N  
Number (typically refers to participants) 
nAb 
Neutralizing antibody 
NIAID  
National Institute of Allergy and Infectious Diseases, NIH 
NIH  
National Institutes of Health 
NHP 
Non-Human Primates 
NOAEL 
No Observable Adverse Effect Level 
NOEL 
No Observable Effect Level 
NP 
Nasopharyngeal 
OHRP  
Office for Human Research Protections 
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The Rockefeller University 
 
IND: 150929 
February 4, 2021 
 
PROTOCOL: RUCOV1 
CONFIDENTIAL 
8 
OHSR  
Office for Human Subjects Research 
PBMC 
Peripheral Blood Mononuclear Cell 
PI  
Principal Investigator 
PK 
Pharmacokinetics 
RU  
The Rockefeller University 
RUH  
The Rockefeller University Hospital 
QA  
Quality Assurance 
QC  
Quality Control 
RBD 
Receptor Binding Domain 
RNA 
Ribonucleic Acid 
SAE  
Serious Adverse Event/Serious Adverse Experience 
SARS-CoV-2 
 
Severe Acute Respiratory Syndrome-associated Coronavirus 2 
S.C.  
Subcutaneously 
SMC 
Safety Monitoring Committee 
SOP  
Standard Operating Procedure 
t1/2 
Half-Life 
T cell 
T lymphocyte 
UAE 
Unanticipated Adverse Event 
 
 
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The Rockefeller University 
 
IND: 150929 
February 4, 2021 
 
PROTOCOL: RUCOV1 
CONFIDENTIAL 
9 
PROTOCOL SUMMARY 
 
Title 
A phase 1 study of the safety and pharmacokinetics of a combination of two anti-SARS-
CoV-2 mAbs (C144-LS and C135-LS) in healthy volunteers 
Short Title 
2 mAbs in Healthy Volunteers
-
CoV
-
SARS
-
RU Anti
 
 
Protocol Number 
RUCOV1 
Phase 
Phase 1 
Investigational 
product 
Two highly neutralizing antibodies directed against SARS-CoV-2 RBD: C144-LS and C135-
LS. 
 
The antibodies are manufactured separately and each will be formulated in a separate vial at a 
concentration of 50 mg/mL. 
 
Indication 
Prevention or therapy of COVID-19 
 
Sample size 
23 to 38 
Number of study 
sites 
Single site – The Rockefeller University Hospital (RUH), New York, NY, U.S.A. 
Study Objectives 
Primary objectives: 
- 
To evaluate the safety and tolerability of subcutaneous injections or single intravenous 
infusions of C144-LS in combination with C135-LS in healthy volunteers. 
- 
To evaluate the pharmacokinetic profile of C144-LS and C135-LS in combination, 
administered subcutaneously or intravenously at increasing dose levels in healthy 
volunteers. 
 
Secondary objectives: 
- 
To assess the occurrence of anti-drug antibody responses. 
- 
To evaluate serum neutralizing activity against SARS-CoV-2 after C144-LS and C135-LS 
administration. 
Study 
Outcomes/Objective
s 
Primary outcomes: 
- 
Rate of solicited and investigational product (IP)-related unsolicited adverse events that 
are Grade 2 and above (including confirmed laboratory abnormalities) 4 weeks after 
administration. 
- 
Rate of solicited and IP-related unsolicited adverse events that are Grade 3 and above 
(including confirmed laboratory abnormalities) 4 weeks after administration. 
- 
Proportion of participants with serious adverse events (SAEs) throughout the study period 
that are considered related to investigational products and their duration. 
- 
The pharmacokinetic profile of C144-LS and C135-LS: elimination half-life (t1/2), 
clearance (CL/F), volume of distribution (Vz/F), AUC and decay curve. 
 
Secondary Outcomes: 
- 
Rate and severity of investigational product (IP)-related adverse events during study 
follow up. 
- 
Frequency and levels of induced anti-C144-LS and anti-C135-LS antibodies in all study 
groups. 
- 
Serum neutralizing activity against SARS-CoV-2 before and after C144-LS and C135-LS 
administration. 
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The Rockefeller University 
 
IND: 150929 
February 4, 2021 
 
PROTOCOL: RUCOV1 
CONFIDENTIAL 
10
Overview of Study 
Design   
This is a first-in-human, single dose, dose-escalation phase 1 study to evaluate the safety and 
pharmacokinetics of a combination of two highly neutralizing anti-SARS-CoV-2 mAbs 
targeting two distinct epitopes on the receptor protein binding domain (RBD) of the SARS-
CoV-2 spike protein in healthy volunteers. 
 
The study consists of two parts. Part A has a standard 3+3 phase 1 dose escalation design. 
Study participants will receive subcutaneous injections of C144-LS and C135-LS at 4ml 
(approximately 100mg of each antibody administered separately) or 8ml (approximately 
200mg of each antibody administered separately), or sequential intravenous infusions of C144-
LS and C135-LS, each administered via a peripheral vein over 60 minutes at one of three 
increasing dose levels (1.5 mg/kg, 5 mg/kg and 15 mg/kg of each antibody). Participants in 
Part B will be randomized to receive subcutaneous injections of C144-LS and C135-LS at 8ml 
(approximately 200mg of each antibody administered separately) or placebo in a 3:1 ratio and 
double-blinded fashion. 
 
Part A has started enrollment. Part B has a planned enrollment of 8 participants (see Table and 
Scheme below). 
 
Study Groups 
 
Part A – Open label 
 
Group 
Antibody 
Dose 
Route 
Regimen 
N 
 
S1 
C144-LS + C135-LS 
 
100 mg 
each mAb 
SC 
Day 0 
3+3 
S2 
C144-LS + C135-LS 
 
200 mg 
each mAb 
SC 
Day 0 
3+3 
V1 
C144-LS + C135-LS 
 
1.5 mg/kg 
each mAb 
IV 
Day 0 
3+3 
V2 
C144-LS + C135-LS 
 
5 mg/kg 
each mAb 
IV 
Day 0 
3+3 
V3 
C144-LS + C135-LS 
 
15 mg/kg 
each mAb 
IV 
Day 0 
3+3 
 
Part B – Randomized, double-blinded 
 
Group 
Antibody 
Dose 
Route 
Regimen 
N 
 
S3 
C144-LS + C135-LS 
 
200 mg 
each mAb 
or placebo 
SC 
Day 0 
8 (6:2) 
 
 
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The Rockefeller University 
 
IND: 150929 
February 4, 2021 
 
PROTOCOL: RUCOV1 
CONFIDENTIAL 
11
 
Part A - Dose escalation plan 
During the subcutaneous and intravenous dose escalation phase of the study, enrollment will 
be staggered by 1 day for the volunteers of each group. 
 
Subcutaneous (SC) Administration (Groups S1 and  S2) 
1. First, eligible participants will be enrolled in Group S1 (C144-LS + C135-LS, 2mL each). 
2. Enrollment in Group S2 (C144-LS + C135-LS, 4mL each) will begin after all three 
participants enrolled in Group S1 reach at least 7 days without a dose limiting toxicity 
(DLT) reported in the group (DLT: any adverse event of grade 3 or greater toxicity, if the 
study investigators recognize a probable or definite attribution to C144- LS and/or C135-
LS). 
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The Rockefeller University 
 
IND: 150929 
February 4, 2021 
 
PROTOCOL: RUCOV1 
CONFIDENTIAL 
12
Overview of Study 
Design   
3. If 1 DLT occurs, 3 additional participants will enroll in Group S1. If no additional dose 
limiting toxicities occur, enrollment in the next dose level will proceed. 
4. If 2 or more DLTs occur, dosing will be halted and the prior lower dose level will be 
declared the maximum subcutaneous tolerated dose (MTD). 
5. Enrollment in Group S2 will follow the same rules. 
 
Intravenous (IV) Administration (Groups V1, V2 and V3) 
1. Enrollment in Group V1 (C144-LS + C135-LS, 1.5mg/kg each, IV) will begin at least 7 
days after the first three participants enrolled in Group S2. 
2. Enrollment in Group V2 (C144-LS + C135-LS, 5mg/kg each, IV) will begin after all three 
participants enrolled in Group V1 reach at least 7 days without a dose limiting toxicity 
(DLT) reported in the group (DLT: any adverse event of grade 3 or greater toxicity, if the 
study investigators recognize a probable or definite attribution to C144-LS and/or C135-
LS). 
3. If 1 DLT occurs, 3 additional participants will enroll in Group V1. If no additional dose 
limiting toxicities occur, enrollment in the next dose level will proceed. 
4. If 2 or more DLTs occur, dosing will be halted and the prior lower dose level will be 
declared the maximum intravenous tolerated dose (MTD). 
5. Enrollment in Group V3 (C144-LS + C135-LS, 15mg/kg each, IV) will follow the same 
rules. 
6. Enrollment in Group V3 will begin at least 7 days after three participants enrolled in 
Group V2 and following SMC review of all available safety data. 
 
Note: As outlined in Section 14.1, the SMC will be asked to review safety data if one or more 
grade 3 or higher adverse events, deemed probably or definitely related to the study drugs 
(DLT) occur. No additional administration of the investigational products will take place 
pending a SMC review. In the event of a DLT, the SMC will make recommendations with 
regards to expansion of a study group from 3 to 6 participants, dose escalation to the next dose 
level, or halting additional enrollment. 
 
Part B 
During the subcutaneous, randomized, double-blinded phase (Part B) of the study, enrollment 
will be limited to a maximum of two participants per day. 
 
Enrollment in Group S3 will begin once all participants in Part A have met eligibility criteria 
and have been scheduled for enrollment (day 0) and after all three participants enrolled in 
Group S2 reach at least 7 days without a dose limiting toxicity (DLT) reported in the group. 
 
Toxicity Evaluations 
Treatment toxicity will be evaluated per the FDA Guidance of Industry Toxicity Grading Scale 
for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. 
 
Participants will be observed at the study site for 24 hours after antibody administration, and 
will return for follow visits over 48 weeks, according to Appendix A, Time of Events Schedule.  
Blood samples will be collected for safety testing at day 1, weeks 1, 4, 8, 12, 18 24, 36 and 48 
following antibody dosing. Pharmacokinetics assessments will be performed before and after 
each antibody dosing and at later time points, as indicated in Appendix A (see below).  
 
Study Duration 
15 months 
 
Inclusion 
and 
Exclusion Criteria 
 
Inclusion Criteria: 
- 
Aged 18 to less than 65. 
- 
If sexually active male or female, and participating in sexual activity that could lead to 
pregnancy, agrees to use one effective method of contraception from 10 days prior to the 
antibody administration until 6 months after investigational product (IP) administration. 
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The Rockefeller University 
 
IND: 150929 
February 4, 2021 
 
PROTOCOL: RUCOV1 
CONFIDENTIAL 
13
Exclusion Criteria: 
- 
Weight > 110 kg for groups S1 and S2 only 
- 
History of prior positive SARS-CoV-2 RT-PCR or SARS-CoV-2 serology. 
- 
Active respiratory or non-respiratory symptoms consistent with COVID-19. 
- 
Medically attended acute illness or hospitalization (ie, >24 hours) for any reason within 
30 days prior to screening. 
- 
Acute exacerbation of a chronic pulmonary condition (eg, chronic obstructive pulmonary 
disease [COPD], asthma exacerbations, or uncontrolled hypertension, as defined by a 
systolic blood pressure > 180 and/or diastolic blood pressure > 120, in the presence or 
absence of anti-hypertensive medications) in the past 6 months prior to screening. 
- 
Use of systemic corticosteroids, immunosuppressive anti-cancer, or other medications 
considered significant by the trial physician within the last 6 months. 
- 
Other clinically significant acute or chronic medical condition that in the opinion of the 
investigator would preclude participation. 
- 
Are eligible for COVID-19 vaccination prior to your entry in the study according to local 
guidelines (e.g. healthcare professionals, non-healthcare professionals such as teachers, 
firefighters, public transit workers). 
- 
Laboratory abnormalities in the parameters listed: 
o 
Absolute neutrophil count ≤ 1,500 K/mcL;  
o 
Hemoglobin ≤ 10.5 gm/dL if female; ≤ 11 gm/dL if male;  
o 
Platelet count ≤ 125,000 K/mcL;  
o 
ALT ≥ 1.25 x ULN; AST ≥ 1.25 x ULN;  
o 
Total bilirubin ≥ 1.25 x ULN;  
o 
Creatinine ≥ 1.1 x ULN;  
- 
Pregnancy or lactation. 
- 
Any vaccination within 14 days prior to SARS-CoV-2 mAbs administration (except 
influenza vaccine). 
- 
History of prior receipt of any SARS-CoV-2 vaccine or antibodies, including convalescent 
plasma. 
- 
Known allergy/sensitivity or any hypersensitivity to components of the investigational 
agents. 
- 
History of severe reaction to a vaccine or monoclonal antibody administration or history 
of severe allergic reactions. 
- 
Participation in another clinical study of an investigational product currently or within past 
12 weeks, or expected participation during this study. 
 
Study 
Product, 
Dose, 
Route, 
Regimen 
- 
Single subcutaneous injections of C144-LS and C135-LS, each mAb dosed at 
approximately 100 mg (two 2 mL injections administered at separate sites) or 200 mg (four 
2 mL injections administered at separate sites). 
- 
Single subcutaneous injections of placebo (buffered solution) as four 2 mL injections 
administered at separate sites. 
- 
One intravenous infusion of C144-LS and C135-LS, each administered via a peripheral 
vein over 60 minutes sequentially. Starting dose level is 1.5 mg/kg of each antibody, with 
0.5 log10 increases to 5 mg/kg and 15 mg/kg. 
 
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IND: 150929 
February 4, 2021 
 
PROTOCOL: RUCOV1 
CONFIDENTIAL 
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Statistical 
Methodology 
A standard “3+3” Phase 1 trial design will be used in the dose-escalation phase (Part A) to 
assess safety; stopping rules (as defined above) will be based on the occurrence of dose-limiting 
toxicity. 
 
Pharmacokinetic parameters will be calculated using standard non-compartmental analysis 
methods. Descriptive results will be presented for the pharmacokinetic parameters by dose 
group. 
 
Continuous data will be summarized by descriptive statistics, including sample size, mean, 
standard deviation, median and range.  Categorical data will be summarized by the number and 
percentage of participants with an outcome. 
 
1 
KEY ROLES 
 
1.1 
Study Site and associated Institutions 
 
The Rockefeller University Hospital, New York NY 
1230 York Ave. 
New York, NY 10065 
Contact Person: Christian Gaebler, MD or Marina Caskey, MD 
Phone Number: (212) 327-8367, (212) 327-7396 
Fax Number: (212) 327-7234 
E-mail: cgaebler01@rockefeller.edu 
             mcaskey@rockefeller.edu     
 
Clinical Laboratories: 
- Quest Diagnostics 
500 Plaza Drive 
Secaucus, NJ, 07094 
 
- New York Presbyterian / Cornell 
525 East 68th street 
New York, NY 10065 
 
- Memorial Sloan Kettering Cancer Center 
1275 York Avenue 
NY, NY, 10065 
 
- LabCorp 
330 W 58th St 
New York, NY, 10019 
 
Research Laboratories: 
- 
Sample processing and storage: 
Laboratory of Molecular Immunology 
The Rockefeller University Hospital, New York NY 
1230 York Ave. 
New York, NY 10065 
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Contact Person: Irina Shimeliovich, MD PhD 
Phone Number: (212) 327-8107 
Fax Number: (212) 327-8875 
E-mail: shimeli@mail.rockefeller.edu 
 
- 
Pharmacokinetics and anti-drug antibodies: 
PPD Laboratories Bioanalytical Services (a contract research organization) 
 
Laboratory of Molecular Neuro-Oncology 
Howard Hughes Medical Institute 
The Rockefeller University 
1230 York Avenue 
Box 226 
New York, NY 10065 
Contact Person: Robert B. Darnell, MD PhD 
Phone Number: 212-327-7474 
Fax Number: 212-327-7109 
E-mail: Robert.Darnell@rockefeller.edu 
 
Funder: National Institute of Allergy and Infectious Diseases (NIAID) 
 
Data Management and External Monitoring: 
EMMES Corporation 
401 N. Washington St. Suite 700 
Rockville, MD 20850 
 
 
1.2 
Study Personnel 
Rockefeller Site 
Principal Investigator 
Christian Gaebler, MD 
Instructor in Clinical Investigation 
The Rockefeller University 
1230 York Avenue, NY, NY 10065 
Phone Number: 212 327-8367 
Fax Number: 212 327-7234 
E-mail: cgaebler01@mail.rockefeller.edu 
 
 
 
Protocol 
Staff 
Personnel 
– 
Co-
investigators 
Marina Caskey, MD 
Michel Nussenzweig, MD, PhD 
Dennis Schaefer-Babajew, MD 
Martina Turroja, MD 
Irina Shimeliovich, MD PhD 
Katrina Millard, ANP 
Arlene Hurley, ANP 
Maggi Pack, PhD 
Melissa La Mar 
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1.3 
External Personnel 
Luis Montaner, D.V.M., M.Sc., D.Phil (consultant) 
The Wistar Institute 
3601 Spruce St., Philadelphia, PA 19104 
 
1.4 
Statistician: 
Caroline Jiang, MS 
The Rockefeller University 
1230 York Avenue 
HOS 237, New York, NY 10065 
Email:  cjiang@rockefeller.edu 
 
 
 
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2 
LAY SUMMARY 
 
The COVID-19 pandemic is currently gripping the world in the absence of any clearly effective 
preventive or therapeutic remedies. Aside from the health consequences, the necessary decrease in 
human activity has resulted in economic losses and expanding social disparities without modern 
precedent, especially in countries where health care and social security systems were not sufficient 
even prior to the pandemic. 
 
It is hoped that one or more currently available drugs can bring a measure of mitigation to meet the 
medical need, however it is unclear whether a repurposed drug can be given safely in high enough 
doses to provide meaningful efficacy against the virus. Multiple vaccines and other preventive or 
therapeutic strategies are being tested in clinical trials. As of December 11, 2020 one vaccine has 
received Emergency Use Approval (EUA) by the FDA for the prevention of SARS-CoV-2 infection. 
Two monoclonal antibodies also received EUA for the treatment of mild to moderate COVID-19. At 
this time, the supply of both vaccine and antibodies remains extremely limited. It is also unclear at this 
time how long protection from the available vaccine will last. Therefore, there is a continued need for 
the development of additional prevention and treatment strategies that can add to the arsenal of 
modalities that have become recently available.  
 
Antibodies are the active agents in most vaccines and have the added benefit of use as therapeutics 
when administered passively. We have identified a set of complementary human antibodies from 
individuals who recovered from COVID-19 that potently neutralize SARS-CoV-2 (the virus that 
causes COVID-19) at low concentrations. The object of this study is to evaluate the safety and 
pharmacokinetics of the combination of two of anti-SARS-CoV-2 monoclonal antibodies in healthy 
volunteers. 
 
3 
OBJECTIVES AND RATIONALE 
3.1 
Background 
 
In December 2019, an outbreak of a novel viral pneumonia of unknown origin was identified in the 
city of Wuhan, China. Shortly thereafter, molecular techniques revealed that the rapidly spreading 
severe acute respiratory syndrome was caused by a novel coronavirus, which was named SARS-CoV-
2. The disease caused by this new pathogen was subsequently named COVID-19. Since then, the 
number of reported cases surpassed 30 million and while drastic public health measures were able to 
curb the exponential spread of this novel pathogen in some areas of the world, the virus is continuing 
to infect millions of people worldwide leading to immense morbidity and mortality, and profound 
economic and societal damage. 
 
SARS-CoV-2 is a member of the coronavirus family, which includes some highly pathogenic viruses 
such as SARS-CoV (Severe Acute Respiratory Syndrome virus; (Drosten et al. 2003) and MERS-CoV 
(Middle Eastern Respiratory Syndrome virus; (Zaki et al. 2012) but also less pathogenic viruses such 
as the common-cold coronaviruses (229E, NL63, OC43 and HKU1), which are endemic seasonal 
pathogens of mild upper respiratory infections (Galanti et al. 2019). Coronaviruses are positive-strand 
non-segmented RNA viruses, with a range of host and tissue tropisms and the potential for cross-
species transmission (Masters 2006). SARS-CoV-2 was named due to its relatedness to its closest 
phylogenetic relative within the coronavirus family, SARS-CoV, a virus that was causative for the 
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IND: 150929 
February 4, 2021 
 
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CONFIDENTIAL 
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first global viral pandemic of the 21st century in 2002-2003. Like SARS-CoV, SARS-CoV-2 is 
thought to have originated in bats from which it has made its way into humans probably via an as of 
yet indeterminate intermediary. Moreover, like SARS-CoV it has been shown to be able to bind to 
human ACE-2, facilitating its tropism for the mucosa of the upper and lower respiratory tract (Walls 
et al. 2020), where both pathogens exert their primary clinical pathology. 
 
Infection with SARS-CoV-2 can lead to a wide variety of clinical outcomes (Guan et al. 2020; 
Richardson et al. 2020). The vast majority of infected individuals develop only mild symptoms akin 
to a common cold. Some individuals, however, particularly those who are elderly and/or have 
comorbidities can progress to a more severe phenotype, which primarily manifests as pneumonia, 
respiratory failure and acute respiratory distress syndrome (ARDS), but can also impair other organ 
systems such as the vasculature, the heart, kidneys, and the central and peripheral nervous system 
among others. Severe COVID-19 disease often requires hospitalization, oxygen supplementation, 
mechanical ventilation and other organ replacement therapy warranting admission to an intensive care 
unit. Moreover, a significant fraction of severe COVID-19 cases eventually succumb to the disease, 
despite maximal treatment with literature reports of mortality rates varying between 10 and 90 percent 
(Docherty et al. 2020; Grasselli et al. 2020; Richardson et al. 2020). 
 
While some risk factors for progression to severe disease, such as older age, cardiovascular disease, 
hypertension, obesity, diabetes mellitus, chronic lung/kidney disease and malignancy have emerged, 
it is far from clear how to predict such adverse outcomes (Williamson et al. 2020). Moreover, a 
significant proportion of the global population possesses above mentioned risk factors making them 
particularly vulnerable to an adverse course of disease. Therefore, there is a dire need to rapidly 
develop therapeutic and prophylactic medicines to prevent severe disease and to protect those most at 
risk. 
 
Innumerable efforts are being undertaken to characterize the human immune responses and develop 
vaccines to SARS-CoV-2. Especially the quality and duration of the humoral immune response 
following natural infection with SARS-CoV-2 is of great importance. 
 
Under protocol DRO-1006, our group began to study the humoral immune responses of a cohort of 
149 COVID-19 convalescent individuals using samples collected an average of 39 days after the onset 
of symptoms. These early studies showed that the initial humoral responses to SARS-CoV-2 are highly 
variable and that 33% of affected individuals failed to develop neutralizing activity above a median 
geometric mean half-maximal neutralization titer (NT50) of 50 (Robbiani et al. 2020). However, 
despite overall low plasma titers, antibody sequencing revealed expanded clones of receptor binding 
domain (RBD)-specific memory B cells expressing closely related antibodies in different individuals. 
Antibodies targeting three distinct epitopes on the RBD of the SARS-CoV-2 spike protein were 
identified, and some of these showed in vitro half-maximal inhibitory concentrations (IC50 values) as 
low as single digit nanograms per milliliter. 
 
Little is known about the dynamic and durability of the humoral immune responses to SARS-CoV-2 
and longitudinal studies that test the evolution of antibodies in circulating memory B cells are currently 
under way. 
 
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The contribution of T cells to SARS-CoV-2 immunity is yet another unresolved question. Declining 
peripheral blood lymphocyte counts have been observed during acute infection and found to be 
correlated with disease severity. This may reflect direct cytotoxic effects of the virus or rather a 
redistribution of lymphocytes to the lung tissue in the setting of an excessive inflammatory response 
(Giamarellos-Bourboulis et al. 2020). An exuberant inflammatory response seems to dominate the 
pathogenesis of the later stages of severe COVID-19, and increases in key inflammatory markers such 
as CRP, Ferritin and IL-6 have been reported. Cytokine blocking therapy (i.e. Tocilizumab) and 
immune suppressive therapy with systemic glucocorticoids (ie dexamethasone) have shown some 
promise for patients with severe late stage disease, but prognosis often remains dismal (Group et al. 
2020). It is currently unclear whether the immune pathology observed in severe COVID-19 is intrinsic 
to this virus or whether the inability to clear the pathogen in a timely manner leads to an overwhelming 
and deleterious immune activation. However, it appears plausible that prevention of infection or swift 
clearance of infection by the adaptive immune system may prevent or curtail such phenomena. 
 
While cellular immunity can play an ameliorating role once an infection is established, in order to 
achieve sterilizing protection from SARS-CoV-2 infection, neutralizing antibodies are essential. 
Historically, this has been illustrated by the fact that most licensed vaccines are thought to exert their 
preventative effects through neutralizing antibodies and even for immunity established via natural 
infection, antibodies are the best characterized correlates of protection from future infection (Plotkin 
2010). COVID-19 antibody therapy in the form of polyclonal plasma from convalescent individuals 
is currently being explored as a therapeutic option and it has even been granted an emergency use 
authorization (EUA) by the FDA on August 23, 2020. However, therapy with convalescent plasma 
has not yet shown efficacy in randomized-controlled trials. 
 
Highly potent neutralizing monoclonal antibodies (nAbs) against SARS-CoV-2 have several 
advantages compared to convalescent plasma: they can be titrated to concentrations of known 
neutralizing activity, they have less potential for off-target binding and subsequent immune pathology 
(ie Transfusion-related acute lung injury (TRALI)), and they show less of the therapeutic variability 
that is inherent to polyclonal remedies. 
 
To this date, there are close to 100 FDA-approved mAbs for treatment or prevention of cancer, 
autoimmune diseases, infectious diseases and other conditions. Palivizumab, for example, a 
humanized monoclonal antibody (IgG) directed against the fusion protein of respiratory syncytial virus 
(RSV), is the first monoclonal antibody approved for clinical use against an infectious pathogen and 
it is indicated for the prevention of serious lower respiratory tract disease caused by RSV in children. 
Another example which illustrates the utility of nABs against viruses, particularly the possibility for 
rapid development in the face of an emerging infection, is the 2014-2016 Ebola epidemic. While an 
initial trial of a triple monoclonal antibody cocktail, ZMapp, did not meet its efficacy endpoints (Group 
et al. 2016), a subsequent RCT showed superior results for day 28 mortality for Inmazeb/REGN-EB3 
(a triple nAb cocktail), leading to approval by the FDA in October 2020. 
 
The use of broadly neutralizing monoclonal antibodies (bNAbs) against HIV is yet another example 
illustrating the clinical translation of monoclonal antibodies to treat or prevent infectious disease. 
During the first decade of the 21st century, trials of first-generation bNAbs (such as 2G12, 4E10, 2F5) 
found them to be safe and well tolerated, but showed rather limited effects on delaying viral rebound 
during analytical treatment interruption of ART (Mehandru et al. 2007; Trkola et al. 2005). It was not 
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The Rockefeller University 
 
IND: 150929 
February 4, 2021 
 
PROTOCOL: RUCOV1 
CONFIDENTIAL 
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until the advent of single-cell cloning techniques (Scheid et al. 2009; Tiller et al. 2008) which allowed 
for the identification and isolation of rare but extremely potent second-generation antibodies. Some of 
these new antibodies showed remarkable in vitro neutralizing activity and breadth (over 90% of 
pseudoviruses from diverse clades), even at low concentrations (Klein et al. 2013; West et al. 2014) 
and made their way into clinical trials. Three well characterized bNAbs VRC01, 3BNC117 (targeting 
the CD4 binding site on the HIV envelope gp120 glycoprotein), and 10-1074 (targeting the V3 epitope 
of the HIV envelope) were able to significantly suppress plasma viral loads in viremic individuals 
when given as monotherapy (Caskey et al. 2015; Caskey et al. 2017; Lynch et al. 2015). Repeated 
infusions of the combination of 3BNC117 and 10-1074 in people living with HIV (PLWH) during 
analytical treatment interruption (ATI) of ART maintained viral suppression for a median of 15 weeks 
after last antibody infusions and prevented selection of escape variants while therapeutic antibody 
levels were maintained (Mendoza et al. 2018). These anti-HIV-1 antibodies were further modified to 
include amino acid mutations in the Fc region to extend biological half-lives (“LS” mutations). Studies 
to date demonstrate that the modified antibodies demonstrate similar safety profiles to the unmodified 
variants (Gaudinski et al. 2018; Gaudinski et al. 2019) and NCT03254277, NCT03554408). 
 
Taken together, passive administration of neutralizing antibodies holds great clinical promise for the 
prevention and treatment of COVID-19. Monoclonal antibodies may prove to be particularly useful in 
preventing SARS-CoV-2 infection in populations who may not mount protective immune responses 
to vaccination (e.g. advanced age, immunocompromise) and as post-exposure prophylaxis in 
individuals at high risk to develop severe COVID-19. Several monoclonal anti-SARS-CoV-2 
antibodies have been isolated by multiple groups and have entered clinical testing, including 
progression to efficacy phase 2/3 studies for both prevention and therapy. 
 
This first-in-human study aims to evaluate the safety, tolerability and pharmacokinetics of two highly 
potent human monoclonal antibodies, C135-LS and C144-LS, that target distinct neutralizing epitopes 
on the RBD of the SARS-CoV-2 spike glycoprotein in healthy volunteers. 
 
3.2 
Preclinical Characterization 
 
3.2.1 Identification of C135 and C144 and in vitro characterization 
 
C-135 and C-144 were identified and cloned at the Rockefeller University from two individuals who 
recovered from Coronavirus Disease 2019 (COVID-19). 
 
Briefly, individual B lymphocytes with receptors that bound to the SARS-CoV-2 receptor binding 
domain (RBD) were isolated by flow cytometry from blood samples of COVID-19 convalescent 
individuals. Paired IgG heavy and light chain (IGH and IGL) paired sequences were obtained by 
reverse transcription and subsequent PCR from individual RBD-binding B cells, and a subset of 
representative antibodies were expressed. The selected antibodies were tested for binding to SARS-
CoV-2 RBD by ELISA and for in vitro neutralizing activity against a SARS-CoV-2 pseudovirus and 
against authentic SARS-CoV-2. 
 
C135 and C144 showed exceptional neutralizing activities against authentic SARS-CoV-2 (strain 
USA-WA1/2020): C135 showed an IC50 of 2.98 ng/ml and C144-LS showed an IC50 of 2.55 ng/ml 
(Figure 1, (Robbiani et al. 2020). 
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The Rockefeller University 
 
IND: 150929 
February 4, 2021 
 
PROTOCOL: RUCOV1 
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Figure 1. In vitro neutralizing activity of selected anti-SARS-CoV-2 antibodies 
(a) Graph shows IC50s for antibodies assayed in an in vitro neutralization assay against SARS-CoV-2 
pseudovirus or against authentic SARS-CoV-2 (strain USA-WA1/2020), (b) shows authentic SARS-CoV-2 
neutralization curves. Infected cells (Y axis) vs. titration of monoclonal antibodies C121, C135 and C144 in 
two independent experiments. 
 
 
3.2.2 In vitro characterization of C135 and C144 
 
The spike (S) protein of SARS-CoV-2 is a trimeric viral glycoprotein that is responsible for mediating 
binding to the angiotensin-converting enzyme 2 (ACE2) receptor, enabling viral entry into host cells 
and subsequent pathology. The S trimer is comprised of 3 copies of the S1 subunit containing the 
receptor-binding domain (RBD) and 3 copies of the S2 subunit, which includes the fusion and 
transmembrane domains. As with other coronaviruses, the RBD of SARS-CoV-2 displays steric 
flexibility. The RBD can present in an “up” conformation enabling it to bind ACE2 or in a “down” 
conformation, in which the closed, pre-fusion S trimer cannot interact with ACE2. Functional assays 
and structural biology methods showed multiple non-overlapping antibody binding domains (Robbiani 
et al. 2020), delineating them into 4 classes of highly potent RBD-specific nAbs with distinct binding 
approaches to the RBD: (1) VH3-53 antibodies with short CDRH3s that block ACE2 and bind only to 
"up" RBDs, (2) ACE2-blocking antibodies that bind both "up" and "down" RBDs and can contact 
adjacent RBDs, (3) nAbs that bind outside the ACE2 site and recognize "up" and "down" RBDs, and 
(4) other antibodies that do not block ACE2 and bind only "up" RBDs (Barnes, Jette, et al. 2020; 
Barnes, West, et al. 2020). 
 
C144 is a class 2 antibody using the VH3-53 heavy chain gene with a relatively long CDRH3. It can 
bind to the RBDs of an S trimer in both the “up” and “down” confirmation, thus conferring the ability 
to attach to the spike of SARS-CoV-2 in various steric configurations. Moreover, the exact epitope of 
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The Rockefeller University 
 
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C144 has been shown to overlap with the binding site for ACE2. This direct competition with ACE2 
could partially explain its potency in neutralizing SARS-CoV-2. An additional aspect contributing to 
the exceptional neutralizing capacity of C144 is the aforementioned length of its CDR3H, which 
enables it to bridge between adjacent “down” configurated RBDs, thus locking the S trimer in a closed, 
prefusion conformation that is unable to engage ACE2. 
 
C135 is a class 3 antibody of exceptional neutralizing potency in vitro. Its binding mechanism is 
distinct from C144. C135 recognizes a glycopeptide epitope on a region of the RBD near the N343RBD 
glycan and non-overlapping with the ACE2 binding site. Importantly, there is no steric competition 
for binding to monomeric RBD between C144 and C135, suggesting that both antibodies can bind to 
and neutralize SARS-CoV-2 when given in combination. 
 
The distinct binding characteristics of C144 and C135 to the RBD of SARS-CoV-2 suggest that 
concurrent administration of the two antibodies could have additive neutralizing effects in vivo and 
would likely confer some degree of protection from viral escape mutations. In fact, in vitro 
experiments with a replication-competent recombinant vesicular stomatitis virus (VSV) pseudotyped 
with the S proteins of SARS-CoV-2 showed that escape mutations are selected in the presence of either 
C144 or C135 alone, but selection does not occur with the antibody combination (Figure 2, see the 
Investigator’s Brochure) (Weisblum et al. 2020).  
 
 
 
Figure 2. SARS-CoV-2 antibody combinations suppress the selection of antibody resistance 
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(A) Examples of neutralization resistance of rVSV/SARS-CoV-2/GFP mutants that were isolated following 
passage in the presence of antibodies. 293T/ACE2cl.22 cells were inoculated with WT or mutant rVSV/SARS-
CoV-2/GFP in the presence of increasing amount of each monoclonal antibody, and infection quantified by 
FACS 16h later. Mean and SD from two independent experiments. (B) Infectious virus yield following two 
passages of rVSV/SARS-CoV-2/GFP in the absence or presence of individual neutralizing antibodies or 
combinations of two antibodies. Titers were determined on 293T/ACE2cl.22 cells. Each symbol represents a 
technical replicate and results from two independent experiments using rVSV/SARS-CoV-2/GFP1D7 and 
rVSV/SARS-CoV-2/GFP2E1 are shown. 
 
 
3.2.3 In vitro characterization of C135-LS and C144-LS 
 
The original C135 and C144 antibodies were modified by two single amino acid modifications 
(M428L/N434S) in the Fc domain to extend the antibodies’ half-lives. The “LS mutations” increase 
the binding affinity of the antibody to FcRn, which in turn protects the bound antibody from 
degradation in lysosomes. These substitutions at the Fc positions do not alter the antibody-antigen 
binding domain or its neutralizing activity. Moreover, C135-LS and C144-LS have preserved Fc 
effector functions. In vitro experiments show that both antibodies can mediate antibody-dependent 
cellular cytotoxicity (ADCC), similarly to the unmodified C135 and C144 (see the Investigator’s 
Brochure). 
 
Several LS-modified antibodies are in clinical development for different indications, including HIV-
1 therapy and prevention. In general, the LS variants have approximately 3-fold longer half-lives in 
comparison to the non-LS molecules, while maintaining similar safety and antiviral activity profiles 
(Gaudinski et al. 2018; Gaudinski et al. 2019), and NCT03254277, NCT03554408). 
 
3.2.4 In vivo characterization of C135-LS and C144-LS 
 
3.2.4.1 Preclinical studies in mice 
 
The pharmacokinetics of C144-LS and C135-LS were evaluated in transgenic mice expressing human 
FcRn. These mice carry a null mutation for the mouse FcRn gene and a transgene expressing the 
human FcRn α-chain. Following a single intravenous dose of 0.5 mg, the estimated half-life of C135-
LS was 4.3 days and of C144-LS was 8.2 days. In comparison, the anti-HIV-1 antibody 10-1074-LS, 
used as control, showed an estimated half-life of 9.2 days in this model and has shown a half-life of 
approximately 80 days in humans. 
 
The C144-LS and C135-LS antibody combination was tested for activity in vivo against a mouse 
adapted strain of SARS-CoV-2. The antibodies were initially tested for neutralizing activity against 
pseudoviruses expressing the mouse adapted S protein on tissue culture cells expressing mouse ACE-
2. The neutralizing activity of the 2 antibodies against the mouse adapted SARS-CoV-2 was very 
similar to that against authentic SARS-CoV-2. C135-LS showed an IC50 of 6.9 ng/mL and C144-LS 
showed an IC50 of 3.2 ng/mL. 
 
The antibody combination was delivered intraperitoneally at different dose levels ranging from 1.8 to 
16 mg/kg of total antibody (i.e. 0.9 to 8 mg/kg of each mAb) (Figure 3). The mice were challenged 
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The Rockefeller University 
 
IND: 150929 
February 4, 2021 
 
PROTOCOL: RUCOV1 
CONFIDENTIAL 
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with 105 plaque forming units (PFUs) of mouse-adapted SARS-CoV-2 intranasally 12 hours after 
antibody injection. Lung titers were measured by plaque forming units per lung lobe 2 days post 
infection, which is the kinetic peak of viral replication in this model. As expected, the isotype control 
antibody failed to reduce virus replication. The C135/C144 combination protected all but one animal 
at doses of 5.3 and 16 mg/kg of total antibody (i.e. 2.65 or 8 mg/kg each mAb). The remaining mouse 
showed low but measurable virus titer. Notably, the 1.8 mg/kg dose of the combination (i.e. 0.9mg/kg 
each mAb) significantly reduced titers as compared to isotype control antibody but was not as effective 
as 5.3 or 16 mg/kg of total antibody (Schafer et al. 2020). 
 
 
 
Figure 3. Antibody combinations synergize to increase in vivo potency. 
SARS-CoV-2 MA lung titer following antibody prophylaxis with isotype control or combinations of C135+121 
or C135+C144 mixed at a ratio of 1:1 for combined dose levels of 16, 5.3 or 1.8 mg/Kg. Antibodies were 
delivered intraperitoneally 12hr prior to infection with 1x105 PFU of SARS-CoV-2 MA. Combined data from 
two independent experiments is shown. For 16mg/kg groups, N = 14-15 mice and all other groups were 9-10 
mice/group. The line is at the geometric mean and each symbol represents the titer for a single animal. Asterisks 
indicate statistical differences as compared to isotype control by one-way ANOVA with a Dunnet’s multiple 
comparison test or ANOVA with a Tukey’s multiple comparison test. 
 
 
Virus neutralization in vitro is independent of antibody Fc effector functions that impact in vivo 
efficacy against other viral infections. The loss of Fc-effector function by the introduction of mutations 
in the Fc domain of selected SARS-CoV-2 antibodies significantly decreased the protective activity 
against mouse-adapted SARS-CoV-2 in vivo ((Schafer et al. 2020), see Investigator’s Brochure). 
C135-LS and C144-LS do not contain mutations that interfere with Fc effector functions. 
 
 
 
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3.2.4.2 Preclinical studies in hamsters 
 
The combination of C144-LS and C135-LS was administered intraperitoneally to hamsters 24 hours 
prior (prophylaxis) or 12 hours after (treatment) intranasal challenge with 104 Plaque forming units 
(PFU) of the WA1-2020 isolate of SARS-CoV-2. Three groups of four hamsters each received doses 
of 2, 6 and 20 mg/kg of total antibody for prophylaxis (i.e. 1, 3 and 10 mg/kg each mAb) and 4, 12 
and 40 mg/kg of total antibody for treatment (i.e. 2, 6 and 20 mg/kg each mAb), respectively (Figure 
4). SARS-CoV-2 lung titers were determined by plaque assay three days after viral challenge. While 
all animals in the control group showed high level viral infection (PFUs around 106), hamsters in 
prophylactic and therapeutic medium and high dose antibody combination groups showed complete 
absence of viral infection with one exception in the therapeutic 20mg/kg dose group. In the prophylaxis 
low dose group (2 mg/kg) 3 out of 4 animals achieved protection, and in the therapy low dose group 
(4 mg/kg of each antibody) all animals had undetectable or very low virus titers. 
 
 
 
 
Figure 4. Evaluation of C144-LS and C135-LS for prophylactic and therapeutic efficacy against 
SARS-CoV-2 infection in Hamsters 
Hamsters were administered with the antibody combination either 24h prior or 12h after viral challenge. Viral 
infection in the lung was measured by plague assays three days after viral challenge. The graph shows the 
number of plaque forming units for the control and different therapeutic (4, 12 and 40 mg/kg of total antibody) 
or prophylactic (2, 6 and 20 mg/kg of total antibody) dose groups respectively. (Lod=Limit of detection). 
 
 
 
 
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3.2.4.3 Preclinical studies in non-human primates 
 
The combination of C144-LS and C135-LS was administered intravenously to 3 Indian origin rhesus 
macaques at a dose of 10 mg/kg of each antibody. The average neutralizing antibody concentration in 
plasma on day 10 after injection was 120 mcg/mL, which is about 2,000 times higher than the IC90 
neutralization titer for the C144 plus C135 combination against SARS-CoV-2 pseudovirus (IC90 61.02 
ng/mL). In rhesus macaques, the estimated average half-life of the C144-LS plus C135-LS 
combination was approximately 46 days. 
 
The combination of C144-LS and C135-LS was administered intravenously to rhesus macaques 24 
hours prior to intranasal, intratracheal and intraocular challenge with 2x106 Plaque forming units 
(PFU) of SARS-CoV-2. Three groups of four animals each received doses of 2, 6 and 20 mg/kg of 
total antibody (i.e. 1, 3 and 10 mg/kg of each mAb). SARS-CoV-2 genomic and subgenomic viral 
copies were determined from sequential nasopharyngeal swabs over the course of seven days after 
viral challenge. While genomic viral copies can detect the presence of residual challenge virus, 
subgenomic viral copies are a measure of de novo replication in infected animals. Levels of genomic 
viral copies were lowest in the animals that received the high dose antibody combination. More 
importantly, all animals in the control group showed high levels of viral copies (around 105), whereas 
all but two macaques in the lowest dose group showed sterilizing protection and absence of productive 
viral infection as determined by subgenomic viral copies (Figure 5). 
 
 
 
Figure 5. C144-LS and C135-LS for prophylaxis against SARS-CoV-2 infection in macaques 
The antibody combination was administered intravenously to rhesus macaques 24h prior to viral challenge. 
Subgenomic viral copies were measured from nasopharyngeal swabs over the course of 7 days after challenge. 
The graph shows the number of subgenomic viral copies for the control and different dose groups (2, 6 or 20 
mg/kg of total antibody) respectively. (Lod = Limit of detection) 
 
 
 
 
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In a separate experiment, the combination of C144-LS and C135-LS was administered intravenously 
to rhesus macaques 24 hours after intranasal, intratracheal and intraocular challenge with 2x106 Plaque 
forming units (PFU) of SARS-CoV-2. Three groups of four animals each received either placebo, low 
dose (12 mg/Kg) or high dose (40 mg/kg) of the antibody combination (i.e. 6 or 20 mg.kg of each 
mAb). The animals were euthanized at 7 days after infection. Microscopic lung sections were blinded 
and assessed by two independent pathologists for different grades of pneumonitis based on the 
depicted grading system. While the placebo control group showed high levels of pneumonitis (average 
grade around 2.7), the animals that received the antibody combination showed significantly lower 
grades of pneumonitis with the high dose group (40 mg/kg of total antibody) demonstrating the lowest 
grades (average grade around 1). (Figure 6). 
 
 
Figure 6. C144-LS and C135-LS for therapy of SARS-CoV-2 infection in macaques 
Four macaques in each group were administered either with placebo (control), the antibody 
combination at low dose (12 mg/kg) or high dose (40 mg/kg) at 24 hours after intranasal, intratracheal 
and intraocular viral infection. Microscopic lung sections were blinded and assessed by two 
independent pathologists for different grades of pneumonitis based on the depicted grading system. 
The box plots on the right show the grades of pneumonitis of hundreds of lung sections from macaques 
of respective control or dose groups. 
 
 
In summary, C135-LS and C144-LS are highly potent broadly neutralizing anti-SARS-CoV-2 RBD 
antibodies with evidence of significant in vivo activity in several relevant animal models. A single 
infusion of C135-LS and C144-LS prevented infection with a mouse-adapted SARS-CoV-2 strain in 
mice. In hamsters and non-human primates, the C135-LS/C144-LS combination conferred protection 
and rapid improvement or clearance of infection when administered intravenously before or within 24 
hours after SARS-CoV-2 challenge. Overall, it is expected that C135-LS and C144-LS may provide 
protection against infection from SARS-CoV-2 and accelerate viral clearance and disease resolution 
in SARS-CoV-2-infected individuals. 
 
 
 
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3.2.5 Toxicology studies 
 
The tissue cross-reactivity studies showed cytoplasmic binding to isolated tissues in both rat and 
human tissue panels. Since C135-LS and C144-LS are antibodies to an infectious disease antigen, no 
on-target binding in these tissue panels was expected. As such, observed binding was concluded to be 
off-target but was limited to binding in the cytoplasmic space. Monoclonal antibody binding to 
cytoplasmic sites in tissue cross-reactivity studies generally is considered of little to no toxicologic 
significance due to the limited ability of antibody therapeutics to access the cytoplasmic compartment 
in vivo. 
 
The combination of C135-LS and C144-LS was evaluated for safety in a multidose study in Sprague 
Dawley rats. The purpose of this study was to evaluate the systemic toxicity, local tolerability, 
toxicokinetics and immunogenicity of C135-LS and C144-LS when administered twice weekly 
intravenously (IV) at doses ranging from 6 to 120 mg/kg of the combination, or subcutaneously (SC) 
at 30 mg/kg for 4 weeks (total of 8 doses) to Sprague Dawley rats, and to assess the reversibility or 
persistence of effects following a 47-Day recovery period. At the time of the IND submission only 
data from the dosing period were available, and conclusions should be viewed as interim. A summary 
of available data is included in Investigator’s Brochure (Section 4.7 Nonclinical Toxicology). 
 
 
3.3 
Clinical experience 
 
3.3.1 Anti-SARS-CoV-2 antibodies to treat or prevent infections 
 
This is the first-in-human study of C135-LS and C144-LS, however passive administration of anti-
SARS-CoV-2 antibodies is currently being evaluated in humans under multiple studies, including 
phase 2/3 efficacy studies. 
 
Important caveats to the use of antibody therapies are whether they can be detrimental to endogenous 
responses or elicit antibody dependent enhancement (ADE). ADE consists on Fc receptor-mediated 
enhanced infection and it was first described in Dengue infection (Halstead and O’Rourke 1977), and 
later suggested for SARS-CoV (Yilla et al. 2005) and MERS (Zhou et al. 2014). Preliminary reports 
of vaccinated NHP do not support ADE in SARS-Cov-2 infection (Gao et al. 2020), and COVID-19 
convalescent plasma therapy appears to be safe ((Joyner et al. 2020), discussed in detail below). 
 
In the absence of alternative treatment strategies, convalescent plasma therapy was one of the first 
emergency approaches to enter clinical trials and to gain Emergency Use Approval by the FDA. On 
September 06, 2020 Joyner et al reported safety information on 20,000 hospitalized COVID-19 
patients who received convalescent COVID-19 plasma. The incidence of all serious adverse events 
was low; these included transfusion reactions (1%), thromboembolic or thrombotic events (1%), and 
cardiac events (~3%). Notably, the vast majority of the thromboembolic or thrombotic events and 
cardiac events were judged to be unrelated to the plasma transfusion per se. The 7-day mortality rate 
was 13.0%, and was higher among more critically ill patients relative to less ill counterparts, including 
patients admitted to the intensive care unit versus those not admitted (15.6 vs 9.3%), mechanically 
ventilated versus not ventilated (18.3% vs 9.9%), and with septic shock or multiple organ 
dysfunction/failure versus those without dysfunction/failure (21.7% vs 11.5%). The authors concluded 
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that transfusion of convalescent plasma is safe in hospitalized COVID-19 patients. However, the 
observation that a significant proportion of convalescent COVID-19 donors have very low to 
undetectable neutralizing antibody responses poses an important technical challenge (Liu et al. 2020; 
Robbiani et al. 2020; Rogers et al. 2020) and may limit the efficacy of this approach. 
 
In parallel to studies of convalescent COVID-19 plasma, several anti-SARS-CoV-2 mAbs have 
entered clinical testing in both therapeutic and preventative settings. 
 
For example REGN-COV-2 (a combination of two mAbs), will be administered to approximately 
2,000 asymptomatic adults who are household contacts of persons with SARS-CoV-2 infection. In 
addition to assessing safety, the trial will seek to define whether REGN-COV-2 can prevent disease 
symptoms in those already infected. The efficacy assessment will be a one-month period following 
administration of REGN-COV-2 or placebo. All trial participants will be followed for safety for seven 
months after efficacy assessment period ends. The study is ongoing (NCT04452318). 
 
On November 10, the anti-SARS-CoV-2 mAb Bamlanivimab (LY-CoV555) was granted emergency 
use authorization (EUA) by the FDA. The antibody treatment was authorized for mild-to-moderate 
COVID-19 in adult and pediatric patients 12 years of age and older weighing at least 40 kilograms, 
and who are at high risk for progressing to severe COVID-19. The data supporting this EUA for 
Bamlanivimab are based on a phase two randomized, double-blind, placebo-controlled clinical trial in 
465 non-hospitalized adults with mild to moderate COVID-19 symptoms. The trial participants 
received antibody doses ranging from 700 to 7,000 mg (the equivalent of 10 to 100 mg/kg for an 
average 70-kg of body weight) and the safety profile was similar in patients receiving any of the three 
Bamlanivimab doses (Food and Drug Administration (FDA) 2020). 
 
3.3.2 Fc-modified antibodies to enhance binding to the FcRn receptor 
 
VRC01LS is a human anti-HIV-1 CD4 binding site antibody that has been modified in the Fc region 
to include the LS substitutions (M428L/N434S), and is being evaluated for HIV-1 therapy and 
prevention. VRC01LS has been evaluated multiple clinical studies in HIV-infected (NCT02840474) 
and HIV-uninfected adults (NCT02599896, NCT02797171), and in infants (NCT02256631). 
VRC01LS showed good safety profile at intravenous doses ranging from 5, 20 or 40 mg/kg. Most 
reported AEs were of grade 1 severity. VRC01LS clearance rate was 36 ± 8 mL/d with an elimination 
half-life of 71 ± 18 days. VRC01LS retained its expected neutralizing activity in serum, and anti-
VRC01 antibody responses were not detected (Gaudinski et al. 2018). 3BNC117-LS and 10-1074-LS, 
two other anti-HIV-1 long acting monoclonal antibodies, are in clinical development (NCT03254277, 
NCT03554408). Twenty-seven participants (6 HIV-infected individuals on suppressive ART) 
received 10-1074-LS at doses ranging from 150 mg or 300 mg SC up to 30 mg/kg IV, and 39 received 
3BNC117-LS at the same dose levels. The admixture of the two antibodies has also been administered 
subcutaneously to 30 HIV-uninfected participants, and intravenously to 5 HIV-uninfected and 5 HIV-
infected participants. Both intravenous infusions and subcutaneous injections have been well tolerated 
without Grade 3 adverse events or serious adverse events deemed possibly related to the antibodies 
reported to date. The safety profiles of the LS-variants so far are similar to the parental antibodies. 
 
 
 
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3.4 
Hypothesis 
 
The subcutaneous and intravenous administration of C144-LS and C135-LS in combination will be 
safe and well tolerated at the tested doses in healthy volunteers. The dose levels studied are expected 
to achieve protective or therapeutic levels of each antibody in serum (estimated as 1,000-fold the in 
vitro IC50 of each antibody against SARS-CoV-2). 
 
3.5 
Study Objectives 
 
Primary objectives: 
- 
To evaluate the safety and tolerability of subcutaneous injections or single intravenous infusions 
of C144-LS in combination with C135-LS in healthy volunteers. 
- 
To evaluate the pharmacokinetic profile of C144-LS and C135-LS in combination, administered 
subcutaneously or intravenously at increasing dose levels in healthy volunteers. 
 
Secondary objective: 
- 
To assess the occurrence of anti-drug antibody responses. 
- 
To evaluate serum neutralizing activity against SARS-CoV-2 after anti-C144-LS and anti-C135-
LS administration. 
 
3.6 
Study Outcomes 
 
Primary Outcomes: 
- 
Rate of solicited and investigational product (IP)-related unsolicited adverse events that are Grade 
2 and above (including confirmed laboratory abnormalities) 4 weeks after administration. 
- 
Rate of solicited and IP-related unsolicited adverse events that are Grade 3 and above (including 
confirmed laboratory abnormalities) 4 weeks after administration. 
- 
Proportion of participants with serious adverse events (SAEs) throughout the study period that are 
considered related to investigational product and their duration. 
- 
The pharmacokinetic profile of C144-LS and C135-LS: elimination half-life (t1/2), clearance 
(CL/F), volume of distribution (Vz/F), AUC and decay curve. 
 
Secondary Outcomes: 
- 
Rate and severity of investigational product (IP)-related adverse events during study follow up. 
- 
Frequency and levels of induced anti-C144-LS and anti-C135-LS antibodies in all study groups. 
- 
Serum neutralizing activity against SARS-CoV-2 after C144-LS and C135-LS administration. 
 
 
 
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4 
STUDY DESIGN 
 
This proposed study is a first-in-human, single dose, dose-escalation phase 1 study to evaluate the 
safety and pharmacokinetics of a combination of two highly neutralizing anti-SARS-CoV-2 mAbs 
C144-LS and C135-LS in healthy volunteers. 
 
The study consists of two parts.  
 
Part A has a standard 3+3 phase 1 dose escalation design. Study participants will receive subcutaneous 
injections of C144-LS and C135-LS at 4ml (2ml or approximately 100mg of each antibody 
administered separately) or 8ml (4 ml or approximately 200mg of each antibody administered 
separately) or sequential intravenous infusions of C144-LS and C135-LS, each administered via a 
peripheral vein over 60 minutes at one of three increasing dose levels (1.5 mg/kg, 5 mg/kg and 15 
mg/kg of each antibody)  
 
Study participants in Part B will be randomized to receive subcutaneous injections of C144-LS and 
C135-LS at 8ml (approximately 200mg of each antibody administered separately) or placebo in a 3:1 
ratio and double-blinded fashion. 
 
Part A has started enrollment. Part B has a planned enrollment of 8 participants (see Table 1 and 
Scheme below).  
 
Table 1. Study Groups 
Part A – Open label 
 
Group Antibody 
Dose 
Route 
Regimen N 
 
S1 
C144-LS + C135-
LS 
 
100 mg 
each mAb 
SC 
Day 0 
3+3 
S2 
C144-LS + C135-
LS 
 
200 mg 
each mAb 
SC 
Day 0 
3+3 
V1 
C144-LS + C135-
LS 
 
1.5 mg/kg 
each mAb 
IV 
Day 0 
3+3 
V2 
C144-LS + C135-
LS 
 
5 mg/kg 
each mAb 
IV 
Day 0 
3+3 
V3 
C144-LS + C135-
LS 
 
15 mg/kg 
each mAb 
IV 
Day 0 
3+3 
 
 
 
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Part B – Randomized, double-blinded 
 
Group Antibody 
Dose 
Route 
Regimen N 
 
S3 
C144-LS + C135-
LS 
 
200 mg 
each mAb 
or placebo 
SC 
Day 0 
8 (6:2) 
 
Following administration of the C144-LS and C135-LS antibody combination at one of three 
increasing dose levels, study participants will return for safety assessments on day 1, and weeks 1, 4, 
8, 12, 18 and 24, 36 and 48 following antibody administration as indicated in the Time of Events 
Schedule (Appendix A, Time of Events Schedule). 
 
Serum samples for Pharmacokinetic (PK) measurements will be collected before and at the end of 
each mAb administration and at multiple subsequent time points during study follow up, as indicated 
in the Time of Events Schedule (Figure 7, Appendix A). Assessments will also include measurement 
of anti-drug antibody (ADA) responses. All participants will be followed for 48weeks after C144-LS 
and C135-LS administration. 
 
 
Figure 7. Schedule of Study Visits and Sample Collection 
 
4.1 
Dose Selection and Dose Escalation Plan 
 
The proposed study doses were chosen based on in vitro and in vivo data that demonstrated the 
neutralizing potency of C144-LS and C135-LS in preclinical experiments in mice, hamsters and non-
human primates. A protection experiment in mice challenged with a mouse adapted strain of SARS-
CoV-2 intranasally showed that an equivalent dose of 2.65 mg/kg of each mAb led to sterile protection 
in 9 out 10 animals. In hamsters and non-human primates, prophylaxis and treatment experiments in 
animals challenged with SARS-CoV-2 showed that 3mg/kg of each antibody protected animals from 
infection, whereas 6 mg/kg of each antibody led to rapid improvement or clearance of infection 
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demonstrated by lower virus titers in lung tissue and lower pneumonitis scores in comparison to 
controls.  
 
The planned starting dose in this first-in-human study is 1.5 mg/kg of each antibody (100mg of each 
antibody subcutaneously) and the target prophylactic dose is between 1.5 and 3mg/kg. It is expected 
that higher doses may be required for therapy. The target therapeutic dose at this time is 5 or 15 mg/kg 
of each antibody, if found to be safe and well tolerated. Similar and higher dose levels have been safely 
evaluated with anti-HIV-1 antibodies as well as with other anti-SARS-CoV-2 RBD monoclonal 
antibodies, according to publicly available data. 
 
It is expected that a 15 mg/kg dose of each antibody will achieve peak serum levels of approximately 
750 mcg/mL. Based on previous studies with anti-HIV-1-antibodies, it is expected that C144-LS and 
C135-LS will have a t1/2 in humans of 60-80 days, and that serum concentrations will be maintained 
above 2.5 mcg/mL (or approximately 1,000 times the in vitro IC50 of either mAb) for approximately 
12 months when C144-LS and C135-LS are administered at 15 mg/kg doses each. 
 
Part A – Dose escalation phase 
 
During the subcutaneous and intravenous dose escalation phase (Part A) of the study, enrollment will 
be staggered by 1 day for the volunteers of each group (Figure 8). 
 
Subcutaneous (SC) Administration (Groups S1 and  S2) 
1. First, eligible participants will be enrolled in Group S1 (C144-LS + C135-LS, 2mL each). 
2. Enrollment in Group S2 (C144-LS + C135-LS, 4mL each) will begin after all three participants 
enrolled in Group S1 reach at least 7 days without a dose limiting toxicity (DLT) reported in the 
group (DLT: any adverse event of grade 3 or greater toxicity, if the study investigators recognize 
a probable or definite attribution to C144- LS and/or C135-LS). 
3. If 1 DLT occurs, 3 additional participants will enroll in Group S1. If no additional dose limiting 
toxicities occur, enrollment in the next dose level will proceed. 
4. If 2 or more DLTs occur, dosing will be halted and the prior lower dose level will be declared the 
maximum subcutaneous tolerated dose (MTD). 
5. Enrollment in Group S2 will follow the same rules. 
 
Intravenous (IV) Administration (Groups V1, V2 and V3) 
1. Enrollment in Group V1 (C144-LS + C135-LS, 1.5mg/kg each, IV) will begin at least 7 days after 
the first three participants enrolled in Group S2. 
2. Enrollment in Group V2 (C144-LS + C135-LS, 5mg/kg each, IV) will begin after all three 
participants enrolled in Group V1 reach at least 7 days without a dose limiting toxicity (DLT) 
reported in the group (DLT: any adverse event of grade 3 or greater toxicity, if the study 
investigators recognize a probable or definite attribution to C144-LS and/or C135-LS). 
3. If 1 DLT occurs, 3 additional participants will enroll in Group V1. If no additional dose limiting 
toxicities occur, enrollment in the next dose level will proceed. 
4. If 2 or more DLTs occur, dosing will be halted and the prior lower dose level will be declared the 
maximum intravenous tolerated dose (MTD). 
5. Enrollment in Group V3 (C144-LS + C135-LS, 15mg/kg each, IV) will follow the same rules. 
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6. Enrollment in Group V3 will begin at least 7 days after three participants enrolled in Group V2 
and following SMC review of all available safety data. 
 
The study investigators will review 1-week safety data prior to dose escalation in the subcutaneous 
groups (S1 and S2) and in the low and mid dose IV groups (V1 and V2). An external Safety Monitoring 
Committee (SMC) will review the 1-week safety data prior to dose escalation from the intravenous 
mid to the high dose groups step (V2 to V3). The SMC will provide a recommendation regarding 
enrollment in subsequent groups. 
 
Note: As outlined in Section 14.1, the SMC will be asked to review safety data if one or more grade 
3 or higher adverse events, deemed probably or definitely related to the study drugs (DLT) occur. No 
additional administration of the investigational products will take place pending a SMC review. In the 
event of a DLT, the SMC will make recommendations with regards to expansion of a study group 
from 3 to 6 participants, dose escalation to the next dose level, or halting additional enrollment. 
 
Part B – Randomized, double-blinded phase 
 
During the subcutaneous, randomized, double-blinded phase (Part B) of the study, enrollment will be 
limited to a maximum of two volunteers per day (Figure 8). 
 
Enrollment in Group S3 will begin once all participants in Part A have met eligibility criteria and 
have been scheduled for enrollment (day 0) and after all three participants enrolled in Group S2 reach 
at least 7 days without a dose limiting toxicity (DLT) reported in the group.  
 
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Figure 8. Study Scheme 
 
4.2 
End of the clinical trial 
 
This clinical trial ends with the last participant’s last visit. 
 
5 
STUDY POPULATION 
 
5.1 
Inclusion Criteria: 
- 
Aged 18 to less than 65. 
- 
If sexually active male or female, and participating in sexual activity that could lead to 
pregnancy, agrees to use one effective method of contraception from 10 days prior to the 
antibody administration until 6 months after IP administration. 
 
Female study participants of reproductive potential are defined as pre-menopausal women who 
have not had a sterilization procedure (e.g. hysterectomy, bilateral oophorectomy, tubal ligation or 
salpingectomy). Women are considered menopausal if they have not had a menses for at least 12 
months and have a FSH of greater than 40 IU/L or if FSH testing is not available, they have had 
amenorrhea for 24 consecutive months. 
 
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5.2 
Exclusion Criteria: 
- 
Weight > 110 kg for groups S1 and S2 only 
- 
History of prior positive SARS-CoV-2 RT-PCR or SARS-CoV-2 serology. 
- 
Active respiratory or non-respiratory symptoms consistent with COVID-19. 
- 
Medically attended acute illness or hospitalization (ie, >24 hours) for any reason within 30 
days prior to screening. 
- 
Acute exacerbation of a chronic pulmonary condition (eg, chronic obstructive pulmonary 
disease [COPD], asthma exacerbations, or uncontrolled hypertension, as defined by a systolic 
blood pressure > 180 and/or diastolic blood pressure > 120, in the presence or absence of anti-
hypertensive medications) in the past 6 months prior to screening. 
- 
Use of systemic corticosteroids, immunosuppressive anti-cancer, or other medications 
considered significant by the trial physician within the last 6 months. 
- 
Other clinically significant acute or chronic medical condition that in the opinion of the 
investigator would preclude participation. 
- 
Are eligible for COVID-19 vaccination prior to your entry in the study according to local 
guidelines (e.g. healthcare professionals, non-healthcare professionals such as teachers, 
firefighters, public transit workers). 
- 
Laboratory abnormalities in the parameters listed: 
o Absolute neutrophil count ≤ 1,500 K/mcL;  
o Hemoglobin ≤ 10.5 gm/dL if female; ≤ 11 gm/dL if male;  
o Platelet count ≤ 125,000 K/mcL;  
o ALT ≥ 1.25 x ULN; AST ≥ 1.25 x ULN;  
o Total bilirubin ≥ 1.25 x ULN;  
o Creatinine ≥ 1.1 x ULN;  
- 
Pregnancy or lactation. 
- 
Any vaccination within 14 days prior to SARS-CoV-2 mAbs administration (except influenza 
vaccine). 
- 
History of prior therapy with any SARS-CoV-2 vaccine or antibodies, including convalescent 
plasma. 
- 
Known allergy/sensitivity or any hypersensitivity to components of the investigational agents. 
- 
History of severe reaction to a vaccine or monoclonal antibody administration or history 
of severe allergic reactions. 
- 
Participation in another clinical study of an investigational product currently or within past 12 
weeks, or expected participation during this study. 
 
6 
METHODS AND PROCEDURES 
 
The study will be conducted as a single-center study at the Rockefeller University Hospital, USA. 
 
6.1 
Screening Procedure and Study Visits 
 
The Time of Events Schedule summarizes the frequency and timing of various study assessments. See 
Appendix A. 
 
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6.1.1 Pre-Screening  
 
Potential participants will first undergo pre-screening by telephone to assess medical history and 
qualification for the study (e.g. review of ongoing medical conditions, current medications, previous 
history of COVID-19). Potential participants will have the opportunity to discuss the study and ask 
questions of the study recruiter at this time. Those who are eligible and interested in participation will 
attend a screening visit at the Rockefeller University Hospital (RUH) Outpatient Clinic. 
 
6.1.2 Screening Visit 
 
Initial Screening Visit: 
Study personnel will answer any questions about the study. Written informed consent will be obtained 
prior to conducting any study procedures. The informed consent process may occur remotely (e.g. by 
telephone or zoom), if needed.  
 
To ensure informed consent, the principal investigator or designee will discuss the following processes 
individually with each potential participant: 
1. Risk-reduction counseling including safe-sex and pregnancy avoidance counseling; 
2. That sexually active males and females, participating in sexual activity that could lead to 
pregnancy, should use one reliable form of contraception for the duration of the trial. 
 
If the potential participant consents to participate, site personnel will: 
- 
Perform complete medical history (including review of concomitant medication); 
- 
Perform a general physical examination including height, weight, vital signs (pulse, respiratory 
rate, blood pressure and temperature), examination of skin, respiratory, cardiovascular and 
abdominal systems; 
- 
Collect blood and urine specimens for all tests as indicated in the Time of Events Schedule 
(Appendix A), 
- 
Perform a pregnancy test for female volunteers of reproductive potential. 
 
If the initial screening visit occurs more than 70 days prior to date of the first C144-LS and C135-LS 
mAb administration, then study procedures for the screening visit must be repeated. The most recent 
set of procedures will be used if there is a discrepancy. 
 
6.1.3 Pre-administration Visit 
 
Obtain a nasopharyngeal or oropharyngeal swab for SARS-CoV-2 PCR testing, according to 
Appendix A. 
 
Note: This sample may be collected at the screening visit if it is anticipated that enrollment will occur 
within 3 days from the screening visit. 
 
6.1.4 C144-LS and C135-LS Administration Visit 
 
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- 
Study participants will be admitted to the RUH inpatient unit the night before or on the day of 
C144-LS and C135-LS administration. 
 
Prior to drug administration, site personnel will: 
- 
Answer any questions about the study; 
- 
Review interim medical history (including concomitant medications); 
- 
Review safety laboratory data, including results of the SARS-CoV-2 PCR test; 
- 
Review the informed consent form administered at screening visit with the participant; 
- 
Perform a physical examination including weight, vital signs (pulse, respiratory rate, blood 
pressure and temperature) and any further examination indicated by history or observation; 
- 
Collect blood and urine specimens for all tests as indicated in the Time of Events Schedule 
(Appendix A); 
- 
Perform pregnancy counseling; 
- 
Perform a pregnancy test for all female volunteers of reproductive potential and obtain results 
prior to drug administration; 
- 
Perform baseline assessment and record any systemic symptoms; 
- 
C144-LS and C135-LS mAb will be prepared for administration according to the RUH 
Pharmacy Standard Operating Procedures; 
 
- 
For the subcutaneous administration, C144-LS and C135-LS or placebo (buffered solution, 
Group S3) will be administered separately as two (approximately 100 mg of each mAb) or four 
2 mL (approximately 200 mg of each mAb) injections at different sites in the abdomen, upper 
arms or thighs 
- 
For the intravenous administration, C144-LS and C135-LS mAb will be administered via a 
peripheral vein over at least 60 minutes in sequential order. The IV line will be flushed with 
normal saline after infusion of C144-LS is completed and the participant will be observed for 
1 hour before initiation of subsequent C135-LS infusion. If participants develop grade 3 acute 
infusion reaction, an immediate hypersensitivity reaction or a life-threatening event during 
C144-LS and C135-LS intravenous administration, the infusion will be discontinued and will 
not be reinitiated (see Section 6.1.7.1). 
- 
For the SC groups, vital signs (pulse, respiratory rate, blood pressure and temperature) will be 
monitored at end of mAb administration (+/- 5 minutes), 1 hour (+/- 10 min), 3 hours (+/- 10 
min), 6 hours (+/- 10 min), 12 hours (+/- 10 min) post administration and prior to discharge 
from in-hospital observation. 
- 
For the IV groups, vital signs will be checked at the end of each mAb infusion (+/- 5 minutes), 
and at 1 hour (+/- 10 min), 3 hours (+/- 10 min), 6 hours (+/- 10 min), 12 hours (+/- 10 min) 
after the C135-LS infusion and prior to discharge from in-hospital observation. 
- 
Presence or absence of reactogenicity adverse events, as well as any other event that occurs, 
will be recorded 30 – 60 minutes after end of antibody dosing, as shown in the Time of Events 
Schedule (Appendix A). 
- 
Rescue medications, including acetaminophen, diphenhydramine or an alternative 
antihistamine, epinephrine and glucocorticoids will be available in the RUH inpatient units for 
use if clinically indicated. 
- 
For SC and IV groups blood samples for pharmacokinetics assessments will be collected (as 
indicated in Appendix A). 
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- 
Study participants will be discharged after at least 24 hours post C144-LS and C135-LS 
administration, after day 1 clinical assessment and study procedures have taken place. Hospital 
discharge will be delayed if clinically indicated. 
 
Specific procedures to be performed at each treatment visit are illustrated in the Time of Events 
Schedule (Appendix A).  
 
6.1.5 Post- C144-LS and C135-LS Administration Visits 
 
Participants will be followed through study week 48. 
 
At these follow up visits the following will be conducted: 
- 
Review of interim medical history and use of concomitant medications; 
- 
If symptoms are present, perform a symptom-directed physical examination; 
- 
Local and systemic reactogenicity adverse events, as well as other adverse events, will be assessed; 
- 
Pregnancy counseling; 
- 
Vital Signs; 
- 
Collect blood and urine specimens for all tests as indicated in the Time of Events Schedule 
(Appendix A); 
- 
In case of adverse event(s), the participant will be assessed and followed up by the clinical team. 
Supplemental visit(s) for further investigation can be planned at the discretion of the principal 
investigator or designee. Supplemental visit(s) may be recommended if clinically indicated or to 
clarify observations. 
 
Specific procedures to be performed at each follow up visit are illustrated in the Time of Events 
Schedules (Appendix A). 
 
Any abnormalities (adverse events) attributed to study drug, including laboratory abnormalities, 
should be subsequently followed until the event or its sequelae resolve or stabilize. 
 
6.1.6 Final Visit/Early termination Visit 
 
Assessments will be undertaken according to the Time of Events Schedule (Appendix A). 
 
6.1.7 Discontinuation of study drug infusions and/or participant withdrawal from study 
 
6.1.7.1 Discontinuation of study drug infusions 
 
Antibody intravenous infusions will be discontinued for any of the following reasons: 
 
1. Grade 3 acute infusion reactions that occur during infusion. 
2. Any immediate hypersensitivity reaction (such as urticarial rash; bronchospasm; laryngeal. 
edema; anaphylaxis; syncope). 
3. Life threatening medical event during C144-LS and C135-LS infusion. 
 
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6.1.7.2 Withdrawal from the study (Participant Early Termination from study) 
 
Participants may be withdrawn from the study permanently for the following reasons: 
1. Participants may withdraw from the study at any time if they wish to do so, for any reason. 
2. Following an adverse event at the discretion of the investigator (or designee). 
3. Request of the primary care provider if s/he thinks the study is no longer in the best interest of 
the participant. 
4. Participant judged by the investigator to be at significant risk of failing to comply with the 
protocol in a manner that might lead to harm to self or seriously interfere with the validity of 
the study results. 
5. At the discretion of the FDA or investigator. 
 
6.1.7.3 Follow up after withdrawal from study (Participant Early Termination from study) 
 
Any adverse event resulting in withdrawal of a participant will be followed up until resolution or until 
the adverse event is judged by the principal investigator or designee to have stabilized where possible. 
 
At the time of withdrawal, provided the participant is willing, all the requested termination visit 
procedures will be performed according to the Time of Events Schedule (Appendix A). 
 
The date and reason for withdrawal from the study (early termination) should be collected and reported 
to the RU sponsor, SMC, and Rockefeller University IRB. 
 
A pregnant participant will not receive the C144-LS and C135-LS administration. If pregnancy occurs 
after C144-LS and C135-LS administration, the participant will be followed until the end of the study 
and until delivery, if delivery occurs after the study has ended. Approximately 2-4 weeks after 
delivery, the baby will be examined by a pediatrician to assess his/her health status. The health status 
of the baby will be reported to the RU sponsor, Rockefeller University IRB, CRSO and the SMC. 
 
6.1.7.4 Premature termination of trial 
 
The RU sponsor has the right to terminate the trial prematurely if there are any relevant medical or 
ethical concerns, or if completing the trial is no longer feasible. If such action is taken, the reasons for 
terminating the trial must be documented in detail. All trial participants still under treatment at the 
time of termination must undergo a final examination which must be documented. The RU sponsor 
must be informed without delay if any investigator has ethical concerns about continuation of the trial. 
 
Premature termination of the trial will be considered if: 
• The risk-benefit balance for the trial participant changes markedly 
• It is no longer ethical to continue administration of the study drug 
• The RU sponsor considers that the trial must be discontinued for safety reasons (e.g. on the 
advice of the SMC) 
• It is no longer feasible to complete the trial 
• The RU sponsor decides on whether to discontinue the trial in consultation with the and SMC. 
 
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6.1.8 Unblinding (Group S3) 
 
Participants enrolled in Group S3 will be informed as to whether they received the study product or 
placebo 3 months after the participant study entry (day 0) and at least 1 month after all 8 participants 
enroll in Group S3.  
 
Following unblinding, placebo recipients will remain in follow up for safety assessments. Samples 
will not be collected for research purposes following unblinding. 
 
6.2 
Study Procedures 
 
6.2.1 Consent Procedure 
Prior to the initiation of any study related procedures, the potential participants will be given a copy 
of the most recent IRB stamped and approved informed consent to read. Additionally, the PI or study 
staff member who has been designated to consent will discuss the specifics of the study including but 
not limited to the purpose of the research, procedures, time commitment, required tasks, test article, 
alternative treatments, benefits, risks, confidentiality etc. in a comprehensible (non-scientific) manner, 
using language readily understandable by the participant. Participants will be told that participation is 
voluntary and that, if they do not consent, they will not be penalized. The person consenting will assure 
the voluntariness of the participant. 
 
A private, confidential setting will be provided for the potential participant to read and discuss the 
informed consent free from coercion, undue influence or constraints of time. The informed consent 
process may occur remotely (e.g. by telephone or zoom), if needed.  
 
All participants will be given a chance to ask questions and express concerns. They will be given the 
option to take the consent home and discuss it with family, friends, and /or health care providers. After 
a participant and the person conducting the consenting process sign and date the consent, the 
participant will be given a copy of the signed informed consent form. 
 
A note will be written in the source document as to who obtained consent, how, when, were questions 
asked and answered, and that a copy of the informed consent was given to the participant. 
 
The "Teach Back" method will be used in the clinical research setting to ask research participants to 
repeat or “teach back” the information, concepts and directions that the staff member has attempted to 
convey to the participant. This method is used to assess comprehension and retention of protocol 
requirements, adverse event information, risks and benefits, and the participant's rights described in 
the Informed Consent process. This will be assessed with the questionnaire included in Appendix D, 
Assessment of Understanding Questionnaire. 
 
6.2.2 Study Assignment 
 
Part A: Enrollment will be open-label, and study participants will be enrolled sequentially as they 
meet enrollment criteria. The RUH pharmacist will dispense C144-LS and C135-LS according to the 
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study dose group. Over-enrollment will only be permitted to replace participants lost to follow up prior 
to week 2, as discussed in Section 8.2 Sample Size Considerations. 
 
Part B: Enrollment in Part B will begin once all participants in Part A have met eligibility criteria and 
have been scheduled for enrollment (day 0). Participants will be randomized in a 3:1 ratio to receive 
the study drugs or placebo. Participants will be enrolled sequentially as they meet enrollment criteria, 
according to the randomization schedule.  
Randomization will be performed by the Rockefeller University Hospital pharmacy.  The 8 
participants in S3 will be randomized in a ratio of 6 study drug recipients to 2 placebo recipients. 
Randomization will be generated using SAS 9.4. The study drugs or placebo preparation will be 
provided to the study nurses for injection under a coded, masked identification. The nurses, study staff, 
investigators, and participants will be blinded as to the identity of the study preparation. Participants 
in Part B will be unblinded according to Section 6.1.8. To accomplish this, study investigators will be 
provided with the randomization code and they will notify each participant. In the event of a medical 
emergency wherein knowledge of the treatment assignment will influence the participant’s care, the 
Principal Investigator may unblind the treatment assignment. 
 
6.2.3 C144-LS and C135-LS Administration Procedure 
 
C144-LS and C135-LS will be provided in single-use vials containing 6 ml of the product at 
concentration of 50 mg/ml. 
 
Part A 
 
Subcutaneous administration: 
The RUH research pharmacist will provide each study drug in a separate syringe ready for 
administration. The number of injections of C144-LS and C135-LS will follow study assignment: 
Group S1, 2 mL of C144-LS and 2 mL of C135-LS, separately.  Group S2, 4 mL of C144-LS and 4 
mL of C135-LS , separately. The total volume of the antibodies will be dispended in two (Group S1) 
or four (Group S2) separate syringes containing either C144-LS or C135-LS for administration in two 
or four separate sites, respectively. The antibodies will be administered subcutaneously in the 
abdomen, upper arms or thighs. Each SC injection should be administered carefully to avoid 
inadvertent deposition into muscular tissue or leakage after needle removal. If leakage occurs, it should 
be noted in the study records.  
 
Intravenous administration: 
The volume of C144-LS to be administered will be calculated by the RUH research pharmacist 
according to study group allocation. Weight measurement collected at the pre-infusion visit or at day 
0 will be used to calculate the dose of C144-LS.  The appropriate volume of C144-LS will be diluted 
in sterile normal saline to a total volume of 100 ml, and will be administered as a slow intravenous 
infusion over 60 minutes. 
 
After infusion of C144-LS is completed, the participant will be observed for 1 hour before initiation 
of subsequent C135-LS infusion. 
 
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The volume of C135-LS to be administered will be calculated by the RUH research pharmacist 
according to study group allocation. Weight measurement collected at the pre-infusion visit or at day 
0 will be used to calculate the dose of C135-LS.  The appropriate volume of C135-LS will be diluted 
in sterile normal saline to a total volume of 100 ml, and will be administered as a slow intravenous 
infusion over 60 minutes sequentially. 
 
The study drugs will be administered intravenously, via a peripheral vein in one of the upper 
extremities. The administration site should be free of potentially complicating dermatologic 
conditions. At the end of infusion, the IV line will be flushed with Normal Saline to ensure all study 
drug has been delivered. 
 
Part B 
 
Subcutaneous administration (Group S3): 
The RUH research pharmacist will provide the study drugs or placebo in separate syringes ready for 
administration. The number of injections of C144-LS and C135-LS will be 4 mL of C144-LS and 4 
mL of C135-LS, separately or 8ml of placebo. The total volume of the antibodies or placebo will be 
dispended in four (Group S3) separate syringes containing either C144-LS or C135-LS or placebo for 
administration in four separate sites. The antibodies or placebo will be administered subcutaneously 
in the abdomen, upper arms or thighs. Each SC injection should be administered carefully to avoid 
inadvertent deposition into muscular tissue or leakage after needle removal. If leakage occurs, it should 
be noted in the study records.  
 
6.2.4 Medical History and Physical Examination 
 
At the time of screening, participant’s past medical history will be collected and will include details 
of any previous reaction to vaccination, and contraceptive practices. Interim medical histories will be 
collected at time-points according to the Time of Events Schedule (Appendix A). 
 
A general physical examination will be conducted including weight, height, vital signs, and 
examination of skin, respiratory, cardiovascular, neurological and abdominal systems. At the time of 
C144-LS and C135-LS administration and at selected time-points thereafter, general and/or directed 
physical examinations will be performed according to the Time of Events Schedule (Appendix A). A 
directed physical examination will include vital signs, examination of administration site, and any 
further examination indicated by history or observation. 
 
6.2.5 Monitoring for cytokine release associated adverse events and treatment of cytokine 
release syndrome 
 
Based on previous clinical experience with similar monoclonal antibodies, it is unlikely that 
administration of C144-LS and C135-LS would lead to cytokine release syndrome. However, a 
potential side effect of a monoclonal antibody can be the stimulation of a massive release of cellular 
cytokines, which can have profound effects on blood pressure, vascular integrity, and myocardial, 
lung, liver, and kidney functions. If cytokine release syndrome occurs, the participant may need to be 
treated with therapies that include, but are not limited to, intravenous fluids, vasopressors, and high-
dose corticosteroids and/or may require ventilatory support. 
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Study participants will be admitted to the Rockefeller University Hospital the night before or on the 
day of C144-LS and C135-LS administration for 24 hours of monitoring. Participants will be closely 
observed for at least 30 – 60 minutes after administration. Access to a twenty-four hour on-call 
physician is available. The RUH outpatient and inpatient units are equipped with crash carts for 
immediate medical care, should the need arise. In case of an emergency at the Rockefeller University 
Hospital, after stabilization of the volunteer, he/she will be transferred to the neighboring tertiary care 
center, New York Presbyterian Hospital (Cornell) for specialized medical care. 
 
6.2.6 SARS-CoV-2 Infection 
 
Participants who develop symptoms suggestive of COVID-19 during study follow up will be mailed 
a kit for collection of saliva specimens (see Appendix C). The specimens will be returned for SARS-
CoV-2 PCR testing at the RU Laboratory of Molecular Neuro-Oncology. The participants will also be 
advised to seek medical care for management of SARS-CoV-2 infection. Participants acquiring SARS-
CoV-2 may remain on study. These participants will not return for in person follow up visits until 
deemed no longer infectious, according to CDC and local institutional guidelines. During this period, 
virtual study visits will be conducted for safety assessments, according to Appendix A. 
 
6.2.7 SARS-CoV-2 Vaccination 
 
At this time, it is not known if the prior receipt of anti-SARS-CoV-2 antibodies can interfere with the 
efficacy of SARS-CoV-2 vaccines, if the vaccine is administered while the anti-SARS-CoV-2 
antibodies are still present. Similarly, the pharmacokinetics and time to clearance of C144-LS and 
C135-LS when administered at different doses are not yet known. As discussed in Section 4.1, based 
on previous studies with anti-HIV-1-antibodies, it is expected that C144-LS and C135-LS will have a 
t1/2 in humans of 60-80 days, and that serum concentrations will be maintained above 2.5 mcg/mL (or 
approximately 1,000 times the in vitro IC50 of either mAb) for approximately 12 months when C144-
LS and C135-LS are administered at 15 mg/kg doses each. 
 
Study participants will be allowed to receive a FDA-approved SARS-CoV-2 vaccine after 
administration of the study antibodies and will be advised that the CDC currently recommends that 
vaccination be delayed for 90 days after receipt of anti-SARS-CoV-2 antibodies and that the period of 
C144-LS and C135-LS clearance is expected to be longer at the higher doses evaluated in this protocol 
(Appendix C, COVID-19 Considerations). 
 
Participants who receive a SARS-CoV-2 vaccine following receipt of C135-LS and C144-LS in this 
study will be offered enrollment in an ongoing observational study (Protocol DRO-1006 “Peripheral 
Blood of Coronavirus Survivors to Identify Virus-Neutralizing Antibodies”). This study aims to 
evaluate both B and T cell responses longitudinally in individuals who recovered from COVID-19 and 
in SARS-CoV-2 vaccine recipients.   
 
6.2.8 Other COVID-19 Considerations 
 
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In the event of travel restrictions, virtual study visits will be conducted for safety assessments, 
according to Appendix A. During such restrictions, if feasible, in person visits will be offered on study 
weeks 1, 4, 12, 24, and 48. These visits will follow Appendix A. 
 
Appendix C. COVID-19 Considerations provides detailed guidance on study conduct in the context 
of the COVID-19 pandemic. 
 
6.2.9 Family Planning Counseling 
 
During screening and subsequent study visits, study personnel will counsel participants about the 
importance of prevention of pregnancies and the use of condoms, as well as other effective family 
planning methods. 
 
Study participants engaging in sexual activity that could lead to pregnancy will be advised to use one 
effective method of contraception from 10 days prior to the C144-LS and C135-LS administration 
until 6 months after IP administration. 
 
Examples of effective contraception methods are: condom with or without spermicide, diaphragm with 
spermicide, hormone-eluting IUD (Mirena), hormone-based contraceptive pills, injections or 
implants. 
 
Should pregnancy occur, a pregnant participant will not receive the C144-LS and C135-LS 
administration. If pregnancy occurs after C144-LS and C135-LS administration, the participant will 
be followed until the end of the study and until delivery, if it occurs after the study has ended. 
Approximately 2-4 weeks after delivery, a pediatrician will examine and assess the health status of the 
baby. The baby’s health status will be reported to the RU sponsor, the RU IRB and the SMC. 
 
6.2.10 Safety Assessments 
 
6.2.10.1 Solicited Adverse Events 
 
Solicited systemic adverse events in this study include presence of feverishness, chills, headache, 
nausea, vomiting, malaise, myalgia and arthralgia occurring 2 weeks following C144-LS and C135-
LS administration. 
 
Solicited local adverse events in this study include presence of pain, tenderness, erythema and 
induration at injection site or infusion site occurring 2 weeks following C144-LS and C135-LS. 
 
Solicited adverse events will be collected prospectively by structured interviews on administration 
and post-administration follow up visits; recorded and graded according to pre-established criteria 
(see Appendix B) in the source document and in specific Reactogenicity eCRFs. The Toxicity Grading 
Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials 
(2007) will be used to grade adverse events. In addition, the Common Terminology Criteria for 
Adverse Events (CTCAE) v5.0 grading scale will be used for reporting and grading adverse events 
related to administration reactions and cytokine release syndromes within 24 hours of the start of 
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C144-LS and C135-LS administration that are considered administration reactions or cytokine release 
syndromes. Symptoms that may constitute an administration reaction or cytokine release syndrome 
include: fever and/or shaking chills, flushing and/or pruritus, alterations in heart rate and blood 
pressure, dyspnea or chest discomfort, back or abdominal pain, nausea, vomiting, and/or diarrhea, skin 
rash. 
 
Vital signs (pulse, respiratory rate, blood pressure and temperature) will be measured according to 
Section 6.1.4 and Appendix A. Vital signs during the 24-hour period after antibody administration 
will be graded according to The Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccine Clinical Trials (2007). All medications required for treatment of 
adverse events will be recorded. 
 
6.2.10.2 Unsolicited Adverse Events 
 
During all follow up visits, the occurrence of unsolicited adverse events will be assessed following an 
open question to participants, with the dates of commencement and resolution and any medication 
required. All adverse events will be followed to resolution. Serious Adverse Events (SAEs) will be 
collected during the entire study period. They will be graded as indicated in Appendix B. 
 
Laboratory abnormalities that are considered clinically significant and are grade 3 or higher will be 
reported as adverse events. 
 
6.2.11 Blood Collection, Storage and Shipment 
 
Venous blood will be collected at every study visit, usually from the antecubital fossa, according to 
the Time of Events Schedule (Appendix A). Up to 100 ml will be collected at day 0. Up to 60 ml will 
be collected at other visits. At no time will the total volume of blood collected exceed 550 ml over an 
8-week period. The total volume of blood samples that will be collected during the entire study will 
be 775ml. 
 
All specimens will be handled according to SOPs that were developed in the GLP-Processing Lab 
within the Laboratory of Molecular Immunology. 
 
Frozen PBMCs, plasma and serum will be processed and stored in the Laboratory of Molecular 
Immunology at Rockefeller University. 
 
6.2.12 Routine Laboratory Parameters 
 
Specimens collected for safety labs at RUH will be transported to Memorial Sloan Kettering Cancer 
Center laboratory (MSKCC) via a courier. Specimens for Weill Cornell Medical Center (WCMC), 
LabCorp or Quest will be picked up by WCMC, LabCorp or Quest staff at RUH. 
 
Laboratory 
parameters 
will 
routinely 
include 
hematology 
(WBC 
and 
differential, 
hemoglobin/hematocrit, platelets), clinical chemistry (Creatinine, Glucose, Total and Direct bilirubin, 
Alkaline phosphatase, AST and ALT), and urinalysis (RBC, WBC, protein). Female participants of 
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reproductive potential will have urine beta-HCG measured at screen, on the day of C144-LS and C135-
LS administration, at selected follow up visits and as clinically indicated. The laboratory samples for 
these tests will be collected at the time points indicated in the Time of Events Schedule (Appendix A). 
 
In the event of an abnormal laboratory value, participants may be asked to have additional sample(s) 
collected at the discretion of the principal investigator or designee. 
 
At screening, participants will be screened for HIV, hepatitis B and C. 
 
SARS-CoV-2 serology will be performed at screen, day 0, weeks 2, 12, 24 and 48. 
 
A nasopharyngeal or oropharyngeal swab will be collected for SARS-CoV-2 PCR at the pre-
administration visit. Saliva samples will be collected for SARS-CoV-2 PCR at weeks 2, 4, 12, 24, 36 
and 48. 
 
In the event a participant develops symptoms suggestive of COVID-19 during study follow up, a kit 
for collection of saliva specimens will be mailed to the participant’s residence. The specimens will be 
returned for SARS-CoV-2 PCR testing at the RU Laboratory of Molecular Neuro-Oncology. 
 
6.2.13 Pharmacokinetics and Immunogenicity Assessments 
 
1. Pharmacokinetics: 
Measurement of C144-LS and C135-LS levels by sandwich ELISA will be performed by PPD 
Laboratory Services (a contract research organization). C144-LS and C135-LS levels will be measured 
before and at the end of the administration, at 1 ,3, 6, 9 and 12 hours, 1, 3, 7 days and on weeks 2, 3, 
4 weeks after administration, and at later time points as outlined in Appendix A. 
 
Pharmacokinetic parameters will be calculated using standard non-compartmental analysis methods. 
Pharmacokinetic parameters to be assessed will include elimination half-life (t1/2), clearance (CL/F), 
volume of distribution (Vz/F), AUC and decay curve. Descriptive results will be presented for the 
pharmacokinetic parameters by dose group. 
 
2. Immunogenicity: 
Anti-drug (C144-LS and C135-LS) antibody responses in serum. Assays will be performed by PPD 
Laboratory Services. The presence of anti-drug antibodies will be assessed at baseline and at weeks 4, 
12, 24 and 48. 
 
Optimal sample collection, processing, cryopreservation, archiving and storage will be maintained. 
Additional studies will be performed as warranted at the discretion of the investigators. 
 
6.2.14 Other Laboratory Assessments 
Serum neutralizing activity: An in vitro neutralization assay will be performed to determine serum 
neutralizing activity against a SARS-CoV-2 pseudovirus following C135-LS and C144-LS 
administration in the Laboratory of Molecular Immunology. 
 
SARS-CoV-2 serology: will be performed at screen, day 0, weeks 2, 12, 24 and 48. 
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SARS-CoV-2 PCR: 
- 
A nasopharyngeal or oropharyngeal swab will be collected for SARS-CoV-2 PCR at the pre- 
administration visit. The sample will be assayed at Memorial Sloan Kettering Cancer Center. 
 
- 
Saliva samples will be collected for SARS-CoV-2 PCR at weeks 2, 4, 12, 24, 36 and 48. These 
samples will be collected at home using a collection kit and brought in during the designated study 
visit. These samples will be assayed at the RU Laboratory of Molecular Neuro-Oncology and 
results will be used for research purposes. In the event of a positive result, the study team will 
contact the participant and refer him/her to have a coronavirus PCR test performed by a 
commercial lab. 
 
In the event a participant develops symptoms suggestive of COVID-19 during study follow up, a 
kit for collection of saliva specimens will be mailed to the participant’s residence. The specimens 
will be returned for SARS-CoV-2 PCR testing at the RU Laboratory of Molecular Neuro-
Oncology. 
 
6.2.15 Compensation 
 
Participants will be compensated according to standards at the study site. 
 
7 
INVESTIGATIONAL PRODUCT 
 
Investigational Drug Name:  
C144-LS, C135-LS and Placebo for C144-LS and C135-LS 
Manufacturer name of drug:  
Bristol Myers Squibb (BMS) 
IND Number:  
 
 
150929 
IND Sponsor:   
 
            The Rockefeller University 
 
7.1 
 Regimen 
 
C144-LS and C135-LS will be administered subcutaneously (separately) at 4ml (approximately 
100mg of each antibody) or 8ml (approximately 200mg of each antibody) or intravenously 
(sequentially) at one of three increasing dose levels 1.5 mg/kg, 5 mg/kg and 15 mg/kg of each antibody 
on day 0.  
 
7.2 
Study Product Formulation and Preparation 
 
Formulation: 
- 
C135-LS will be provided by Bristol Myers Squibb (BMS) in single-use vials containing 50 
mg/mL of protein in 6ml of buffered solution. C135-LS is a clear to opalescent, colorless to yellow 
liquid, which may contain light (few) particulates (consistent in appearance to protein particulates). 
The drug product is monitored for particulates in the stability program and is in compliance with 
USP particulate limits. 
The drug product is a sterile, nonpyrogenic, single-use, preservative-free, isotonic aqueous 
solution for intravenous (IV) administration formulated at 50 mg/mL in a buffered solution 
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consisting of histidine, sucrose, pentetic acid (diethylenetriaminepentaacetic acid, DTPA), 
polysorbate 80, and water for injection, at pH 6.0. Each vial includes a 0.5-mL overfill to account 
for vial, needle, and syringe (VNS) holdup. The drug product is supplied in a 6-mL Type I flint 
glass vial stoppered with a fluoropolymer film-laminated rubber stopper and sealed with an 
aluminum seal. 
- 
C144-LS will be provided by Bristol Myers Squibb (BMS) in single-use vials containing 50 
mg/mL of protein in 6 ml of buffered solution. C144-LS is a clear to opalescent, colorless to yellow 
liquid, which may contain light (few) particulates (consistent in appearance to protein particulates). 
The drug product is monitored for particulates in the stability program and is in compliance with 
USP particulate limits. 
The drug product is a sterile, nonpyrogenic, single-use, preservative-free, isotonic aqueous 
solution for intravenous or subcutaneous administration formulated at 50 mg/mL in a buffered 
solution consisting of histidine, sucrose, pentetic acid, polysorbate 80, and water for injection, at 
pH 6.0. Each vial includes a 0.5-mL overfill to account for VNS holdup. The drug product is 
supplied in a 6-mL Type I flint glass vial stoppered with a fluoropolymer film-laminated rubber 
stopper and sealed with an aluminum seal. 
- 
Placebo for C135-LS and C144-LS will be a buffered solution provided by BMS in single-use 
vials containing 2 ml of buffered solution. The placebo is a sterile, nonpyrogenic, preservative-
free, single-use, subcutaneous injectable product consisting of a buffered solution of histidine, 
sucrose, pentetic acid (diethylenetriaminepentaacetic acid, DTPA), polysorbate 80 and water for 
injection at pH 6.0. It is packaged in a 6-mL Type I flint glass vial, stoppered with a 20-mm 
fluoropolymer film-laminated rubber stopper, and sealed with a 20-mm aluminum flip-off seal. 
The placebo for BMS-C44-LS and C135-LS injection contain the same formulation as the 
respective active drug products, but without the active drug products. 
 
Preparation: 
- 
Each mAb will be diluted in normal saline (NaCl 0.9%) to a volume of 100 mL for intravenous 
infusion. Normal saline will be obtained by the local site pharmacy. 
- 
C144-LS-LS and C135-LS are stored at 5 ± 3°C. The appropriate dose of each mAb should be 
drawn soon after vials are removed from the refrigerator. Vials should be inspected for particulate 
matter and discoloration. Discard if cloudy, discolored, or contain extraneous particulate matter. 
Do not shake (see Investigator’s Brochure). 
- 
Placebo for C135-LS and C144-LS should be stored at the site Pharmacy at 5 ± 3°C. The 
appropriate dose of placebo should be drawn soon after vials are removed from the refrigerator. 
 
Part A: 
 
Subcutaneous groups 
- 
Subcutaneous groups: The RUH research pharmacist will provide each mAb in a syringe ready for 
administration (in 3 mL syringes attached to a 18G x 1.5 inch needle). The volume of C144-LS 
and C135-LS will follow study assignment. In both groups the mAbs will be prepared separately 
and the total volume of the individual antibodies will be dispended in two or four separate syringes 
for administration in two or four separate sites respectively.   
 
Intravenous groups 
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- 
The appropriate dose will be calculated by the site research pharmacist according to participant’s 
weight (measured at the pre-infusion or day 0 visits) and study group allocation. C144-LS and 
C135-LS will be dispensed in a small volume parenteral infusion, diluted in normal saline (NaCl 
0.9%) ready for administration by the study investigators. Standard 18G needles are recommended 
to draw the required dose of each mAb to decrease the preparation time. Prior to injection of the 
mAb solution into the IV bag, remove air from the syringe and inject slowly, to avoid foaming. 
After preparation, infusion bags should be handled gently to avoid foaming (do not shake). 
Infusion bags should also be checked for particulates. 
- 
C144-LS and C135-LS should be administered through a 0.2 or 0.22 micron in-line filter. 
 
Part B: 
 
Subcutaneous Group S3 
- 
The RUH research pharmacist will provide each mAb or placebo in a syringe ready for 
administration (in 3 mL syringes attached to a 18G x 1.5 inch needle). The volume of C144-LS 
and C135-LS or placebo will be dispended in four (Group S3) separate syringes containing either 
C144-LS or C135-LS or placebo for administration in four separate sites respectively. 
 
7.3 
Dispensing and Handling of Investigational Product: 
 
C144-LS, C135-LS and  placebo will be shipped from Bristol Myers Squibb (BMS) and will be stored 
in the RUH Pharmacy at 5 ± 3°C. C144-LS, C135-LS and placebo will be dispensed by the RUH 
pharmacist. Trial personnel will ensure that the study ID number on the syringe or infusion bag 
matches the study ID assigned to the participant prior to administration. 
 
7.4 
Accountability and Disposal of Used and Unused Investigational Product 
 
The date, allocation number and location of storage of the vials will be recorded in a log.  During the 
trial, the product accountability form, and the dispensing log will be monitored. At the end of the trial, 
unused vials will be returned to Bristol Myers Squibb (BMS), transferred to the Laboratory of 
Molecular Immunology at RU or destroyed. 
 
7.5 
Concomitant Medications and Procedures 
 
Use of concomitant medications will be reviewed at each study visit. Each participant will have a 
medication reconciliation record, which will be updated if schedule or dose level changes, and if new 
medications are initiated. 
 
7.6 
Permitted Medications and Procedures 
 
Significant drug interactions with the study products are not anticipated at this time, therefore, if 
clinically necessary, participants can be initiated on other medications for intercurrent illnesses that 
might occur during their study participation. 
 
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Study participants will be allowed to receive a FDA-approved SARS-CoV-2 vaccine after after 
administration of the study antibodies, but will be advised that the CDC currently recommends that 
vaccination be delayed for 90 days after receipt of anti-SARS-CoV-2 antibodies and that it is expected 
that C144-LS and C135-LS will take longer to clear when dosed at the higher doses of 5 and 15 mg/kg. 
(Appendix C, COVID-19 Considerations). 
 
7.7 
Prohibited Medications and Procedures 
 
Significant drug interactions with the study products are not anticipated at this time. Participants who 
enroll in the study agree to not participate in other studies of investigational drugs. In addition, they 
should not participate in studies that require frequent blood sample collection. 
 
Use of systemic corticosteroids (long term use), immunosuppressive anti-cancer, interleukins, 
systemic interferons, systemic chemotherapy within 6 months of study enrollment is not permitted. 
Short term use of systemic steroids (e.g. steroid taper for allergic or administration reactions or asthma 
exacerbation) is permitted. 
 
7.8 
Precautionary Medications and Procedures 
Significant drug interactions with the study products are not anticipated at this time. Participants who 
enroll in the study agree to not participate in other studies of investigational drugs. In addition, they 
should not participate in studies that require frequent blood sample collection. 
 
7.9 
Required Medications 
Not applicable. 
 
7.10 Rescue Medications 
If participants develop grade 3 acute infusion reaction, an immediate hypersensitivity reaction or a 
life-threatening event during study drug administration, the infusion will be discontinued and will not 
be reinitiated (see Section 6.1.7.1). Rescue medications, including acetaminophen, diphenhydramine, 
epinephrine and glucocorticoids will be available at the clinical sites for use if clinically indicated. 
 
8 
DATA ANALYSIS 
 
The proposed study is a first-in-human, single dose, dose-escalation phase 1 study of C144-LS and 
C135-LS in healthy volunteers (Table 1, Study groups and Section 4, Study Design - Dose escalation 
plan). Study participants will be enrolled sequentially. 
 
Study participants will be administered C144-LS and C135-LS subcutaneously or intravenously at 
increasing dose levels. In Group S3 participants will be administered C144-LS and C135-LS or 
placebo subcutaneously in a 3:1 ratio. 
 
This is an exploratory proof of concept trial and analysis will be descriptive. A standard “3+3” Phase 
1 trial design is used; stopping rules will be based on the occurrence of dose-limiting toxicity. 
 
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8.1 
Analysis of Safety, PK and Antiretroviral effects 
 
Primary Outcomes 
 
Safety: The safety population will include all participants who receive C144-LS and C135-LS. A 
baseline measurement and at least one laboratory, vital sign, or other safety-related measurement 
obtained after C144-LS and C135-LS administration may be required for inclusion in the analysis of 
a specific safety parameter. 
 
The number and percentage of participants experiencing one or more AEs will be summarized by 
study group, relationship to study drug, and severity. AEs will be summarized by the number and 
percentage of participants who experienced the event, according to system organ class (SOC) and 
preferred term. AEs will also be summarized by severity grade and by relationship to study drug 
according to the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in 
Preventive Vaccine Clinical Trials. The CTCAE v5.0 grading scale will be used for reporting and 
grading adverse events related to administration reactions and cytokine release syndromes in all 
groups (Appendix A). Changes in hematology, chemistry, and other laboratory values will be 
summarized descriptively. Changes will be calculated relative to the values collected at baseline. 
 
Pharmacokinetic parameters: will be calculated using standard non-compartmental analysis methods. 
Descriptive results will be presented for the pharmacokinetic parameters by dose group. 
Pharmacokinetic parameters, including AUC, Cmax, T1/2, Tmax and others will be summarized. 
ANOVA model will be used to compare group differences for AUC and Cmax. The dose 
proportionality for the 2 parameters (AUC and Cmax) will be examined by regression analysis. 
Pharmacokinetic parameters will be examined to correlate exposure with safety and pharmacodynamic 
parameters, and variance based on population intrinsic factors such as weight and gender will be 
explored. 
 
Secondary outcomes 
 
Anti-C144-LS and anti-C135-LS antibodies: The frequency of induced anti-C144-LS or anti-C135-
LS antibodies will be reported. Occurrence of anti-drug antibodies (ADA) will be evaluated by a three-
tiered approach using validated screening and confirmatory assays, followed by tittering of responses 
to determine if responses were treatment-induced or treatment-boosted. 
 
Serum neutralizing activity against SARS-CoV-2: The SARS-CoV-2 neutralizing activity in serum 
will be determined by an in vitro neutralization assay before and after anti-C144-LS and anti-C135-
LS administration. 
 
Continuous data will be summarized by descriptive statistics, including the sample size, mean, 
standard deviation, median and range. Categorical data will be summarized by the number and 
percentage of participants. 
 
The analysis of study data will be primarily descriptive, with emphasis on tabular and graphical 
displays. Summary statistics will be calculated, along with point and interval estimates of solicited 
and unsolicited adverse events. The pharmacokinetic profile of a single administration of C144-LS 
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and C135-LS will also be determined. This study is exploratory, and any statistical inferences will be 
hypothesis generating and not confirmatory. 
 
8.2 
Sample Size Considerations 
 
The sample size will be of 23 to 38 participants according to the dose escalation design used to 
characterize the safety and the pharmacokinetics profile of combined C144-LS and C135-LS 
administration at increasing dose levels, to healthy volunteers. Replacement of 2 participants lost to 
follow up prior to week 4 will be allowed. 
 
- 
Pharmacokinetics: 
The pharmacokinetic profile of C144-LS and C135-LS will be evaluated in this study. The target dose 
of C144-LS and C135-LS at this time is 5 mg/kg or 15 mg/kg. Based on the PK profile of other human 
monoclonal antibodies with the LS mutations, it is expected that the half-life of C144-LS and C135-
LS will be 60 to 80 days. 
 
- 
Safety: 
It is expected that the administration of C144-LS in combination with C135-LS will be generally safe 
and well tolerated. 
 
The sample size of 21 participants receiving C-144-LS and C-135-LS in combination will provide 
95% probability of observing a treatment-related AE that would occur in 13.4% or more of treated 
participants. If none of the participants experiences a grade 2 or higher AE related to C-144-LS and/or 
C-135-LS, the one-sided 95% upper confidence bound for the rate of AEs in the population is 13.3%. 
 
9 
DATA AND SAMPLE STORAGE 
 
The Principal Investigator will oversee how the data are collected, entered, and protected. All study 
data will be collected by the clinical study staff using designated source documents and entered onto 
the appropriate electronic case report forms (eCRFs). Data collection forms (DCFs) will be provided 
by Emmes Corporation for use as source documents as appropriate.  All study data must be verifiable 
to the source documentation. All source documents will be kept in a locked facility at the clinical site 
and remain separate from participant identification information (name, address, etc.) to ensure 
confidentiality. All medical records (when not being reviewed by the research team) will be kept under 
lock and key in the Medical Record Department of the hospital with access limited to the appropriate 
RUH personnel, members of the RU IRB and the FDA. Source documentation will be available for 
review to ensure that the collected data are consistent with the eCRFs. 
 
All eCRFs and laboratory reports will be reviewed by the clinical team, who will ensure that they are 
accurate and complete. 
 
All research samples will have a unique identifier. The PI will be responsible for ensuring project 
compliance, data analysis and entry, regulatory monitoring, and coordination of the activities of the 
entire study team.  Standard GCP practices will be followed to ensure accurate, reliable and consistent 
data collection. 
 
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Source documents include, but are not limited to: 
- 
Signed Informed Consent Documents 
- 
Dates of visits including date of C144-LS and C135-LS administration 
- 
Documentation of any existing conditions or past conditions relevant to eligibility 
- 
Reported laboratory results 
- 
All adverse events 
- 
Concomitant medications 
- 
Reactogenicity adverse events 
 
10 RECRUITMENT AND ADVERTISING 
 
Both men and women aged 18 or older will be recruited for the study from the community at large and 
will be referred by physicians in the community.   We will make every effort to recruit minorities and 
women. 
 
Advertisements – The RUH Clinical Research Support Office (CRSO) will utilize the Volunteer 
Repository. Advertisements will also be placed: online (e.g. Craigslist, Centerwatch, etc), and in 
newspapers (Metro, AMNY). 
 
Centralized Call Management – The RUH CRSO will conduct telephone screenings of selected 
Volunteer Repository members, and of volunteers who call 1800-RUCARES, to facilitate screening 
efficiently. Based on IRB approved eligibility criteria, potentially eligible candidates pre-screened by 
CRSO staff will be referred to the study coordinator/investigator for further evaluation. The research 
team and CRSO will work together on a protocol-specific pre-screening script to optimize the process. 
 
11 POTENTIAL BENEFITS TO PARTICIPANTS 
 
This is the first-in-human study of these monoclonal antibodies. There are no direct benefits to healthy 
volunteers that enroll in this study. 
 
12 POTENTIAL RISKS TO THE PARTICIPANT INCLUDING TO THE FETUS 
 
While each mAb product has unique safety issues related to its mechanism of action, the major safety 
concern related to monoclonal antibodies (mAbs) in general is an administration/hypersensitivity 
reaction. These types of reactions are more common for mAbs that contain murine elements compared 
to human mAbs, such as C144-LS and C135-LS. Passive administration of antiviral antibodies has 
been evaluated in humans in the past. As observed with other monoclonal antibodies, e.g. anti-HIV-1 
antibodies were generally safe and well tolerated and most adverse events observed were infusion-
related events and grade 1 in severity. 
 
This study entails “significant” risk to participants since C144-LS and C135-LS have not been tested 
in humans yet. Potential study participants will be informed about the possible risks associated with 
C144-LS and C135-LS mAb administration and that there may be unknown risks. 
 
- 
Immunologic symptoms such as listed below are possible with administration of a monoclonal 
antibody and will be considered adverse events of interest.  Potential allergic-type reactions during 
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and immediately following the administration of C144-LS and C135-LS will be carefully 
monitored.  
o Constitutional symptoms, such as fever, rigors/chills; 
o Administration site reaction/extravasation changes, pruritus, urticaria; 
o Serum sickness like syndromes as evidenced by fever, rash, arthralgia, arthritis, nephritis; 
o Deposition of immune complexes in the kidneys leading to renal insufficiency; 
o Adult Respiratory Distress Syndrome, bronchospasm/wheezing, anaphylaxis; 
o Cytokine release syndrome/ acute administration reaction. 
 
- 
There is a theoretical concern that non-neutralizing or decaying levels of antibodies could lead to 
antibody-dependent enhancement of infection should a participant acquire SARS-CoV-2 after 
receiving C144-LS and C135-LS. However, this phenomenon has not been observed in multiple 
studies of SARS-CoV-2 convalescent plasma transfusions, which contain polyclonal antibodies of 
varying neutralizing potencies.  
 
- 
There is also a theoretical concern that the receipt of anti-SARS-CoV2- antibodies, such as C144-
LS and C135-LS may interfere with the efficacy of COVID-19 vaccines, if the vaccine is given 
while the anti-SARS-CoV-2 antibodies are still present. It is not yet known how long it will take 
for C144-LS and C135-LS to be cleared when given at different doses.  
 
- 
Blood drawing and phlebotomy can be associated with pain, bruising, anemia or infection at the 
site of venipuncture. Rarely, fainting may follow phlebotomy. 
 
- 
The adverse effects C144-LS and C135-LS administration would have in a fetus are unknown. 
 
- 
Participants may engage in increased risk taking after receiving anti-SARS-CoV-2 mAbs. One to 
one counseling will be routinely performed. 
 
13 PROCEDURES TO MINIMIZE RISK 
 
- 
As outlined above, this study will be a first-in-human dose escalation phase 1 trial of C144-LS and 
C135-LS in humans. Potential study participants will be informed about possible risks of the 
monoclonal antibodies and that there may be unknown risks. 
 
- 
Medical records and routine laboratory data will be handled with HIPAA compliance and protected 
by the rules and regulations of the RUH. 
 
- 
With any new medicine or monoclonal antibody, there is a possibility of totally unexpected side 
effects. Participants will be admitted the night prior or on the day of C144-LS and C135-LS 
administration for close monitoring for 24 hours after administration. The RUH inpatient unit is 
equipped for providing emergency medical interventions in the unlikely event of acute allergic or 
other reactions. In case of an emergency at the Rockefeller University Hospital, after stabilization 
of the participant, he/she will be transferred to the neighboring tertiary care center, New York 
Presbyterian Hospital (Cornell) for specialized medical care. 
 
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- 
To minimize risks associated with antibody administration, C144-LS and C135-LS will be 
administered as separate subcutaneous injections. During the sequential intravenous infusions, the 
participants will be observed for 1 hour after the first C144-LS infusion before proceeding with 
subsequent infusion of C135-LS. 
 
- 
Enrollment will be staggered by 1 day for participants enrolled in each subcutaneous or 
intravenous dose group in Part A of the study. If 1 DLT occurs, 3 additional participants will enroll 
in each respective dose group. If no additional dose limiting toxicities occur, enrollment in the next 
dose level will proceed. If 2 or more DLTs occur, dosing will be halted and the prior lower dose 
level will be declared the maximum subcutaneous tolerated dose (MTD). 
 
- 
The study investigators will review 1 week safety data prior to dose escalation from the low to the 
mid dose groups step. An external Safety Monitoring Committee (SMC) will review the 1 week 
safety data prior to dose escalation from the mid to the high intravenous dose groups step. The 
SMC will provide a recommendation regarding enrollment in subsequent groups. 
 
- 
If, at any time, a fatal, life-threatening or permanently disabling SAE with a suspected causal 
relationship to C144-LS and C135-LS occurs, no further administration of the investigational 
product will occur until a consensus plan forward has been approved by investigators, SMC, the 
IRB and the FDA. 
 
- 
Participants will be advised that the CDC currently recommends that vaccination be delayed for at 
90 days after receipt of anti-SARS-CoV-2 antibodies and that it is expected that C144-LS and 
C135-LS will take longer to clear when dosed at the higher doses of 5 and 15 mg/kg. In addition, 
participants who are eligible to SARS-CoV-2 vaccination according to current local guidelines 
will be excluded from participation.  
 
- 
To minimize risks associated with phlebotomy, blood drawing will be performed by experienced 
phlebotomists. Should discomfort occur, they will provide appropriate treatment. 
 
- 
To minimize risks associated with blood drawing, participants will be closely monitored for signs 
and symptoms of anemia. 
 
- 
Females of childbearing potential and who participate in sexual activity that might lead to 
pregnancy will be advised to use one reliable form of contraception (i.e. condom with spermicide, 
diaphragm with spermicide, hormone-eluting IUD, hormone-based contraceptive with condom) 
from 10 days prior to and until 6 months after the C144-LS and C135-LS administration. In 
addition, a pregnancy test will be performed at screening, on the day of antibody administration, 
and throughout the course of the study according to Appendix A and as clinically indicated.  Males 
who are not anatomically sterile and who participate in sexual activity that might lead to pregnancy 
will be advised to use one reliable form of contraception from 10 days prior to and until 6 months 
after the C144-LS and C135-LS administration until the end of the study to avoid pregnancy in a 
spouse or partner. Condoms will be provided. 
 
- 
Participants will have regularly scheduled visits to the outpatient clinic and routine safety 
laboratories will be checked according to the Time of Events Schedule (Appendix A). 
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- 
Adverse events will be monitored and graded using the Toxicity Grading Scale for Healthy Adult 
and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. The CTCAE v5.0 
grading scale will be used for reporting and grading adverse events related to administration 
reactions and cytokine release syndromes in all groups (Appendix A). 
 
- 
Adverse events will be managed by the clinical trial team who will assess and treat the event as 
appropriate, including referral to an independent physician and/or department. 
 
- 
Safety monitoring will be conducted by the study investigators and by an external Study 
Monitoring Committee (SMC). The RU IRB will conduct the initial review of the proposed study 
and will follow progress through annual reports and by immediate notification of serious adverse 
events. Any serious and unanticipated adverse events will be immediately reviewed by the study 
investigators. Investigators will notify the local IRB and the RU sponsor within 2 working days 
from the investigators being made aware of the event. The RU sponsor will notify the FDA, per 
21 CFR 312. The SMC will be available to the investigators for consultation and review of severe 
adverse events if needed. 
 
14 DATA AND SAFETY MONITORING PLAN 
 
This is a first-in-human phase 1 study, which exposes study participants to “significant risk”. A Study 
Monitoring Committee (SMC) will be established to monitor the study. 
 
14.1 Safety Monitoring Committee 
 
The charter of the Safety Monitoring Committee (SMC) is to provide an ongoing assessment of 
participant safety during the conduct of the study.  The SMC consists of three independent individuals 
who have no relationship to the Principal Investigator and Co-Investigators involved in the trial. No 
member of the SMC will have any direct responsibility for the clinical care of study participants.  No 
representative of Bristol Myers Squibb (BMS), the Rockefeller University, or their designees may be 
a member of the SMC. However, the SMC may invite the principal investigator (PI) or designee and 
a BMS, and/or Rockefeller University representative to an open session of a SMC meeting to provide 
information on study conduct, present data, or to respond to the members’ questions. 
 
The names, university affiliation and title, area of expertise, and contact information of each of the 
SMC members are provided below: 
 
1. Trevor Crowell, MD PhD 
Assistant Professor of Medicine, Division of Infectious Diseases 
F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences 
Associate Director, Department of Epidemiology and Threat Assessment 
Henry M. Jackson Foundation for the Advancement of Military Medicine/U.S. Military HIV Research 
Phone:  301-500-3990 
tcrowell@hivresearch.org 
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Clinical expertise: infectious diseases, HIV vaccines and monoclonal antibodies. 
 
2. Christopher Palma, MD 
Assistant Professor of Medicine, Division of Allergy Immunology and Rheumatology 
University of Rochester School of Medicine & Dentistry 
Phone: 585-486-0901 
Christopher_palma@urmc.rochester.edu 
Clinical expertise: immunotherapy, COVID-19 interventional trials (including anti-SARS CoV2 
mAbs). 
 
3. Sanjay Mehta, MD 
Associate Professor of Medicine and Pathology, Division of Infectious Diseases and Global Public 
Health 
University of California, San Diego 
Phone: 858-552-7446 
sanjay.mehta2@va.gov 
Clinical expertise: clinical management of HIV and SARS-CoV-2 infection. 
 
3. Randall L. Tressler, MD (non-voting member) 
Medical Officer 
Division of AIDS/NIAID/NIH 
5601 Fishers Lane, Rm 9E49 
Rockville, MD 20852 
Email: randall.tressler@nih.gov 
Areas of expertise: clinical evaluation of antiretrovirals 
 
At least two members of the SMC must be in attendance (phone, video, or in-person meetings) to 
constitute a quorum for an SMC meeting. SMC members may also review and comment by email, if 
scheduling cannot be worked out in a timely manner.  One member of the SMC will be appointed as 
chair of the committee.  The SMC chair (or his/her alternate) will be responsible for summarizing and 
communicating in writing SMC acknowledgments and recommendations to the PI within 3 business 
days following each SMC meeting and/or review.  
 
The SMC will be asked to review on an interim basis and in the following scenarios: 
 
1. The SMC will review the 1-week safety data prior to dose escalation from the mid to the high dose 
intravenous groups step. The SMC will provide a recommendation regarding enrollment in 
subsequent groups. 
 
2. The SMC will review all available safety and PK data when 4-wk safety and 2-wk PK data from 
the last enrolled group (V3) becomes available. Following review, the SMC will provide a 
recommendation regarding initiation of future phase 2 studies. 
 
3. Grade 3 solicited and unsolicited adverse events judged by the principal investigator or designee 
to be possibly, probably or definitely related to C135-LS and/or C144-LS. 
 
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4. Grade 3 laboratory adverse events confirmed on retest and judged by the principal investigator or 
designee to be possibly, probably or definitely related to C135-LS and/C144-LS. 
 
5. The investigator will report any “late occurring” DLT (i.e., a DLT occurring after 12 weeks of 
dosing) to the SMC. The investigators and SMC will mutually assess this information, along with 
safety from other participants, to determine whether a change to study conduct is warranted. 
 
6. If one or more grade 3 or higher adverse events, deemed probably or definitely related to the study 
drugs occur, no additional administration of the investigational products will take place pending a 
Safety Monitoring Committee (SMC) review. In the event of a DLT, the SMC will make 
recommendations with regards to expansion of a study group from 3 to 6 participants, dose 
escalation to the next dose level, or halting additional enrollment. The investigators and SMC will 
mutually assess available information, along with safety from subsequent study groups, to 
determine whether a change to study conduct is warranted. 
 
7. SAEs, which are deemed possibly, probably or definitely related to C144-LS and C135-LS by the 
principal investigator or designee, and unanticipated adverse events will be reported to the 
SMC within 2 working days of the site becoming aware of the event. 
 
If there is one SAE, grade 3 or higher, and judged as possibly, probably or definitely related to the 
administration of C144-LS and C135-LS by the principal investigator or designee, no additional 
administration of the investigational product will take place pending a review by at least two 
members of the SMC. Following this review, the SMC will make a recommendation to the 
principal investigator regarding the continuation of investigational product administration. 
 
8. If, at any time, a fatal, life-threatening or permanently disabling SAE with a suspected causal 
relationship to C144-LS and C135-LS occurs, no further administration of the investigational 
product will occur until a consensus plan forward has been approved by investigators, SMC, the 
IRB and the FDA. 
 
All updated versions of the protocol will be provided to the SMC. The review of trial data by the SMC 
will take place at least bi-annually. Prior to data review, the study team will provide the SMC with 
updated records of all adverse events (AEs) of a grade 2 or higher. 
 
The SMC will acknowledge receipt of annual reports and will indicate if there are concerns with the 
continuation of the study. The SMC will provide a written report to the RU sponsor and the site PIs 
after each evaluation. The PIs in turn will distribute these reports to the study team and the local IRB. 
 
14.2 Monitoring 
 
Safety monitoring will be conducted by the study investigators and by the external Study Monitoring 
Committee (SMC). The RU IRB will conduct the initial review of the proposed study and will follow 
progress through annual reports and by immediate notification of serious adverse events. External 
monitoring will occur at least quarterly, and will be conducted by the Emmes Corporation. 
 
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14.3 Adverse Event Definition and Classification 
 
An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or diagnosis that occurs in a study participant during the conduct of the study 
REGARDLESS of the attribution (i.e., relationship of event to medical treatment/study product/device 
or procedure/intervention). This includes any occurrence that is new in onset or aggravated in severity 
or frequency from the baseline condition. 
 
Scales to be used: the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled 
in Preventive Vaccine Clinical Trials. The CTCAE v5.0 grading scale will be used for reporting and 
grading adverse events related to administration reactions and cytokine release syndromes in all 
groups (Appendix B). 
 
14.4 Reporting Adverse Events 
 
All adverse events will be reported to the IRB and the SMC at least annually. Serious Adverse Events, 
(SAEs) will be reported to the IRB and the SMC, within two (2) working days of identification of the 
SAE.  SAEs will be reported directly to the FDA, per 21 CFR 312. 
 
An adverse event is reported as a SAE if it meets any of the following criteria (as per International 
Conference on Harmonisation [ICH] guidance for Clinical Safety Data Management: Definitions and 
Standards for Expedited Reporting.): 
 
Any untoward medical occurrence that at any dose: 
• Results in death Is life-threatening 
 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity, or 
• Is a congenital anomaly/birth defect or spontaneous abortion 
• Any other important medical condition that requires medical or surgical intervention to prevent 
permanent impairment of a body function or structure 
 
Elective surgery for pre-existing condition that did not increase in severity or frequency is not 
considered an SAE. 
 
14.5 Reporting Unanticipated AEs 
 
Any adverse event that is not consistent with the known, predicted possible effects of the research 
protocol.  An unanticipated adverse event varies in nature, intensity or frequency from information on 
the investigational product provided in the Investigator's Brochure, package insert, safety reports, 
clinical protocol, or listed in the consent form. 
 
Unanticipated Adverse Events (UAEs) will be reported to the IRB and SMC.  UAEs that are related 
and greater than moderate severity must be reported to the IRB and SMC, within two working days of 
identification of the UAE.  UAEs will be reported to the FDA, per 21 CRF 312. 
 
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14.6 Clinical Laboratory Improvement Amendment/Clinical Laboratory Evaluation Program 
(CLIA/CLEP) 
 
This study includes tests that are not CLIA/CLEP certified. The results of such tests will not be used 
in clinical decision-making or shared with participants or their health care providers. 
 
14.7 Toxicity Management and Stopping Rules 
 
A dose limiting toxicity (DLT) will be defined as any adverse event of Grade 3 or greater toxicity, if 
the study investigators recognize a probable or definite attribution to C144-LS and C135-LS mAb. 
Grade 3 laboratory abnormalities must be confirmed by a repeat test, obtained as soon as possible 
following the initial result. 
 
In general, the following rules in dose escalation will be followed: 
 
During the subcutaneous and intravenous dose escalation phase (Part A) of the study, enrollment will 
be staggered by 1 day for the volunteers of each group. 
 
Subcutaneous (SC) Administration (Groups S1 and  S2) 
1. First, eligible participants will be enrolled in Group S1 (C144-LS + C135-LS, 2mL each). 
2. Enrollment in Group S2 (C144-LS + C135-LS, 4mL each) will begin after all three participants 
enrolled in Group S1 reach at least 7 days without a dose limiting toxicity (DLT) reported in the 
group (DLT: any adverse event of grade 3 or greater toxicity, if the study investigators recognize 
a probable or definite attribution to C144- LS and/or C135-LS). 
3. If 1 DLT occurs, 3 additional participants will enroll in Group S1. If no additional dose limiting 
toxicities occur, enrollment in the next dose level will proceed. 
4. If 2 or more DLTs occur, dosing will be halted and the prior lower dose level will be declared the 
maximum subcutaneous tolerated dose (MTD). 
Enrollment in Group S2 will follow the same rules. 
 
Intravenous (IV) Administration (Groups V1, V2 and V3) 
1. Enrollment in Group V1 (C144-LS + C135-LS, 1.5mg/kg each, IV) will begin at least 7 days after 
the first three participants enrolled in Group S2. 
2. Enrollment in Group V2 (C144-LS + C135-LS, 5mg/kg each, IV) will begin after all three 
participants enrolled in Group V1 reach at least 7 days without a dose limiting toxicity (DLT) 
reported in the group (DLT: any adverse event of grade 3 or greater toxicity, if the study 
investigators recognize a probable or definite attribution to C144-LS and/or C135-LS). 
3. If 1 DLT occurs, 3 additional participants will enroll in Group V1. If no additional dose limiting 
toxicities occur, enrollment in the next dose level will proceed. 
4. If 2 or more DLTs occur, dosing will be halted and the prior lower dose level will be declared the 
maximum intravenous tolerated dose (MTD). 
5. Enrollment in Group V3 (C144-LS + C135-LS, 15mg/kg each, IV) will follow the same rules. 
6. Enrollment in Group V3 will begin at least 7 days after three participants enrolled in Group V2 
and following SMC review of all available safety data. 
 
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During the subcutaneous, randomized, double-blinded phase (Part B) of the study, enrollment will be 
limited to a maximum of two volunteers per day. 
 
Subcutaneous (SC) Administration (Group S3) 
 
Enrollment in Group S3 will begin once all participants in Part A have met eligibility criteria and 
have been scheduled for enrollment (day 0) and after all three participants enrolled in Group S2 reach 
at least 7 days without a dose limiting toxicity (DLT) reported in the group.  
 
Note: As outlined in Section 14.1, the SMC will be asked to review safety data if one or more grade 
3 or higher adverse events, deemed probably or definitely related to the study drugs (DLT) occur. No 
additional administration of the investigational products will take place pending a SMC review. In the 
event of a DLT, the SMC will make recommendations with regards to expansion of a study group 
from 3 to 6 participants, dose escalation to the next dose level, or halting additional enrollment. 
 
The study investigators will review 1-week safety data prior to dose escalation from the low (Group 
V1 and S1) to the mid (Group V2 and S2) dose groups step. An external Safety Monitoring Committee 
(SMC) will review the 1-week safety data prior to dose escalation from the mid (Group V2) to the 
high (Group V3) dose groups step. The SMC will provide a recommendation regarding enrollment in 
subsequent groups. 
 
The SMC will review the 4-week safety and 2-week PK data after dosing in all study groups is 
completed. Following review, the SMC will provide a recommendation regarding initiation of future 
phase 2 studies. 
 
14.8 Other Disease Events 
 
Adverse events will be followed until resolved or considered stable during each scheduled study visit 
or during unscheduled study visits if warranted. If adverse events deemed related to the study drugs 
are not resolved at the time of final study visit, participants will be referred for appropriate medical 
care until the symptoms resolve or the participant’s condition becomes stable. 
 
15 CLINICAL TRIAL REGISTRATION 
 
The proposed study involves testing of FDA regulated drugs or biologics and will be registered at 
www.ClinicalTrials.gov. 
 
 
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16 BIBLIOGRAPHY 
 
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IND: 150929 
February 4, 2021 
 
PROTOCOL: RUCOV1 
CONFIDENTIAL 
64
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IND: 150929 
February 4, 2021 
 
PROTOCOL: RUCOV1 
CONFIDENTIAL 
65
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IND: 150929 
February 4, 2021 
 
PROTOCOL: RUCOV1 
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66
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February 4, 2021 
 
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Statistical Analysis Plan - The Rockefeller University 
Version 2.0 
PROTOCOL: RUCOV1 - IND: 150929 
09JUN2022 
Confidential  
Page 1 of 104 
 
 
STATISTICAL ANALYSIS PLAN 
for 
Rockefeller Protocol: RUCOV1 
Study Title: 
A Phase 1 Study of the Safety and 
Pharmacokinetics of a Combination of  
Two Anti-SARS-CoV-2 mAbs  
(C144-LS and C135-LS)  
in Healthy Volunteers 
 
IND # 150929 
DAIDS-ES ID 38798 
 
 
Version 2.0 
09 JUN 2022 
 
THIS COMMUNICATION IS PRIVILEGED AND CONFIDENTIAL  
 
 

Statistical Analysis Plan - The Rockefeller University 
Version 2.0 
PROTOCOL: RUCOV1 - IND: 150929 
09JUN2022 
Confidential  
Page 2 of 104 
Title 
A phase 1 study of the safety and pharmacokinetics of a combination of two  
anti-SARS-CoV-2 mAbs (C144-LS and C135-LS) in healthy participants 
Short Title 
s
Participant
s in Healthy 
mAb
2 
-
CoV
-
SARS
-
RU Anti
 
Protocol Number 
RUCOV1 
Phase 
Phase 1 
Investigational 
product 
Two highly neutralizing antibodies directed against SARS-CoV-2 RBD:  
C144-LS and C135-LS. 
The antibodies are manufactured, and each will be formulated in a separate vial at a 
concentration of 50 mg/mL. 
Indication 
Prevention or therapy of COVID-19 
Sample size 
23 to 38 
Number of study 
sites 
Single site – The Rockefeller University Hospital (RUH), New York, NY, U.S.A. 
Study Objectives 
Primary objectives: 
• 
To evaluate the safety and tolerability of subcutaneous injections or single 
intravenous infusions of C144-LS in combination with C135-LS in healthy 
participants. 
• 
To evaluate the pharmacokinetic profile of C144-LS and C135-LS in combination, 
administered subcutaneously or intravenously at increasing dose levels in healthy 
participants. 
Secondary objectives: 
• 
To assess the occurrence of anti-drug antibody responses. 
• 
To evaluate serum neutralizing activity against SARS-CoV-2 after C144-LS and 
C135-LS administration. 
Study Outcomes/ 
Objectives 
Primary outcomes: 
• 
Rate of solicited and investigational product (IP)-related unsolicited adverse events 
that are Grade 2 and above (including confirmed laboratory abnormalities) 4 weeks 
after administration. 
• 
Rate of solicited and IP-related unsolicited adverse events that are Grade 3 and 
above (including confirmed laboratory abnormalities) 4 weeks after administration. 
• 
Proportion of participants with serious adverse events (SAEs) throughout the study 
period that are considered related to investigational products and their duration. 
• 
The pharmacokinetic profile of C144-LS and C135-LS: elimination half-life (t1/2), 
clearance (CL/F), volume of distribution (Vz/F), AUC and decay curve. 
Secondary Outcomes: 
• 
Rate and severity of investigational product (IP)-related adverse events during 
study follow up. 
• 
Frequency and levels of induced anti-C144-LS and anti-C135-LS antibodies in all 
study groups. 
• 
Serum neutralizing activity against SARS-CoV-2 before and after C144-LS and 
C135-LS administration. 

Statistical Analysis Plan - The Rockefeller University 
Version 2.0 
PROTOCOL: RUCOV1 - IND: 150929 
09JUN2022 
Confidential  
Page 3 of 104 
Study Duration 
15 months 
Study Product, 
Dose, Route, 
Regimen 
Single subcutaneous injections of C144-LS and C135-LS, each mAbs dosed at 
approximately 100 mg (two 2 mL injections administered at separate sites) or 200 mg 
(four 2 mL injections administered at separate sites). 
Single subcutaneous injections of placebo (sterile saline) as four 2 mL injections 
administered at separate sites. 
One intravenous infusion of C144-LS and C135-LS, each administered via a peripheral 
vein over 60 minutes sequentially. Starting dose level is 1.5 mg/kg of each antibody, 
with 0.5 log10 increases to 5 mg/kg and 15 mg/kg. 
 
This study was performed in compliance with Good Clinical Practice. 
 
Information contained in this publication is the property of The Rockefeller University Hospital (RUH) and is 
confidential. This information may not be disclosed to third parties without written authorization from RUH.  
This report may not be reproduced, stored in a retrieval system or transmitted in any form or by any means - 
electronic, mechanical, recording or otherwise - without prior authorization from RUH.  
This document must be returned to RUH upon request. 
 
 
 
 

Statistical Analysis Plan - The Rockefeller University 
Version 2.0 
PROTOCOL: RUCOV1 - IND: 150929 
09JUN2022 
Confidential  
Page 4 of 104 
SIGNATURE PAGE 
 
PROTOCOL RUCOV1 
A Phase 1 Study of the Safety and Pharmacokinetics of a Combination of Two  
Anti-SARS-CoV-2 mAbs (C144-LS and C135-LS) in Healthy Volunteers 
 
I have read this Statistical Analysis Plan and approve its contents. 
 
The Rockefeller University Hospital 
Marina Caskey, MD 
Medical Monitor and Co-investigator 
 
 
Bristol Myers Squibb (BMS) 
Atalanta Ghosh, PhD 
ED Immuno-science Stats Lead 
 
Edgar D. Charles, MD 
Clinical Program Team Lead 
 
 
The Emmes Company, LLC (Emmes) 
Shanna Jiang, MSc 
Biostatistician 
 
Burc Barin, MSc 
Senior Biostatistician and Project Leader 
 

Statistical Analysis Plan - The Rockefeller University 
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PROTOCOL: RUCOV1 - IND: 150929 
09JUN2022 
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Page 5 of 104 
TABLE OF CONTENTS 
SIGNATURE PAGE .......................................................................................................................4 
1. 
PREFACE .............................................................................................................................10 
2. 
INTRODUCTION ................................................................................................................10 
2.1. 
Purpose of the Analyses ..................................................................................................10 
3. 
STUDY OBJECTIVES AND ENDPOINTS ........................................................................11 
3.1. 
Study Objectives .............................................................................................................11 
3.1.1. 
Primary Objectives.................................................................................................11 
3.1.2. 
Secondary Objectives.............................................................................................11 
3.2. 
Outcomes ........................................................................................................................11 
3.2.1. 
Primary Outcomes .................................................................................................11 
3.2.2. 
Secondary Outcomes .............................................................................................11 
3.3. 
Study Definitions and Derived Variables .......................................................................12 
3.3.1. 
Study Group ...........................................................................................................12 
3.3.2. 
Dose Group ............................................................................................................12 
3.3.3. 
Baseline ..................................................................................................................14 
3.3.4. 
Study Day...............................................................................................................14 
4. 
INVESTIGATIONAL PLAN ...............................................................................................15 
4.1. 
Overall Study Design and Plan .......................................................................................15 
4.2. 
Selection of Study Population .........................................................................................15 
4.3. 
Treatments.......................................................................................................................17 
4.3.1. 
Treatments Administered .......................................................................................17 
4.3.2. 
Identity of Investigational Product(s) ....................................................................17 
4.3.3. 
Method of Assigning Participants to Dose Groups (Randomization) ...................18 
4.3.4. 
Selection of Doses in the Study .............................................................................18 
4.3.5. 
Concomitant Therapy.............................................................................................18 
4.3.6. 
Treatment Compliance ...........................................................................................18 
4.4. 
Safety, Pharmacokinetic, and Immunogenicity Variables ..............................................18 
5. 
SAMPLE SIZE CONSIDERATIONS ..................................................................................20 
6. 
GENERAL STATISTICAL CONSIDERATIONS ..............................................................20 
6.1. 
General Principles ...........................................................................................................20 
6.2. 
Timing of Analyses .........................................................................................................20 
6.3. 
Analysis Populations .......................................................................................................21 
6.3.1. 
Safety Population ...................................................................................................21 
6.3.2. 
PK Population ........................................................................................................21 
6.3.3. 
Immunogenicity Populations .................................................................................21 
6.4. 
Covariates and Subgroups...............................................................................................22 

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6.5. 
Missing or Unquantifiable Data ......................................................................................22 
6.6. 
Interim Analyses and Data Monitoring...........................................................................22 
6.7. 
Multicenter Studies .........................................................................................................23 
6.8. 
Multiple Comparisons/Multiplicity ................................................................................23 
7. 
STUDY PARTICIPANTS ....................................................................................................23 
7.1. 
Disposition of Participants ..............................................................................................23 
7.2. 
Protocol Deviations .........................................................................................................23 
8. 
EFFICACY EVALUATION ................................................................................................23 
9. 
SAFETY EVALUATION ....................................................................................................24 
9.1. 
Demographic and Other Baseline Characteristics ..........................................................24 
9.1.1. 
Medical History .....................................................................................................24 
9.1.2. 
Concomitant Medications ......................................................................................24 
9.2. 
Measurements of Treatment Compliance .......................................................................24 
9.3. 
Adverse Events ...............................................................................................................25 
9.3.1. 
Solicited Events and Symptoms.............................................................................25 
9.3.2. 
Unsolicited Adverse Events ...................................................................................25 
9.4. 
Deaths, Serious Adverse Events and other Significant Adverse Events ........................26 
9.5. 
Pregnancies .....................................................................................................................26 
9.6. 
Clinical Laboratory Evaluations .....................................................................................26 
9.7. 
Vital Signs and Physical Evaluations .............................................................................27 
9.8. 
Other Safety Measures ....................................................................................................28 
10. PHARMACOKINETICS ......................................................................................................28 
10.1. Graphical and Tabular Summaries of Pharmacokinetic Profiles ....................................28 
10.2. Noncompartmental Analysis ...........................................................................................30 
10.3. Statistical Analysis ..........................................................................................................32 
10.3.1. Assessment of Dose Proportionality ......................................................................32 
11. IMMUNOGENICITY...........................................................................................................34 
11.1.1. Assessment of Anti-Drug Antibody (ADA) Responses ........................................34 
12. REPORTING CONVENTIONS ...........................................................................................35 
13. TECHNICAL DETAILS ......................................................................................................36 
14. SUMMARY OF CHANGES IN THE CONDUCT OF THE STUDY OR 
PLANNED ANALYSES ......................................................................................................36 
15. REFERENCES .....................................................................................................................36 

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16. APPENDICES: LIST OF TABLES, FIGURES, AND LISTINGS .....................................37 
APPENDIX 1. 
TABLE MOCK-UPS .......................................................................................38 
Safety Tables ........................................................................................................................48 
Pharmacokinetics ..................................................................................................................57 
Immunogenicity ....................................................................................................................64 
APPENDIX 2. 
FIGURE MOCK-UPS .....................................................................................67 
Safety Figures .......................................................................................................................71 
Pharmacokinetics ..................................................................................................................81 
Immunogenicity ....................................................................................................................88 
APPENDIX 3. 
LISTINGS MOCK-UPS ..................................................................................90 
16.2 
Data Listings by Participant ...................................................................................91 
16.2.1 
Participant Disposition .....................................................................................91 
16.2.2 
Protocol Deviations ..........................................................................................91 
16.2.3 
Participants Excluded from the Analysis Populations .....................................92 
16.2.4 
Demographic/Baseline Characteristics Data ....................................................92 
16.2.5. 
Extent of Exposure Data ..................................................................................93 
16.2.7 
Adverse Events ................................................................................................94 
16.2.8 
Individual Laboratory Data and Other Safety-Related Data ............................97 
16.2.9 
Vital Signs and Physical Exam Findings .........................................................98 
16.2.9. 
Pharmacokinetic Data ....................................................................................100 
16.2.10 
Pregnancy Reports .........................................................................................102 
16.2.11 
Immunogenicity .............................................................................................104 
 

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LIST OF ABBREVIATIONS 
ADA 
Anti-drug antibody 
ADaM 
Analysis Data Model 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
BMS 
Bristol Myers Squibb 
BQL 
Below the Limit of Quantification 
CHEM 
Clinical Chemistry 
CI 
Confidence Interval 
CV 
Coefficient of Variation 
DLT 
Dose Limiting Toxicity 
FDA 
Food and Drug Administration 
FWCL 
Family Wise Confidence Level  
GM 
Geometric Mean 
HEM 
Hematology 
ICH 
International Conference on Harmonisation 
IP  
Investigational Product 
IV 
Intravenous 
LLOQ 
Lower Limit of Quantification 
mAb 
Monoclonal Antibody 
Max 
Maximum Value 
MedDRA 
Medical Dictionary for Regulatory Activities  
mg 
Milligram 
Min 
Minimum Value 
mL 
Milliliter 
N 
Number (typically refers to participants) 
PK 
Pharmacokinetic 
PT 
Preferred Term 
RBC 
Red Blood Cell 
RBD 
Receptor Protein Binding Domain 
RUH 
Rockefeller University Hospital 
SAE 
Serious Adverse Event 
SAP  
Statistical Analysis Plan 
SC 
Subcutaneous 

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SD 
Standard Deviation 
SDTM 
Study Data Tabulation Model 
SMC 
Safety Monitoring Committee 
SOC  
System Organ Class 
UA 
Urinalysis 
ULN 
Upper Limit of Normal 
VNS 
Vial, Needle, and Syringe 
VS 
Vital Signs 
WBC 
White Blood Cell 
WHO 
World Health Organization 
 

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1. 
PREFACE 
This Statistical Analysis Plan (SAP) for “A phase 1 study of the safety and pharmacokinetics of 
a combination of two anti-SARS-CoV-2 mAbs (C144-LS and C135-LS) in healthy participants” 
(Rockefeller University Protocol RUCOV1) covering the study follow-up period through 
48 weeks of follow-up after IP administration describes and expands upon the statistical 
information presented in the protocol and SAP version 1.0 that covered interim analyses through 
24 weeks of follow-up after IP administration.  
This document describes all planned safety, pharmacokinetic (PK), and immunogenicity analyses 
for the Clinical Study Report (CSR) that reflect all collected safety, PK, and immunogenicity 
data in the study to date and provides reasons and justifications for these analyses. It also 
includes shells for the tables, figures, and listings planned for the safety, PK, and 
immunogenicity analyses. Regarding the safety, PK, and immunogenicity analyses in the CSR, 
this SAP follows the International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use (ICH) Guidelines, as indicated in Topic E3 
(Structure and Content of Clinical Study Reports), and more generally is consistent with Topic 
E8 (General Considerations for Clinical Trials) and Topic E9 (Statistical Principles for Clinical 
Trials). The structure and content of the SAP provides sufficient detail for pre-specification of all 
analyses in accordance with FDA and ICH guidelines.  
Any deviation from this SAP will be described and justified in the CSR, as appropriate. The 
reader of this SAP is encouraged to also review the study protocol for details on conduct of the 
study and the operational aspects of clinical assessments. 
2. 
INTRODUCTION 
2.1. 
Purpose of the Analyses 
These analyses will assess safety, PK, and immunogenicity data from a Phase 1 study of two 
monoclonal antibodies (mAbs), C144-LS and C135-LS over the entire planned study follow-up 
(48 weeks after IP administration). The goal of the analysis is to present PK profiles for each 
study drug and cumulative outcome data for safety and immunogenicity of the investigational 
product (IP).  

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3. 
STUDY OBJECTIVES AND ENDPOINTS 
3.1. 
Study Objectives 
3.1.1. 
Primary Objectives 
• To evaluate the safety and tolerability of subcutaneous injections or single intravenous 
infusions of C144-LS in combination with C135-LS in healthy participants. 
• To evaluate the pharmacokinetic profile of C144-LS and C135-LS in combination, 
administered subcutaneously or intravenously at increasing dose levels in healthy 
participants. 
3.1.2. 
Secondary Objectives 
• To assess the occurrence of anti-drug antibody responses. 
• To evaluate serum neutralizing activity against SARS-CoV-2 after anti-C144-LS and 
anti-C135-LS administration. 
3.2. 
Outcomes 
3.2.1. 
Primary Outcomes 
• Rate of solicited and investigational product (IP)-related unsolicited adverse events that 
are Grade 2 and above (including confirmed laboratory abnormalities) 4 weeks after 
administration. 
• Rate of solicited and IP-related unsolicited adverse events that are Grade 3 and above 
(including confirmed laboratory abnormalities) 4 weeks after administration. 
• Proportion of participants with serious adverse events (SAEs) throughout the study 
period that are considered related to investigational product and their duration. 
• The pharmacokinetic profile of C144-LS and C135-LS: elimination half-life (t1/2), 
clearance (CL/F), volume of distribution (Vz/F), AUC and decay curve. 
3.2.2. 
Secondary Outcomes 
• Rate and severity of investigational product (IP)-related adverse events during study 
follow up. 
• Frequency and levels of induced anti-C144-LS and anti-C135-LS antibodies in all study 
groups. 
• Serum neutralizing activity against SARS-CoV-2 after C144-LS and C135-LS 
administration. 

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3.3. 
Study Definitions and Derived Variables  
3.3.1. 
Study Group 
Study Groups in the SAP are defined to match identically with study groups as defined in the 
protocol. All the study groups in Part A of the study, 2 of the subcutaneous (SC) and all the 
intravenous (IV) study groups, are open label and do not include any placebo participants.  
Subcutaneous study groups:  
• Part A, S1: All participants assigned to receive 4 mL (approximately 100 mg of each 
mAbs) of C144-LS and C135-LS in two separate SC injections (3 to 6 participants) in an 
unblinded fashion.  
• Part A, S2: All participants assigned to receive 8 mL (approximately 200 mg of each 
mAbs) of C144-LS and C135-LS in two separate SC injections (3 to 6 participants) in an 
unblinded fashion.  
• Part B, S3 Active and Placebo: All participants assigned to receive 8 mL (approximately 
200 mg of each mAbs) of C144-LS and C135-LS in two separate SC injections 
(6 participants) or matching placebo (2 participants) in a blinded fashion.  
Intravenous injection study groups:  
• Part A, V1: All participants assigned to receive sequential IV infusions of C144-LS then 
C135-LS, each administered via peripheral vein over 60 minutes at a dose level of 
1.5 mg/kg (3 to 6 participants) in an unblinded fashion. 
• Part A, V2: All participants assigned to receive sequential IV infusions of C144-LS then 
C135-LS, each administered via peripheral vein over 60 minutes at a dose level of 
5 mg/kg (3 to 6 participants) in an unblinded fashion. 
• Part A, V3: All participants assigned to receive sequential IV infusions of C144-LS then 
C135-LS, each administered via peripheral vein over 60 minutes at a dose level of 
15 mg/kg (3 to 6 participants) in an unblinded fashion. 
3.3.2. 
Dose Group 
Dose Group defines a grouping of participants for statistical analysis, where participants within a 
dose group received the same study product and dose under the same administration method. 
Three pooled dose groups, the Any Dose Group, SC Dose Group, and IV Dose Group, will 
include all participants who received a dose of the IP (not placebo), regardless of the dose 
received, and will be used for high-level demographic and safety summaries. For data from a 
participant to be analyzed as part of their dose group, the participant must also qualify for 
inclusion into the respective analysis population (Section 6.3) for that data. The pooled dose 
groups in the order they will be presented in the high-level demographic and safety analyses 
(Table 6, Table 7, and Table 9 through Table 16) are defined as follows:  
• Any Dose Group: All participants who received a complete or incomplete dose of the IP 
regardless of dose or administration method.  
• SC Dose Group: All participants who received a complete or incomplete dose of the IP 
via SC administration, regardless of dose.  
• IV Dose Group: All participants who received a complete or incomplete dose of the IP 
via IV infusion, regardless of dose. 

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The high-level demographic and safety summary tables (Table 6, Table 7, and Table 9 through 
Table 16) will display the following pooled dose group break-down in the order specified: 
[Pooled Safety Group 1] 
Any Dose Group  
(S1+S2+S3 Active +V1+V2+V3) 
[Pooled Safety Group 2]  
Any SC Dose Group  
(S1+S2+S3 Active) 
[Pooled Safety Group 3]  
Any IV Dose Group  
(V1+V2+V3) 
The individual safety, immunogenicity, and PK dose groups described below will be used to 
present results in the tables, figures, and listings. Specified high-level demographic and safety 
summary tables will be presented by pooled dose group in addition to the summaries by 
individual dose group (Table 6, Table 7, and Table 9 through Table 16).  
The individual dose groups in the order they will be presented in the detailed safety analyses are 
defined as follows:  
• 100 mg, SC: All participants who received a complete or incomplete dose of 100 mg of 
the IP via SC administration; 
• 200 mg, SC: All participants who received a complete or incomplete active dose of 200 
mg of the IP via SC administration; 
• 1.5 mg/kg, IV: All participants who received a complete or incomplete dose of 1.5 mg/kg 
of the IP via IV administration; 
• 5 mg/kg, IV: All participants who received a complete or incomplete dose of 5 mg/kg of 
the IP via IV administration; 
• 15 mg/kg, IV: All participants who received a complete or incomplete dose of 15 mg/kg 
of the IP via IV administration; 
• Placebo, SC: All participants who received a complete or incomplete dose of placebo via 
SC administration.  
The safety summary tables/figures will display the following individual study group break-down 
in the order specified: 
[Safety Group 1] 
100 mg, SC  
(S1) 
[Safety Group 2] 
200 mg, SC  
(S2 + S3 Active) 
[Safety Group 3] 
1.5 mg/kg, IV  
(V1) 
[Safety Group 4] 
5 mg/kg, IV 
(V2) 
[Safety Group 5] 
15 mg/kg, IV  
(V3) 
[Safety Group 6] 
Placebo, SC  
(S3) 
The immunogenicity summary tables/figures will use the same individual study group break-
down as for the safety summary tables/figures: 
[Immunogenicity 
Group 1]  
100 mg, SC  
(S1) 
[Immunogenicity 
Group 2]  
200 mg, SC  
(S2 + S3 Active) 
[Immunogenicity 
Group 3]  
1.5 mg/kg, IV  
(V1) 
[Immunogenicity 
Group 4]  
5 mg/kg, IV 
(V2) 
[Immunogenicity 
Group 5]  
15 mg/kg, IV  
(V3) 
[Immunogenicity 
Group 6]  
Placebo, SC  
(S3) 

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The PK summary tables/figures will display the following dose group break-down in the order 
specified: 
[PK SC Group 1] 
100 mg SC  
(S1) 
[PK SC Group 2] 
200 mg SC  
(S2+S3 Active) 
[PK IV Group 1] 
1.5 mg/kg IV  
(V1) 
[PK IV Group 2]  
5 mg/kg IV  
(V2)  
[PK IV Group 3]  
15 mg/kg IV  
(V3) 
The example table, figure, and listing shells (Appendix 1, Appendix 2, and Appendix 3, 
respectively) display generic dose group names in brackets which will be replaced with the final 
determined dose group names above in the actual CSR.  
Appendix A of the study protocol detail the analysis timepoints at which safety, PK, and 
immunogenicity assessments will be conducted. Outcomes analyzed by timepoint include vital 
sign (VS) results; clinical laboratory results: hematology clinical laboratory results (HEM), 
chemistry clinical laboratory results (CHEM), and urinalysis laboratory results (UA); PK results; 
and immunogenicity results. 
3.3.3. 
Baseline 
Baseline for VS, clinical laboratory results, PK, and immunogenicity samples is defined as the 
last result obtained before the study product administration. For the IV dose groups this is 
defined as the last result obtained before start of infusion of either mAb.  
Baseline height, weight, and body mass index (BMI) will be the measurements obtained at Day 0 
prior to IP administration. Age will be based on age at the time of enrollment. Age at enrollment 
is an integer value with units of years, calculated from the participant’s enrollment date 
(ENRCONDT) and birth date (BRTHDT) using the following algorithm. 
• If month(ENRCONDT) > month(BRTHDT), then AGE = year(ENRCONDT) – 
year(BRTHDT) 
• If month(ENRCONDT) < month(BRTHDT), then AGE = year(ENRCONDT) – 
year(BRTHDT) – 1 
• If month(ENRCONDT) = month(BRTHDT) and day(ENRCONDT) ≥ day(BRTHDT), 
then AGE = year(ENRCONDT) – year(BRTHDT) 
• If month(ENRCONDT) = month(BRTHDT) and day(ENRCONDT) < day(BRTHDT), 
then AGE = year(ENRCONDT) – year(BRTHDT) – 1 
3.3.4. 
Study Day 
Study Day will primarily be used to refer to the timing of assessments and events relative to 
study product administration. Study day will be defined differently in the Study Data Tabulation 
Model (SDTM) and Analysis Data Model (ADaM) datasets. In SDTM, the day that the IP was 
received is considered Study Day 1 for each participant in each study group. The day prior to IP 
administration is Day -1. In compliance with CDISC standards, there is no Day 0 in SDTM 
datasets. In the ADaM datasets (ADY, Analysis Day), the day that the IP was received is 
considered Study Day 0 for each participant in each study group. The day prior to IP 
administration is considered Study Day -1. In all tables, figures, and listings, study day will be 
presented as defined in the protocol and in the ADaM datasets.  

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4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design and Plan 
This is first-in-human, single dose, dose-escalation phase 1 study to evaluate the safety and 
pharmacokinetics of a combination of two highly neutralizing anti-SARS-CoV-2 mAbs targeting 
two distinct epitopes on the receptor protein binding domain (RBD) of SARS-CoV-2 spike 
protein in healthy participants.  
This study consists of two parts. Part A has a standard 3+3 phase 1 dose escalation design. Study 
participants will receive subcutaneous injections of C144-LS and C135-LS at one of two 
increasing dose levels (4 mL, approximately 100 mg of each antibody administered separately or 
8 mL, approximately 200 mg of each antibody administered separately), or sequential 
intravenous infusions of C144-LS and C135-LS, each administered via peripheral vein over 
60 minutes at one of three increasing dose levels (1.5 mg/kg, 5 mg/kg, and 15 mg/kg of each 
antibody). Participants in Part B will be randomized to receive subcutaneous injections of 
C144-LS and C135-LS at 8 mL (approximately 200 mg of each antibody administered 
separately) or placebo in a 3:1 ratio and double-blinded fashion.  
This study will be conducted at a single site and will enroll a maximum of 38 participants. A 
schedule of study procedures is detailed in Appendix A of the study protocol. Screening, 
baseline, and follow-up procedures will follow the same process for all study groups.  
 
4.2. 
Selection of Study Population 
Only participants who meet all of the inclusion and none of the exclusion criteria will be eligible 
for enrollment into this study. No exemptions are granted on Inclusion/Exclusion Criteria. Up to 
38 healthy male and female participants, ages 18 to less than 65, will be enrolled into the study 
groups listed in Section 3.3. Neither women nor minorities will be excluded from participation in 
this study. Women of childbearing potential may be included as per the inclusion criteria (See 
inclusion criteria below). Participants will be recruited without regard to gender or race. It is 
expected that race will reflect that within the community. The demographics in the local 
population should ensure that male and female minorities will be represented in the enrolled 
population. 
Eligibility criteria from version 2.1 of the study protocol are listed below:  
Inclusion Criteria: 
• Aged 18 to less than 65. 
• If sexually active male or female, and participating in sexual activity that could lead to 
pregnancy, agrees to use one effective method of contraception from 10 days prior to the 
antibody administration until 6 months after investigational product (IP) administration. 

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Exclusion Criteria: 
• Weight > 110 kg for groups S1 and S2 only. 
• History of prior positive SARS-CoV-2 RT-PCR or SARS-CoV-2 serology. 
• Active respiratory or non-respiratory symptoms consistent with COVID-19. 
• Medically attended acute illness or hospitalization (i.e., >24 hours) for any reason within 
30 days prior to screening. 
• Acute exacerbation of a chronic pulmonary condition (e.g., chronic obstructive 
pulmonary disease [COPD], asthma exacerbations, or uncontrolled hypertension, as 
defined by a systolic blood pressure > 180 and/or diastolic blood pressure > 120, in the 
presence or absence of anti-hypertensive medications) in the past 6 months prior to 
screening. 
• Use of systemic corticosteroids, immunosuppressive anti-cancer, or other medications 
considered significant by the trial physician within the last 6 months. 
• Other clinically significant acute or chronic medical condition that in the opinion of the 
investigator would preclude participation. 
• Are eligible for COVID-19 vaccination prior to your entry in the study according to local 
guidelines (e.g. healthcare professionals, non-healthcare professionals such as teachers, 
firefighters, public transit workers). 
• Laboratory abnormalities in the parameters listed: 
− Absolute neutrophil count ≤ 1,500 K/mcL;  
− Hemoglobin ≤ 10.5 gm/dL if female; ≤ 11 gm/dL if male;  
− Platelet count ≤ 125,000 K/mcL;  
− ALT ≥ 1.25 x ULN; AST ≥ 1.25 x ULN;  
− Total bilirubin ≥ 1.25 x ULN;  
− Creatinine ≥ 1.1 x ULN. 
• Pregnancy or lactation. 
• Any vaccination within 14 days prior to SARS-CoV-2 mAbs administration (except 
influenza vaccine). 
• History of prior receipt of any SARS-CoV-2 vaccine or antibodies, including 
convalescent plasma. 
• Known allergy/sensitivity or any hypersensitivity to components of the investigational 
agents. 
• History of severe reaction to a vaccine or monoclonal antibody administration or history 
of severe allergic reactions. 
• Participation in another clinical study of an investigational product currently or within 
past 12 weeks, or expected participation during this study. 

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4.3. 
Treatments 
4.3.1. 
Treatments Administered  
Participants will receive a single dose of each C144-LS and C135-LS, either administered 
subcutaneously at 4 mL (approximately 100 mg of each mAb administered separately) or 8 mL 
(approximately 200 mg of each mAb administered separately) or administered intravenously at a 
dose of 1.5 mg/kg, 5 mg/kg, or 15 mg/kg of each mAb according to study group. Placebo 
treatments will only be administered as part of study group S3 (200 mg of each mAb or placebo, 
administered SC) in Part B. 
Each antibody will be administered separately in both the SC and IV study groups. Subcutaneous 
administration will occur in 2 (2 mL) or 4 (4 mL) injections at the same number of sites as 
injections: abdomen, upper arms, or thighs. Each SC injection will be administered carefully to 
avoid inadvertent deposition into muscular tissue and leakage after needle removal. The volume 
of C144-LS and C135-LS to be administered via intravenous administration will be calculated by 
the Rockefeller University Hospital (RUH) research pharmacist, according to the baseline weight 
measurement. The appropriate volume of each antibody will be diluted in sterile normal saline to 
a total volume of 100 mL. First C144-LS will be administered as a slow IV infusion over 
60 minutes. After infusion of C144-LS is completed, the participant will be observed for 1 hour 
before initiation of subsequent C135-LS infusion. The appropriate volume of C135-LS will be 
diluted similarly to C144-LS to a volume of 100 mL and will be administered as a slow IV 
infusion over 60 minutes. IV administration of study drugs will occur via a peripheral vein in one 
of the upper extremities. At the end of infusion, the IV line will be flushed with normal saline to 
ensure all study drug has been delivered.  
4.3.2. 
Identity of Investigational Product(s) 
Both C144-LS and C135-LS will be provided by Bristol Myers Squibb (BMS) in single-use vials 
containing 50 mg/mL of protein in 6 mL of buffered solution. Both mAbs are clear to opalescent, 
colorless to yellow liquid, and may contain light (few) particulates (consistent in appearance to 
protein particulates). The drug products are monitored for particulates in the stability program 
and is in compliance with USP particulate limits.  
Both products are sterile, nonpyrogenic, single-use, preservative-free, isotonic aqueous solutions. 
C135-LS is for intravenous administration and C144-LS is for intravenous or subcutaneous 
administration formulated at 50 mg/mL in a buffered solution consisting of histidine, sucrose, 
pentetic acid (diethylenetriamine pentacetic acid, DTPA), polysorbate 80, and water for injection 
at pH 6.0. Each vial includes a 0.5-mL overfill to account for vial, needle, and syringe (VNS) 
holdup. The drug products are supplied in a 6-mL Type I flint glass vial stoppered with a 
fluoropolymer film-laminated rubber stopper and sealed with an aluminum seal.  
Placebo for both C144-LS and C135-LS will be a buffered solution provided by BMS in single-
use vials containing 2 mL of buffered solution. The placebo is a sterile, nonpyrogenic, 
preservative-free, single-use, subcutaneous injectable product consisting of a buffered solution of 
histidine, sucrose, pentetic acid (diethylenetriamine pentacetic acid, DTPA), polysorbate 80, and 
water for injection at pH 6.0. It is packaged in a 6 mL Type I flint glass vial, stoppered with a 
20-mm fluoropolymer film-laminated rubber stopper, and sealed with a 20-mm aluminum 
flip-off seal. The placebo for BMS-C144-LS and C135-LS injection contain the same 
formulation as the respective active drug products, but without the active drug products.  

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4.3.3. 
Method of Assigning Participants to Dose Groups (Randomization) 
Enrollment in Part A of the study is open-label, and study participants will be enrolled 
sequentially as they meet enrollment criteria. C144-LS and C135-LS will be dispensed according 
to study group. Part B of the study (study group S3) is double-blinded. The packaging and 
formulation of study drugs and placebo will look identical to maintain the blind. Enrollment in 
Part B will be randomized in a 3:1 ratio (study drugs to placebo, 6 study drug recipients to 
2 placebo recipients). Study product administration will follow the procedures outlined in the 
study protocol. Participants will be enrolled sequentially as they meet enrollment criteria, 
according to the randomization schedule. Randomization will be performed by the RUH 
pharmacy. Randomization will be generated using SAS 9.4. Preparation of study drugs or 
placebo will be provided to study nurses for injection under a coded, masked identification. 
Nurses, study staff, investigators, and participants will be blinded as to the identity of the study 
preparation. Participants enrolled in Group S3 will be unblinded 23 months after participant 
study entry (Day 0) and at least 1 month after all participants enrolled in Group S3. Following 
unblinding, placebo recipients will remain in follow up for safety assessments. Samples will not 
be collected for research purposes following unblinding. 
4.3.4. 
Selection of Doses in the Study 
The proposed study doses were chosen based on in vitro and in vivo data that demonstrated the 
neutralizing potency of C144-LS and C135-LS in preclinical experiments in mice, hamsters, and 
non-human primates. Similar and higher dose levels have been safely evaluated with anti-HIV-1 
antibodies as well as other anti-SARS-CoV-2 RBD mAbs, according to publicly available data. 
See Section 4.1 of the study protocol (v2.1) for further details of the rationale for dose selection.  
4.3.5. 
Concomitant Therapy  
Use of concomitant medications will be reviewed at each study visit. Concomitant medications 
will be listed in Listing 19. 
4.3.6. 
Treatment Compliance 
Study products will be administered at RUH by site personnel in accordance with treatment 
assignment or randomization. Participant compliance is not anticipated to be an issue. Complete 
information regarding any partial or interrupted dosing will be documented. Start times and 
administration site of each SC injection, and start and end times of each IV infusion will be 
recorded (Listing 7). 
4.4. 
Safety, Pharmacokinetic, and Immunogenicity Variables 
The following section describes the safety, PK, and immunogenicity outcomes of this study. 
Refer to Section 3 for a list of the primary and secondary objectives and outcomes. Definitions of 
baseline measurements are included in Section 3.3.  
Incidence, relatedness, and severity of treatment-emergent AEs and SAEs will be recorded from 
the time of IP administration to the final study visit. Any AEs due to study related procedures 
and prior to IP administration will also be listed. AEs and SAEs are defined in Section 14.3 and 
Section 14.4 of the study protocol (v2.1). Adverse events will be graded using the FDA 
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Enrolled in Preventive Vaccine Clinical Trials (2007). For the dose-escalation part of the study 
(Part A), dose limiting toxicities (DLTs) will be monitored. A dose limiting toxicity (DLT) 
will be defined as any adverse event of Grade 3 or greater toxicity, if the study investigators 
recognize a probable or definite attribution to C144-LS and C135-LS mAb. In addition to AEs, 
the following safety outcomes will be assessed. Blood and urine samples for the assessment of 
clinical laboratory results will be collected according to the schedule of study procedures listed 
in Appendix A of the study protocol (v2.1). 
• VS parameters: pulse, respiration rate, systolic blood pressure, diastolic blood pressure, 
temperature 
• Clinical laboratory safety parameters:  
− HEM parameters: white blood cell count (WBC), neutrophils, lymphocytes, 
monocytes (toxicity grading criteria not defined, so will not be graded), eosinophils, 
basophils (toxicity grading criteria not defined, so will not be graded), hemoglobin, 
hematocrit, and platelet count. 
− CHEM parameters: creatinine, non-fasting glucose, total bilirubin, direct bilirubin, 
alkaline phosphatase, aspartate aminotransferase (AST), and alanine 
aminotransferase (ALT).  
− UA parameters: red blood cell count (RBC), WBC, and protein.  
• Physical exams:  
− General physical exams include: weight, height, vital signs, and examination of skin, 
respiratory, cardiovascular, neurological, and abdominal systems.  
− Directed physical exams include: vital signs, examination of administration site, and 
any further examination indicated by history or observation. Directed physical exams 
will be performed at all other times, according to Appendix A of the study protocol, 
Times of Events Schedule.  
VS, HEM, CHEM, and UA results will also be assessed using the FDA Guidance of Industry 
Toxicity Grading Scale for Healthy Adult and Adolescent Participants Enrolled in Preventive 
Vaccine Clinical Trials (2007). 
Assays for PK and ADA will be performed by PPD Laboratory Services, according to the 
schedule of study procedures listed in Appendix A of the study protocol. For PK, C144-LS and 
C135-LS levels will be measured by sandwich ELISA.  

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5. 
SAMPLE SIZE CONSIDERATIONS 
The sample size of 23 to 38 participants was determined according to the dose escalation design 
used to characterize the safety and the pharmacokinetics profile of combined C144-LS and 
C135-LS administration at increasing dose levels, to healthy participants. Replacement of 
2 participants lost to follow up prior to Week 4 will be allowed.  
A sample size of 21 participants receiving C144-LS and C135-LS in combination will provide 
95% probability of observing a treatment-related AE that would occur in 13.4% or more of 
treated participants. If none of the participants experiences a grade 2 or higher AE related to 
C144-LS and/or C135-LS, the one-sided exact Clopper-Pearson 95% upper confidence bound 
for the rate of AEs in the population is 13.3%.  
6. 
GENERAL STATISTICAL CONSIDERATIONS 
6.1. 
General Principles 
Summary statistics for continuous data will include the number of participants included in the 
analysis (n), mean, standard deviation (SD), median, minimum value (min), and maximum value 
(max). Summary statistics for discrete data will include frequencies and proportions, and may 
include confidence intervals (CIs) for the proportion. When 95% CIs are given for a proportion, 
exact (Clopper-Pearson) CIs will be used, unless otherwise specified. All enrolled participants 
will be included in the summaries of participant demographics. The Safety Population will be 
used for summaries of safety outcomes, the PK Population will be used for summaries of 
PK outcomes, and the Immunogenicity Population will be used for summaries of the 
immunogenicity outcomes.  
Denominators for safety outcomes will be the number of participants in the Safety Population. 
Denominators for VS and clinical laboratory results at planned study timepoints will be the 
number of participants with available results at the specified timepoint for that parameter. 
Denominators for the conceptual “Maximum Severity Post Baseline” timepoint for VS and 
clinical laboratory results will be the number of participants with an observed result for that 
parameter, obtained post-dose.  
The sort order of VS and clinical laboratory test parameters is described in Section 9. The 
sort order for listings will be by: dose group, participant ID, mAb (if applicable, PK and 
immunogenicity only), and sequence number or date field (whichever is presented first). 
For participants in Safety Group 2, PK SC Group 2 (200 mg, SC; S2+S3 Active), or 
Immunogenicity SC Group 2 (200 mg, SC; S2+S3 Active), the listings will be separated out 
and sorted in the order of "200 mg, SC (S2)" and "200 mg, SC (S3 Active)". All safety, PK, 
and immunogenicity analyses will be performed by dose group as described in Section 3.3.2. 
Participant ID will be USUBJID (not PATID) for purposes of de-identification.  
6.2. 
Timing of Analyses 
The safety, PK and immunogenicity analyses will occur after all study groups have enrolled and 
all participants have been followed through the final study visit (Week 48) (or terminated the 
study early). The final analysis will include/present cumulative safety, PK, and immunogenicity 
data from the entire study follow-up period. 

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6.3. 
Analysis Populations 
All analysis populations to be used in the final analysis are described in this section. A tabular 
listing of all enrolled participants excluded from an analysis population (Safety Population, PK 
Population, or Immunogenicity Population) will be included in the CSR (Listing 4). Participant 
enrollment in the study follows the standard definition of participants meeting eligibility criteria, 
signing informed consent, and being included in the study via either assignment of the IP for 
participants in Part A, or via randomization to the active study IP or placebo in Part B. In the 
case that there are multiple reasons for exclusion from the PK Analysis Population, only one 
reason will be counted when summarizing reasons for exclusion from analysis populations in 
Table 4. The order that reasons will be considered for exclusion from the PK Population will be: 
the participant received placebo, the assigned dose was not received or completed, the participant 
had no measurable antibody (C144-LS or C135-LS) concentration in serum, and the participant 
had a protocol deviation with potential impact to PK. The order that reasons will be considered 
for exclusion from the Immunogenicity Population will be: the participant did not have any post 
dose samples with valid results reported, and/or the participant did not contribute a pre dose 
baseline sample.  
6.3.1. 
Safety Population 
The Safety Population will include all participants that received any amount of the IP, including 
placebo. This population will be analyzed by the defined dose groups for both high-level and 
detailed analyses as outlined in Section 3.3. 
6.3.2. 
PK Population 
The PK Population will consist of all participants who received an active dose of the IP 
(C144-LS and/or C135-LS), have at least 1 quantifiable post dose serum sample with a 
measurable antibody concentration, and who did not have a protocol deviation with potential 
impact to PK (such as drug administration errors, not meeting eligibility criteria for body weight, 
or prior/baseline positivity for SARS-CoV-2). Protocol deviations for PK samples taken outside 
of the protocol window will not result in exclusion. Results from the PK Population will be 
analyzed by dose group and by antibody (C144-LS or C135-LS). Participants enrolled and 
assigned to receive some dose of the IP who did not complete their dose, or otherwise received 
an incorrect dose, will not be included in the respective dose group for analysis. However, 
listings will include concentrations and parameter estimates for those participants. Regardless 
of the participant’s inclusion in the PK Population, all C144-LS and C135-LS results will be 
included in listings, including any results from placebo participants from samples taken before 
unblinding occurred. 
6.3.3. 
Immunogenicity Populations  
The C144-LS Immunogenicity Population will consist of all participants who received an 
active dose of C144-LS, contributed a pre-dose serum immunogenicity sample, and have at least 
1 quantifiable post-baseline serum immunogenicity sample for which valid results were reported.  
The C135-LS Immunogenicity Population will consist of all participants who received an 
active dose of C135-LS, contributed a pre-dose serum immunogenicity sample, and have at least 
1 quantifiable post-baseline serum immunogenicity sample for which valid results were reported.  

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6.4. 
Covariates and Subgroups 
The protocol does not define any formal subgroup analyses.  
6.5. 
Missing or Unquantifiable Data 
All attempts will be made to collect data per protocol. Any missing data or data anomalies will 
be communicated to the study site for clarification and resolution. Missing collection times for 
PK samples may be imputed as the nominal time if the sample was confirmed to have been 
collected within the protocol defined window. Further details on imputation of BQL sample 
concentrations and missing PK collection times are included in Section 10.1. Samples which 
are negative for the presence of ADA will be represented in summary tables and figures with 
a titer value of one (equivalent to a log titer value of 0). Positive but unquantifiable ADA 
titration results (samples confirmed positive for ADA but that have titration results lower than 
the minimum required dilution of 100) will be imputed as 50 for summary tables and figures 
but presented as “<100” in listings. No further imputation of missing or unquantifiable data 
is planned.  
6.6. 
Interim Analyses and Data Monitoring 
The Safety Monitoring Committee (SMC) will provide ongoing assessment of participant safety 
during the conduct of the study. Interim reviews of safety data by the SMC will occur at the 
following pre-determined study milestones: 
• When the 1-week safety data is available prior to dose escalation from study group V2 
to study group V3; 
• Prior to enrolling participants in Part B (study group S3) of the study; 
• If any Grade 3 solicited or unsolicited AEs occur that are deemed to be possibly, 
probably, or definitely related to C144-LS and/or C135-LS; The SMC will review safety 
data; 
• If any grade 3 laboratory AE is reported, confirmed on retest, and is judged by the 
principal investigator or designee to be possibly, probably, or definitely related to 
C144-LS and/or C135-LS; 
• Any “late occurring” DLT (DLT occurring after 12 weeks of dosing);  
• SAEs, which are deemed possibly, probably, or definitely related to C144-LS and 
C135-LS by the principal investigator or designee, and unanticipated AEs.  
In addition, interim analysis of safety and PK endpoints was conducted according to SAP 
version 1.0 once all study groups were enrolled, and each participant completed follow-up 
through Week 24 or discontinued the study prior to their Week 24 visit. The interim analysis was 
not part of the planned analyses in the protocol, but was conducted to facilitate provision of data 
to support an Emergency Use Authorization (EUA) application for the study IPs.  

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6.7. 
Multicenter Studies 
This is a single-site study.  
6.8. 
Multiple Comparisons/Multiplicity 
This is a Phase 1 first-in-human study with multiple primary outcomes. Because analyses of 
primary safety outcomes are descriptive rather than hypothesis tests, no adjustments for multiple 
testing are planned for analysis of safety outcomes.  
ANOVA pairwise comparisons of PK exposure parameters will be adjusted using Tukey’s 
correction for multiple hypotheses, with a 90% Family Wise Confidence Level (FWCL). 
Additional details are included in the Statistical Analysis section (Section 10.3).  
7. 
STUDY PARTICIPANTS 
7.1. 
Disposition of Participants 
The number of participants included in each analysis population will be included in Table 3. 
Screened participants who were ineligible for enrollment in the study (screen failures) or eligible 
but not enrolled will be summarized by analysis population exclusion criteria (Table 5). Enrolled 
participants who were ineligible for inclusion in analysis populations will be summarized by 
dose group and reason for exclusion (Table 4). The number of enrolled participants who met 
criteria for each analysis population will also be summarized in Table 3. Individual listings of 
participants who were excluded from the Safety Population, PK Population, or Immunogenicity 
Population will be listed (Listing 4).  
Participant disposition will be summarized (Table 1), showing the number of participants who 
were screened, enrolled, received the study product, received all scheduled study product 
administrations, completed all safety blood draws and urine sample collections, completed all 
planned PK samples, completed all planned immunogenicity samples, completed final study 
visit, early termination, and completed the study per protocol.  
Participants who discontinued dosing or terminated early from the study will be listed (Listing ). 
A flowchart displaying the disposition of study participants will be included (Figure 1). This 
figure will present the number of participants screened, enrolled, and lost-to follow up by dose 
group.  
7.2. 
Protocol Deviations 
A summary of protocol deviations will be presented by deviation category, deviation type, and 
dose group (Table 2). This table will provide both the number of participants and the number of 
deviations for each deviation category and type. All participant specific and non-protocol 
specific protocol deviations will be listed in Listing 2 and Listing 3, respectively.  
8. 
EFFICACY EVALUATION 
There are no efficacy outcomes included in this report.  

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9. 
SAFETY EVALUATION 
All safety analyses will be performed using the Safety Population and results will be presented 
by individual dose group. In addition, demographic and safety results will be presented twice: by 
individual dose group and at a high-level by pooled dose group (Section 3.3.2). Any medical 
condition that is present at the time of screening will be considered baseline and will not be 
reported as an AE, unless the condition worsens in severity or increases in frequency during the 
study. The denominators for proportions will be indicated within the table or table header.  
Solicited AEs, VS and clinical laboratory results will also be used to assess safety. Results from 
these assessments will be graded by severity and presented in tables and figures by dose group 
for each post baseline timepoint. See Appendix A of the study protocol, the Times of Events 
Schedule, for the analysis timepoints that will be summarized are presented for each safety 
assessment.  
Toxicity grading scales for clinical adverse events, solicited AEs, VS results, and clinical 
laboratory results are provided in the FDA Guidance for Industry Toxicity Grading Scale for 
Healthy Adult and Adolescent Participants Enrolled in Preventive Vaccine Clinical Trials 
(2007).  
9.1. 
Demographic and Other Baseline Characteristics 
Sex, ethnicity, and race for all participants will be summarized by dose group (Table 6). 
Ethnicity will be categorized as “Hispanic or Latino”, “Not Hispanic or Latino”, “Unknown”, 
or “Not Reported” in accordance with National Institutes of Health (NIH) reporting policies. 
Participants may self-designate as belonging to more than one race or may refuse to identify a 
race. Age, height, weight, and BMI at enrollment will be summarized by dose group (Table 7). 
Demographic data for all participants will also be listed (Listing 5). 
9.1.1. 
Medical History  
All current illnesses and past pre-existing medical conditions (medical history) will be MedDRA 
coded using MedDRA dictionary version 24.1. Summaries of participant pre-existing medical 
conditions will be presented by MedDRA system organ class (SOC) and dose group (Table 8). 
Individual participant listings will be presented for all medical conditions (Listing 6).  
9.1.2. 
Concomitant Medications  
All medications will be coded to the Anatomical Therapeutic Classification (ATC) using the 
WHODrug Global C3 September 1, 2021 version of the WHO Drug Dictionary. The use of prior 
and concomitant medications taken during the study will be summarized by ATC 1 and ATC 2 
(Table 17). Individual participant listings will be presented for all prior and concomitant 
medications (Listing 19).  
9.2. 
Measurements of Treatment Compliance 
Date and time of study product administration, along with information on whether the participant 
was dosed according to protocol will be included in Listing 7.  

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9.3. 
Adverse Events 
The Safety Population will be used for all analyses of AEs. An overall summary of AEs, 
including solicited symptoms (both systemic and local reactogenicity events), unsolicited events, 
grade 2 or higher laboratory AEs, grade 3 or higher laboratory AEs, grade 3 or higher laboratory 
AEs which are probably or definitely related to the IP, SAEs, and AEs which led to IP or study 
discontinuation will be summarized in Table 9. 
9.3.1. 
Solicited Events and Symptoms 
Solicited AEs (both local and systemic reactogenicity symptoms) will be collected during in 
person visits as detailed in Appendix A of the study protocol, the Times of Events Schedule, up 
to Day 14 after IP administration. Any events reported or continuing after Day 14 would need to 
be reported as AEs. Reported events will be presented in Table 10. Denominators for proportions 
are the number of participants in the Safety Population in each group.  
The following solicited parameters will be presented in order:  
• Systemic reactogenicity symptoms: feverishness, chills, headache, nausea, vomiting, 
malaise, myalgia, and arthralgia; 
• Local reactogenicity symptoms (occurring at the injection site): pain, tenderness, 
erythema, and induration.  
The following summaries of solicited AEs will be presented:  
• The number, percent, and 95% CI for the percent or participants who experienced any 
solicited reactogenicity symptom and each solicited reactogenicity symptom parameter 
will be tabulated (Table 10). The 95% CIs will be calculated using the Clopper-Pearson 
method.  
• Maximum severity of systemic reactogenicity symptoms (Figure 2) and local 
reactogenicity symptoms (Figure 3) experienced per dose group.  
• Solicited adverse events will be listed separately for systemic reactogenicity symptoms 
(Listing 8) and local reactogenicity symptoms (Listing 9).  
9.3.2. 
Unsolicited Adverse Events 
All AEs will be presented in Listing 10. The AE listing will include the relationship to the IP, 
action taken with the IP, and whether the participant discontinued due to the AE/SAE 
information as well.  
Denominators for proportions are the number of participants in the Safety Population in each 
dose group. In summaries of AEs, participants who experienced an adverse event will only be 
counted once within the same MedDRA category for the worst severity recorded. The worst 
severity reported will be counted separately for related and unrelated AEs when both severity 
and relatedness are tabulated. Repeated AEs will be included in summaries of the number of 
AEs. The following summaries for unsolicited, non-serious, AEs will be presented:  
• The number and percent of participants experiencing unsolicited AEs by MedDRA 
SOC/PT, and maximum severity grade of each SOC/PT, for each dose group (Table 11), 
related AEs will be summarized in  
• Table 12.  

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• The proportion of participants experiencing related AEs (Figure 4) and the number of 
events reported (Figure 5) will be summarized by MedDRA SOC and maximum severity 
will be displayed in bar charts for each dose group.  
• Details for each unsolicited AE reported, including AEs that occurred prior to IP 
administration as a result of study procedures will be listed (Listing 10), and will include, 
MedDRA SOC/PT, the number of days post IP administration that the AE occurred, its 
severity, whether the event was an AE, the relationship to the study treatment, the action 
taken with the study treatment, whether the participant was discontinued due to the AE, 
and the AE outcome. 
9.4. 
Deaths, Serious Adverse Events and other Significant Adverse 
Events 
Individual data listings of DLTs will be provided (Listing 13). The listing will include dose 
group, the AE description, the number of days post dose that the event occurred and its duration, 
its severity, the event’s relationship to the study treatment, the action taken with the IP, whether 
the participant discontinued due to the AE, the outcome, and MedDRA SOC/PT. Individual data 
listings of all SAEs, including deaths, will be provided (Listing 11). This listing will include all 
of the fields in the DLT listing, the reason the event was reported as an SAE, and the event 
outcome. Individual data listings of any deaths that occurred at any time will be provided 
(Listing 12). 
9.5. 
Pregnancies 
Individual data listings of pregnancy reports will be provided if a pregnancy occurs post dosing 
during the study:  
• Maternal information will be presented in Listing 23. 
• Gravida and para information will be presented in Listing 24.  
• Live birth outcomes will be presented in Listing 25 and still birth outcomes will be 
presented in Listing 26.  
• Spontaneous, elective, or therapeutic abortion outcomes will be presented in Listing 27.  
9.6. 
Clinical Laboratory Evaluations 
The most extreme clinical laboratory severity grades observed after dosing will be summarized 
(Maximum Severity Post Baseline) and will include results from unscheduled visits. Parameters 
will be displayed by event direction (increase or decrease). Unscheduled clinical laboratory 
evaluations will be included in listings of all clinical laboratory results, but excluded from 
tabular and graphical summaries by timepoint, except when calculating the maximum severity 
post baseline. Any pre-existing abnormal laboratory results at screening will be graded and 
presented in listings but will not be reported as AEs unless they are treatment-emergent (severity 
worsens after dosing). Clinical laboratory parameters that have grading criteria for both 
decreases (result lower than normal range) and increases (result higher than normal range) will 
be summarized separately by direction.  

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The following laboratory parameters will be presented (in order):  
• HEM: WBC, neutrophils, lymphocytes, monocytes, eosinophils, basophils, hemoglobin, 
hematocrit, platelets (monocytes and basophils will not be graded for toxicity);  
• CHEM: creatinine, glucose, total bilirubin, direct bilirubin, alkaline phosphatase, AST, 
ALT; 
• UA: RBC, WBC, protein.  
Clinical laboratory results will be summarized in tables and figures and listed in listings:  
• Number, proportion, and 95% CI of participants with mild, moderate, severe, or 
potentially life threatening clinical laboratory results by parameter, direction, and dose 
group for the maximum severity reported post baseline will be reported for chemistry 
(Table 13), hematology (Table 14), and urinalysis (Table 15) parameters;  
• Graphical presentation of change from baseline by parameter, dose group, and timepoint 
for chemistry (Figure 7, Figure 8, Figure 9, Figure 10, Figure 11, and Figure 12), and 
hematology (Figure 13, Figure 14, Figure 15, Figure 16, Figure 17, Figure 18, Figure 19, 
Figure 20, and Figure 21);  
• All chemistry results will be listed in Listing 14. All hematology results will be listed in 
Listing 15. All urinalysis results will be listed in Listing 16.  
9.7. 
Vital Signs and Physical Evaluations 
The most extreme vital sign severity grades observed after dosing will be summarized 
(Maximum Severity Post Baseline) and will include results from unscheduled visits. 
Unscheduled VS evaluations will be included in listings of all VS results, but excluded from 
tabular and graphical summaries by timepoint, except when calculating the maximum severity 
post baseline. VS parameters that have grading criteria for both decreases (result lower than 
normal range) and increases (result higher than normal range) will be summarized separately 
by direction. 
The following VS parameters will be presented (in order): pulse (decrease then increase) 
respiratory rate (increase), systolic blood pressure (decrease then increase), diastolic blood 
pressure (increase), and temperature (increase).  
VS results will be summarized in tables, figures, and listings:  
• Number, proportion, and 95% CI of participants with mild, moderate, severe, or 
potentially life threatening VS results by parameter, direction, and dose group at the 
maximum severity reported post baseline, including a summary of all VS parameters 
(Table 16);  
• Graphical presentation of change from baseline by parameter, dose group, and timepoint 
for baseline through Day 1 timepoints (Figure 22, Figure 24, Figure 26, Figure 28, and 
Figure 30) and for all timepoints (Figure 23, Figure 25, Figure 27, Figure 29, and 
Figure 31);  
• All VS measurements, including weight, and height will be presented in Listing 17.  
• Abnormal physical exam findings will be presented in Listing 18. 

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9.8. 
Other Safety Measures 
No additional safety measures are planned.  
10. 
PHARMACOKINETICS 
10.1. 
Graphical and Tabular Summaries of Pharmacokinetic Profiles 
The PK Population will be used when summarizing serum PK concentrations. For both study 
drugs, concentrations less than the lower limit of quantification (LLOQ) will be displayed as 
"<LLOQ" in listings and treated as missing in summary tables and figures. Pre-dose concentrations 
and concentrations collected before the first measurable PK concentration above the LLOQ will be 
treated as 0 for the purposes of calculating PK parameters. All other concentrations less than the 
LLOQ, for each study drug, observed after the first measurable concentration of the respective 
study drug will be considered missing when calculating PK parameters. There will be no 
imputation of missing concentrations. The geometric mean (GM) and coefficient of variation 
(CV)% of concentrations will be treated as missing for sets of data points containing a 
concentration below the limit of quantification (BQL). If sets of data points contain one BQL value 
at the majority of timepoints, this specification may be relaxed to treat GM and CV% as missing if 
2 or more data points in the set contain a BQL value. If relaxed, this will be described in the CSR.  
Collection of serum samples outside of the protocol defined time window for a timepoint will not 
result in exclusion of the sample result from the noncompartmental analysis (NCA). Results from 
PK serum samples that were collected substantially outside of the protocol defined time window 
will be excluded from concentration summary statistics by nominal timepoint and plots of mean 
concentration by nominal timepoint. Time interval windows for PK sample timepoints  are defined 
as follows: + 15 minutes of the nominal timepoint for the samples taken after the C144-LS IV 
infusion (before C135-LS IV infusion) and after complete IP administration for the IV dose 
groups; ± 15 minutes of the nominal timepoint for the remaining post dose samples on Day 0; 
± 1 day for the Day 1 and Day 3 samples; ± 3 days for the Day 7, Day 14, and Day 28 samples; 
± 4 days for the Day 21 sample; ± 5 days for the Week 8 and Week 12 samples, and ± 7 days for 
the Week 18, Week 24, Week 36, and Week 48 samples. Pre-dose samples taken at any point 
before the first IP administration on the date of IP administration will be considered in-window; 
otherwise, they will be considered substantially out-of-window. For other time points, substantially 
out-of-window samples are defined to be twice the size of the sample timepoint windows described 
above.  
If the exact time of serum PK sample collection is not recorded then the collection time will be 
imputed as the planned time for analysis, as long as it is not known that the sample was collected 
outside of the protocol defined window. If it is known that a sample was collected substantially 
outside of the protocol defined window then the sample will be excluded from concentration 
summaries in tables and figures. Rationale for excluding results from tables, figures, and NCA 
will be described in the CSR. Results from samples with imputed collection times will be 
indicated in listings of PK sample concentrations. 

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All participants who meet the criteria specified in Section 6.3.2 will be included in the PK 
population. The bioanalytical laboratory will report C144-LS and C135-LS concentrations in 
serum in units of µg/mL. Summary statistics for PK concentrations include n (the number of 
data points used to compute the summary statistics), mean, SD, min, max, GM, and CV%.  
The definition of CV is described below. 
For an independent identically distributed random sample {x1, x2, …, xn} from a log-normal 
distribution, let s2 be the sample variance statistic of the natural log-transformed values of 
the sample. The CV will be defined as: 
CV = ඥexp(s2) −1 
PK concentrations will be presented in tables, figures, and listings:  
• Mean and standard deviation for C144-LS and C135-LS concentrations by dose group 
and timepoint for the SC dose group (Table 18) and the IV dose group (Table 19); 
• Individual concentrations in serum will be presented graphically for all sample timepoints 
from BL to 72 h post IP administration for each dose group on a linear and semi-log 
scale. Sample times include immediately after the C144-LS IV infusion (for the IV dose 
groups), immediately after C135-LS administration (for the IV dose groups), and 1 hour, 
3 hours, 6 hours, 9 hours, 12 hours, and 72 hours post IP administration. C144-LS 
concentrations will be presented in Figure 32, Figure 34, Figure 36, Figure 38, and 
Figure 40 and C135-LS concentrations will be presented in Figure 42, Figure 44, 
Figure 46, Figure 48, and Figure 50;  
• Individual concentrations in serum will be presented graphically over all sampling 
timepoints for each dose group separately on a linear and semi-log scale for C144-LS 
(Figure 33, Figure 35, Figure 37, Figure 39, Figure 41) and C135-LS (Figure 43, 
Figure 45, Figure 47, Figure 49, Figure 51); 
• Plots of mean (± SD) concentration in serum profiles will be presented on linear and 
semi-log scales for both C144-LS (Figure 52 for baseline to 72 h post dose and Figure 53 
for all post dose timepoints) and C135-LS (Figure 54 for baseline to 72 h post dose and 
Figure 55 for all post dose timepoints) by dose group.  
• Participant specific serum PK concentrations of C144-LS and C135-LS will be listed in 
Listing 20, and will include nominal time, actual sample collection time, laboratory 
reported concentration, analysis concentration, and whether the sample was used in 
λz calculations.  
The participant level PK concentration listing will include separate columns for concentrations 
reported by the lab and concentrations used for analysis. The lab reported concentrations may 
include codes, such as: “BQL” or “QNS” (Quantity not Sufficient), while the analysis 
concentrations will contain numeric data only, including imputed values such as 0 for pre-dose 
timepoints and BQL samples prior to the first quantifiable sample. The listing will also indicate 
the nominal time (i.e., the planned time) and actual post dose time in hours associated with the 
sample and will note sample times which were collected out of window, substantially out of 
window, or imputed. 

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10.2. 
Noncompartmental Analysis 
PK parameters from serum PK data will be estimated through NCA using version 8.2 or higher 
of Phoenix WinNonlin®. Actual post dose time will be used for the estimation of serum PK 
parameters instead of nominal time. In the case of imputed sample collection times, the imputed 
time will be included in the NCA. Any outliers identified in the PK analysis will be discussed in 
the analysis report. Outliers will not be excluded from the PK analysis. 
Phoenix WinNonlin® NCA will use the following settings to compute parameters from serum 
PK data:  
• Linear Up Log Down calculation method 
• Uniform weighting 
• Oral dosing for SC dose groups, IV dosing for IV dose groups.  
• Lambda Z Acceptance Criteria 
− Rsq_adjusted > 0.90 
− Includes at least 3 timepoints after Tmax 
Only the PK parameters that meet the predefined criteria listed above will be included in 
summary tables and figures and statistical analyses. In the case that the Rsq_adjusted Lambda Z 
acceptance criteria is not met, the terminal phase PK parameters (λz, T-HALF, AUC (INF), CLT 
(or CLT/F), and Vz/F (or Vss)), defined below, will be excluded from summary presentations 
and statistical analyses. Regardless of whether the criteria was met, all PK parameters will be 
reported in listings (Listing 21 and Listing 22).  
Cmax 
Cmax is defined as the maximum drug or metabolite concentration observed in serum over all 
PK sample concentrations. It will be obtained from the Cmax parameter calculated by 
WinNonlin®. If there is no measurable concentration in the participant’s PK profile, then Cmax 
will be missing for that participant. Cmax will be reported in units of µg/mL. 
Tmax 
Time of maximum concentration (Tmax) is defined as the time at which the Cmax occurs. It will 
be obtained from the Tmax parameter calculated by WinNonlin®. If there is no measurable 
Cmax in the participant’s PK profile, then Tmax will be missing for that participant. Tmax will 
be reported in units of h. 
λz 
The terminal phase elimination rate constant (λz) is defined as the first-order rate constant 
describing the rate of decrease of drug or metabolite concentration in the terminal phase 
(defined as the terminal region of the PK curve where drug or metabolite concentration follows 
first-order elimination kinetics). λz will be computed as the slope of a terminal region consisting 
of ≥ 3 successive points in the plot of log-transformed concentration data versus time. λz will 
be estimated using uniform weighting.  
Timepoints used in the estimation of λz will only be selected using the WinNonlin® automatic 
algorithm.  
This parameter will be obtained from the Lambda_z parameter calculated by WinNonlin®. λz 
will be reported in units of 1/day.  

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T-HALF (t1/2 as shown in protocol) 
The T-HALF is defined as the time required for the drug or metabolite concentration to decrease 
by a factor of one-half in the terminal phase. The T-HALF can be estimated as ln(2)/ λz. It will be 
obtained from the HL_Lambda_z parameter calculated by WinNonlin®. Half-life will be 
reported in units of days.  
AUC 
AUC(0-T) is defined as the area under the concentration-time curve from the start of dosing 
(time 0) to the time of the last measured concentration. AUC(0-T) will be estimated using the 
Linear Up Log Down calculation method and obtained from the AUClast parameter calculated 
by WinNonlin®. 
AUC(INF) is defined as the total area under the concentration-time curve from the start of dosing 
(time 0) taken to the limit as the end time becomes arbitrarily large. AUC(INF) can be calculated 
by adding AUC(0-T)to an extrapolated value equal to the last measured concentration greater 
than the lower limit of quantification (LLOQ) divided by λz: 
AUC(INF) = AUC(0-T) + Clast
 𝛌𝛌𝒛𝒛
 
Where Clast is the last measured concentration ≥ LLOQ. AUC(INF) will be obtained from the 
AUCINF_obs parameter calculated by WinNonlin®.  
%AUCex is defined as percentage of AUC(INF) obtained by extrapolation from time of the last 
measured concentration to infinity. %AUCex can be calculated by dividing AUC from time of the 
last measured concentration to infinity by AUC(INF):  
%AUC𝑒𝑒𝑒𝑒= 𝐴𝐴𝐴𝐴𝐴𝐴(𝐼𝐼𝐼𝐼𝐼𝐼) −AUC(0 −T)
𝐴𝐴𝐴𝐴𝐴𝐴(𝐼𝐼𝐼𝐼𝐼𝐼)
, 
If %AUCex is >20%, the estimated AUC(INF) will be excluded from statistical summaries of PK 
parameter estimates and downstream calculations. %AUCex will be obtained from the 
AUC_%Extrap_obs parameter calculated by WinNonlin®.  
All AUCs will be reported in units of µg*day/mL. 
CLT 
Clearance (CLT) is defined as the volume of serum completely cleared of drug per unit time and 
is estimated in trials of an IV-administered drug as the actual dose divided by the AUC(INF). It 
will be obtained from the Cl_obs parameter calculated by WinNonlin® only for participants in 
the IV dose groups. If the amount extrapolated portion of AUC(INF) is >20%, the estimated 
CLT value will be flagged when listed in the report and will be excluded from statistical 
summaries of parameter estimates and downstream calculations. CLT will be reported in units 
of mL/day.  

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CLT/F 
Apparent oral clearance (CLT/F) will be calculated as Dose/AUC(INF). If %AUCex is >20%, the 
estimated CLT/F value will be excluded from statistical summaries of parameter estimates and 
downstream calculations. CLT/F will be obtained from the CL_F_obs parameter calculated by 
WinNonlin® only for participants in the SC dose groups. Clearance will be reported in units 
of mL/day.  
Vss 
Apparent volume of distribution at a steady state (Vss) is estimated in trials of an 
IV-administered drug and can be calculated using the AUC and area under the first moment 
curve (AUMC). It will be obtained from the Vss_obs parameter calculated by WinNonlin® only 
for participants in the IV dose groups. If the amount extrapolated portion of AUC(INF) is >20%, 
the estimated Vss value will be flagged when listed in the report and will be excluded from 
statistical summaries of parameter estimates and downstream calculations. Volume of 
distribution at steady state will be reported in units of L.  
Vz/F 
Apparent volume of distribution (Vz/F) will be calculated as (CLT/F)/λz. If %AUCex is >20%, 
the estimated Vz/F value will be excluded from statistical summaries of parameter estimates and 
downstream calculations. Vz/F will be obtained from Vz_F_obs calculated by WinNonlin® only 
for participants in the SC dose groups. Volume will be reported in units of L.  
Serum PK parameters will be summarized and presented tabularly for C144-LS and C135-LS for 
the PK SC dose groups (Table 20) and the PK IV dose groups (Table 21); 
• Participant specific serum PK parameters will be listed for C144-LS (Listing 21) and 
C135-LS (Listing 22).  
10.3. 
Statistical Analysis 
The PK Population will be used for statistical analyses of serum PK parameters described above. 
All individual PK parameters will be listed including any exclusions and reasons for exclusion. 
Summary statistics will be tabulated for each PK parameters by treatment. Geometric means and 
coefficients of variation will be presented for Cmax, AUC(0-T), AUC(INF), CLT, CLT/F, Vss, 
and Vz/F. Medians and ranges will be presented for Tmax. Means and standard deviations will 
be presented for T-HALF. 
10.3.1. 
Assessment of Dose Proportionality 
The presence of dose proportionality in serum will firstly be assessed by comparing dose 
adjusted concentrations and exposure parameters graphically and using descriptive statistics. 
Dose adjusted exposure parameters will be calculated by dividing each exposure parameter 
(AUC(0-T), AUC(INF), and Cmax) by the corresponding dose for each dose group.  
Comparison of dose adjusted exposure parameters will be presented tabularly and graphically: 
• Summary statistics of dose adjusted exposure parameters will be presented tabularly for 
C144-LS and C135-LS for the SC PK groups (Table 22) and for the IV PK groups 
(Table 23) separately; 

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• Dose adjusted exposure parameters will be compared graphically in boxplots for each 
dose group for both C144-LS and C135-LS (Figure 56 and Figure 57). 
Pairwise comparisons of exposure parameters (AUC(0-T), AUC(INF), and Cmax) will be 
conducted between dose groups using the PK Population. The pairwise comparison ratios will 
be displayed as follows: 
• SC 2,3 / SC 1 
• IV2 / IV 1 
• IV3 / IV 1 
• IV3 / IV 2 
Results of the 90% confidence interval for the ratio of each exposure parameter compared 
between dose groups will be presented in Table 24. The estimated ratio of exposure parameters 
between doses will be graphically compared to the expected ratio given dose proportionality 
(dose ratio), along with the estimated CI for each pairwise comparison in a forest plot for both 
C144-LS and C135-LS (Figure 58 and Figure 59). 
Since the confidence intervals will be for the ratio of each exposure parameter compared 
between dose groups, the values will be log transformed before using PROC ANOVA, and the 
resulting confidence intervals will be exponentiated to present the final results. The expected 
ratio for each comparison will be the ratio of the doses in the dose groups that are compared. 
Pseudo code to estimate pairwise comparisons of the ratio of exposure parameters between dose 
groups is presented below. Variables used in the model are also detailed below:  
• AVAL = log transformed value of the exposure parameter value for each exposure 
parameter (ex, AUC(0-T), AUC(INF), or Cmax) 
• TRT = dose group indicator 
Pseudo code for estimating the ratio of exposure parameters between each dose group using 
Tukey’s correction for multiple hypotheses is below:  
PROC ANOVA data= ADPP; 
 
class TRT; 
 
model AVAL=TRT; 
 
means TRT / tukey alpha = 0.10; 
run; 
The resulting confidence limit values and parameter estimates will then be exponentiated to give 
the estimate of the ratio of the exposure parameters and associated confidence limit on the linear 
scale. This analysis will be conducted for all exposure parameters (AUC(0-T), AUC(INF), and 
Cmax), for both C144-LS and C135-LS.  
A power model of each exposure parameter will be used to further assess dose proportionality in 
the IV dose groups.  
𝑌𝑌=  𝛼𝛼+ 𝛽𝛽𝛽𝛽𝛽𝛽(𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑) +  𝜀𝜀 
Where Y is the log transformed value of the exposure parameter being assessed. Coefficient 
estimates and 95% confidence intervals for the dose coefficient will be provided in Table 25.  
A β power coefficient estimate of approximately 1 is consistent with dose proportionality. 
A comparison of each model fit versus the exposure parameter values for each dose level will 
be presented in Figure 60 for C144-LS and Figure 61 for C135-LS.  

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11. 
IMMUNOGENICITY 
All immunogenicity results and analyses will be presented using the C144-LS and C135-LS 
immunogenicity populations by individual dose group. The denominators for proportions will be 
indicated within the table or table header. Immunogenicity serum samples will be collected at the 
times specified in Appendix A of the Study Protocol (Times of Events Schedule). 
11.1.1. 
Assessment of Anti-Drug Antibody (ADA) Responses 
The occurrence of ADA responses will be evaluated by a three-tiered approach using validated 
screening and confirmatory assays, followed by titering of responses to determine if the 
responses were treatment-induced or treatment-boosted. Confirmatory assays will only be 
conducted for samples with positive screening results. Response titrations will only be conducted 
for confirmed positive samples. An ADA response will be considered to have occurred if both 
the screening and confirmatory results are positive. An ADA response will be considered to not 
have occurred if either the screening or confirmatory result is negative. Serum ADA results will 
be summarized by the number of participants with available samples for testing. Refer to 
Section 6.5 for how samples negative or inconclusive for the presence of ADA, and positive but 
unquantifiable will be handled in summary tables and figures.  
Sample ADA status will be defined as follows:  
• Baseline ADA-positive sample: ADA is detected in the Day 0 sample, before IP 
administration. 
• Baseline ADA-negative sample: ADA is not detected in the Day 0 sample, before IP 
administration. 
• ADA-positive sample: After initiation of treatment, (1) an ADA detected (positive 
seroconversion) sample in a participant for whom ADA is not detected at baseline, or  
(2) an ADA detected sample with an increase of at least 4-fold in ADA titer from 
baseline.  
• ADA-negative sample: After initiation of treatment, ADA not positive sample relative to 
baseline. 
Sample ADA status will be used to define participant ADA status: 
• Baseline ADA-positive participant: A participant with baseline ADA-positive sample. 
• ADA-positive participant: A participant with at least one ADA positive-sample relative 
to baseline at any time after IP administration. 
− Persistent Positive (PP): ADA-positive sample at 2 or more consecutive timepoints 
where the first and last consecutive ADA-positive samples are at least 16 weeks apart. 
− Not PP-Last Sample Positive: Not persistent positive with ADA-positive sample at 
the participant’s last sampling timepoint.  
− Other Positive: Not persistent positive but with some ADA-positive sample and with 
ADA-negative sample at the participant’s last sampling timepoint.  
• ADA-negative participant: A participant with no ADA-positive sample after IP 
administration.  

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The following summaries of ADA sample and participant results will be presented:  
• Summary of confirmed positive ADA sample results will be presented by sample 
timepoint in Table 26 for the C144-LS Immunogenicity Population and Table 27 for the 
C135-LS Immunogenicity Population.  
• Summary of ADA participant results over the entire study period will be presented in 
Table 28 for the C144-LS Immunogenicity Population and Table 29 for the C135-LS 
Immunogenicity Population.  
• Summary statistics (number with results, Geometric Mean Titer (GMT), and 95% CI for 
the GMT) of all ADA titer levels will be presented by sample timepoint in Table 30 for 
the C144-LS Immunogenicity Population and Table 31 for the C135-LS Immunogenicity 
Population.  
• ADA titration results will be presented graphically in boxplots by dose group and time 
point in Figure 62 and Figure 63 for the C144-LS Immunogenicity Population (SC and 
IV dose groups, respectively) and Figure 64 and Figure 65 for the C135-LS 
Immunogenicity Population (SC and IV dose groups, respectively). 
• All ADA screening, confirmation, and titer results will be listed by dose group for the 
C144-LS and C135-LS immunogenicity populations in Listing 28 and Listing 29, 
respectively.  
All ADA samples will be summarized in tables, figures, and listings, regardless of whether the 
sample was collected within the protocol defined window or not. ADA samples collected outside 
of the protocol defined window will be noted in Listing 28 and Listing 29.  
12. 
REPORTING CONVENTIONS 
The mean, median, SD, and any other statistics (other than quantiles), will be reported to one 
decimal place greater than the original data. Order statistics, such as the min and max values, 
will be reported to the same number of decimal places as the original data. Proportions and 
percentages will be presented as 2 decimal places; values <0.01 will be presented as “<0.01”. 
Estimated parameters not on the same scale as raw observations (e.g., regression coefficients) 
will be reported to 3 significant figures.  
Cmax will be reported with the same number of significant digits as the measurement. Other PK 
parameters will be reported using 3 significant digits. 
Listings of individual participant data will include a Participant ID column. The participant 
identifiers assigned by site staff are replaced throughout this report with the SDTM variable 
USUBJID to protect the confidentiality of those who participated to participate in this protocol. 
USUBJID has been created as a composite of the platform code followed by a numeric identifier 
assigned chronologically to enrolled participants as well as screening failures across all sites and 
protocols in the EDC platforms. Any data sharing activities will include the USUBJID and not 
the participant identifiers assigned at the study site. 

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13. 
TECHNICAL DETAILS 
SAS version 9.4 or above and R version 4.1 or above will be used to generate tables, figures, and 
listings. PK parameters will be estimated through NCA using Phoenix® WinNonlin® version 8.2 
or later. 
 
14. 
SUMMARY OF CHANGES IN THE CONDUCT OF THE STUDY 
OR PLANNED ANALYSES 
The interim analysis per SAP Version 1.0, covering follow-up through Week 24 timepoint was 
conducted for timely dissemination of results for the planned Emergency Use Authorization 
application. 
 
15. 
REFERENCES 
1. ICH Harmonised Tripartite Guideline. Structure and Content of Clinical Study Reports 
E3. International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use. 1995. Retrieved from: 
https://database.ich.org/sites/default/files/E3_Guideline.pdf 
2. ICH Harmonised Tripartite Guideline. General Considerations for Clinical Trials E8. 
International Conference on Harmonisation of Technical Requirements for Registration 
of Pharmaceuticals for Human Use. 1997. Retrieved from: 
https://database.ich.org/sites/default/files/E8_Guideline.pdf 
3. ICH Harmonised Tripartite Guideline. Statistical Principles for Clinical Trials E9. 
International Conference on Harmonisation of Technical Requirements for Registration 
of Pharmaceuticals for Human Use. 1998. Retrieved from: 
https://database.ich.org/sites/default/files/E9_Guideline.pdf 
4. Food and Drug Administration (FDA). Guidance for Industry: Toxicity Grading Scale for 
Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. 
September 2007. Retrieved from: https://www.fda.gov/media/73679/download. 
5. A phase 1 study of the safety and pharmacokinetics of a combination of two anti-SARS-
CoV-2 mAbs (C144-LS and C135-LS) in healthy volunteers v2.1. Protocol Number: 
RUCOV1. The Rockefeller University; February 2021. 
 
 

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16. 
APPENDICES: LIST OF TABLES, FIGURES, AND LISTINGS  
 
Table, figure, and listing shells are presented in Appendices 1, 2, and 3, respectively. 
 

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APPENDIX 1. TABLE MOCK-UPS 
LIST OF TABLES 
Table 1: 
Participant Disposition of Enrolled Participants by Dose Group – Safety Population ......................... 39 
Table 2: 
Distribution of Protocol Deviations on Enrolled Participants by Category, Type, and Dose Group .... 40 
Table 3: 
Analysis Populations by Dose Group – All Enrolled Participants ........................................................ 42 
Table 4: 
Analysis Population Exclusions by Dose Group – All Enrolled Participants ....................................... 43 
Table 5: 
Summary of Screen Failures and Eligible Non-Enrollments ................................................................ 44 
Table 6: 
Summary of Categorical Demographic and Baseline Characteristics by Dose Group – Safety 
Population ............................................................................................................................................. 45 
Table 7: 
Summary of Continuous Demographic and Baseline Characteristics by Dose Group – Safety 
Population ............................................................................................................................................. 46 
Table 8: 
Summary of Participants with Pre-Existing Medical Conditions by MedDRA System Organ Class 
and Dose Group – Safety Population .................................................................................................... 47 
Table 9: 
Overall Summary of Adverse Events – Safety Population ................................................................... 48 
Table 10: 
Number and Percentage of Participants Experiencing Solicited Events with 95% Confidence 
Intervals by Symptom, and Dose Group – Safety Population............................................................... 50 
Table 11: 
Unsolicited Adverse Events by MedDRA System Organ Class and Preferred Term, Maximum 
Severity, and Dose Group – Safety Population ..................................................................................... 51 
Table 12: 
Related Unsolicited Adverse Events by MedDRA System Organ Class and Preferred Term, 
Maximum Severity and Dose Group – Safety Population .................................................................... 51 
Table 13: 
Laboratory Results Maximum Severity Post-Baseline by Dose Group, Chemistry – Safety 
Population ............................................................................................................................................. 52 
Table 14: 
Laboratory Results Maximum Severity Post-Baseline by Dose Group, Hematology – Safety 
Population ............................................................................................................................................. 53 
Table 15: 
Laboratory Results Maximum Severity Post-Baseline by Dose Group, Urinalysis – Safety 
Population ............................................................................................................................................. 54 
Table 16: 
Vital Sign Results Maximum Severity Post-Baseline by Dose Group – Safety Population ................. 55 
Table 17: 
Summary of Participants with Concurrent Medications by WHO Drug Classification – Safety 
Population ............................................................................................................................................. 56 
Table 18: 
Summary of C144-LS and C135-LS Concentrations in Serum by Dose Group: All Timepoints, 
PK Population – SC Dose Groups ........................................................................................................ 57 
Table 19: 
Summary of C144-LS and C135-LS Concentrations in Serum by Dose Group: All Timepoints, 
PK Population – IV Dose Groups ......................................................................................................... 58 
Table 20: 
Summary Statistics of Serum PK Parameters by Dose Group, PK Population – SC Dose Groups ...... 59 
Table 21: 
Summary Statistics of Serum PK Parameters by Dose Group, PK Population – IV Dose Groups ....... 60 
Table 22: 
Summary Statistics for Dose Adjusted Exposure Parameters, PK Population – SC Dose Groups ....... 61 
Table 23: 
Summary Statistics for Dose Adjusted Exposure Parameters, PK Population – IV Dose Groups ....... 62 
Table 24: 
Comparison of Exposure Parameters Between Dose Groups, Pairwise Comparisons, PK 
Population – All PK Dose Groups ........................................................................................................ 63 
Table 25: 
Power Model Coefficient Estimates from Dose Proportionality Assessment Among IV Dose 
Groups – PK Population ....................................................................................................................... 63 
Table 26: 
Summary of Confirmed Positive Anti-Drug Antibody Results, C144-LS - Immunogenicity 
Population ............................................................................................................................................. 64 
Table 27: 
Summary of Confirmed Positive Anti-Drug Antibody Results, C135-LS - Immunogenicity 
Population ............................................................................................................................................. 64 
Table 28: 
Summary of Anti-Drug Antibody Participant Results, C144-LS - Immunogenicity Population .......... 65 
Table 29: 
Summary of Anti-Drug Antibody Participant Results, C135-LS - Immunogenicity Population .......... 65 
Table 30: 
Summary of Anti-Drug Antibody Titration Results and Fold Rise from Baseline, C144-LS - 
Immunogenicity Population .................................................................................................................. 66 
Table 31: 
Summary of Anti-Drug Antibody Titration Results and Fold Rise from Baseline, C135-LS - 
Immunogenicity Population .................................................................................................................. 66 

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Table 1: 
Participant Disposition of Enrolled Participants by Dose Group – Safety Population 
Participant Disposition 
[Safety 
Group 1] 
(N=X) 
[Safety 
Group 2] 
(N=X) 
[Safety 
Group 3] 
 (N=X) 
[Safety 
Group 4] 
(N=X) 
[Safety 
Group 5] 
(N=X) 
[Safety 
Group 6] 
(N=X) 
All Participants 
(N=X) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Received IP a 
x (xx.x) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Received all assigned IP injections/ 
infusions, uninterrupted  
 
 
 
 
 
 
 
Completed all Safety Blood Draws 
 
 
 
 
 
 
 
Completed all PK Blood Draws 
 
 
 
 
 
 
 
Completed all Immunogenicity (ADA) 
Blood Draws 
 
 
 
 
 
 
 
Completed Follow-up 
 
 
 
 
 
 
 
Discontinued/Interrupted IPb 
 
 
 
 
 
 
 
Reason for Discontinuation/Interruption 
 
 
 
 
 
 
 
     [Reason 1] 
 
 
 
 
 
 
 
     [Reason 2] 
 
 
 
 
 
 
 
Early Terminationb 
 
 
 
 
 
 
 
Reason for Early Termination 
 
 
 
 
 
 
 
     [Reason 1] 
 
 
 
 
 
 
 
     [Reason 2] 
 
 
 
 
 
 
 
Notes: N = Number of participants in the safety analysis population.  
a Participants in study Part A were not randomized. Enrolled refers to participants in study Part A who were assigned study product. Only participants in 
study Part B were randomized.  
b Refer to Listing  for detailed reasons participants discontinued or terminated early. Discontinued is defined as partial dosing that was started and stopped 
without being restarted, or full dosing of only one mAB. Interruption is defined as stopped and restarted infusion, or a change in infusion location/IV site.  
 

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Table 2: 
Distribution of Protocol Deviations on Enrolled Participants by Category, Type, and Dose Group 
Category 
Deviation Type 
Number of Participants (Number of Deviations) 
[Safety 
Group 1] 
(N=X) 
[Safety 
Group 2] 
(N=X) 
[Safety 
Group 3] 
(N=X) 
[Safety 
Group 4] 
(N=X) 
[Safety 
Group 5] 
(N=X) 
[Safety 
Group 6] 
(N=X) 
All 
Participants 
(N=X) 
Eligibility/enrollment 
Any type 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
  
Did not meet inclusion 
criterion 
  
  
  
  
  
  
  
  
Met exclusion criterion 
  
  
  
  
  
  
  
  
ICF not signed prior to 
study procedures 
  
  
  
  
  
  
  
  
Other 
  
  
  
  
  
  
  
IP administration 
schedule 
Any type 
  
  
  
  
  
  
  
  
Out of window visit 
  
  
  
  
  
  
  
  
Missed visit/visit not 
conducted  
  
  
  
  
  
  
  
  
Missed IP 
administration 
  
  
  
  
  
  
  
  
Delayed IP 
administration  
  
  
  
  
  
  
  
  
Required procedure 
done incorrectly 
  
  
  
  
  
  
  
  
Study product 
temperature excursion  
  
  
  
  
  
  
  
  
Other 
  
  
  
  
  
  
  
Follow-up visit 
schedule 
Any type 
  
  
  
  
  
  
  
  
Out of window visit 
  
  
  
  
  
  
  
  
Missed visit/visit not 
conducted 
  
  
  
  
  
  
  
  
Other 
  
  
  
  
  
  
  

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Table 2: 
Distribution of Protocol Deviations by Category, Type, and Dose Group (continued) 
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Category 
Deviation Type 
Number of Participants (Number of Deviations) 
[Safety 
Group 1] 
(N=X) 
[Safety 
Group 2] 
(N=X) 
[Safety 
Group 3] 
(N=X) 
[Safety 
Group 4] 
(N=X) 
[Safety 
Group 5] 
(N=X) 
[Safety 
Group 6] 
(N=X) 
All 
Participants 
(N=X) 
Protocol 
procedure/assessment 
Any type 
  
  
  
  
  
  
  
  
Incorrect version of ICF 
signed 
  
  
  
  
  
  
  
  
Blood not collected 
  
  
  
  
  
  
  
  
Urine not collected 
  
  
  
  
  
  
  
  
Swab not collected 
  
  
  
  
  
  
  
  
Other specimen not 
collected 
  
  
  
  
  
  
  
  
Specimen result not 
obtained  
  
  
  
  
  
  
  
  
Required procedure not 
conducted 
  
  
  
  
  
  
  
  
Required procedure 
done incorrectly 
  
  
  
  
  
  
  
  
Required procedure out 
of window  
  
  
  
  
  
  
  
  
Study product 
temperature excursion 
  
  
  
  
  
  
  
  
Specimen temperature 
excursion 
  
  
  
  
  
  
  
  
Sponsor halted IP 
administration 
  
  
  
  
  
  
  
  
Other 
  
  
  
  
  
  
  
Note: N=Number of participants in the safety analysis population. 
 
 

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Table 3: 
Analysis Populations by Dose Group – All Enrolled Participants 
Analysis Populations  
[Safety 
Group 1] 
[Safety 
Group 2] 
[Safety 
Group 3] 
[Safety 
Group 4] 
[Safety 
Group 5] 
[Safety 
Group 6] 
[All 
Participants] 
(N=X) 
(N=X) 
(N=X) 
(N=X) 
(N=X) 
(N=X) 
(N=X) 
 
n 
n 
n 
n 
n 
n 
n 
Safety Population 
x 
x 
x 
x 
x 
x 
x 
PK Population 
x 
x 
x 
x 
x 
x 
x 
Immunogenicity Population (ADA) 
x 
x 
x 
x 
x 
x 
x 
Programming note: If C144-LS and C135-LS Immunogenicity Populations are different, they will be presented in separate rows in the table. 
 
 

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Table 4: 
Analysis Population Exclusions by Dose Group – All Enrolled Participants 
Analysis 
Population 
Exclusions 
Reason for Inclusion/Exclusion 
[Safety 
Group 1] 
[Safety 
Group 2] 
[Safety 
Group 3] 
[Safety 
Group 4] 
[Safety 
Group 5] 
[Safety 
Group 6] 
[All 
Participants] 
(N=X) 
(N=X) 
(N=X) 
(N=X) 
(N=X) 
(N=X) 
(N=X) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Reasons for Exclusion 
Safety Population 
Did not receive any amount of the IPa 
x (x.x) 
x (x.x) 
x (x.x) 
x (x.x) 
x (x.x) 
x (x.x) 
x (x.x) 
PK Population 
Any reason 
x (x.x) 
x (x.x) 
x (x.x) 
x (x.x) 
x (x.x) 
x (100)  
 x (x.x) 
Received placebo 
  
  
  
  
  
x (100) 
  
No post dose serum sample with a 
measurable concentration of C144-LS or 
C135-LS  
  
  
  
  
  
  
  
Protocol deviation(s) with potential to 
impact PK  
  
  
  
  
  
  
  
Immunogenicity 
Population (ADA) 
Any reason 
x (x.x) 
x (x.x) 
x (x.x) 
x (x.x) 
x (x.x) 
x (x.x) 
x (x.x) 
 
No post dose sample with a valid result 
 
 
 
 
 
 
 
 
No pre dose sample with a valid result 
 
 
 
 
 
 
 
Notes:  
N = Number of enrolled participants.  
The order that reasons were considered for exclusion from analysis populations follows the order that reasons are presented in the table.  
a Includes placebo.  
Programming note: If C144-LS and C135-LS Immunogenicity Populations are different, they will be presented in separate rows in the table. 

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Table 5: 
Summary of Screen Failures and Eligible Non-Enrollments 
Category 
Screen Failure or Eligible Non-Enrollment Criterion 
na 
%b 
Inclusion and 
Exclusion 
Number of participants failing any eligibility criterion 
x 
100 
Inclusion 
Any inclusion criterion 
x 
xx.x 
 
Aged 18 to <65 
x 
xx.x 
 
If sexually active male or female and participating in sexual activity that could lead to 
pregnancy, agrees to use one effective method of contraception from 10 days prior to 
the antibody administration until 6 months after IP administration 
x 
xx.x 
Exclusion 
Any exclusion criterion 
x 
xx.x 
 
Weight > 110 kg (groups S1 and S2 only) 
 
 
 
History of prior positive SARS-CoV-2 RT-PCR or SARS- CoV-2 serology 
 
 
 
Active respiratory or non-respiratory systems consistent with COVID-19 
 
 
 
Medically attended acute illness or hospitalization (i.e., >24 hours) for any reason 
within 30 days prior to screening 
 
 
 
Acute exacerbation of a chronic pulmonary condition (e.g., chronic obstructive 
pulmonary disease [COPD], asthma exacerbations, or uncontrolled hypertension, as 
defined by a systolic blood pressure > 180 and or diastolic blood pressure > 120, in 
the presence or absence of antihypertensive medications) in the past 6 months.  
 
 
 
Use of systemic corticosteroids, immunosuppressive anti-cancer, or other medications 
considered significant by the trial physician within the last 6 months.  
 
 
 
Other clinically significant acute or chronic medical condition that in the opinion of 
the investigator would preclude participation.  
x 
xx.x 
 
Are eligible for COVID-19 vaccination prior to your entry in the study according to 
local guidelines (e.g., healthcare professionals, non-healthcare professionals such as 
teachers, firefighters, public transit workers).  
x 
xx.x 
 
Laboratory abnormalities in the parameters listed:  
• 
Absolute neutrophil count ≤ 1,500 K/mcL 
• 
Hemoglobin ≤ 10.5 gm/dL if female; 11 gm/dL if male; 
• 
Platelet count ≤ 125,000 K/mcL; 
• 
ALT ≥ 1.25 x ULN; AST ≥ 1.25 X ULN; 
• 
Total bilirubin ≥ 1.25 x ULN; 
• 
Creatinine ≥ 1.1 x ULN 
x 
xx.x 
 
Pregnancy or lactation 
 
 
 
Any vaccination within 14 days prior to SARS-CoV-2 mAbs administration (except 
influenza vaccine). 
 
 
 
History of prior therapy with any SARS-CoV-2 vaccine or antibodies, including 
convalescent plasma. 
 
 
 
Known allergy/sensitivity or any hypersensitivity to components of the 
investigational agents. 
 
 
 
History of severe reaction to a vaccine or monoclonal antibody administration or 
history of severe allergic reactions. 
 
 
 
Participation in another clinical study of an investigational product currently or 
within the past 12 weeks, or expected participation during this study.  
 
 
Eligible but 
Not Enrolled 
Any reason for being eligible but not enrolled 
 
 
 
[Reason 1] 
 
 
 
[Reason 2] 
 
 
a More than one criterion may be marked per participant. 
b Denominator for percentages is the total number of screen failures. 
 

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Table 6: 
Summary of Categorical Demographic and Baseline Characteristics by Dose Group – Safety Population 
This table will be repeated for the pooled safety dose groups, excluding the “all participants” column.  
Variable 
Characteristic 
[Safety 
Group 1] 
(N=X) 
[Safety 
Group 2] 
(N=X) 
[Safety 
Group 3] 
(N=X) 
[Safety 
Group 4] 
(N=X) 
[Safety 
Group 5] 
(N=X) 
[Safety 
Group 6] 
(N=X) 
All 
Participants 
(N=X) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Sex  
Male 
x (xx.x) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
  
Female 
  
  
  
  
  
  
  
Ethnicity  
Not Hispanic or Latino 
  
  
  
  
  
  
  
  
Hispanic or Latino 
  
  
  
  
  
  
  
  
Not Reported 
  
  
  
  
  
  
  
  
Unknown 
  
  
  
  
  
  
  
Race  
American Indian or 
Alaska Native 
  
  
  
  
  
  
  
  
Asian 
  
  
  
  
  
  
  
  
Black or African 
American 
  
  
  
  
  
  
  
  
Native Hawaiian or 
Other Pacific Islander 
  
  
  
  
  
  
  
  
White 
  
  
  
  
  
  
  
  
Multi-Racial 
  
  
  
  
  
  
  
  
Not Reported 
  
  
  
  
  
  
  
  
Other/Unknown/Refused 
to specify 
  
  
  
  
  
  
  
Notes: N = Number of participants in the safety analysis population. 
 

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Table 7: 
Summary of Continuous Demographic and Baseline Characteristics by Dose Group – Safety Population 
This table will be repeated for the pooled safety dose groups, excluding the “all participants” column. 
Variable 
Statistic 
[Safety 
Group 1] 
(N=X) 
[Safety 
Group 2] 
(N=X) 
[Safety 
Group 3] 
(N=X) 
[Safety 
Group 4] 
(N=X) 
[Safety 
Group 5] 
(N=X) 
[Safety 
Group 6] 
(N=X) 
All 
Participants 
(N=X) 
Age 
Mean 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
  
Standard Deviation 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
  
Median 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
  
Minimum 
x 
x 
x 
x 
x 
x 
x 
  
Maximum 
x 
x 
x 
x 
x 
x 
x 
Height 
Mean 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
  
Standard Deviation 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
  
Median 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
  
Minimum 
x 
x 
x 
x 
x 
x 
x 
  
Maximum 
x 
x 
x 
x 
x 
x 
x 
Weight 
Mean 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
  
Standard Deviation 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
  
Median 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
  
Minimum 
x 
x 
x 
x 
x 
x 
x 
  
Maximum 
x 
x 
x 
x 
x 
x 
x 
BMI 
Mean 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
  
Standard Deviation 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
  
Median 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
  
Minimum 
x 
x 
x 
x 
x 
x 
x 
 
Maximum 
x 
x 
x 
x 
x 
x 
x 
Note: N = Number of participants in the safety analysis population.  

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Table 8: 
Summary of Participants with Pre-Existing Medical Conditions by MedDRA System Organ Class and Dose 
Group – Safety Population 
MedDRA 
System 
Organ Class 
[Safety Group 1] 
(N=X) 
[Safety Group 2] 
(N=X) 
[Safety Group 3] 
(N=X) 
[Safety Group 4] 
(N=X) 
[Safety Group 5] 
(N=X) 
[Safety Group 6] 
(N=X) 
All Participants 
(N=X) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Any SOC 
x (xx.x) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
[SOC 1] 
  
  
  
  
  
  
  
[SOC 2] 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Note: N = Number of participants in the safety analysis population; n = Number of participants reporting medical history within the specified SOC. Each 
participant is only counted once per SOC.  
 
 
 

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Safety Tables 
Table 9: 
Overall Summary of Adverse Events – Safety Population 
This table will be repeated for the pooled safety dose groups. 
 
[Safety Group 1] 
(N=X) 
[Safety Group 2] 
(N=X) 
[Safety Group 3] 
(N=X) 
[Safety Group 4] 
(N=X) 
[Safety Group 5] 
(N=X) 
[Safety Group 6] 
(N=X) 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
Any AE1,2,4 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
Any Solicited Symptom2,3 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
     Systemic Symptoms (All Grades) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
          Grade 2 or Higher 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
          Grade 3 or Higher 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
     Local Symptoms (All Grades) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
          Grade 2 or Higher 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
          Grade 3 or Higher 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
Any Unsolicited AE within 4 weeks of IP4 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
     Related5 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
     Grade 2 or Higher 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
     Grade 3 or Higher 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
     Related5 and Grade 2 or Higher 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
     Related5 and Grade 3 or Higher 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 

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[Safety Group 1] 
(N=X) 
[Safety Group 2] 
(N=X) 
[Safety Group 3] 
(N=X) 
[Safety Group 4] 
(N=X) 
[Safety Group 5] 
(N=X) 
[Safety Group 6] 
(N=X) 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
Any Unsolicited AE during the study follow-up4 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
     Related5 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
     Grade 2 or Higher 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
     Grade 3 or Higher 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
     Related5 and Grade 2 or Higher 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
     Related5 and Grade 3 or Higher 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
Any Grade 2 or Higher Laboratory Result6 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
Any Grade 3 or Higher Laboratory Result6 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
     Probably or Definitely Related5 Grade 3 or Higher 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
Any SAE7 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
     Related5 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
AE Leading to Treatment Discontinuation  
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
AE Leading to Study Discontinuation 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
xx 
(xx.x) 
(xx.x, 
xx.x) 
N = Number of participants in the safety analysis population 
n = Number of participants who experienced at least one event (participants with >1 reported event are counted only once in each category). 
% = Percentage of participants who experienced events in each category relative to the total number within each dose group.  
95% CI = Exact Clopper-Pearson 95% confidence interval for the percent.  
¹ Includes solicited AEs and unsolicited AEs. 
2 Solicited symptoms are reported through 14 days post-vaccination (i.e., 15-day follow-up period). 
3 By definition, solicited symptoms (local and systemic) are considered related to IP. 
4 Includes SAEs..  
5 “Related” is defined as possibly, probably, or definitely related to the IP. 
6 Chemistry or hematology laboratory results post-IP administration and through 28 days after each vaccination. Only Grade 3 or higher laboratory results were assessed for relationship to IP.  
7 SAE: Serious Adverse Event reported at any time during the study, including death.  

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Table 10: 
Number and Percentage of Participants Experiencing Solicited Events with 95% Confidence Intervals by 
Symptom, and Dose Group – Safety Population 
This table will be repeated for the pooled safety dose groups. 
Symptom 
[Safety Group 1] 
(N=X) 
[Safety Group 2] 
(N=X) 
[Safety Group 3] 
(N=X) 
[Safety Group 4] 
(N=X) 
[Safety Group 5] 
(N=X) 
[Safety Group 6] 
(N=X) 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
Any Solicited Symptom 
     Any  
x (xx.x) 
xx.x, 
xx.x 
x (xx.x) 
xx.x, 
xx.x 
x (xx.x) 
xx.x, 
xx.x 
x (xx.x) 
xx.x, 
xx.x 
x (xx.x) 
xx.x, 
xx.x 
x (xx.x) 
xx.x, 
xx.x 
     Grade 1 
  
  
  
  
  
  
  
  
  
  
  
  
     Grade 2 
  
  
  
  
  
  
  
  
  
  
  
  
     Grade 3 
  
  
  
  
  
  
  
  
  
  
  
  
     Grade 4 
  
  
  
  
  
  
  
  
  
  
  
  
     Grade 5 
  
  
  
  
  
  
  
  
  
  
  
  
Repeat For: 
Any Systemic Symptom 
     Feverishness 
     Chills 
     Headache 
     Nausea 
     Vomiting 
     Malaise  
     Arthralgia 
Any Local Symptom 
     Pain1 
     Tenderness1 
     Erythema1 
     Induration1 
Notes: N = Total number of participants in the safety analysis population. 
n (%) = Number and percent of participants with an event (% of N). 
95% CI = Exact Clopper-Pearson 95% confidence interval for the percent. 
Solicited symptoms are reported through 2 weeks following IP administration. The maximum severity experienced over the 2-week period is summarized. 
1 Occurring at injection or infusion site. 

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Table 11: 
Unsolicited Adverse Events by MedDRA System Organ Class and Preferred Term, Maximum Severity, and 
Dose Group – Safety Population 
This table will be repeated for the pooled safety dose groups. 
MedDRA SOC/PT 
Severity 
Grade 
[Safety Group 1] 
(N=X) 
[Safety Group 2] 
(N=X) 
[Safety Group 3] 
(N=X) 
[Safety Group 4] 
(N=X) 
[Safety Group 5] 
(N=X) 
[Safety Group 6] 
(N=X) 
n (%) 
Number 
of Events 
n (%) 
Number 
of Events 
n (%) 
Number 
of Events 
n (%) 
Number 
of Events 
n (%) 
Number 
of Events 
n (%) 
Number 
of Events 
Any AE 
Any SOC/PT 
Any 
x (xx.x) 
x 
x (xx.x) 
x 
x (xx.x) 
x 
x (xx.x) 
x 
x (xx.x) 
x 
x (xx.x) 
x 
Grade 1 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 2 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 3 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 4 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 5 
  
  
  
  
  
  
  
  
  
  
  
  
SOC 1 
Any PT 
Any 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 1 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 2 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 3 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 4 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 5 
  
  
  
  
  
  
  
  
  
  
  
  
PT 1 
Any 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 1 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 2 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 3 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 4 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 5 
  
  
  
  
  
  
  
  
  
  
  
  
Notes: N = Number of participants in the safety analysis population. 
n = Number of participants who experienced at least one event (participants with >1 reported event are counted only once for each SOC/PT for the highest severity reported). 
% = Percentage of participants who experienced events in each SOC/PT relative to the total number within each dose group. 
Number of Events = The total number of AEs reported in each SOC/PT combination for the specified grade.  
 
Table 12: 
Related Unsolicited Adverse Events by MedDRA System Organ Class and Preferred Term, Maximum Severity 
and Dose Group – Safety Population  
This table will repeat Table 11 for related unsolicited adverse events.  

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Table 13: 
Laboratory Results Maximum Severity Post-Baseline by Dose Group, Chemistry – Safety Population 
This table will be repeated for the pooled safety dose groups. 
Parameter/ 
Maximum Severity 
Post-Baseline1 
[Safety Group 1] 
(N=X) 
[Safety Group 2] 
(N=X) 
[Safety Group 3] 
(N=X) 
[Safety Group 4] 
(N=X) 
[Safety Group 5] 
(N=X) 
[Safety Group 6] 
(N=X) 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
Any Chemistry Parameter 
None2 
x (xx.x) xx.x, xx.x x (xx.x) xx.x, xx.x x (xx.x) xx.x, xx.x x (xx.x) xx.x, xx.x x (xx.x) xx.x, xx.x x (xx.x) xx.x, xx.x 
Grade 1 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 2 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 3 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 4 
  
  
  
  
  
  
  
  
  
  
  
  
Missing 
  
  
  
  
  
  
  
  
  
  
  
  
Repeat for:  
Creatinine, Increase 
  
  
  
  
  
  
  
  
  
  
  
  
Glucose, Decrease 
  
  
  
  
  
  
  
  
  
  
  
  
Glucose, Increase 
  
  
  
  
  
  
  
  
  
  
  
  
Total Bilirubin, 
Increase 
  
  
  
  
  
  
  
  
  
  
  
  
Direct Bilirubin, 
Increase 
  
  
  
  
  
  
  
  
  
  
  
  
Alkaline Phosphatase, 
Increase 
  
  
  
  
  
  
  
  
  
  
  
  
AST, Increase 
  
  
  
  
  
  
  
  
  
  
  
  
ALT, Increase 
  
  
  
  
  
  
  
  
  
  
  
  
Notes: N = Number of participants in the safety analysis population with available results. 
n (%) = Number and percent of participants with a reported event (% of N). 
95% CI = Exact Clopper-Pearson 95% confidence interval for the percent. 
1 “Maximum Post Baseline” indicates the maximum severity experienced by each participant at any timepoint post baseline, including unscheduled assessments. 
2 Severity grade of “None” refers to results within the site reference range, or results outside of the site reference range that do not meet the Grade 1 criteria as 
defined by the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical 
Trials (2007). 
 

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Table 14: 
Laboratory Results Maximum Severity Post-Baseline by Dose Group, Hematology – Safety Population 
This table will be repeated for the pooled safety dose groups. 
Parameter/ 
Maximum Severity 
Post-Baseline1 
[Safety Group 1] 
(N=X) 
[Safety Group 2] 
(N=X) 
[Safety Group 3] 
(N=X) 
[Safety Group 4] 
(N=X) 
[Safety Group 5] 
(N=X) 
[Safety Group 6] 
(N=X) 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
Any Hematology Parameter 
None2 
x (xx.x) 
xx.x, 
xx.x 
x (xx.x) 
xx.x, 
xx.x 
x (xx.x) 
xx.x, 
xx.x 
x (xx.x) 
xx.x, 
xx.x 
x (xx.x) 
xx.x, 
xx.x 
x (xx.x) 
xx.x, 
xx.x 
Grade 1 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 2 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 3 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 4 
  
  
  
  
  
  
  
  
  
  
  
  
Missing 
  
  
  
  
  
  
  
  
  
  
  
  
Repeat for:  
White Blood Cells, 
Decrease 
  
  
  
  
  
  
  
  
  
  
  
  
White Blood Cells, 
Increase 
  
  
  
  
  
  
  
  
  
  
  
  
Neutrophils, Decrease 
  
  
  
  
  
  
  
  
  
  
  
  
Lymphocytes, 
Decrease 
  
  
  
  
  
  
  
  
  
  
  
  
Eosinophils, Increase 
  
  
  
  
  
  
  
  
  
  
  
  
Hemoglobin, 
Decrease 
  
  
  
  
  
  
  
  
  
  
  
  
Hematocrit, Decrease 
  
  
  
  
  
  
  
  
  
  
  
  
Platelets, Decrease 
  
  
  
  
  
  
  
  
  
  
  
  
Notes: N = Number of participants in the safety analysis population with available results. 
n (%) = Number and percent of participants with a reported event (% of N). 
95% CI = Exact Clopper-Pearson 95% confidence interval for the percent. 
1 “Maximum Post Baseline” indicates the maximum severity experienced by each participant at any timepoint post baseline, including unscheduled assessments. 
2 Severity grade of “None” refers to results within the site reference range, or results outside of the site reference range that do not meet the Grade 1 criteria as 
defined by the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical 
Trials (2007). 
 

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Table 15: 
Laboratory Results Maximum Severity Post-Baseline by Dose Group, Urinalysis – Safety Population 
Parameter/ 
Maximum Severity 
Post-Baseline1 
[Safety Group 1] 
(N=X) 
[Safety Group 2] 
(N=X) 
[Safety Group 3] 
(N=X) 
[Safety Group 4] 
(N=X) 
[Safety Group 5] 
(N=X) 
[Safety Group 6] 
(N=X) 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
Any Urinalysis Parameter 
None 
x (xx.x) 
xx.x, 
xx.x 
x (xx.x) 
xx.x, 
xx.x 
x (xx.x) 
xx.x, 
xx.x 
x (xx.x) 
xx.x, 
xx.x 
x (xx.x) 
xx.x, 
xx.x 
x (xx.x) 
xx.x, 
xx.x 
Grade 1 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 2 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 3 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 4 
  
  
  
  
  
  
  
  
  
  
  
  
Missing 
  
  
  
  
  
  
  
  
  
  
  
  
Repeat for:  
Red Blood Cells, 
Increase 
  
  
  
  
  
  
  
  
  
  
  
  
Protein, Increase 
  
  
  
  
  
  
  
  
  
  
  
  
Notes: N = Number of participants in the safety analysis population with available results. 
n (%) = Number and percent of participants with a reported event (% of N). 
95% CI = Exact Clopper-Pearson 95% confidence interval for the percent. 
1 “Maximum Post Baseline” indicates the maximum severity experienced by each participant at any timepoint post baseline, including unscheduled assessments. 
  

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Table 16: 
Vital Sign Results Maximum Severity Post-Baseline by Dose Group – Safety Population 
This table will be repeated for the pooled safety dose groups. 
Parameter/ 
Maximum Severity 
Post-Baseline1 
[Safety Group 1] 
(N=X) 
[Safety Group 2] 
(N=X) 
[Safety Group 3] 
(N=X) 
[Safety Group 4] 
(N=X) 
[Safety Group 5] 
(N=X) 
[Safety Group 6] 
(N=X) 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
Any VS Parameter 
None 
x (xx.x) 
xx.x, 
xx.x 
x (xx.x) 
xx.x, 
xx.x 
x (xx.x) 
xx.x, 
xx.x 
x (xx.x) 
xx.x, 
xx.x 
x (xx.x) 
xx.x, 
xx.x 
x (xx.x) 
xx.x, 
xx.x 
Grade 1 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 2 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 3 
  
  
  
  
  
  
  
  
  
  
  
  
Grade 4 
  
  
  
  
  
  
  
  
  
  
  
  
Missing 
  
  
  
  
  
  
  
  
  
  
  
  
Repeat for:  
Pulse, Decrease 
  
  
  
  
  
  
  
  
  
  
  
  
Pulse, Increase 
  
  
  
  
  
  
  
  
  
  
  
  
Respiratory Rate, 
Increase 
  
  
  
  
  
  
  
  
  
  
  
  
Systolic Blood 
Pressure, Decrease 
  
  
  
  
  
  
  
  
  
  
  
  
Systolic Blood 
Pressure, Increase 
  
  
  
  
  
  
  
  
  
  
  
  
Diastolic Blood 
Pressure, Increase 
  
  
  
  
  
  
  
  
  
  
  
  
Temperature, 
Increase 
  
  
  
  
  
  
  
  
  
  
  
  
Notes: N = Number of participants in the safety analysis population with available results. 
n (%) = Number and percent of participants with a reported event (% of N). 
95% CI = Exact Clopper-Pearson 95% confidence interval for the percent. 
1 “Maximum Post Baseline” indicates the maximum severity experienced by each participant at any timepoint post baseline, including unscheduled assessments. 

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Table 17: 
Summary of Participants with Concurrent Medications by WHO Drug Classification – Safety Population 
WHO Drug Code 
Level 1, Anatomic Group /  
Level 2, Therapeutic Subgroup 
[Safety Group 1] 
(N=X) 
[Safety Group 2] 
(N=X) 
[Safety Group 3] 
(N=X) 
[Safety Group 4] 
(N=X) 
[Safety Group 5] 
(N=X) 
[Safety Group 6] 
(N=X) 
All Participants 
(N=X) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Any Level 1 Codes 
Any Level 2 Codes 
x (xx.x) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
[ATC Level 1 - 1] 
Any [ATC 1 - 1] 
  
  
  
  
  
  
  
ATC [2 -1] 
  
  
  
  
  
  
  
ATC [2 -2] 
  
  
  
  
  
  
  
ATC [2 -3] 
  
  
  
  
  
  
  
[ATC Level 1 - 2] 
ATC [2 -1] 
  
  
  
  
  
  
  
ATC [2 -2] 
  
  
  
  
  
  
  
ATC [2 -3] 
  
  
  
  
  
  
  
Note: N = Number of participants in the Safety Population. 
 
 

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Pharmacokinetics 
Table 18: 
Summary of C144-LS and C135-LS Concentrations in Serum by Dose 
Group: All Timepoints, PK Population – SC Dose Groups 
 
Nominal Timea (h) 
Mean (SD) 
C144-LS 
C135-LS 
[PK SC Group 1] 
(N=X) 
[PK SC Group 2] 
(N=X) 
[PK SC Group 1] 
(N=X) 
[PK SC Group 2] 
(N=X) 
D0 - prior to IP 
Administration  
x (x.x) [n] 
x (x.x) [n] 
x (x.x) [n] 
x (x.x) [n] 
D0 - 1 h post end of 
IP Administration 
 
 
 
 
D0 - 3 h post end of 
IP Administration 
 
 
 
 
D0 - 6 h post end of 
IP Administration 
 
 
 
 
D0 - 9 h post end of 
IP Administration 
 
 
 
 
D0 - 12 h post end of 
IP Administration 
 
 
 
 
D1 
 
 
 
 
D3 
 
 
 
 
D7 
 
 
 
 
D14 
 
 
 
 
D21 
 
 
 
 
D28 
 
 
 
 
W8 
 
 
 
 
W12 
 
 
 
 
W18 
 
 
 
 
W24 
 
 
 
 
W36 
 
 
 
 
W48 
 
 
 
 
Notes:  
N = Number of participants in the PK population in each dose group.  
Mean concentration at each timepoint is reported in units of µg/mL. SD is reported in parentheses next to the mean. The 
number of data points used to compute summary statistics at each time point are included in brackets. All BQL values 
were treated as missing. 
a Times are relative to time of dosing. 
 

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Table 19: 
Summary of C144-LS and C135-LS Concentrations in Serum by Dose 
Group: All Timepoints, PK Population – IV Dose Groups 
Nominal Timea (h) 
Mean (SD) 
C144-LS 
C135-LS 
[PK IV 
Group 1] 
[PK IV 
Group 2] 
[PK IV 
Group 3] 
[PK IV 
Group 1] 
[PK IV 
Group 2] 
[PK IV 
Group 3] 
(N=X) 
(N=X) 
(N=X) 
(N=X) 
(N=X) 
(N=X) 
D0 - prior to C144-LS Infusion 
x (x.x) [n] 
x (x.x) [n] 
x (x.x) [n] 
x (x.x) [n] 
x (x.x) [n] 
x (x.x) [n] 
D0 - end of C144-LS Infusion 
(prior to C135-LS Infusion) 
  
  
  
  
  
  
D0 - end of C135-LS Infusion 
  
  
  
  
  
  
D0 - 1 h post end of IP 
Administration 
  
  
  
  
  
  
D0 - 3 h post end of IP 
Administration 
  
  
  
  
  
  
D0 - 6 h post end of IP 
Administration 
  
  
  
  
  
  
D0 - 9 h post end of IP 
Administration 
 
 
 
 
 
 
D0 - 12 h post end of IP 
Administration 
  
  
  
  
  
  
D1 
  
  
  
  
  
  
D3 
  
  
  
  
  
  
D7 
  
  
  
  
  
  
D14 
  
  
  
  
  
  
D21 
  
  
  
  
  
  
D28 
  
  
  
  
  
  
W8 
  
  
  
  
  
  
W12 
  
  
  
  
  
  
W18 
  
  
  
  
  
  
W24 
  
  
  
  
  
  
W36 
 
 
 
 
 
 
W48 
 
 
 
 
 
 
Notes:  
N = Number of participants in the PK population in each dose group.  
Mean concentration at each timepoint is reported in units of µg/mL. SD is reported in parentheses next to the mean. The 
number of data points used to compute summary statistics at each time point are included in brackets. All BQL values 
were treated as missing. 
a Times are relative to time of dosing. 
 

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Table 20: 
Summary Statistics of Serum PK Parameters by Dose Group, PK Population – SC Dose Groups 
PK Parameter (Units) 
C144-LS 
C135-LS 
PK SC Group 1  
(N=X) 
PK SC Group 2 
(N=X) 
PK SC Group 1  
(N=X) 
PK SC Group 2 
(N=X) 
Cmax, (µg/mL) 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
Tmax, (h) 
x (x - x) [n] 
x (x - x) [n] 
x (x - x) [n] 
x (x - x) [n] 
AUC(0-T), (µg*day/mL)  
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
AUC(INF), (µg*day/mL)  
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
λz, (1/day) 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
T-HALF, (day) 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
CLT/F, (mL/day)  
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
Vz/F, (L)  
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
Notes: N = Number of participants included in the PK analysis population for each group.  
Values of GM (CV %) [n] are shown, except for Tmax for which values of median (min-max) are shown and T-HALF for which 
values of mean (SD) are shown. n represents the number of data points used to compute the summary statistics.  
Terminal phase parameters were excluded from summary statistics if the R squared adjusted was < 0.9. AUC(INF), clearance, and 
volume parameters were excluded if the percentage of AUC(INF) obtained by extrapolation was > 20%.  
 
 
 

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Table 21: 
Summary Statistics of Serum PK Parameters by Dose Group, PK Population – IV Dose Groups  
PK Parameter (Units) 
C144-LS 
C135-LS 
PK IV Group 1  
(N=X) 
PK IV Group 2 
(N=X) 
PK IV Group 3 
(N=X) 
PK IV Group 1  
(N=X) 
PK IV Group 2 
(N=X) 
PK IV Group 3 
(N=X) 
Cmax, (µg/mL) 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
Tmax, (h) 
x (x - x) [n] 
x (x - x) [n] 
x (x - x) [n] 
x (x - x) [n] 
x (x - x) [n] 
x (x - x) [n] 
AUC(0-T), (µg*day/mL)  
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
AUC(INF), (µg*day/mL)  
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
λz, (1/day) 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
T-HALF, (day) 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
CLT (mL/day) 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
Vss (L) 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
x (x) [n] 
Notes: N = Number of participants included in the PK analysis population for each group.  
Values of GM (CV %) [n] are shown, except for Tmax for which values of median (min-max) are shown and T-HALF for which values of mean (SD) 
are shown. n represents the number of data points used to compute the summary statistics.  
Terminal phase parameters were excluded from summary statistics if the R squared adjusted was < 0.9. AUC(INF), clearance, and volume parameters 
were excluded if the percentage of AUC(INF) obtained by extrapolation was > 20%. 
 

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Table 22: 
Summary Statistics for Dose Adjusted Exposure Parameters, PK Population – SC Dose Groups 
mAb/Dose Adjusted  
Exposure Parameter 
Dose 
Group 
N 
Mean 
SD 
Median 
Min 
Max 
GM 
CV % 
C144-LS 
AUC(0-T)/Dose, (µg*day/mg*mL) 
SC1 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
 
SC2 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
AUC(INF)/Dose, (µg*day/mg*mL) 
SC1 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
 
SC2 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
Cmax/Dose, (µg/mg*mL) 
SC1 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
 
SC2 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
C135-LS 
AUC(0-T)/Dose, (µg*day/mg*mL) 
SC1 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
 
SC2 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
AUC(INF)/Dose, (µg*day/mg*mL) 
SC1 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
 
SC2 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
Cmax/Dose, (µg/mg*mL) 
SC1 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
 
SC2 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
Notes:  
N = Number of data points used to compute the summary statistics.  
GM=geometric mean, CV=coefficient of variation. 
 
 
 

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Table 23: 
Summary Statistics for Dose Adjusted Exposure Parameters, PK Population – IV Dose Groups 
mAb/Dose Adjusted 
Exposure Parameter 
Dose 
Group 
N 
Mean 
SD 
Median 
Min 
Max 
GM 
CV % 
C144-LS 
AUC(0-T)/Dose, 
(µg*day/mg*mL/kg) 
IV1 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
IV2 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
IV3 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
AUC(INF)/Dose, 
(µg*day/mg*mL/kg) 
IV1 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
IV2 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
IV3 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
Cmax/Dose, (µg/mg*mL/kg) 
IV1 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
IV2 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
IV3 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
C135-LS 
AUC(0-T)/Dose, 
(µg*day/mg*mL/kg) 
IV1 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
IV2 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
IV3 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
AUC(INF)/Dose, 
(µg*day/mg*mL/kg) 
IV1 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
IV2 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
IV3 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
Cmax/Dose, (µg/mg*mL/kg) 
IV1 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
IV2 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
IV3 
x 
x.x 
x.x 
x.x 
x 
x 
x.x 
x.x 
Notes: 
N = Number of data points used to compute the summary statistics. 
GM=geometric mean, CV=coefficient of variation. 
 

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Table 24: 
Comparison of Exposure Parameters Between Dose Groups, Pairwise 
Comparisons, PK Population – All PK Dose Groups 
Exposure 
Parameter/Comparison 
Dose Ratio 
C144-LS 
C135-LS 
Estimate 
90% CI1 
Estimate 
90% CI1 
AUC(0-T) 
SC2/SC1 
x.xx 
x.xx 
(x.xx, x.xx) 
x.xx 
(x.xx, x.xx) 
IV2/IV1 
  
  
  
  
  
IV3/IV1 
  
  
  
  
  
IV3/IV2 
  
  
  
  
  
AUC(INF) 
SC2/SC1 
  
  
  
  
  
IV2/IV1 
  
  
  
  
  
IV3/IV1 
  
  
  
  
  
IV3/IV2 
  
  
  
  
  
Cmax 
SC2/SC1 
  
  
  
  
  
IV2/IV1 
  
  
  
  
  
IV3/IV1 
  
  
  
  
  
IV3/IV2 
  
  
  
  
  
Notes: 
n = Number of participants in the PK analysis group subset with results included in the ANOVA test comparison. 
1 Student’s t-distribution was used to estimate 90% confidence intervals for the SC dose group comparisons. 
ANOVA pairwise comparisons using Tukey's correction for multiple hypotheses was used to estimate the 90% 
confidence intervals for the IV dose group comparisons.  
 
 
Table 25: 
Power Model Coefficient Estimates from Dose Proportionality Assessment 
Among IV Dose Groups – PK Population 
Exposure Parameter 
C144-LS 
C135-LS 
Estimate 
95% CI 
Estimate 
95% CI 
AUC(0-T) 
x 
x.xx, x.xx 
x 
x.xx, x.xx 
AUC(INF) 
  
  
  
  
Cmax 
  
  
  
  
Note: A β power coefficient estimate of 1 is consistent with dose proportionality. 
 

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Immunogenicity 
 
Table 26: 
Summary of Confirmed Positive Anti-Drug Antibody Results, C144-LS - Immunogenicity Population 
Study Day 
[Immunogenicity 
Group 1] 
100 mg, SC 
 (S1) 
(N=X) 
[Immunogenicity 
Group 2] 
200 mg, SC 
 (S2 + S3 Active) 
(N=X) 
[Immunogenicity 
Group 3]  
1.5 mg/kg, IV  
(V1) 
(N=X) 
[Immunogenicity 
Group 4] 
5 mg/kg, IV  
(V2) 
(N=X) 
[Immunogenicity 
Group 5] 
15 mg/kg, IV  
(V3) 
(N=X) 
[Immunogenicity 
Group 6] 
Placebo 
 
(N=X) 
D0 (Baseline) 
x/x (xx.x) 
x/x (xx.x) 
x/x (xx.x) 
x/x (xx.x) 
x/x (xx.x) 
x/x (xx.x) 
D28 
 
 
 
 
 
 
W12 
 
 
 
 
 
 
W24 
 
 
 
 
 
 
W48 
 
 
 
 
 
 
Any Post-Baseline 
Timepoint 
x/x (xx.x) 
x/x (xx.x) 
x/x (xx.x) 
x/x (xx.x) 
x/x (xx.x) 
x/x (xx.x) 
N=the number of participants in the C144-LS Immunogenicity Population in each dose group. 
Result numerators displayed represent the number of confirmed positive anti-C144-LS antibody samples within each dose group at each study day. Denominators 
represent the total number of samples tested for ADA within each dose group at each study day. The corresponding percentage is displayed in parentheses for each 
dose group and study day. 
An ADA positive sample at baseline is defined as: ADA detected in the Day 0 sample, before IP administration. 
An ADA positive sample post-baseline is defined as: (1) an ADA detected (positive seroconversion) sample in a participant for whom ADA is not detected at baseline, 
or (2) an ADA detected sample with an increase of at least 4-fold in ADA titer from baseline. 
 
 
Table 27: 
Summary of Confirmed Positive Anti-Drug Antibody Results, C135-LS - Immunogenicity Population 
This table will repeat the above table for C135-LS. 
 

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Table 28: 
Summary of Anti-Drug Antibody Participant Results, C144-LS - Immunogenicity Population 
ADA Result 
Participant 
ADA Response 
Type 
[Immunogenicity 
Group 1] 
100 mg, SC 
 (S1) 
(N=X) 
[Immunogenicity 
Group 2] 
 200 mg, SC 
 (S2 + S3 Active) 
(N=X) 
[Immunogenicity 
Group 3]  
1.5 mg/kg, IV  
(V1) 
(N=X) 
[Immunogenicity 
Group 4] 
 5 mg/kg, IV  
(V2) 
(N=X) 
[Immunogenicity 
Group 5] 
 15 mg/kg, IV  
(V3) 
(N=X) 
[Immunogenicity 
Group 6] 
 Placebo 
 
(N=X) 
Baseline ADA 
Positive 
- 
x (xx.x) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
ADA Positive 
Persistent 
Positive 
  
  
  
  
  
  
Not PP-Last 
Sample Positive 
  
  
  
  
  
  
Other Positive 
  
  
  
  
  
  
ADA Negative 
- 
  
  
  
  
  
  
N=the number of participants in the C144-LS Immunogenicity Population in each dose group. 
Result numbers displayed represent the number of participants contributing each ADA response type. N was used as the percent denominator. The corresponding 
percentage is displayed in parentheses for each dose group. 
Persistent Positive (PP): A participant with an ADA-positive sample at 2 or more consecutive timepoints where the first and last consecutive ADA-positive samples are 
at least 16 weeks apart. 
Not PP-Last Sample Positive: A participant who is not persistent positive with ADA-positive sample at the last sampling timepoint.  
Other Positive: A participant who is not persistent positive but with some ADA-positive sample and with the last sample being ADA negative. 
 
 
Table 29: 
Summary of Anti-Drug Antibody Participant Results, C135-LS - Immunogenicity Population 
This table will repeat the above table for C135-LS. 
 

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Table 30: 
Summary of Anti-Drug Antibody Titration Results and Fold Rise from Baseline, C144-LS - Immunogenicity 
Population 
Study Day 
Statistic 
[Immunogenicity 
Group 1] 
100 mg, SC  
(S1) 
(N=X) 
[Immunogenicity 
Group 2] 
200 mg, SC  
(S2 + S3 Active) 
(N=X) 
[Immunogenicity 
Group 3]  
1.5 mg/kg, IV  
(V1) 
(N=X) 
[Immunogenicity 
Group 4] 
5 mg/kg, IV  
(V2) 
(N=X) 
[Immunogenicity 
Group 5] 
15 mg/kg, IV  
(V3) 
(N=X) 
[Immunogenicity 
Group 6] 
Placebo 
 
(N=X) 
D0 (Baseline) 
n 
x 
 
 
 
 
 
  
GMT 
xxx.x 
 
 
 
 
 
  
95% CI 
(xxx.x, xxx.x) 
 
 
 
 
 
D28 
n 
x 
 
 
 
 
 
  
GMT 
xxx.x 
 
 
 
 
 
  
95% CI 
(xxx.x, xxx.x) 
 
 
 
 
 
W12 
… 
 
 
 
 
 
 
W24 
… 
 
 
 
 
 
 
W48 
… 
 
 
 
 
 
 
Peak Titer Post-
Baseline 
… 
 
 
 
 
 
 
GMT=Geometric Mean Titer 
N=the number of participants in the C144-LS Immunogenicity Population in each dose group. 
n=the number of samples with quantifiable titration results in each dose group at each sample timepoint. 
Titration results which were positive for ADA but have titers below the minimum required dilution (100) were analyzed as 50. Titration results which were negative for the 
presence of ADA were analyzed as 1. 
 
 
Table 31: 
Summary of Anti-Drug Antibody Titration Results and Fold Rise from Baseline, C135-LS - Immunogenicity 
Population 
This table will repeat the above table for C135-LS. 
 
 

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APPENDIX 2. FIGURE MOCK-UPS 
LIST OF FIGURES 
Figure 1: 
CONSORT Flow Diagram.................................................................................................................... 70 
Figure 2: 
Maximum Severity of Solicited Systemic Symptoms per Dose Group by Day Post IP 
Administration ...................................................................................................................................... 71 
Figure 3: 
Maximum Severity of Solicited Local Symptoms per Dose Group by Day Post IP Administration .... 72 
Figure 4: 
Proportion of Participants with Related Adverse Events by MedDRA® System Organ Class and 
Maximum Severity ............................................................................................................................... 73 
Figure 5: 
Frequency of Related Adverse Events by MedDRA® System Organ Class and Maximum 
Severity ................................................................................................................................................. 74 
Figure 6: 
Chemistry Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group 
– Creatinine ........................................................................................................................................... 75 
Figure 7: 
Chemistry Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group 
–Glucose ............................................................................................................................................... 76 
Figure 8: 
Chemistry Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group 
–Total Bilirubin .................................................................................................................................... 76 
Figure 9: 
Chemistry Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group 
–Direct Bilirubin ................................................................................................................................... 76 
Figure 10: 
Chemistry Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group 
–Alkaline Phosphatase .......................................................................................................................... 76 
Figure 11: 
Chemistry Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group 
–AST ..................................................................................................................................................... 76 
Figure 12: 
Chemistry Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group 
–ALT .................................................................................................................................................... 76 
Figure 13: 
Hematology Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose 
Group –WBC ........................................................................................................................................ 76 
Figure 14: 
Hematology Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose 
Group –Neutrophils .............................................................................................................................. 76 
Figure 15: 
Hematology Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose 
Group –Lymphocytes ........................................................................................................................... 76 
Figure 16: 
Hematology Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose 
Group –Monocytes ............................................................................................................................... 76 
Figure 17: 
Hematology Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose 
Group –Eosinophils .............................................................................................................................. 77 
Figure 18: 
Hematology Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose 
Group –Basophils ................................................................................................................................. 77 
Figure 19: 
Hematology Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose 
Group –Hemoglobin ............................................................................................................................. 77 
Figure 20: 
Hematology Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose 
Group –Hematocrit ............................................................................................................................... 77 
Figure 21: 
Hematology Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose 
Group –Platelets.................................................................................................................................... 77 
Figure 22: 
Vital Sign Results by Scheduled Visits: Mean Change from Baseline by Dose Group –Pulse at 
Screening, Baseline to Day 1 ................................................................................................................ 78 
Figure 23: 
Vital Sign Results by Scheduled Visits: Mean Change from Baseline by Dose Group –Pulse, 
Entire Study Period ............................................................................................................................... 79 
Figure 24: 
Vital Sign Results by Scheduled Visits: Mean Change from Baseline by Dose Group –
Respiration Rate at Screening, Baseline to Day 1 ................................................................................ 80 
Figure 25: 
Vital Sign Results by Scheduled Visits: Mean Change from Baseline by Dose Group –
Respiration Rate, Entire Study Period .................................................................................................. 80 
Figure 26: 
Vital Sign Results by Scheduled Visits: Mean Change from Baseline by Dose Group – Systolic 
Blood Pressure at Screening, Baseline to Day 1 ................................................................................... 80 

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Figure 27: 
Vital Sign Results by Scheduled Visits: Mean Change from Baseline by Dose Group – Systolic 
Blood Pressure, Entire Study Period ..................................................................................................... 80 
Figure 28: 
Vital Sign Results by Scheduled Visits: Mean Change from Baseline by Dose Group – Diastolic 
Blood Pressure at Screening, Baseline to Day 1 ................................................................................... 80 
Figure 29: 
Vital Sign Results by Scheduled Visits: Mean Change from Baseline by Dose Group – Diastolic 
Blood Pressure, Entire Study Period ..................................................................................................... 80 
Figure 30: 
Vital Sign Results by Scheduled Visits: Mean Change from Baseline by Dose Group –
Temperature at Screening, Baseline to Day 1 ....................................................................................... 80 
Figure 31: 
Vital Sign Results by Scheduled Visits: Mean Change from Baseline by Dose Group –
Temperature, Entire Study Period ......................................................................................................... 80 
Figure 32: 
Overlay of Individual C144-LS Concentration in Serum Profiles by Dose Group, Baseline to 72 h 
Post IP Administration – PK Population – SC Group 1 ........................................................................ 81 
Figure 33: 
Overlay of Individual C144-LS Concentration in Serum Profiles by Dose Group, All Timepoints- 
PK Population – SC Group 1 ................................................................................................................ 82 
Figure 34: 
Overlay of Individual C144-LS Concentration in Serum Profiles by Dose Group, Baseline to 72 h 
Post IP Admin – PK Population – SC Group 2 ..................................................................................... 82 
Figure 35: 
Overlay of Individual C144-LS Concentration in Serum Profiles by Dose Group, All Timepoints- 
PK Population – SC Group 2 ................................................................................................................ 82 
Figure 36: 
Overlay of Individual C144-LS Concentration in Serum Profiles by Dose Group, Baseline to 72 h 
Post IP Admin – PK Population – IV Group 1 ..................................................................................... 82 
Figure 37: 
Overlay of Individual C144-LS Concentration in Serum Profiles by Dose Group, All Timepoints- 
PK IV Group 1 ...................................................................................................................................... 82 
Figure 38: 
Overlay of Individual C144-LS Concentration in Serum Profiles by Dose Group, Baseline to 72 h 
Post IP Admin – PK Population – IV Group 2 ..................................................................................... 82 
Figure 39: 
Overlay of Individual C144-LS Concentration in Serum Profiles by Dose Group, All Timepoints- 
PK Population – IV Group 2 ................................................................................................................. 82 
Figure 40: 
Overlay of Individual C144-LS Concentration in Serum Profiles by Dose Group, Baseline to 72 h 
Post IP Admin – PK Population – IV Group 3 ..................................................................................... 82 
Figure 41: 
Overlay of Individual C144-LS Concentration in Serum Profiles by Dose Group, All Timepoints- 
PK Population – IV Group 3 ................................................................................................................. 82 
Figure 42: 
Overlay of Individual C135-LS Concentration in Serum Profiles by Dose Group, Baseline to 72 h 
Post IP Admin – PK Population – SC Group 1 ..................................................................................... 82 
Figure 43: 
Overlay of Individual C135-LS Concentration in Serum Profiles by Dose Group, All Timepoints- 
PK Population – SC Group 1 ................................................................................................................ 82 
Figure 44: 
Overlay of Individual C135-LS Concentration in Serum Profiles by Dose Group, Baseline to 72 h 
Post IP Admin – PK Population – SC Group 2 ..................................................................................... 83 
Figure 45: 
Overlay of Individual C135-LS Concentration in Serum Profiles by Dose Group, All Timepoints- 
PK Population – SC Group 2 ................................................................................................................ 83 
Figure 46: 
Overlay of Individual C135-LS Concentration in Serum Profiles by Dose Group, Baseline to 72 h 
Post IP Admin – PK Population – IV Group 1 ..................................................................................... 83 
Figure 47: 
Overlay of Individual C135-LS Concentration in Serum Profiles by Dose Group, All Timepoints- 
PK Population – IV Group 1 ................................................................................................................. 83 
Figure 48: 
Overlay of Individual C135-LS Concentration in Serum Profiles by Dose Group, Baseline to 72 h 
Post IP Admin – PK Population – IV Group 2 ..................................................................................... 83 
Figure 49: 
Overlay of Individual C135-LS Concentration in Serum Profiles by Dose Group, All Timepoints- 
PK Population – IV Group 2 ................................................................................................................. 83 
Figure 50: 
Overlay of Individual C135-LS Concentration in Serum Profiles by Dose Group, Baseline to 72 h 
Post IP Admin – PK Population – IV Group 3 ..................................................................................... 83 
Figure 51: 
Overlay of Individual C135-LS Concentration in Serum Profiles by Dose Group, All Timepoints- 
PK Population – IV Group 3 ................................................................................................................. 83 
Figure 52: 
Mean (±SD) C144-LS Concentration in Serum Profiles by Dose Group, Baseline to 72 h Post IP 
Admin, PK Population .......................................................................................................................... 84 
Figure 53: 
Mean C144-LS Concentration in Serum Profiles by Dose Group, All Timepoints, PK Population ..... 84 

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Figure 54: 
Mean C135-LS Concentration in Serum Profiles by Dose Group, Baseline to 72 h Post IP Admin, 
PK Population ....................................................................................................................................... 84 
Figure 55: 
Mean C135-LS Concentration in Serum Profiles by Dose Group, All Timepoints, PK Population ..... 84 
Figure 56: 
Comparisons of Dose Adjusted Exposure Parameters, C144-LS, PK Population ................................ 85 
Figure 57: 
Comparisons of Dose Adjusted Exposure Parameters, C135-LS, PK Population ................................ 85 
Figure 58: 
Pairwise Comparison of PK Exposure Parameters, C144-LS, PK Population ..................................... 86 
Figure 59: 
Pairwise Comparison of PK Exposure Parameters, C135-LS, PK Population ..................................... 86 
Figure 60: 
Dose Proportionality Power Model Among IV Dose Groups, C144-LS, PK Population ..................... 87 
Figure 61: 
Dose Proportionality Power Model Among IV Dose Groups, C135-LS, PK Population ..................... 87 
Figure 62: 
Summary Boxplots of Anti-Drug Antibody Titration Results by Study Visit, C144-LS, 
Immunogenicity Population – SC Dose Groups ................................................................................... 88 
Figure 63: 
Summary Boxplots of Anti-Drug Antibody Titration Results by Study Visit, C144-LS, 
Immunogenicity Population – IV Dose Groups .................................................................................... 89 
Figure 64: 
Summary Boxplots of Anti-Drug Antibody Titration Results by Study Visit, C135-LS, 
Immunogenicity Population – SC Dose Groups ................................................................................... 89 
Figure 65: 
Summary Boxplots of Anti-Drug Antibody Titration Results by Study Visit, C135-LS, 
Immunogenicity Population – IV Dose Groups .................................................................................... 89 
 
 

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Figure 1: 
CONSORT Flow Diagram 
 
Assessed for Eligibility  
(n=x) 
Excluded* (n=x) 
• 
[Reason 1] (n=x) 
• 
Concern of potential risk (n=x) 
Analysed for Safety (n=x) 
♦ Excluded from safety analyses 
(n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for PK (n=x) 
♦ Excluded from PK analyses  
(n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for Immunogenicity (n=x) 
♦ Excluded from Immunogenicity 
(ADA) analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Enrolled/Randomized  
(n=x) 
Enrollment 
Analysis 
Analysed for Safety (n=x) 
♦ Excluded from safety analyses 
(n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for PK (n=x) 
♦ Excluded from PK analyses  
(n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for Immunogenicity (n=x) 
♦ Excluded from Immunogenicity 
(ADA) analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analysed for Safety (n=x) 
♦ Excluded from safety analyses 
(n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for PK (n=x) 
♦ Excluded from PK analyses  
(n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for Immunogenicity (n=x) 
♦ Excluded from Immunogenicity 
(ADA) analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analysed for Safety (n=x) 
♦ Excluded from safety analyses 
(n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for PK (n=x) 
♦ Excluded from PK analyses  
(n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for Immunogenicity (n=x) 
♦ Excluded from Immunogenicity 
(ADA) analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Allocated to [Safety Group 1] 
(n=x) 
♦Received allocated IP (n=x) 
♦Did not receive allocated IP 
(n=x) 
[Reason 1] (x), [Reason 2] (x) 
Allocation 
Allocated to [Safety Group 2] 
(n=x) 
♦Received allocated IP (n=x) 
♦Did not receive allocated IP 
(n=x) 
Allocated to [Safety Group 3] 
(n=x) 
♦Received allocated IP (n=x) 
♦Did not receive allocated IP 
(n=x) 
Allocated to [Safety Group 4] 
(n=x) 
♦Received allocated IP (n=x) 
♦Did not receive allocated IP 
(n=x) 
[Reason 1] (x), [Reason 2] (x) 
Allocated to [Safety Group 5] 
(n=x) 
♦Received allocated IP (n=x) 
♦Did not receive allocated IP 
(n=x) 
Allocated to [Safety Group 6] 
(n=x) 
♦Received allocated IP (n=x) 
♦Did not receive allocated IP 
(n=x) 
Analysed for Safety (n=x) 
♦ Excluded from safety analyses 
(n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for PK (n=x) 
♦ Excluded from PK analyses  
(n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for Immunogenicity (n=x) 
♦ Excluded from Immunogenicity 
(ADA) analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analysed for Safety (n=x) 
♦ Excluded from safety analyses 
(n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for PK (n=x) 
♦ Excluded from PK analyses  
(n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for Immunogenicity (n=x) 
♦ Excluded from Immunogenicity 
(ADA) analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Follow-Up 
IP Administration Interrupted 
(n=x) 
♦[Reason 1] (x), [Reason 2] (x) 
Early Termination (n=x) 
♦[Reason 1] (x), [Reason 2] (x) 
IP Administration Interrupted 
(n=x) 
♦[Reason 1] (x), [Reason 2] (x) 
Early Termination (n=x) 
♦[Reason 1] (x), [Reason 2] (x) 
IP Administration Interrupted 
(n=x) 
♦[Reason 1] (x), [Reason 2] (x) 
Early Termination (n=x) 
♦[Reason 1] (x), [Reason 2] (x) 
IP Administration Interrupted 
(n=x) 
♦[Reason 1] (x), [Reason 2] (x) 
Early Termination (n=x) 
♦[Reason 1] (x), [Reason 2] (x) 
IP Administration Interrupted 
(n=x) 
♦[Reason 1] (x), [Reason 2] (x) 
Early Termination (n=x) 
♦[Reason 1] (x), [Reason 2] (x) 
IP Administration Interrupted 
(n=x) 
♦[Reason 1] (x), [Reason 2] (x) 
Early Termination (n=x) 
♦[Reason 1] (x), [Reason 2] (x) 

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Safety Figures 
Figure 2: 
Maximum Severity of Solicited Systemic Symptoms per Dose Group by Day Post IP Administration 
 
 

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Figure 3: 
Maximum Severity of Solicited Local Symptoms per Dose Group by Day Post IP Administration 
 
 

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14.3.1.2 
Unsolicited Adverse Events 
Figure 4: 
Proportion of Participants with Related Adverse Events by MedDRA® System Organ Class and Maximum 
Severity 
 
 

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Figure 5: 
Frequency of Related Adverse Events by MedDRA® System Organ Class and Maximum Severity  
 
 

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Figure 6: 
Chemistry Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group – Creatinine 
 
 
 
0
mg/dL
-2.0
-1.5
-1.0
-0.5
0.0
0.5
1.0
1.5
2.0
IP Adm
Scheduled Visit and Week
Scr
D0
D1
D7
W8
W12
W24
W36
W48
*D0 timepoints represent the following visits, in order: post C144- LS, post IP Admin, 1 h post IP admin, 3 h post IP admin, 6 h post IP Admin, and 12 h post IP admin.
Dose Group
[Safety Group 1]
[Safety Group 2]
[Safety Group 3]
[Safety Group 4]
[Safety Group 5]
[Safety Group 6]

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Figure 7: 
Chemistry Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group –Glucose 
This figure will repeat Figure 6 for glucose. 
Figure 8: 
Chemistry Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group –Total 
Bilirubin 
This figure will repeat Figure 6 for total bilirubin. 
Figure 9: 
Chemistry Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group –Direct 
Bilirubin 
This figure will repeat Figure 6 for direct bilirubin. 
Figure 10: 
Chemistry Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group –Alkaline 
Phosphatase 
This figure will repeat Figure 6 for alkaline phosphatase. 
Figure 11: 
Chemistry Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group –AST 
This figure will repeat Figure 6 for AST. 
Figure 12: 
Chemistry Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group –ALT 
This figure will repeat Figure 6 for ALT. 
Figure 13: 
Hematology Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group –WBC 
This figure will repeat Figure 6 for white blood cells. 
Figure 14: 
Hematology Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group –Neutrophils 
This figure will repeat Figure 6 for neutrophils. 
Figure 15: 
Hematology Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group –
Lymphocytes 
This figure will repeat Figure 6 for lymphocytes. 
Figure 16: 
Hematology Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group –Monocytes 
This figure will repeat Figure 6 for monocytes. 

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Figure 17: 
Hematology Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group –Eosinophils 
This figure will repeat Figure 6 for eosinophils. 
Figure 18: 
Hematology Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group –Basophils 
This figure will repeat Figure 6 for basophils. 
Figure 19: 
Hematology Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group –
Hemoglobin  
This figure will repeat Figure 6 for hemoglobin. 
Figure 20: 
Hematology Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group –Hematocrit  
This figure will repeat Figure 6 for hematocrit. 
Figure 21: 
Hematology Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Dose Group –Platelets 
This figure will repeat Figure 6 for platelets. 
 

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Figure 22: 
Vital Sign Results by Scheduled Visits: Mean Change from Baseline by Dose Group –Pulse at Screening, 
Baseline to Day 1 
 
0
bpm
-2.0
-1.5
-1.0
-0.5
0.0
0.5
1.0
1.5
2.0
IP Adm
Scheduled Visit and Week
Scr
Baseline
Post C144-LS
Post IP Admin
1 h Post IP Admin
3 h Post IP Admin
6 h Post IP Admin
12 h Post IP Admin
*D0 timepoints represent the following visits, in order: post C144-LS, post IP Admin, 1 h post IP admin, 3 h post IP admin, 6 h post IP Admin, and 12 h post IP admin.
Dose Group
[Safety Group 1]
[Safety Group 2]
[Safety Group 3]
[Safety Group 4]
[Safety Group 5]
[Safety Group 6]

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Figure 23: 
Vital Sign Results by Scheduled Visits: Mean Change from Baseline by Dose Group –Pulse, Entire Study Period 
 
 
0
bpm
-2.0
-1.5
-1.0
-0.5
0.0
0.5
1.0
1.5
2.0
IP Adm
Scheduled Visit and Week
Scr
BL
D0*
D0*
D0*
D0*
D0*
D0*
D1
D3
D7
D14
D21
W4
W8
W12
W18
W24
W36
W48
*D0 timepoints represent the following visits, in order: post C144- LS, post IP Admin, 1 h post IP admin, 3 h post IP admin, 6 h post IP Admin, and 12 h post IP admin.
Dose Group
[Safety Group 1]
[Safety Group 2]
[Safety Group 3]
[Safety Group 4]
[Safety Group 5]
[Safety Group 6]

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Figure 24: 
Vital Sign Results by Scheduled Visits: Mean Change from Baseline by Dose Group –Respiration Rate at 
Screening, Baseline to Day 1 
This figure will repeat Figure 22 for respiration rate. 
Figure 25: 
Vital Sign Results by Scheduled Visits: Mean Change from Baseline by Dose Group –Respiration Rate, Entire 
Study Period 
This figure will repeat Figure 23 for respiration rate. 
Figure 26: 
Vital Sign Results by Scheduled Visits: Mean Change from Baseline by Dose Group – Systolic Blood Pressure at 
Screening, Baseline to Day 1 
This figure will repeat Figure 22 for systolic blood pressure. 
Figure 27: 
Vital Sign Results by Scheduled Visits: Mean Change from Baseline by Dose Group – Systolic Blood Pressure, 
Entire Study Period 
This figure will repeat Figure 23 for systolic blood pressure. 
Figure 28: 
Vital Sign Results by Scheduled Visits: Mean Change from Baseline by Dose Group – Diastolic Blood Pressure 
at Screening, Baseline to Day 1 
This figure will repeat Figure 22 for diastolic blood pressure. 
Figure 29: 
Vital Sign Results by Scheduled Visits: Mean Change from Baseline by Dose Group – Diastolic Blood Pressure, 
Entire Study Period 
This figure will repeat Figure 23 for diastolic blood pressure. 
Figure 30: 
Vital Sign Results by Scheduled Visits: Mean Change from Baseline by Dose Group –Temperature at Screening, 
Baseline to Day 1 
This figure will repeat Figure 22 for Temperature. 
Figure 31: 
Vital Sign Results by Scheduled Visits: Mean Change from Baseline by Dose Group –Temperature, Entire 
Study Period 
This figure will repeat Figure 23 for Temperature. 

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Pharmacokinetics 
 
Figure 32: 
Overlay of Individual C144-LS Concentration in Serum Profiles by Dose 
Group, Baseline to 72 h Post IP Administration – PK Population – 
SC Group 1  
 
 
 
 

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Figure 33: 
Overlay of Individual C144-LS Concentration in Serum Profiles by Dose 
Group, All Timepoints- PK Population – SC Group 1 
This figure will repeat Figure 32 for all PK sample timepoints.  
Figure 34: 
Overlay of Individual C144-LS Concentration in Serum Profiles by Dose 
Group, Baseline to 72 h Post IP Admin – PK Population – SC Group 2 
This figure will repeat Figure 32 for PK SC Group 2. 
Figure 35: 
Overlay of Individual C144-LS Concentration in Serum Profiles by Dose 
Group, All Timepoints- PK Population – SC Group 2 
This figure will repeat Figure 32 for all PK sample timepoints for PK SC Group 2. 
Figure 36: 
Overlay of Individual C144-LS Concentration in Serum Profiles by Dose 
Group, Baseline to 72 h Post IP Admin – PK Population – IV Group 1 
This figure will repeat Figure 32 for PK IV Group 1. 
Figure 37: 
Overlay of Individual C144-LS Concentration in Serum Profiles by Dose 
Group, All Timepoints- PK IV Group 1 
This figure will repeat Figure 32 for all PK sample timepoints for PK IV Group 1. 
Figure 38: 
Overlay of Individual C144-LS Concentration in Serum Profiles by Dose 
Group, Baseline to 72 h Post IP Admin – PK Population – IV Group 2 
This figure will repeat Figure 32 for PK IV Group 2. 
Figure 39: 
Overlay of Individual C144-LS Concentration in Serum Profiles by Dose 
Group, All Timepoints- PK Population – IV Group 2 
This figure will repeat Figure 32 for all PK sample timepoints for PK IV Group 2. 
Figure 40: 
Overlay of Individual C144-LS Concentration in Serum Profiles by Dose 
Group, Baseline to 72 h Post IP Admin – PK Population – IV Group 3 
This figure will repeat Figure 32 for PK IV Group 3. 
Figure 41: 
Overlay of Individual C144-LS Concentration in Serum Profiles by Dose 
Group, All Timepoints- PK Population – IV Group 3 
This figure will repeat Figure 32 for all PK sample timepoints for PK IV Group 3. 
Figure 42: 
Overlay of Individual C135-LS Concentration in Serum Profiles by Dose 
Group, Baseline to 72 h Post IP Admin – PK Population – SC Group 1 
This figure will repeat Figure 32 for PK SC Group 1 for C135-LS. 
Figure 43: 
Overlay of Individual C135-LS Concentration in Serum Profiles by Dose 
Group, All Timepoints- PK Population – SC Group 1 
This figure will repeat Figure 32 for all PK sample timepoints for PK SC Group 1 for C135-LS. 

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Figure 44: 
Overlay of Individual C135-LS Concentration in Serum Profiles by Dose 
Group, Baseline to 72 h Post IP Admin – PK Population – SC Group 2 
This figure will repeat Figure 32 for PK SC Group 2 for C135-LS. 
Figure 45: 
Overlay of Individual C135-LS Concentration in Serum Profiles by Dose 
Group, All Timepoints- PK Population – SC Group 2 
This figure will repeat Figure 32 for all PK sample timepoints for PK SC Group 2 for C135-LS. 
Figure 46: 
Overlay of Individual C135-LS Concentration in Serum Profiles by Dose 
Group, Baseline to 72 h Post IP Admin – PK Population – IV Group 1 
This figure will repeat Figure 32 for PK IV Group 1 for C135-LS. 
Figure 47: 
Overlay of Individual C135-LS Concentration in Serum Profiles by Dose 
Group, All Timepoints- PK Population – IV Group 1 
This figure will repeat Figure 32 for all PK sample timepoints for PK IV Group 1 for C135-LS. 
Figure 48: 
Overlay of Individual C135-LS Concentration in Serum Profiles by Dose 
Group, Baseline to 72 h Post IP Admin – PK Population – IV Group 2 
This figure will repeat Figure 32 for PK IV Group 2 for C135-LS. 
Figure 49: 
Overlay of Individual C135-LS Concentration in Serum Profiles by Dose 
Group, All Timepoints- PK Population – IV Group 2 
This figure will repeat Figure 32 for all PK sample timepoints for PK IV Group 2 for C135-LS. 
Figure 50: 
Overlay of Individual C135-LS Concentration in Serum Profiles by Dose 
Group, Baseline to 72 h Post IP Admin – PK Population – IV Group 3 
This figure will repeat Figure 32 for PK IV Group 3 for C135-LS. 
Figure 51: 
Overlay of Individual C135-LS Concentration in Serum Profiles by Dose 
Group, All Timepoints- PK Population – IV Group 3 
This figure will repeat Figure 32 for all PK sample timepoints for PK IV Group 3 for C135-LS. 
 
 
 

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Figure 52: 
Mean (±SD) C144-LS Concentration in Serum Profiles by Dose Group, 
Baseline to 72 h Post IP Admin, PK Population 
 
Figure 53: 
Mean C144-LS Concentration in Serum Profiles by Dose Group, All 
Timepoints, PK Population  
This figure will repeat Figure 52 for all PK sample timepoints.  
Figure 54: 
Mean C135-LS Concentration in Serum Profiles by Dose Group, Baseline to 
72 h Post IP Admin, PK Population  
This figure will repeat Figure 52 for all C135-LS concentrations.  
Figure 55: 
Mean C135-LS Concentration in Serum Profiles by Dose Group, All 
Timepoints, PK Population  
This figure will repeat Figure 52 for all C135-LS concentrations at all PK sample timepoints.  

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Figure 56: 
Comparisons of Dose Adjusted Exposure Parameters, C144-LS, PK 
Population  
 
 
Figure 57: 
Comparisons of Dose Adjusted Exposure Parameters, C135-LS, PK 
Population  
This figure will repeat Figure 56 for C135-LS. 

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Figure 58: 
Pairwise Comparison of PK Exposure Parameters, C144-LS, PK Population  
 
 
 
 
Figure 59: 
Pairwise Comparison of PK Exposure Parameters, C135-LS, PK Population  
This figure will repeat Figure 58 for C135-LS. 

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Figure 60: 
Dose Proportionality Power Model Among IV Dose Groups, C144-LS, PK 
Population  
 
Figure 61: 
Dose Proportionality Power Model Among IV Dose Groups, C135-LS, PK 
Population  
This figure will repeat Figure 60 for C135-LS. 

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Immunogenicity 
 
Figure 62: 
Summary Boxplots of Anti-Drug Antibody Titration Results by Study Visit, 
C144-LS, Immunogenicity Population – SC Dose Groups 
 
 
 

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Figure 63: 
Summary Boxplots of Anti-Drug Antibody Titration Results by Study Visit, 
C144-LS, Immunogenicity Population – IV Dose Groups 
Repeat Figure 62 for the IV dose groups.  
 
Figure 64: 
Summary Boxplots of Anti-Drug Antibody Titration Results by Study Visit, 
C135-LS, Immunogenicity Population – SC Dose Groups 
Repeat Figure 62 for the C135-LS. 
 
Figure 65: 
Summary Boxplots of Anti-Drug Antibody Titration Results by Study Visit, 
C135-LS, Immunogenicity Population – IV Dose Groups 
Repeat Figure 62 for the C135-LS and IV dose groups.  
 

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APPENDIX 3. LISTINGS MOCK-UPS 
LISTINGS 
Listing 1: 
Early Terminations or Discontinued Participants, All Enrolled Participants ........................................ 91 
Listing 2: 
Participant Specific Protocol Deviations, All Enrolled Participants ..................................................... 91 
Listing 3: 
Non-Participant -Specific Protocol Deviations, All Enrolled Participants ........................................... 91 
Listing 4: 
Participants Excluded from Analysis Populations, All Enrolled Participants ....................................... 92 
Listing 5: 
Demographic Data, Safety Population .................................................................................................. 92 
Listing 6: 
Medical History, Safety Population ...................................................................................................... 93 
Listing 7: 
Treatment Compliance, Safety Population ........................................................................................... 93 
Listing 8: 
Solicited Events – Systemic Symptoms, Safety Population ................................................................. 94 
Listing 9: 
Solicited Events – Local Symptoms, Safety Population ....................................................................... 94 
Listing 10: 
Unsolicited Adverse Events, Safety Population ................................................................................... 95 
Listing 11: 
Serious Adverse Events, Including Deaths ........................................................................................... 95 
Listing 12: 
Listing of Deaths................................................................................................................................... 96 
Listing 13: 
Dose Limiting Toxicities ...................................................................................................................... 96 
Listing 14: 
Clinical Laboratory Results – Chemistry, Safety Population ............................................................... 97 
Listing 15: 
Clinical Laboratory Results – Hematology, Safety Population ............................................................ 97 
Listing 16: 
Clinical Laboratory Results – Urinalysis, Safety Population ................................................................ 98 
Listing 17: 
Vital Signs, Safety Population .............................................................................................................. 98 
Listing 18: 
Physical Exam Findings, Safety Population ......................................................................................... 99 
Listing 19: 
Concomitant Medications, Safety Population ....................................................................................... 99 
Listing 20: 
Participant Level C144-LS and C135-LS Concentrations in Serum, PK Population ......................... 100 
Listing 21: 
Participant Specific C144-LS Serum PK Parameters, PK Population ................................................ 101 
Listing 22: 
Participant Specific C135-LS Serum PK Parameters, PK Population ................................................ 101 
Listing 23: 
Pregnancy Reports – Maternal Information, Safety Population ......................................................... 102 
Listing 24: 
Pregnancy Reports – Gravida and Para, Safety Population ................................................................ 102 
Listing 25: 
Pregnancy Reports – Live Birth Outcomes, Safety Population .......................................................... 103 
Listing 26: 
Pregnancy Reports – Still Birth Outcomes, Safety Population ........................................................... 103 
Listing 27: 
Pregnancy Reports – Spontaneous, Elective, or Therapeutic Abortion Outcomes, Safety 
Population ........................................................................................................................................... 103 
Listing 28: 
Anti-Drug Antibody Titration Results, C144-LS - Immunogenicity Population ................................ 104 
Listing 29: 
Anti-Drug Antibody Titration Results, C135-LS - Immunogenicity Population ................................ 104 
 
 

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16.2 
Data Listings by Participant 
16.2.1 
Participant Disposition 
Listing 1: 
Early Terminations or Discontinued Participants, All Enrolled Participants 
Dose Group 
Participant ID 
Category 
Reason for Early Termination or Treatment Discontinuation 
Study Day 
[Safety Group 1] 
 
 
 
 
[Safety Group 2] 
(S2) 
 
 
 
 
 
 
 
 
 
16.2.2 
Protocol Deviations 
Listing 2: 
Participant Specific Protocol Deviations, All Enrolled Participants 
Dose Group 
Participant 
ID 
Sequence 
Number 
Deviation 
Deviation 
Category 
Visit 
Number 
Reason for 
Deviation 
Deviation 
Resulted 
in AE? 
Deviation Resulted 
in Participant 
Termination? 
Deviation 
Resolution 
Comments 
[Safety Group 1] 
 
 
 
 
 
 
 
 
 
 
[Safety Group 2] 
(S2) 
 
 
 
 
 
 
 
 
 
 
 
Listing 3: 
Non-Participant -Specific Protocol Deviations, All Enrolled Participants 
Site 
Start Date 
Deviation 
Reason for 
Deviation 
Deviation Resulted in 
Participant 
Termination? 
Deviation 
Category 
Deviation 
Resolution 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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16.2.3 
Participants Excluded from the Analysis Populations 
Listing 4: 
Participants Excluded from Analysis Populations, All Enrolled Participants 
Dose Group 
Participant ID 
Analyses in which 
Participant is Included 
Analyses from which 
Participant is Excluded 
Any Safety  
Results 
Available? 
Any PK  
Results 
Available? 
Any Immunogenicity 
(ADA) Results 
Available? 
Reason 
Participant 
Excluded 
[Safety Group 1] 
[e.g., Safety, Enrolled, PK, 
Immunogenicity (ADA)] 
[e.g., Safety, PK, 
Immunogenicity (ADA)] 
 
[Safety Group 2] 
(S2) 
 
[Safety Group 2] 
(S3 Active) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: “Yes” in the “Results available” column indicates that available data were removed from the analysis. “No” indicates that no data were available for inclusion 
in the analysis. 
 
16.2.4 
Demographic/Baseline Characteristics Data 
Listing 5: 
Demographic Data, Safety Population 
Dose Group 
Participant ID 
Sex 
Age at Enrollment 
(Years) 
Ethnicity 
Race 
[Safety Group 1] 
 
 
 
 
 
[Safety Group 2] 
(S2) 
 
 
 
 
 
[Safety Group 2] 
(S3 Active) 
 
 
 
 
 
 
 
 
 
 
 
 

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Listing 6: 
Medical History, Safety Population 
Dose Group 
Participant ID 
Sequence Number 
Medical 
History Term 
MedDRA 
System Organ 
Class 
MedDRA 
Preferred Term 
Condition Start 
Day 
Ongoing at 
Enrollment? 
[Safety Group 1] 
 
 
 
 
 
 
 
[Safety Group 2] 
(S2) 
 
 
 
 
 
 
 
[Safety Group 2] 
(S3 Active) 
 
 
 
 
 
 
 
 
16.2.5. 
Extent of Exposure Data 
Listing 7: 
Treatment Compliance, Safety Population  
Dose Group 
Participant 
ID 
mAB 
Route 
Dosed 
According to 
Protocol? 
IP 
Administration 
Date 
Start 
Time 
End 
Time 
Number of 
Injections 
Location 
Dose Interrupted  
(AE Description; 
Number) 
[Safety Group 1] 
 
 
 
 
 
 
 
 
 
 
[Safety Group 2] 
(S2) 
 
 
 
 
 
 
 
 
 
 
[Safety Group 2] 
(S3 Active) 
 
 
 
 
 
 
 
 
 
 
 
 
 

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16.2.7 
Adverse Events 
Listing 8: 
Solicited Events – Systemic Symptoms, Safety Population 
Dose Group 
Participant ID 
Post Dose Day 
Symptom 
Severity 
Relatedness 
Associated with 
Cytokine Release 
Syndrome? 
[Safety Group 1] 
 
 
 
 
 
 
[Safety Group 2] 
(S2) 
 
 
 
 
 
 
[Safety Group 2] 
(S3 Active) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 9: 
Solicited Events – Local Symptoms, Safety Population 
Dose Group 
Participant ID 
Post Dose Day 
Symptom 
Severity 
Relatedness 
Associated with 
Cytokine Release 
Syndrome? 
[Safety Group 1] 
 
 
 
 
 
 
[Safety Group 2] 
(S2) 
 
 
 
 
 
 
[Safety Group 2] 
(S3 Active) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Listing 10: 
Unsolicited Adverse Events, Safety Population 
Adverse 
Event 
MedDRA 
System 
Organ Class 
MedDRA 
Preferred 
Term 
Day of 
Onset 
Post-IP 
Duration 
(Days) 
Severity 
SAE? 
Relationship to 
IP 
Action Taken 
with IP 
Participant 
Discontinued 
Due to AE 
Outcome 
Dose Group: Participant ID: AE Number:  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Dose Group: Participant ID: AE Number:  
  
  
  
  
  
  
  
  
  
  
  
Note: For additional details about SAEs, see Listing 11. 
 
 
Listing 11: 
Serious Adverse Events, Including Deaths 
Serious 
Adverse 
Event 
Day of 
Onset 
Post IP 
Duration 
(Days) 
No. of Days 
Post IP the 
Event Became 
Serious 
Reason 
Reported as 
an SAE 
Was the 
Event a 
DLT? 
Severity 
Relationship 
to Study 
Treatment 
Action Taken 
with Study 
Treatment 
Participant 
Discontinued 
Due to AE 
Outcome 
MedDRA 
System 
Organ Class 
MedDRA 
Preferred 
Term 
Dose Group: Participant ID: AE Number:  
  
  
  
  
  
  
  
  
  
  
  
  
  
Comments: 
  
  
  
  
  
  
  
  
  
  
  
  
  
Dose Group: Participant ID: AE Number:  
  
  
  
  
  
  
  
  
  
  
  
  
  
Comments: 
 

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Listing 12: 
Listing of Deaths 
Serious Adverse 
Event 
Day of 
Onset 
Post IP 
Duration 
(Days) 
No. of Days Post 
Dose the Event 
Became Serious 
Reason 
Reported as 
an SAE 
Was the 
Event a 
DLT? 
Severity 
Relationship 
to IP 
Action 
Taken with 
IP 
Participant 
Discontinued 
Due to SAE 
MedDRA 
System Organ 
Class 
MedDRA 
Preferred 
Term 
Dose Group: Participant ID: AE Number:  
  
  
  
  
  
  
  
  
  
  
  
  
Comments: 
  
  
  
  
  
  
  
  
  
  
  
  
Dose Group: Participant ID: AE Number:  
  
  
  
  
  
  
  
  
  
  
  
  
Comments: 
 
 
Listing 13: 
Dose Limiting Toxicities 
Adverse Event 
Day of 
Onset 
Post IP 
Duration 
(Days) 
SAE? 
Severity 
Relationship 
to IP 
Action Taken with 
IP 
Participant 
Discontinued 
Due to AE 
Outcome 
MedDRA System 
Organ Class 
MedDRA 
Preferred Term 
Dose Group: Participant ID: AE Number:  
  
  
  
  
  
  
  
  
  
  
  
Comments: 
  
  
  
  
  
  
  
  
  
  
  
Dose Group: Participant ID: AE Number:  
  
  
  
  
  
  
  
  
  
  
  
Comments: 
 
 
 

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16.2.8 
Individual Laboratory Data and Other Safety-Related Data 
Listing 14: 
Clinical Laboratory Results – Chemistry, Safety Population 
Dose Group 
Participant 
ID 
Planned 
Time Point  
Actual 
Study 
Day  
Sex  
Age 
(Years) 
Laboratory 
Parameter 
(Units) 
Result  
(Severity 
Grade) 
Change 
from 
Baseline 
Reference 
Range Low 
Reference 
Range High 
[Safety Group 1] 
 
 
 
 
 
 
 
 
 
 
[Safety Group 2] 
(S2) 
 
 
 
 
 
 
 
 
 
 
[Safety Group 2] 
(S3 Active) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 15: 
Clinical Laboratory Results – Hematology, Safety Population 
Dose Group 
Participant 
ID 
Planned 
Time Point  
Actual 
Study 
Day  
Sex  
Age 
(Years) 
Laboratory 
Parameter 
(Units) 
Result  
(Severity 
Grade) 
Change 
from 
Baseline 
Reference 
Range Low 
Reference 
Range High 
[Safety Group 1] 
 
 
 
 
 
 
 
 
 
 
[Safety Group 2] 
(S2) 
 
 
 
 
 
 
 
 
 
 
[Safety Group 2] 
(S3 Active) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Listing 16: 
Clinical Laboratory Results – Urinalysis, Safety Population 
Dose Group 
Participant 
ID 
Planned 
Time Point  
Actual 
Study Day  
Sex  
Age 
(Years) 
Laboratory 
Parameter (Units) 
Result  
(Severity Grade) 
Reference 
Range Low 
Reference 
Range High 
[Safety Group 1] 
 
 
 
 
 
 
 
 
 
[Safety Group 2] 
(S2) 
 
 
 
 
 
 
 
 
 
[Safety Group 2] 
(S3 Active) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
16.2.9 
Vital Signs and Physical Exam Findings 
Listing 17: 
Vital Signs, Safety Population 
Dose Group 
Participant 
ID 
Planned 
Time 
Point 
Actual 
Study 
Day 
Pulse 
(beats/min) 
Respiratory 
Rate 
(breaths/min) 
Systolic 
Blood 
Pressure 
(mmHg) 
Diastolic 
Blood 
Pressure 
(mmHg) 
Temperature 
(°C) 
Weight 
(kg) 
Height 
(cm) 
BMI 
(kg/m2) 
[Safety Group 1] 
 
 
 
 
 
 
 
 
 
 
 
[Safety Group 2] 
(S2) 
 
 
 
 
 
 
 
 
 
 
 
[Safety Group 2] 
(S3 Active) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Listing 18: 
Physical Exam Findings, Safety Population 
Dose Group 
Participant 
ID 
Planned Time 
Point 
Actual Study 
Day 
Body System 
Abnormal 
Finding 
Reported as a Reactogenicity 
Event? 
(Description; Number) 
Reported as an AE? 
(AE Description; Number) 
[Safety Group 1] 
 
 
 
 
 
 
 
[Safety Group 2] 
(S2) 
 
 
 
 
 
 
 
[Safety Group 2] 
(S3 Active) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 19: 
Concomitant Medications, Safety Population 
Dose Group 
Participant 
ID 
CM 
Sequence 
Number 
Medication 
Medication 
Start Day 
Medication 
End Day 
Indication 
Taken for an AE? 
(AE Description; 
Number) 
Taken for a 
condition on 
Medical History? 
(MH Description; 
Number) 
ATC Level 1 
(ATC Level 2) 
[Safety Group 1] 
 
 
 
 
 
 
 
 
 
[Safety Group 2] 
(S2) 
 
 
 
 
 
 
 
 
 
 
 
 

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16.2.9. 
Pharmacokinetic Data 
Listing 20: 
Participant Level C144-LS and C135-LS Concentrations in Serum, PK Population 
Dose Group 
mAB 
Participant 
ID 
Nominal 
Timea 
Actual Timea 
Laboratory Reported 
Concentration 
(µg/mL) 
Analysis 
Concentrations 
(µg/mL) 
Excluded 
from NCA 
Used in λz 
Calculations 
[Safety Group 1] 
 
 
 
 
 
 
 
 
[Safety Group 2] (S2) 
 
 
 
 
 
 
 
 
Notes: a Times are relative to time of dosing. For actual time, out of window times are indicated by an asterisk (*), substantially out of window times are indicated by 
two asterisks (**) and imputed times are indicated by three asterisks (***).  
BQL = Below the Limit of Quantification. 
 
 
 

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Listing 21: 
Participant Specific C144-LS Serum PK Parameters, PK Population 
Dose  
Group 
Participant 
ID 
Cmax  
(µ/mL) 
Cmax/Dose 
((µg/mL/mg) or 
((µg/mL)/kg/mg)1 
Tmax 
(h) 
AUC(0-T) 
(µg* 
day/mL) 
AUC(0-T)/Dose 
((μg day/mL)/mg)  
or ((μg day/mL) 
kg/mg)2  
AUC(INF) 
(µg*day/mL) 
AUC(INF)/Dose 
((μg day/mL)/mg)  
or ((μg day/mL) 
kg/mg)2  
λz 
(1/day) 
T-HALF 
(day) 
CLT/F 
(mL/day)  
or CLT  
(mL/day)3 
Vz/F (L)  
or  
Vss (L)3  
[Safety Group 1] 
 
 
 
 
 
 
 
 
 
 
 
 
[Safety Group 2] 
(S2) 
 
 
 
 
 
 
 
 
 
 
 
 
[Safety Group 2] 
(S3 Active) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1Dose adjustments were made by the assigned dose. Units of (µg/mL)/mg are for SC groups and units of (µg/mL)*kg/mg are for IV groups. 
2Dose adjustments were made by the assigned dose. Units of (µg*day/mL)/mg are for SC groups and units of (µg*day/mL)*kg/mg are for IV groups. 
3CLT/F and Vz/F are presented for participants in the SC dose groups. CLT and Vss are presented for participants in the IV dose groups. 
Parameters values where the λz acceptance criteria were not met are indicated by an asterisk (*).  
Terminal phase parameter values where the %AUCex criteria was not met are indicated by a circumflex (^). 
 
Listing 22: 
Participant Specific C135-LS Serum PK Parameters, PK Population 
This listing will repeat Listing 21 for C135-LS. 

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16.2.10 
Pregnancy Reports 
Listing 23: 
Pregnancy Reports – Maternal Information, Safety Population 
Dose Group 
Participant 
ID 
Report 
Number 
Study Day 
Corresponding 
to Estimated 
Date of 
Conception 
Source of 
Maternal 
Information 
Pregnancy 
Status 
Mother’s  
Pre-Pregnancy 
BMI 
Medications 
During Pregnancy? 
Maternal 
Complications 
During 
Pregnancy? 
Maternal 
Complications 
During Labor, 
Delivery, or  
Post-Partum? 
[Safety Group 1] 
 
 
 
 
 
 
 
 
 
[Safety Group 2] 
(S2) 
 
 
 
 
 
 
 
 
 
Note: Maternal Complications and medications taken during pregnancy are included in Listing 19. 
 
 
Listing 24: 
Pregnancy Reports – Gravida and Para, Safety Population 
Dose Group 
Participant 
ID 
Pregnancy 
Number 
Gravida 
Birth Type 
Spontaneous 
Abortion/ 
Miscarriage 
Elective 
Abortions 
Therapeutic 
Abortions 
Major Congenital 
Anomaly with 
Previous 
Pregnancy? 
[Safety Group 1] 
 
 
 
 
 
 
 
 
[Safety Group 2] 
(S2) 
 
 
 
 
 
 
 
 
Note: Gravida includes the current pregnancy, para events do not. 
 
 
 

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Listing 25: 
Pregnancy Reports – Live Birth Outcomes, Safety Population 
Participant 
ID 
Pregnancy 
Number 
Fetus 
Number 
Pregnancy 
Outcome 
(for this 
Fetus) 
Fetal 
Distress 
During 
Labor and 
Delivery? 
Delivery 
Method 
Gestational 
Age at Live 
Birth  
Size for 
Gestational 
Age 
Apgar 
Score, 1 
minute 
Apgar 
Score, 5 
minutes 
Cord 
pH 
Congenital 
Anomalies? 
Illnesses/ 
Hospitalizations 
within 1 Month 
of Birth? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Congenital anomalies are included in Listing 20. 
 
 
Listing 26: 
Pregnancy Reports – Still Birth Outcomes, Safety Population 
Participant 
ID 
Date of 
Initial 
Report 
Fetus 
Number 
Pregnancy 
Outcome  
(for this Fetus) 
Delivery 
Method 
Gestational Age 
at Still Birth 
Size for 
Gestational Age 
Congenital 
Anomalies? 
Autopsy 
Performed? 
If Autopsy, 
Etiology for 
Still Birth 
Identified? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 27: 
Pregnancy Reports – Spontaneous, Elective, or Therapeutic Abortion Outcomes, Safety Population 
Participant ID 
Date of Initial 
Report 
Fetus 
Number 
Pregnancy Outcome  
(for this Fetus) 
Gestational Age at 
Termination 
Reason for Therapeutic Abortion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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16.2.11 
Immunogenicity 
Listing 28: 
Anti-Drug Antibody Titration Results, C144-LS - Immunogenicity Population 
Dose Group 
Participant ID 
Visit 
Sample 
Collection Date a 
Screening 
Result 
Confirmation 
Result 
Reported 
Titration Result 
Analysis Titration 
Result b 
[Immunogenicity 
Group 1]  
 
 
 
 
 
 
 
[Immunogenicity 
Group 2] (S2) 
 
 
 
 
 
 
 
[Immunogenicity 
Group 2] (S3 Active) 
 
 
 
 
 
 
 
Notes:  
a Samples collected outside of the protocol defined visit window are indicated with an asterisk (*). The number of days before or after the protocol defined visit 
window that the sample was collected is included in parentheses next to the sample collection date. 
b Results that were inconclusive for the presence of ADA were analyzed as ADA negative. Samples with positive results for ADA for which the ADA titration 
result was unquantifiable were reported as "<100" and analyzed as 50 in tables and figures. Samples which were negative for presence of ADA were analyzed 
as 1 in tables and figures. 
 
Listing 29: 
Anti-Drug Antibody Titration Results, C135-LS - Immunogenicity Population 
Dose Group 
Participant ID 
Visit 
Sample 
Collection Date a 
Screening 
Result 
Confirmation 
Result 
Reported 
Titration Result 
Analysis Titration 
Result b 
[Immunogenicity 
Group 1]  
 
 
 
 
 
 
 
[Immunogenicity 
Group 2] (S2) 
 
 
 
 
 
 
 
[Immunogenicity 
Group 2] (S3 Active) 
 
 
 
 
 
 
 
Notes:  
a Samples collected outside of the protocol defined visit window are indicated with an asterisk (*). The number of days before or after the protocol defined visit 
window that the sample was collected is included in parentheses next to the sample collection date. 
b Results that were inconclusive for the presence of ADA were analyzed as ADA negative. Samples with positive results for ADA for which the ADA titration 
result was unquantifiable were reported as "<100" and analyzed as 50 in tables and figures. Samples which were negative for presence of ADA were analyzed 
as 1 in tables and figures.