A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of LY3471851 (NKTR-358) in Adults With Systemic Lupus Erythematosus
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Sponsor: Nektar Therapeutics

 
 
 
Protocol J1P-MC-KFAJ(a) 
 
 
A Randomized, Double-Blind, Placebo-Controlled, 
Phase 2 Study of LY3471851 (NKTR-358) in Adults 
with Systemic Lupus Erythematosus 
 
NCT04433585 
 
Approval Date: 19August2020 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
1 
Approval Date: 19-Aug-2020 GMT 
Title Page 
Confidential Information 
The information contained in this document is confidential and is intended for the use of clinical investigators. It is the property of 
Eli Lilly and Company or its subsidiaries and should not be copied by or distributed to persons not involved in the clinical 
investigation of LY3471851, unless such persons are bound by a confidentiality agreement with  
Eli Lilly and Company or its subsidiaries. 
 
Note to Regulatory Authorities: This document may contain protected personal data and/or commercially confidential information 
exempt from public disclosure. Eli Lilly and Company requests consultation regarding release/redaction prior to any public release. 
In the United States, this document is subject to Freedom of Information Act (FOIA) Exemption 4 and may not be reproduced or 
otherwise disseminated without the written approval of Eli Lilly and Company or its subsidiaries. 
 
Protocol Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of 
LY3471851 (NKTR-358) in Adults with Systemic Lupus Erythematosus 
Protocol Number: J1P-MC-KFAJ 
Amendment Number: a 
Compound: LY3471851 
Study Phase: 2 
Short Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of  
LY3471851 (NKTR-358) in Adults with Systemic Lupus Erythematosus 
Acronym: ISLAND-SLE 
Sponsor Name: Eli Lilly and Company 
Legal Registered Address: Indianapolis, Indiana USA 46285 
Regulatory Agency Identifier Numbers 
IND 132275 
EudraCT 2019-003323-38 
Approval Date: Protocol Amendment (a) Electronically Signed and Approved by Lilly on date 
provided below. 
 
 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
2 
Medical Monitor Name and Contact Information will be provided separately. 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
3 
Protocol Amendment Summary of Changes Table 
DOCUMENT HISTORY 
Document 
Date 
KFAJ Protocol  
 
Amendment [a]  
This amendment occurred before any study participant was consented or dosed at any study site 
in Europe.  
Overall Rationale for the Amendment: 
The purpose of this protocol amendment is to correct typographical errors and clarify study 
procedures and statistical analysis plans in response to European regulatory agency feedback.  
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
4 
Table of Contents 
1. 
Protocol Summary ..........................................................................................................8 
1.1. 
Synopsis ............................................................................................................................8 
1.2. 
Schema ............................................................................................................................11 
1.3. 
Schedule of Activities (SoA) ..........................................................................................12 
2. 
Introduction ...................................................................................................................25 
2.1. 
Study Rationale ...............................................................................................................25 
2.2. 
Background .....................................................................................................................25 
2.3. 
Benefit/Risk Assessment ................................................................................................26 
3. 
Objectives and Endpoints ............................................................................................27 
4. 
Study Design ..................................................................................................................29 
4.1. 
Overall Design ................................................................................................................29 
4.2. 
Scientific Rationale for Study Design ............................................................................30 
4.2.1. 
Participant Input into Design ..........................................................................................31 
4.3. 
Justification for Dose ......................................................................................................32 
4.4. 
End-of-Study Definition .................................................................................................33 
5. 
Study Population ...........................................................................................................34 
5.1. 
Inclusion Criteria ............................................................................................................34 
5.2. 
Exclusion Criteria ...........................................................................................................35 
5.3. 
Lifestyle Considerations .................................................................................................39 
5.4. 
Screen Failures ................................................................................................................39 
5.4.1. 
Allowed Retesting of Screening Investigations ..............................................................40 
5.4.2. 
Rescreening of Individuals Who Failed Screening .........................................................40 
6. 
Study Intervention ........................................................................................................41 
6.1. 
Study Interventions Administered ..................................................................................41 
6.2. 
Preparation/Handling/Storage/Accountability ................................................................41 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ............................................42 
6.4. 
Study Intervention Compliance ......................................................................................43 
6.5. 
Concomitant Therapy .....................................................................................................44 
6.5.1. 
Corticosteroid Management Program .............................................................................44 
 
 
6.7. 
Intervention after the End of the Study ...........................................................................46 
7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal........................................................................................47 
7.1. 
Discontinuation of Study Intervention ............................................................................47 
7.1.1. 
Criteria for Permanent Discontinuation of Study Drug ..................................................47 
7.1.2. 
Criteria for Temporary Interruption (Withholding) of Study Drug ................................50 
7.2. 
Participant Discontinuation/Withdrawal from the Study ................................................50 
7.2.1. 
Discontinuation of Inadvertently Enrolled Participants ..................................................51 
7.3. 
Lost to Follow up ............................................................................................................51 
8. 
Study Assessments and Procedures.............................................................................52 
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
5 
8.1. 
Efficacy Assessments .....................................................................................................52 
8.1.1. 
Primary Efficacy Outcome Measure: SLEDAI-4 ...........................................................52 
8.1.2. 
Secondary Efficacy Outcome Measures .........................................................................52 
8.2. 
Safety Assessments .........................................................................................................53 
8.2.1. 
Vital Signs .......................................................................................................................54 
8.2.2. 
Physical Examinations ....................................................................................................54 
8.2.3. 
Electrocardiograms .........................................................................................................55 
8.2.4. 
Chest Radiography ..........................................................................................................55 
8.2.5. 
Laboratory Tests .............................................................................................................56 
8.2.6. 
Tuberculosis Testing and Monitoring .............................................................................57 
8.2.7. 
Hepatitis B Testing and Monitoring ...............................................................................58 
8.2.8. 
Hepatitis C Testing and Monitoring ...............................................................................59 
8.2.9. 
Hepatic Safety Monitoring ..............................................................................................60 
8.2.10. Suicidal Ideation and Behavior Risk Monitoring ...........................................................61 
8.2.11. Injection Site Assessment ...............................................................................................62 
8.3. 
Adverse Events and Serious Adverse Events .................................................................62 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information .....................................................................................................................63 
8.3.2. 
Method of Detecting AEs and SAEs ..............................................................................63 
8.3.3. 
Follow-up of AEs and SAEs ...........................................................................................64 
8.3.4. 
Regulatory Reporting Requirements for SAEs ...............................................................64 
8.3.5. 
Pregnancy ........................................................................................................................64 
 
 
8.3.7. 
Complaint Handling ........................................................................................................65 
8.4. 
Treatment of Overdose ...................................................................................................66 
8.5. 
Pharmacokinetics ............................................................................................................66 
 
 
 
 
 
 
 
 
8.10. 
Medical Resource Utilization and Health Economics ....................................................68 
9. 
Statistical Considerations .............................................................................................69 
9.1. 
Statistical Hypotheses .....................................................................................................69 
9.2. 
Sample Size Determination ............................................................................................69 
9.3. 
Populations for Analyses ................................................................................................69 
9.4. 
Statistical Analyses .........................................................................................................69 
9.4.1. 
General Considerations ...................................................................................................69 
9.4.2. 
Primary Endpoints ..........................................................................................................71 
9.4.3. 
Secondary Efficacy Endpoints ........................................................................................71 
 
 
9.4.5. 
Safety Analyses ...............................................................................................................72 
 
 
 
 
9.6. 
Data Monitoring Committee (DMC) ..............................................................................74 
10. 
Supporting Documentation and Operational Considerations ..................................75 
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
6 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ................................................................................................................75 
10.1.1. Regulatory and Ethical Considerations ...........................................................................75 
10.1.2. Financial Disclosure........................................................................................................75 
10.1.3. Informed Consent Process ..............................................................................................76 
10.1.4. Data Protection................................................................................................................76 
10.1.5. Committees Structure......................................................................................................76 
10.1.6. Dissemination of Clinical Study Data.............................................................................77 
10.1.7. Data Quality Assurance ..................................................................................................77 
10.1.8. Source Documents ..........................................................................................................79 
10.1.9. Study and Site Start and Closure ....................................................................................79 
10.1.10. Publication Policy ...........................................................................................................80 
10.1.11. Investigator Information .................................................................................................80 
 
10.2. 
Appendix 2: Clinical Laboratory Tests ...........................................................................82 
10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .........................................................86 
10.3.1. Definition of AE .............................................................................................................86 
10.3.2. Definition of SAE ...........................................................................................................87 
10.3.3. Recording and Follow-Up of AE and/or SAE ................................................................88 
10.3.4. Reporting of SAEs ..........................................................................................................89 
10.4. 
Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information ...................................................................................................91 
10.4.1. Definitions.......................................................................................................................91 
10.4.2. Contraception ..................................................................................................................92 
10.4.3. Collection of Pregnancy Information..............................................................................92 
10.5. 
Appendix 5: Liver Safety: Hepatic Monitoring Tests ....................................................94 
10.6. 
Appendix 6: Examples of Infections That May Be Considered 
Opportunistic in the Setting of Biologic Therapy ...........................................................95 
10.7. 
Appendix 7: Efficacy and Patient-Reported Outcomes 
Assessments ....................................................................................................................97 
10.7.1. British Isles Lupus Assessment Group 2004 (BILAG-2004) .........................................97 
 
 
 
10.7.3. Physician’s Global Assessment (PGA) of Disease Activity – 
Visual Analog Scale ........................................................................................................97 
10.7.4. Systemic Lupus Erythematosus Disease Activity Index 2000 
(SLEDAI-2K) .................................................................................................................97 
10.7.5. Systemic Lupus Erythematosus Disease Activity Index 
(SLEDAI) Flare Index ....................................................................................................98 
 
 
 
 
 
 
 
 
 
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
7 
 
 
 
 
 
 
 
 
 
 
 
10.8. 
Appendix 8: Abbreviations ...........................................................................................101 
11. 
References ....................................................................................................................105 
 
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
10 
Intervention Groups and Duration: 
Participants will be randomized in a 1:1:1:1 ratio 
 to receive one of the following 
study interventions: 
●  
 LY3471851 Q2W 
●  
 LY3471851 Q2W 
●  
 LY3471851 Q2W, or 
●  placebo Q2W. 
Data Monitoring Committee: No 
 
CCI
CCI
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
22 
Abbreviations: ACR = American College of Rheumatology; 
 
 BILAG 
= British Isles Lupus Assessment Group; 
 C-SSRS = Columbia–Suicide Severity 
Rating Scale; DNA = deoxyribonucleic acid; ECG = electrocardiogram; ETV = early termination visit; 
 
;HBV = hepatitis B virus; IL = interleukin; 
 
 QIDS-SR16 = 16-Item Quick Inventory of Depressive Symptomatology–Self Report; 
 
 SLE = systemic lupus erythematosus; SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index 
2000; 
 V = visit; VAS = visual analog scale.  
 
CCI
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
25 
2. 
Introduction 
2.1. 
Study Rationale 
LY3471851 (also known as NKTR-358) is a polyethylene glycol (PEG)-conjugated recombinant 
human interleukin (IL)-2 (rhIL-2) with the capacity to promote the expansion and activation of 
regulatory T cells (Tregs) with relatively minimal effect on conventional T cells (Tcons). When 
compared to rhIL-2, PEGylation results in prolonged systemic exposure and improved binding to 
the high affinity IL-2 receptor most present on regulatory T cells (Tregs). In preliminary clinical 
studies, low-dose recombinant human IL-2 was shown to reverse IL-2 deficiency and the Treg 
deficit typically observed in patients with systemic lupus erythematosus (SLE) (von Spee-Mayer 
et al. 2016). Moreover, low-dose IL-2 therapy was associated with improvements in SELENA-
SLEDAI and SLE Response Index (SRI-4 response) (He et al. 2016, He et al. 2020). 
Study J1P-MC-KFAJ (KFAJ) is a Phase 2 study to evaluate the efficacy and safety of 
LY3471851 in adult patients with SLE. Results of this study will be used to guide the dose 
selection for future studies and to further characterize the benefit/risk profile of LY3471851. 
2.2. 
Background 
Systemic lupus erythematosus is a chronic, debilitating, autoimmune disease characterized by the 
presence of autoreactive B cells and elevated levels of autoantibodies. The disease can affect 
multiple organ systems and follows an unpredictable clinical course. Patients may present with 
arthralgia, arthritis, skin rash, alopecia, oral ulcers, pleuritis, pericarditis, nephritis, vasculitis, 
stroke, seizure, leukopenia, thrombocytopenia, anemia, photosensitivity, and the presence of 
autoantibodies directed to nuclear antigens. More than 60% of patients with SLE will develop 
clinically detectable organ damage about 4 years after the diagnosis, as measured by the 
Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage 
Index (SDI) (Cooper et al. 2007). 
The standard-of-care for SLE varies widely and currently includes the use of corticosteroids, 
nonsteroidal anti-inflammatory drugs (NSAIDs), antimalarial medication, cytotoxic agents, and 
immunosuppressants. Unfortunately, the morbidity of the disease remains substantial, as 
measured by various tools for evaluating health-related quality of life, loss of work productivity, 
pain, and fatigue (Ad Hoc Committee on Systemic Lupus Erythematosus Response Criteria for 
Fatigue 2007; Özel and Argon 2015). A meta-analysis involving more than 27,000 patients 
showed that SLE patients had a 3-fold increase in risk of death compared with the general 
population (Yurkovich et al. 2014). Patients with SLE need better treatment options. 
The dysfunction in Treg cell biology has been proposed as a key defect in SLE, leading to the 
breakdown of immune self-tolerance (Ohl and Tenbrock 2015). The goal of LY3471851 therapy 
is to increase Treg number and function, with a minimal effect on Tcons and natural killer (NK) 
cells. 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
26 
2.3. 
Benefit/Risk Assessment 
The Investigator’s Brochure (IB) designates local injection site reactions (ISR) as an identified 
risk of LY3471851, based on reports of primarily low-grade injection site reactions in the Phase 
1 studies. Reports of cytokine release syndrome (CRS) and clinical symptom complex attributed 
to elevated cytokine levels were of Grade 1 severity. Eosinophilia without evidence of target 
organ damage was observed in some participants in the Phase 1 study in SLE. The safety 
findings from Phase 1 studies showed no evidence of adverse events characteristic of capillary 
leak syndrome, increased risk of infection, worsening or new onset autoimmune disease, cardiac 
disorders (cardiac rhythm disturbances, angina, or myocardial infarction), pulmonary disorders, 
central nervous system effects, or severe anemia/thrombocytopenia known to be associated with 
high-dose IL-2 (aldesleukin). 
To minimize study participant risk in Study KFAJ, enrolled participants will receive study drug 
doses in the clinic to enable appropriate pre-dose safety assessments and post-dose monitoring. 
The routine safety assessments include physical examinations, clinical safety laboratory tests 
(including hematology and chemistry), suicidality/self-harm and depression evaluations, and 
collection of vital signs and spontaneously reported adverse events. The study design includes a 
post-treatment follow-up period with at least one study visit for safety assessments. 
 
 
 
 
 
 
 
In addition, based on observations of treatment-related biliary hyperplasia noted in nonclinical 
studies, as described in the IB, investigators should be aware of the possible occurrence of 
treatment-related hepatobiliary changes that could possibly include cholestasis. The protocol 
includes hepatic-related laboratory testing to support intensive monitoring for symptoms and 
physical signs suggestive of liver or biliary toxicity, including jaundice, scleral icterus, and 
pruritis. See also Section 8.2.9. 
Ongoing study-level monitoring of safety data will be performed, as described in Section 8.2. 
 
 
The efficacy of LY3471851 in SLE has not been established. Participants may benefit by 
receiving personal health information from the physical examinations and from other routine 
safety assessments performed in this study. 
In summary, in the context of the cumulative knowledge for LY3471851, the benefit/risk balance 
for this study is assessed to be acceptable for testing in Phase 2. 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of LY3471851 may be found in the IB. 
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
29 
4. 
Study Design 
4.1. 
Overall Design 
Study KFAJ is a multicenter, randomized, double-blind, placebo-controlled, parallel-group 
Phase 2 study to evaluate the efficacy and safety of LY3471851 in adult study participants with 
at least moderately active SLE. The study has 3 required study periods and an optional 
prescreening period. A schematic of the study design is presented in Section 1.2. 
Optional prescreening period 
Study participants must have positive antinuclear, 
 at 
Visit 1 to be eligible for randomization at Visit 2. The optional prescreening visit (Visit 601) is 
intended for those investigators who opt for central laboratory assessment of the prospective 
participant’s antinuclear antibodies (ANA), 
 status before full 
screening activities are initiated. 
If opted for, the prescreening determination of ANA, 
 status 
will be described in an appropriate informed consent form (ICF). Informed consent for the 
prescreening activities will be obtained, a participant identification number will be assigned, and 
samples for specified laboratory tests will be obtained. The optional prescreening visit can be 
repeated 2 times (no more) per participant, with a minimum of 4 weeks between visits. Repeated 
visits in the prescreening visit will not require re-consenting or assignment of a new participant 
identification number. 
Note: If the optional prescreening is opted for, central laboratory testing for ANA, 
 is still required as part of the screening procedures 
conducted at Visit 1. Participants with negative results at Visit 1 will not be eligible for 
enrollment, despite positive values in prescreening. 
Screening period 
The required screening period begins with Visit 1, which occurs within 5 weeks before the 
planned randomization visit. If the participant had an optional prescreening visit, an assessment 
of ANA, 
will be repeated at Visit 1 for confirmation of 
study eligibility. The main Study KFAJ ICF will be signed before Visit 1 procedures are 
performed. A participant identification number will be assigned at Visit 1, if one was not 
assigned at Visit 601. Participant eligibility will be reviewed and confirmed by an eligibility 
review committee prior to randomization. 
Participants found to be eligible according to all of the study entry criteria will be randomly 
assigned in a 1:1:1:1 ratio to receive one of the following study interventions: 
●  
 LY3471851 every 2 weeks (Q2W) 
●  
 LY3471851 Q2W 
●  
 LY3471851 Q2W, or 
●  placebo Q2W. 
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
30 
 
 Study interventions 
will be administered via subcutaneous injection (SC). 
Double-blind treatment period 
Randomized participants will begin the double-blind, placebo-controlled, 24-week treatment 
period at Visit 2. Participants will receive the first dose of the assigned study intervention at that 
visit and will continue to receive doses through the last scheduled dosing visit specified in the 
Schedule of Activities (SoA, Section 1.3). Participants will maintain their usual standard-of-care 
medication regimen for SLE and for other diseases throughout the study, unless these medication 
regimens are specifically excluded by the study entry criteria. Safety and efficacy assessments 
and laboratory sample collections will be performed as specified in the SoA. 
Follow-up period 
All participants will have a post-treatment follow-up visit (Visit 801) for safety assessments. 
Randomized participants who were positive for hepatitis B core antigen (anti-HBc) at screening 
will have one additional post-treatment follow-up visit (Visit 802). 
Early discontinuation 
Participants who permanently discontinue the study drug early or withdraw from the study 
(Section 7) will undergo early termination procedures, including an early termination visit (ETV) 
and the post-treatment follow-up visits specified in the SOA. 
4.2. 
Scientific Rationale for Study Design 
SLEDAI-4 response as the primary endpoint 
The primary endpoint is the proportion of participants who achieve a SLEDAI-4 response at 
Week 24 (Section 8.1.1). The selection of SLEDAI-4 for the primary endpoint measure was 
based on analyses from 2 recent SLE Phase 3 studies involving more than 2200 patients in a 
similar patient population (Isenberg et al. 2016; Merrill et al. 2016). The purpose of those 
analyses was to characterize the clinical signs and symptoms most responsible for achieving 
responder status with Systemic Lupus Erythematosus Responder Index-5 (SRI-5), and then to 
use this information to design a more efficient study with clinically relevant endpoints (Kalunian 
et al. 2018). The primary endpoint of those 2 recent studies required a 5-point reduction in 
SLEDAI with no worsening in British Isles Lupus Assessment Group (BILAG) score or 
Physician’s Global Assessment of Disease Activity (PGA). The analyses found that fewer than 
1% of the study participants failed on SRI-5 due to BILAG or PGA worsening after achieving a 
≥5-point reduction in SLEDAI. Also, in the belimumab phase 3 SLE trials (as reported in 
Arthritis Advisory Committee meeting briefing document 2010), the proportion of patients with 
a ≥4-point reduction in SLEDAI that failed to achieve a Systemic Lupus Erythematosus 
Responder Index-4 (SRI-4) due to worsening of the BILAG or PGA ranged from 0.3% to 2.2% 
(Kalunian et al. 2018). These data provide a rationale to focus on SLEDAI as the primary driver 
of clinical response. A 4-point reduction in SLEDAI is considered clinically meaningful and 
serves as the basis for the primary endpoint of SLEDAI-4 (Gladman et al. 2000). 
 
 
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
31 
Appropriateness of study population 
Patients with at least moderately active SLE are an appropriate study population for a novel 
investigational product with immunomodulating properties. The study entry criteria will enable 
enrollment of patients who are representative of the general population of patients with at least 
moderately active SLE as defined by Systemic Lupus Erythematosus Disease Activity Index 
(SLEDAI) ≥6 during screening and ≥4 for clinical features at randomization before 
administration of study drug. This SLEDAI cutoff has been used in other Phase 2 studies of SLE 
(van Vollenhoven et al. 2018; Wallace et al. 2018). 
Choice of control and number of treatment groups 
A double-blind, placebo-controlled design limits bias for both participant assessments and 
investigator assessments and enables a clearer interpretation of the effects of active drug. The 
selection of placebo as a comparator for this study is warranted because there are few approved 
therapies for SLE and because study participants will be permitted to receive concomitant 
standard-of-care therapies. The multiple active dose levels will allow for an evaluation of safety 
and efficacy across a broad dose range and so provide information to guide dose selection for 
future studies. 
Duration of treatment period and post-treatment follow-up 
Evaluation of measures of efficacy at the Week 24 time point is consistent with the duration of 
treatment at the primary endpoint for proof-of-concept studies of other interventions for SLE 
(Furie et al. 2017; van Vollenhoven et al. 2018; Wallace et al. 2018). 
In longer studies, SLE efficacy outcomes at Week 24 are similar to those observed at Week 52, 
which is the time point typically used for registration studies (Furie et al. 2011; Navarra et al. 
2011; Isenberg et al. 2016; Merrill et al. 2016). Clinically meaningful effects were observed 
earlier than 24 weeks in open-label SLE studies of low-dose IL-2 formulations (He et al. 2016 
[rhIL-2Ser125]; Rosenzwajg et al. 2019 [aldesleukin and ILT-101]), which are hypothesized to 
work through a mechanism of action similar to that of LY3471851. 
A post-treatment study visit will occur at Week 30, which is 8 weeks after the last dose of 
investigational product and corresponds to approximately 5 half-lives. 
Optional prescreening period 
An optional prescreening period was included in the study design to reduce the number of screen 
failures. In previous studies of SLE, the absence of autoantibodies, as assessed by the central 
laboratory during the screening period, has been a major reason for screening failures. 
4.2.1. 
Participant Input into Design 
The sponsor involved patients in the design of this study by engaging patients in simulations and 
other face-to-face or virtual collaborative events for related SLE trials. The insights gained from 
these events were used to ensure that this study design is supportive of the well-being of the 
study participants and that the study procedures can be implemented effectively at the 
investigative sites. 
 
 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
32 
4.3. 
Justification for Dose 
Dose selection 
The doses were selected based on evaluation of clinical safety, pharmacokinetic (PK), and 
pharmacodynamic (PD) data from a single-ascending dose study in healthy volunteers (SAD, 
Study 16-358-01), a multiple-ascending dose study in SLE patients (MAD, Study 17-358-02), 
and on nonclinical toxicology data. 
The available clinical safety data, 
 
 supports 
continued development over a longer time course in Phase 2, given the safety monitoring 
planned for individual participants and the planned safety data reviews (Section 8.2). 
The lowest dose 
 is predicted to achieve exposures that are within the range of exposures 
achieved with the 
 doses previously administered in the SAD and MAD 
studies. These doses were associated with pharmacological effects. For example, up to a 
 
 from baseline was observed in the percentage of CD25bright Tregs, with a similar 
fold change in absolute numbers of CD25bright Tregs reported. 
The highest dose 
 is predicted to achieve exposures that are similar to a dose of 
 the highest dose tested in the MAD study. This dose was associated with 
pharmacological effects; increases in CD25bright Tregs and total Tregs were observed at this 
dose. An approximate 
 increase from baseline was observed in the absolute 
numbers of CD25bright Tregs reported, which did not return to baseline between doses. 
The numbers of NK cells were highly variable across patients, with an increase in the absolute 
numbers of NK cells observed 
 
 
 
 
 
 
 
An intermediate dose 
 will also be evaluated. This dose is predicted to achieve 
exposures that are similar to a dose 
 tested in both the SAD and the MAD 
studies. In the MAD study, the 
 dose was associated with increases in CD25bright Tregs 
and total Tregs; an approximate 
 increase from baseline was observed in the 
absolute numbers of CD25bright Tregs reported after each of the three doses, which did not return 
to baseline between doses. There was minimal effect on absolute numbers of NK cells at this 
dose level.  
 
 
 
 
 
 
 
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
33 
4.4. 
End-of-Study Definition 
A participant is considered to have completed the study if he or she has completed all required 
periods of the study, including the last visit or the last scheduled procedure shown in the SoA 
(Section 1.3). 
The “end of the study” is defined as the date of the last visit or last scheduled procedure shown 
in the SoA for the last participant in the study globally. 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
34 
5. 
Study Population 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
All screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria. Participant eligibility will be reviewed and confirmed by an eligibility 
review committee prior to randomization. 
The investigator will maintain a screening log to record details of all participants screened and to 
confirm eligibility or record reasons for screening failure, as applicable. 
For rescreening and retesting activities within the screening period, see Section 5.4. 
5.1. 
Inclusion Criteria 
Patients will be included in the study only if all of the following inclusion criteria are met: 
Informed consent 
[1]  Are capable of giving signed informed consent as described in Appendix 10.1, which 
includes compliance with the requirements and restrictions listed in the ICF and in this 
protocol. 
Participant characteristics 
[2]  Are male or female patients from 18 to 65 years of age (inclusive), at the time of screening 
(Visit 1). 
Note: Contraceptive use by men or women should be consistent with local regulations 
regarding the methods of contraception for those participating in clinical studies. For the 
contraception requirements of this protocol, see Appendix 10.4. 
SLE-related inclusion criteria 
[3]  Have received a clinical diagnosis of SLE at least 24 weeks before the screening visit 
(Visit 1). 
[4]  Have documentation of having met at least 4 of the 11 Revised Criteria for Classification of 
Systemic Lupus Erythematosus according to the 1997 Update of the 1982 ACR (Tan et al. 
1982; Hochberg 1997) before randomization. 
[5]  Have a positive ANA (titer ≥1:80) and/or a positive 
 
antibody test at screening (Visit 1) as assessed by the central laboratory. 
Note: This criterion must be assessed on the samples collected at Visit 1, not the 
prescreening samples collected at Visit 601. For repeat testing for ANA,
 
during the screening period, see Section 5.4.1. 
[6]  Have a SLEDAI-2K score ≥6 at screening (Visit 1) and clinical SLEDAI-2K score ≥4 at 
randomization (Visit 2). 
[7]  Have active arthritis and/or active rash as defined by the SLEDAI-2K at screening and at 
randomization. 
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
35 
5.2. 
Exclusion Criteria 
Patients will be excluded from the study if any one of the following criteria are met: 
Corticosteroid use 
[8]  Are currently receiving oral corticosteroids at doses >20 mg per day of prednisone (or 
equivalent) or have adjusted the dosage of corticosteroids within 2 weeks before 
randomization (Visit 2). 
[9]  Have received topical corticosteroids, other than stable doses of Class VI (mild, such as 
desonide) or Class VII (least potent, such as hydrocortisone), within 8 weeks before 
randomization (Visit 2). 
[10]  Have received parenteral (that is, intravenous or intramuscular) corticosteroids within 12 
weeks before randomization (Visit 2) or are expected to require parenteral corticosteroids 
during the study. 
Other prior or concomitant therapy 
[11]  Have started treatment with or adjusted the dosage of NSAIDs intended for treatment of 
signs and symptoms of SLE within 2 weeks before randomization (Visit 2). 
[12]  Have started treatment with or adjusted the dosage of an antimalarial (such as 
hydroxychloroquine, chloroquine, or quinacrine) within 12 weeks before randomization 
(Visit 2); or have received more than a single antimalarial within 12 weeks before 
randomization (Visit 2). 
[13]  Have started treatment with or adjusted the dosage of an immunosuppressant (such as 
methotrexate, azathioprine, mycophenolate mofetil, or mizoribine,) within 12 weeks before 
randomization (Visit 2); or have received more than a single immunosuppressant within 12 
weeks before randomization (Visit 2). 
[14]  Have received an oral calcineurin inhibitor, such as cyclosporine, tacrolimus, sirolimus, or 
voclosporin, within 12 weeks before randomization (Visit 2). 
[15]  Have received an oral Janus kinase (JAK) inhibitor, including but not limited to baricitinib, 
tofacitinib, and upacitinib, within 12 weeks before randomization (Visit 2). 
[16]  Have received cyclophosphamide (or any other cytotoxic agent) within 12 weeks before 
randomization (Visit 2). 
[17]  Have received biologic therapies in the specified number of weeks before screening: 
[17a]  rituximab or ustekinumab within 24 weeks before randomization (Visit 2), 
[17b]  other biologic therapies including, but not limited to, anticytokine or receptor 
blocker (etanercept, infliximab, certolizumab, adalimumab, golimumab, tocilizumab, 
anakinra, ixekizumab, secukinumab, belimumab, abatacept) within 12 weeks before 
randomization (Visit 2). 
[18]  Have received intravenous Ig within 24 weeks before randomization (Visit 2). 
[19]  Have received plasmapheresis within 12 weeks before randomization (Visit 2). 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
36 
[20]  Have received any live vaccine (that is, live attenuated) within 12 weeks of screening 
(Visit 1), or intend to receive a live vaccine during the study, or plan to receive such 
vaccine within 8 weeks of completing treatment in this study. 
[21]  Have received a Bacillus Calmette-Guerin (BCG) vaccination or treatment within 
12 months of screening (Visit 1) or intend to have vaccination with BCG during the course 
of the study, or plan to receive such vaccination within 8 weeks of completing treatment in 
this study. 
[22]  Have participated within the last 30 days in a clinical study involving an investigational 
product. If the previous investigational product has a long half-life, at least 5 half-lives or 
30 days (whichever is longer) should have passed before the randomization visit (Visit 2) 
of Study KFAJ. 
[23]  Have received treatment with aldesleukin or other IL-2–related treatment. 
Current or historical infections 
[24]  Have a current or recent acute, active infection. For at least 30 days prior to screening 
(Visit 1) and up to the time of randomization (Visit 2), participants must have no symptoms 
or signs of confirmed or suspected infection, and must have completed any appropriate 
anti-infective treatment. 
Note: Participants with an upper respiratory infection or a vaginal/oral candida infection 
being treated only symptomatically and not requiring systemic anti-infectives may be 
considered for enrollment if other eligibility criteria are met. Other uncomplicated local 
infections should be discussed with the sponsor’s medical monitor. 
[25]  Have had, within 12 weeks before randomization (Visit 2), any of the following types of 
infection: 
○  Serious (requiring hospitalization, and/or intravenous or equivalent oral antibiotic 
treatment), 
○  Opportunistic (as defined in Winthrop at al. 2015),  
Note: Herpes zoster is considered active and ongoing until all vesicles are dry and 
crusted over, 
○  Chronic (duration of symptoms, signs, and/or treatment of 6 weeks or longer), 
○  Recurring (including, but not limited to, herpes simplex, herpes zoster, recurring 
cellulitis, chronic osteomyelitis). 
Note: Participants with only recurrent, mild and uncomplicated orolabial and/or genital 
herpes may be considered for enrollment if discussed with the sponsor’s designated 
medical monitor and if other eligibility criteria are met. 
[26]  Have human immunodeficiency virus (HIV) infection. 
[27]  Have a current infection with hepatitis B virus (HBV DNA) (that is, positive for hepatitis B 
surface antigen [HBsAg] and/or PCR positive for HBV DNA). 
[28]  Have a current infection with hepatitis C virus (that is, positive for HCV RNA). 
[29]  Have current or past history of active tuberculosis (TB) (see Section 8.2.6). 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
37 
[30]  Have or have had latent TB infection (LTBI) that has not been treated with a complete 
course of appropriate therapy as defined by the World Health Organization and/or the 
United States Centers for Disease Control and Prevention, unless such treatment is 
underway (see Section 8.2.6). 
Other current or historical medical conditions 
[31]  Have severe active lupus nephritis defined clinically and/or by urine protein/creatinine 
ratio >300 mg/mmol (as an estimate of approximate proteinuria >3 g/day) or active urinary 
sediment with red blood cell cast(s), or histological evidence of lupus nephritis (Class III, 
IV, V, or VI according to the International Society of Nephrology classification criteria) 
within 12 weeks before randomization (Visit 2). 
Note: For laboratory retesting related to lupus nephritis, see Section 5.4.1. 
[32]  Have active severe central nervous system lupus including aseptic meningitis, cerebral 
vasculitis, demyelinating syndrome, myelopathy, acute confusional state, psychosis, acute 
inflammatory demyelinating polyradiculoneuropathy, cranial neuropathy, plexopathy, 
status epilepticus, or cerebellar ataxia within 24 weeks before randomization (Visit 2). 
[33]  Have active fibromyalgia that, in the investigator’s opinion, would make it difficult to 
appropriately assess SLE activity for the purposes of this study. 
[34]  Have been treated for or had an active occurrence of a systemic inflammatory condition 
other than SLE, such as, but not limited to, rheumatoid arthritis, juvenile chronic arthritis, 
spondyloarthropathy, Crohn’s disease, ulcerative colitis, or psoriatic arthritis in the 
12 weeks before randomization (Visit 2). 
Note: Participants with secondary Sjögren’s syndrome are not excluded. 
[35]  Have experienced a thrombotic event within 24 weeks before randomization or are on 
anticoagulants and in the opinion of the investigator are not well-controlled regarding 
management of hypercoagulable risk. 
[36]  Have experienced any of the following within 12 months before screening: myocardial 
infarction, unstable ischemic heart disease, stroke, or New York Heart Association Stage 
IV heart failure. 
[37]  Have a history of clinically significant or uncontrolled cardiovascular disease (for example, 
hypertension, angina, congestive heart failure); endocrine disorder (for example, diabetes, 
thyroid dysfunction); or respiratory, hepatic, renal, gastrointestinal, hematologic, or 
neuropsychiatric disorder; or any other serious and/or unstable illness that in the opinion of 
the investigator, could constitute an unacceptable risk to the participant when taking an 
investigational product or could interfere with the interpretation of study data. 
[38]  Are, in the judgment of the investigator, actively suicidal and therefore deemed to be at 
significant risk for suicide. 
[39]  Have answered “yes” to either Question 4 or Question 5 on the “Suicidal Ideation” portion 
of the Columbia-Suicide Severity Rating Scale (C-SSRS) or 
have answered “yes” to any of the suicide-related behaviors on the “suicidal behavior” 
portion of the C-SSRS, 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
38 
and the ideation or behavior occurred within 4 weeks prior to randomization (Visit 2). 
[40]  Have a history of lymphoproliferative disease; or have signs or symptoms suggestive of 
possible lymphoproliferative disease, including lymphadenopathy or splenomegaly (other 
than primarily because of SLE); or have active primary or recurrent malignant disease; or 
have been in remission from clinically significant malignancy for <5 years. 
Exceptions:  
○  Participants with cervical carcinoma in situ that has been resected with no evidence of 
recurrence or metastatic disease for at least 3 years may participate in the study if other 
study entry are met. 
○  Participants with basal cell or squamous epithelial skin cancers that have been 
completely resected with no evidence of recurrence for at least 3 years may participate 
in the study if other study entry criteria are met. 
[41]  Have had any major surgery within 12 weeks before randomization (Visit 2)  or will require 
major surgery during the study that, in the opinion of the investigator in consultation with 
Lilly or its designee, would pose an unacceptable risk to the participant. 
[42]  Have a known allergy to the investigational intervention or any of its excipients, clinically 
significant multiple or severe drug allergies, intolerance to topical corticosteroids, or 
history of severe post-treatment hypersensitivity reactions, including, but not limited to, 
erythema multiforme major, linear immunoglobulin A (IgA) dermatosis, toxic epidermal 
necrolysis, or exfoliative dermatitis. 
Diagnostic assessments or abnormal laboratory values 
[43]  Have any of the following specific abnormalities on screening laboratory tests: 
●  alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 times upper 
limit of normal (ULN) 
●  total bilirubin level (TBL) ≥1.5 times ULN 
●  hemoglobin <8.5 g/dL (<85.0 g/L) 
●  total white blood cell count (WBC) <2500 cells/µL (<2.50 × 103/µL or <2.50 GI/L) 
●  eosinophilia (absolute eosinophil count >3000 cells/µL (>3.0 × 103/µL or >3.0 GI/L) 
●  neutropenia – absolute neutrophil count (ANC) <1000 cells/µL  
(<1.00 × 103/µL or <1.00 GI/L) 
●  lymphopenia – absolute lymphocyte count (ALC) <500 cells /µL  
(<0.50 × 103/µL or <0.50 GI/L) 
●  thrombocytopenia  – platelets <50,000 cells/µL (<50 × 103/µL or <50 GI/L) 
●  estimated glomerular filtration rate (eGFR) (Modification of Diet in Renal Disease 
[MDRD]) <50 mL/min/1.73 m2 (FDA 2010). 
Note: For repeat testing of screening laboratory tests, see Section 5.4.1. 
[44]  Have known hypogammaglobulinemia or a screening immunoglobulin G (IgG) 
level <565 mg/dL (<5.65 g/L). 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
39 
[45]  Have other abnormal laboratory values at screening that, in the opinion of the investigator, 
indicate unacceptable risk for the participant’s safety in the study. 
[46]  Have screening electrocardiogram (ECG) abnormalities that, in the opinion of the 
investigator, are clinically significant and indicate an unacceptable risk for the participant’s 
safety in the study.  
Previous or concurrent clinical study experience 
[47]  Have previously been randomized in this study or have received LY3471851 in any 
previous study. 
[48]  Are currently enrolled in any other clinical study involving an investigational product or 
any other type of medical research judged not to be scientifically or medically compatible 
with this study. 
Other exclusions 
[49]  Are largely or wholly incapacitated, permitting little or no self-care, such as being 
bedridden or confined to wheelchair. 
[50]  Have donated more than a single unit of blood within 4 weeks before randomization 
(Visit 2)  or intend to donate blood during the course of the study. 
[51]  Have a history of chronic alcohol abuse, intravenous (IV) drug abuse, or other illicit drug 
abuse within 1 year before screening. 
Note: Marijuana is considered an illicit drug for the purposes of this study, regardless of 
local laws. Cannabidiol (CBD) products may be used during the study if they are derived 
exclusively from hemp. Participants who use hemp-based CBD products must be on a 
stable dose for at least 10 days prior to randomization, and participants must remain on that 
stable dose during the study. 
[52]  Are unable or unwilling to make themselves available for the required number of study 
visits or unwilling to follow the restrictions and procedures of the study. 
[53]  Are women who intend to become pregnant or breastfeed at any time in the study. 
[54]  Are investigative site personnel directly affiliated with this study and/or their immediate 
families. Immediate family is defined as a spouse, parent, child, or sibling, whether 
biological or legally adopted. 
[55]  Are employees of Eli Lilly and Company (Lilly) or are employees of a third-party 
organization involved in the study, which requires exclusion of their employees. 
5.3. 
Lifestyle Considerations 
Not applicable. 
5.4. 
Screen Failures 
Screen failure is defined as participants who consent to participate in the clinical study but are 
not subsequently randomly assigned to study intervention. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants to meet the 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
40 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes demography, 
screen failure details, eligibility criteria, and any serious adverse event (SAE). 
5.4.1. 
Allowed Retesting of Screening Investigations 
Repeating laboratory tests during the screening period does not constitute rescreening. 
In particular, the following laboratory tests may be repeated once during the screening period to 
determine a participant’s eligibility for randomization:  
●  tests for ANA,
 
●  tests related to lupus nephritis, and 
●  clinical chemistry, hematology, calculation of estimated glomerular filtration rate. 
See Section 8.2.6 for retesting related to TB. 
5.4.2. 
Rescreening of Individuals Who Failed Screening 
Informed consent for rescreenings 
Individuals who are to be rescreened must first sign a new ICF (Appendix 10.1, Section 10.1.3). 
Such individuals will be assigned a new participant number. 
Rescreening after failure to meet study entry criteria 
An individual who does not meet the criteria for participation in this study may be rescreened 
one time if the reason for the screen failure has resolved and if the sponsor has approved the 
rescreening. The interval between the failure to meet study entry criteria and the start of 
rescreening should be at least 4 weeks. 
Rescreening for administrative reasons 
An individual may be rescreened one time for an administrative reason, including, for example, 
but not limited to, falling out of the screening window because of scheduling conflicts. The 
sponsor does not need to approve rescreening for an administrative reason. The rescreening can 
start immediately after the administrative reason has resolved. 
Procedures not required to be repeated during rescreening 
Individuals in rescreening who have already completed the protocol-required screening 
chest x-ray (CXR) or TB tests are not required to repeat these procedures if they were performed 
within 90 days before the date of signing the rescreening ICF. However, these procedures can be 
repeated at the discretion of the investigator. 
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
42 
Investigators should consult the information provided in the Pharmacy Manual or the label for 
specific preparation and administration information, including warnings, precautions, 
contraindications, adverse reactions, and dose modifications. 
Preparation 
The IPs must be prepared by an unblinded pharmacist (or other unblinded qualified individual) 
who is not involved in any other study-related procedures. 
Handling and storage 
Follow the storage and handling instructions for the IP as noted in the IP packaging. The 
handling and storage information for the administered product is located in the Pharmacy 
Manual. 
Site responsibilities and accountability 
The following are responsibilities of the investigator or his or her designee: 
●  The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and that any discrepancies are 
reported and resolved before use of the study intervention. 
●  Only participants enrolled in the study may receive study intervention, and only 
authorized site staff may supply or administer study intervention. All study intervention 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labeled storage conditions with access limited to 
the investigator and authorized site staff. 
●  The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(that is, receipt, reconciliation, and final disposition records). 
Further guidance and information for the final disposition of unused study interventions are 
provided in the Pharmacy Manual. 
The investigator or designee is also responsible for 
•  explaining the correct use of the study interventions 
•  verifying that instructions are followed properly 
•  maintaining accurate records of IP dispensing and collection, and 
•  returning all unused medication to Lilly or its designee at the end of the study. 
Note: In some cases, sites may destroy the material if, during the investigative site 
selection, the evaluator has verified and documented that the site has appropriate 
facilities and written procedures to dispose of clinical materials. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
Blinding will be maintained throughout the conduct of the study as described in the separate 
Unblinding Plan. 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
43 
Method of treatment assignment 
Assignment to treatment groups will be determined by a computer-generated random sequence 
using an interactive web-response system (IWRS). 
Unblinded pharmacist 
Investigators and all individuals involved in administering the blinded treatment or performing 
assessments will remain blinded to each participant’s assigned study intervention throughout the 
course of the study. To maintain this blind, an otherwise uninvolved party (unblinded pharmacist 
or other unblinded qualified individual) will be responsible for the preparation and dispensation 
of all study intervention. Blinded site personnel will administer the study intervention to the 
participant. 
Independent assessor for injection site reactions 
At every visit following the first dose and prior to any blinded study activity, an independent 
Injection Site Reaction (ISR) assessor who is not involved with other study procedures will 
evaluate each participant for the presence of ISRs. If the participant presents with symptoms of 
an ISR (see Section 8.2.11), the ISR assessor will examine the impacted areas and record the 
information in the electronic case report form (eCRF). 
Whether an ISR is present or not, the ISR assessor will use a bandage (or similar material) to 
cover the anatomical area where the participant received his or her last dose. The purpose of 
covering this area is to minimize bias when blinded study personnel conduct other study 
assessments, given the known frequency of ISRs with the molecule. 
Emergency unblinding 
Emergency unblinding for adverse events may be performed through the IWRS. This option may 
be used ONLY if the participant’s well-being requires knowledge of the participant’s treatment 
assignment. All actions resulting in an unblinding event are recorded and reported by the IWRS. 
If a participant’s study treatment assignment is unblinded to blinded site personnel performing 
assessments, including the investigator, or to the participant, the participant must be discontinued 
from study drug, unless the investigator obtains specific approval from the sponsor’s medical 
monitor for the participant to continue (Section 7.1.1). 
In case of an emergency, the investigator has the sole responsibility for determining if unblinding 
of a participants’ intervention assignment is warranted. Participant safety must always be the first 
consideration in making such a determination. If the investigator decides that unblinding is 
warranted, it is the responsibility of the investigator to promptly document the decision and 
rationale and notify the sponsor as soon as possible. 
In cases where there are ethical reasons to have the participant remain in the study, the 
investigator must obtain specific approval from the sponsor’s clinical research physician for the 
participant to continue in the study. 
6.4. 
Study Intervention Compliance 
Participants will receive study intervention directly from the investigator or designee at the study 
site, under medical supervision. The date and time of each dose administered in the clinic will be 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
44 
recorded in the source documents and recorded in the eCRF. Deviations from the prescribed 
dosage regimen should be recorded in the eCRF. 
6.5. 
Concomitant Therapy 
Participants will be instructed to consult the investigator or other appropriate study site personnel 
before taking any new medications or supplements during the study. The sponsor’s medical 
monitor should be contacted if there are any questions. 
Recording of concomitant therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements) that the participant is receiving at the time of enrollment or receives 
during the study must be recorded along with 
•  reason for use,  
•  route of administration, and 
•  dates of administration, including start and end dates. 
For concomitant therapies of special interest, dosage information will also be collected as well as 
reason for use and route and dates of administration. 
Allowed concomitant therapy 
Participants will maintain their usual medication regimen for SLE and for any other diseases 
throughout the study unless specifically excluded in the protocol (Section 5.2). Doses must be 
stable prior to randomization, as stated in the exclusion criteria. Permitted concomitant 
background standard-of-care medications for SLE can include any combination of these: 
•  NSAIDs,  
•  a single antimalarial (such as hydroxychloroquine, chloroquine, or quinacrine),  
•  a single oral immunosuppressant from the following list: methotrexate, azathioprine, 
mycophenolate mofetil, or mizoribine,  
•  a single corticosteroid. 
Dose adjustment for NSAIDs, antimalarials, and immunosuppressants 
Doses of NSAIDs intended for treatment of signs and symptoms of SLE, antimalarials, and 
immunosuppressants should not be adjusted during the study’s double-blind treatment period. 
Participants who require initiation or increase in dosage of NSAIDs for treatment of signs and 
symptoms of SLE, or of antimalarials, or of immunosuppressants after randomization may 
remain in the study and continue receiving study drug. 
Dose adjustment for corticosteroids 
See Section 6.5.1. 
6.5.1. 
Corticosteroid Management Program 
Key elements of the corticosteroid management program of this study include the following: 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
45 
●  Participants are restricted to prednisone ≤20 mg per day (or equivalent) at randomization 
(Visit 2), having been on stable doses for at least 2 weeks prior to randomization. 
●  Following randomization, the dose of prednisone (or equivalent) should not be increased 
above the participant’s background level. 
●  Participants on >10 mg per day are required to taper their dose to ≤10 mg per day by 
Week 12 to be considered responders. 
●  The corticosteroid doses should not be changed after Week 18. 
●  Participants with intolerable or exacerbating disease are allowed access to standard-of- 
care therapy, including increasing the dose of prednisone (or equivalent). Such 
participants are allowed to remain in the study and continue receiving study drug, but they 
will be considered nonresponders for the efficacy analyses from the time of the 
medication change onward. 
Guidance on corticosteroid tapering 
The following guidance on corticosteroid tapering is provided for participants taking >10 mg 
prednisone (or equivalent) at baseline. 
●  Steroid tapering should begin no sooner than 4 weeks after randomization. 
●  Tapering should include a stepwise reduction in 2.5 mg/d to 5 mg/d increments, with each 
step reduction occurring at 2-week intervals. Thus, the stepwise reduction will occur in 
intervals that are consistent with the visit schedule. 
●  Participants who do not tolerate a reduction can increase the dose up to, but not exceeding, 
the dose at randomization. 
Under this schedule, a participant on the highest allowed dose of 20 mg per day at randomization 
would taper his or her steroid dose in 2.5 mg per day increments at 2-week intervals to achieve 
the target of ≤10 mg per day in time for the assessments at Week 12. 
Participants who are taking ≤10 mg prednisone (or equivalent) at baseline may have their dose 
tapered at the discretion of the investigator. However, the corticosteroid doses should not be 
changed after Week 18. 
These recommendations recognize that there is variability in how corticosteroids are 
administered. The intent is to allow investigators flexibility in how corticosteroids are tapered for 
individual participants, provided that the participants reach the goal of ≤10 mg per day in time 
for the assessments at Week 12. 
Concomitant therapy after permanent discontinuation of study drug 
Standard-of-care therapy can be resumed after the participant is permanently discontinued from 
study drug. 
6.6. 
Dose Modification 
Modification of the dose of the study intervention is not permitted in this study. 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
46 
6.7. 
Intervention after the End of the Study 
LY3471851 will not be available to participants following completion of the study. 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
47 
7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal 
In rare instances, it may be necessary for a participant to permanently discontinue study drug. 
These sections describe reasons for a participant’s 
•  permanent or temporary discontinuation of study drug (Section 7.1), or 
•  discontinuation (withdrawal) from the study (Section 7.2). 
Discontinuation of specific sites or the trial as a whole (“stopping rules”) are handled as part of 
regulatory, ethical, and trial oversight considerations in Appendix 10.1, Section 10.1.9. 
7.1. 
Discontinuation of Study Intervention 
Study drug may be permanently discontinued or temporarily withheld during the study. 
Participants who permanently discontinue study drug early will undergo early termination 
procedures, which include 
• an early termination visit (ETV)  
   AND, 
• post-treatment follow-up visits, as shown in the SOA. 
7.1.1. 
Criteria for Permanent Discontinuation of Study Drug 
Data collection and safety follow-up when study drug is permanently discontinued 
If study drug is permanently discontinued, the participant will remain in the study to have an 
ETV and post-treatment follow-up visits, as shown in the SoA (Section 1.3). 
See the SoA for data to be collected at the time of discontinuation and follow-up and for any 
further evaluations that need to be completed. Safety follow-up is as outlined in the SoA (Section 
1.3), Section 8.2 (“Safety Assessments), 
 
 of the protocol. 
The presence or absence of a clinically significant ISR will not unblind participants and is 
therefore not a protocol deviation.  
Criteria for permanent discontinuation of study drug 
Possible reasons for permanent discontinuation of study drug include, but are not limited to, the 
following: 
Participant decision 
●  The participant requests to discontinue the study drug. 
Pregnancy 
●  The participant becomes pregnant during the study (see Section 8.2.5.1). 
Safety considerations 
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
48 
●  The participant develops any of the following conditions during the study: 
−  malignancy (except for successfully treated basal or squamous cell skin carcinoma) 
−  HIV/acquired immune deficiency syndrome (AIDS) infection 
−  active TB infection or untreated LTBI (Section 7.1.2; Section 8.2.6) 
−  HCV RNA positive (Section 8.2.8) 
−  HBV DNA positive and clinical assessment consistent with HBV reactivation 
Note: The HBV DNA result is to be confirmed if initial positive test result is 
positive but below the level of quantification (Section 7.1.2; Section 8.2.7). The 
participant is to be referred to, evaluated, and managed by a specialist physician 
with expertise in evaluation and management of viral hepatitis prior to 
discontinuation of any immunomodulatory and/or immunosuppressive therapy, 
including study drug. Timing of discontinuation from study drug relative to the 
initiation of any antiviral treatment for hepatitis is to be based on the 
recommendation of the consulting specialist physician, in conjunction with the 
investigator, and aligned with medical guidelines and standard of care. 
●  The participant answered yes" to Question 4 or Question 5 on the "Suicidal Ideation" 
portion of the C-SSRS, or answered "yes" to any of the suicide-related behaviors on the 
Suicidal Behavior portion of the C-SSRS. 
Note: A psychiatrist or appropriately trained professional may assist in the decision 
to discontinue the participant. 
●  The investigator, after consultation with the sponsor’s designated medical monitor, 
determines that a systemic hypersensitivity reaction has occurred and is related to study 
drug administration. 
●  The participant has any of the following results on 2 consecutive samples taken at least 
48 hours, but no more than 1 week, apart. 
−  Total WBC <1000 cells/L 
−  ANC <500 cells/L 
−  ALC <200 cells/L 
−  Hemoglobin <6.5 g/dL 
●  The participant develops CRS. In consultation with the Lilly medical monitor, if an 
adverse event is deemed possibly or probably due to CRS based on the details and 
severity of clinical signs and symptoms, time course of symptom onset relative to 
study drug administration, and if possible, a cytokine panel from a blood sample 
obtained at the time of the event, the participant will be discontinued from study 
treatment, and will continue safety follow-up. 
●  The participant develops hypereosinophilia. 
○  Participants with absolute eosinophil counts >1500 cells/µL and signs and/or 
symptoms of target organ involvement that is not consistent with lupus and/or with the 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
49 
participant’s lupus and medical history will be discontinued from study drug in 
consultation with the medical monitor. Participants will undergo appropriate medical 
evaluation, which should take into account the participant’s known lupus and past 
medical history according to the participant’s history and medical records, including 
previous imaging, biopsies and laboratory findings. Evaluation of target organ 
involvement will involve additional diagnostic tests as appropriate, including 
laboratory tests, imaging (for example, echocardiogram, CXR, computed tomography 
[CT] scan) and biopsies. New onset cardiac, pulmonary, and skin findings in the 
setting of peripheral eosinophilia will be considered as target organ involvement, 
unless attributable to other causes. 
○  Asymptomatic participants with an absolute eosinophil count >5000 cells/µL should 
have a repeat measurement to confirm the count. If the count is confirmed, the 
participant will be permanently discontinued from study drug and undergo appropriate 
medical evaluation. 
●  The participant has an adverse event or a SAE or a clinically significant change in a 
laboratory value that, in the opinion of the investigator, merits the discontinuation of the 
study drug and appropriate measures being taken. 
Hepatic event or liver test abnormality 
●  Participants who are discontinued from study drug because of a hepatic event or liver test 
abnormality should have additional hepatic safety data collected via the hepatic eCRF 
packet. Discontinuation of study drug because of abnormal liver tests should be 
considered by the investigator when a participant meets one of the following conditions 
after consultation with the sponsor’s designated medical monitor (see Section 8.2.9). 
−  ALT or AST >8 times ULN 
−  ALT or AST >5 times ULN sustained for more than 2 weeks 
−  ALT or AST >3 times ULN and TBL >2 times ULN or international normalized ratio 
(INR) >1.5 
−  ALT or AST >3 times ULN with the appearance of fatigue, nausea, vomiting, right 
upper-quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%) 
−  alkaline phosphatase (ALP) >3 times ULN 
−  ALP >2.5 times ULN and TBL >2 times ULN, or 
−  ALP >2.5 times ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%). 
Other reasons 
●  Unblinding: If an investigator, blinded site personnel who are performing assessments, or 
participant is unblinded to a participant’s treatment assignment, the participant must be 
discontinued from the study drug and continue to post-treatment follow-up. In cases where 
there are ethical reasons to have the participant continue on study drug, the investigator 
must obtain specific approval from the sponsor’s designated medical monitor for the 
participant to continue. 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
50 
7.1.2. 
Criteria for Temporary Interruption (Withholding) of Study Drug 
7.1.2.1. 
Infection-Related Criteria for Temporary Withholding of Study Drug 
Temporary withholding of study drug is required for the development of any of the following 
infection-related criteria during the study: 
●  Serious or opportunistic infections, as defined in Exclusion Criteria (Section 5.2). Study 
drug is to be withheld until resolution of all acute clinical signs and symptoms, and 
completion of all appropriate anti-infective treatment (exception for LTBI, noted below). 
●  Participants diagnosed with LTBI during the study are to be permanently discontinued 
from study drug unless the participant is a candidate for LTBI treatment, and is treated for 
LTBI as follows: 
−  Study drug is temporarily withheld for at least the first 4 weeks of LTBI treatment. 
−  After receiving at least 4 weeks of appropriate LTBI therapy (as per World Health 
Organization and/or the United States Centers for Disease Control guidelines), if there 
is no evidence of hepatotoxicity (ALT/AST must remain ≤2 times ULN) or other 
treatment intolerance, study drug may be resumed. 
−  The participant must complete appropriate LTBI therapy to remain eligible to receive 
study drug. 
●  HBV DNA results that are reported as positive, or as detecting HBV DNA, but HBV DNA 
is below the level of quantification. The sponsor’s designated medical monitor should be 
contacted regarding study status of the participant. HBV DNA testing is to be repeated as 
soon as is feasible. If HBV DNA is confirmed as positive, the participant must be 
permanently discontinued from study drug (Section 7.1). 
7.1.2.2. 
Other Criteria for Temporary Withholding of Study Drug 
In some circumstances, it may be advisable to temporarily interrupt study drug as a result of 
adverse events or abnormal laboratory values that have an unclear relationship to study drug. 
Except in an emergency, the investigator should consult with sponsor’s designated medical 
monitor whenever possible before temporarily withholding study drug for reasons not specified 
in Section 7.1.2.1 above. 
7.2. 
Participant Discontinuation/Withdrawal from the Study 
Participant discontinuation (withdrawal from the study) is expected to be uncommon. 
A participant will withdraw from the study in the following circumstances: 
●  at any time at his or her own request, or at the request of his or her designee (for example, 
parents or legal guardian) 
●  at the discretion of the investigator for safety, behavioral, compliance, or administrative 
reasons 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
51 
●  if the participant enrolls in any other clinical study involving an investigational medicinal 
product or enrollment in any other type of medical research judged not to be scientifically 
or medically compatible with this study 
●  if the participant, for any reason, requires treatment with another therapeutic agent that has 
been demonstrated to be effective for treatment of the study indication. In this case, 
discontinuation from the study occurs prior to introduction of the new agent. 
Data collection and follow-up for participants who discontinue the study 
At the time of discontinuing from the study, an ETV should be conducted, if possible, as shown 
in the SoA (Section 1.3). See the SoA for data to be collected at the time of study discontinuation 
and follow-up and for any further evaluations that need to be completed. The participant will be 
permanently discontinued both from the study drug and from the study. 
No follow-up procedures will be performed for a participant who withdraws informed consent 
unless he or she has explicitly provided permission and consent. 
Withdrawal of consent for disclosure 
If the participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. If a participant 
withdraws from the study, he or she may request destruction of any samples taken and not tested, 
and the investigator must document this in the site study records. 
7.2.1. 
Discontinuation of Inadvertently Enrolled Participants 
If the sponsor or investigator identifies a participant who did not meet enrollment criteria and 
was inadvertently enrolled, then the participant should be discontinued from study treatment 
unless there are extenuating circumstances that make it medically necessary for the participant to 
continue on study treatment. If the investigator and the sponsor’s clinical research physician 
agree that it is medically appropriate to continue, the investigator must obtain documented 
approval from the sponsor’s clinical research physician to allow the inadvertently enrolled 
participant to continue in the study with or without treatment with investigational medicinal 
product. Safety follow-up is as outlined in the SoA (Section 1.3), Section 8.2 (“Safety 
Assessments), and Section 8.3 (“Adverse Events and Serious Adverse Events”) of the protocol. 
7.3. 
Lost to Follow up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. Site personnel are expected to 
make diligent attempts to contact participants who fail to return for a scheduled visit or were 
otherwise unable to be followed up by the site. 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
52 
8. 
Study Assessments and Procedures 
Study procedures and their timing are summarized in the SoA (Section 1.3). Protocol waivers or 
exemptions are not allowed. 
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 
8.1. 
Efficacy Assessments 
Efficacy and patient-reported outcome assessments are described in Appendix 10.7. The primary 
and secondary efficacy endpoints are described in the following subsections. 
The self-reported questionnaires will be administered in countries where the questionnaires have 
been translated into the native language of the region and linguistically validated. Any outcome 
measures that are participants’ self-assessments should be completed before any clinical 
examinations are performed. 
All patient-reported and clinician-reported efficacy assessments will be captured on an electronic 
tablet collected at site visits. 
8.1.1. 
Primary Efficacy Outcome Measure: SLEDAI-4 
The primary efficacy endpoint is the proportion of participants who achieve a SLEDAI-4 
response at Week 24. A SLEDAI-4 response is defined as a ≥4-point reduction in Systemic 
Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score from baseline. To be 
considered a SLEDAI-4 responder, participants must complete the 24-week treatment period and 
comply with concomitant medication rules (Section 9.4.1). Section 4.2 provides the rationale for 
the selection of SLEDAI-4 as the primary efficacy measure. 
8.1.2. 
Secondary Efficacy Outcome Measures 
8.1.2.1. 
British Isles Lupus Assessment Group (BILAG)-based Composite Lupus 
Assessment (BICLA) 
The BILAG-based Composite Lupus Assessment (BICLA) is a composite index used to assess 
disease activity in SLE. A BICLA response is defined as follows: 
●  Reduction of all baseline BILAG-2004 A to B or C or D; and baseline BILAG-2004 B to 
C or D; and no BILAG-2004 worsening in other organ systems, as defined by ≥1 new 
BILAG-2004 A or ≥2 new BILAG-2004 B 
●  No worsening from baseline in SLEDAI-2K, where worsening is defined as any increase 
from baseline in SLEDAI-2K 
●  No worsening from baseline in participants’ lupus disease activity, where worsening is 
defined by an increase ≥0.30 points on a 3-point PGA visual analogue scale (VAS) 
●  No permanent discontinuation of investigational product, and 
●  No use of restricted medications beyond the protocol-allowed threshold before assessment. 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
53 
8.1.2.2. 
Systemic Lupus Erythematosus Responder Index-4 (SRI-4) 
The SRI-4 is a composite index used to assess disease activity in SLE. The SLEDAI-2K 
component is used to capture clinically meaningful improvement in disease activity, while the 
BILAG and PGA of Disease Activity components ensure that the improvement in overall disease 
is not accompanied by disease worsening in other organ systems. A SRI-4 response is defined as 
follows: 
●  Reduction of ≥4 points from baseline in SLEDAI-2K score 
●  No new BILAG-2004 A or no more than 1 new BILAG -2004 B disease activity score, 
and 
●  No worsening (defined as an increase of ≥0.3 points [10 mm] from baseline) in PGA of 
Disease Activity. 
Participants must complete 24 weeks of the study and comply with concomitant medication rules 
to be considered a responder for the SRI-4 analysis (Section 9.4.1). 
8.1.2.3. 
Lupus Low Disease Activity State (LLDAS) 
An LLDAS response is defined as a low level of disease activity attained with or without use of 
low-dose steroids and/or tolerated standard maintenance doses of standard-of-care 
immunosuppressant medications (Franklyn et al. 2016). 
8.2. 
Safety Assessments 
Visits and order of safety assessments 
Safety assessments occur at visits specified in the SoA (Section 1.3). If multiple safety 
assessments are scheduled for the same visit, the preferred order of completion is 
1)  ECG and then vital signs, 
2)  other safety assessments, including physical examinations and nonleading (spontaneous) 
adverse event collection, followed by C-SSRS (Section 8.3.1.1), and finally 
4) blood sample collection for clinical laboratory, 
 
 
Data collection and reporting 
The adverse event data collection and reporting requirements are described in Section 8.3 and 
Appendix 10.3. 
 
 
Any clinically significant findings that result in a diagnosis and that occur after the participant 
receives the first dose of study drug should be reported to Lilly or its designee as an adverse 
event via eCRF. 
Safety monitoring 
The principle investigator will monitor the safety data throughout the study and should discuss 
immediate safety concerns with the sponsor immediately upon occurrence or awareness to 
determine whether the participant should continue or discontinue the study drug. 
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
54 
The sponsor will monitor the safety data, including adverse events and SAE, discontinuations, 
vital signs, and clinical laboratory results by means of blinded reviews performed at least 
quarterly and by other appropriate methods. These methods include reviews by a functionally 
independent safety physician and/or clinical research scientist who regularly reviews SAE 
reports in real time and across studies, and who reviews applicable clinical safety and 
epidemiological publications from the literature. If this safety monitoring uncovers an issue that 
needs to be addressed by unblinding at the individual or group level, additional analyses of the 
safety data can be performed by the sponsor’s independent internal safety review committee 
(Section 10.1.5). 
Appropriateness of safety assessments 
The safety assessments used in this study are routine elements of clinical health assessment and 
Phase 2 drug development. 
8.2.1. 
Vital Signs 
Vital signs (blood pressure, pulse rate, body temperature) will be measured as specified in the 
SoA (Section 1.3) and as clinically indicated. Additional vital signs may be measured during the 
study visits if warranted, as determined by the investigator. 
Blood pressure and pulse rate should be measured after the participant has been sitting for at 
least 5 minutes. 
Unscheduled orthostatic vital signs should be assessed, if possible, during any adverse event of 
dizziness or posture-induced symptoms. If the participant feels unable to stand, sitting or supine 
vital signs will be recorded. 
8.2.2. 
Physical Examinations 
A complete physical examinations and symptom-directed physical examinations will be 
conducted at the visits specified in the SoA (Section 1.3). Symptom-directed physical 
examinations may also be conducted at other visits, as determined by the investigator, if a 
participant presents with complaints. 
At screening and at approximately every third month thereafter, the specified physical 
examination, whether complete or symptom-directed, should include an assessment of TB risk 
factors and symptoms or signs of TB, including an assessment of peripheral lymph nodes (see 
Section 8.2.6). 
The complete physical examination should include the following regions and body systems: 
●  general appearance 
●  skin (other than the area covered by the bandage to assess ISRs) 
●  head, ears, eyes, nose, throat 
●  lymph nodes 
●  cardiovascular 
●  respiratory 
●  abdominal 
●  genitourinary (only as clinically indicated) 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
55 
●  extremities (tender/swollen joint counts to be documented separately), and 
●  neurologic. 
Height (without shoes) and weight will also be measured and recorded as specified in the SoA 
(Section 1.3). 
8.2.3. 
Electrocardiograms 
For each participant, 12-lead ECGs will be collected as specified in the SoA (Section 1.3). The 
ECGs should be recorded before collecting any blood for safety or PK tests. Participants must be 
supine for approximately 5 to 10 minutes before ECG collection and remain supine but awake 
during ECG collection. 
Electrocardiograms may be obtained at additional times, when deemed clinically necessary. 
Collection of additional ECGs at a particular time point is allowed to ensure high quality records. 
Electrocardiograms will be interpreted by a qualified physician (the investigator or qualified 
designee) at the study site as soon after the time of ECG collection as possible, and ideally while 
the participant is still present, to determine whether the participant meets the study entry criteria 
and for immediate participant management, should any clinically relevant findings be identified. 
If a clinically significant finding is identified (including, but not limited to changes from baseline 
in QT/QTc interval from baseline) after enrollment, the investigator or qualified designee, in 
conjunction with the sponsor’s medical monitor, will determine whether the participant can 
continue in the study and if any change in participant management is needed. 
The investigator or qualified designee must document his or her review of the ECG printed at 
collection. Any new clinically relevant finding will be reported as an AE. 
8.2.4. 
Chest Radiography 
A posterior–anterior (PA) CXR, interpreted and reported by a radiologist or pulmonologist, will 
be obtained as specified in the SoA (Section 1.3). 
A lateral CXR can also be obtained if, in the opinion of the investigator, a lateral view is 
indicated. 
Note: Participants do not need to have a CXR at screening if, based on the judgment of 
the investigator, both of the following two conditions are met: 
•  the CXR was performed within 3 months before initial screening, and 
•  documentation of the CXR, read by a qualified radiologist or pulmonologist, is 
sufficient for TB evaluation according to local standard of care. 
For each participant, the CXR films or images or a radiology report must be available to the 
investigator for review before the participant is randomized. Certain findings from CXR may be 
consistent with a condition that excludes a participant from the study; see Section 5.2. 
Note: Results of a chest CT scan or other imaging study similar to a CXR may be 
substituted in place of the CXR as described above, in consultation with the sponsor’s 
medical monitor. 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
56 
8.2.5. 
Laboratory Tests 
Appendix 10.2 lists the clinical laboratory tests to be performed, and the SoA (Section 1.3) 
specifies the study visits at which samples are routinely collected for clinical laboratory tests. 
Samples for laboratory testing will be obtained in the event of anaphylaxis or generalized 
urticaria, as described in Section 8.3.6.1 and Appendix 10.2. Additional tests may be performed 
at any time during the study as deemed necessary by the investigator or as required by local 
regulations. 
All protocol-required laboratory assessments, as defined in Appendix 10.2, must be conducted in 
accordance with the laboratory manual and the SoA (Section 1.3). 
If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the investigator (for example, SAE or adverse event or dose 
modification), then the results must be recorded in the eCRF. 
Reviewing and recording test results 
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the adverse event section of the eCRF. 
The laboratory reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those which are not associated with the underlying disease, unless judged 
by the investigator to be more severe than expected for the participant's condition. 
Repeat testing after clinically significant abnormal findings 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study or within 8 weeks after the last dose of study intervention should be repeated until 
the values return to normal or baseline or are no longer considered clinically significant by the 
investigator or the medical monitor. If such values do not return to normal/baseline within a 
period of time judged reasonable by the investigator, the etiology should be identified and the 
sponsor notified. 
Blinding of laboratory test results 
Laboratory results that could unblind the study will not be reported to investigative sites or other 
blinded personnel (Appendix 10.2). 
Sample retention 
Unless otherwise specified 
 
 all samples collected for specified laboratory tests will be 
destroyed within 60 days of receipt of confirmed test results. Certain samples may be retained for 
a longer period, if necessary, to comply with applicable laws, regulations, or laboratory 
certification standards. 
8.2.5.1. 
Pregnancy Testing 
Pregnancy testing is to be performed on women of childbearing potential (WOCBP) and women 
with a history of tubal ligation. Participants who are pregnant will be discontinued from the study 
(Section 7.1.1). 
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
57 
Visits and times 
Serum pregnancy test will be done at screening only, and results will be confirmed by the central 
laboratory. 
Urine pregnancy testing will be performed locally at visits specified in the SoA (Section 1.3). If 
the specified visit includes study drug administration, the urine pregnancy test must be 
“negative” within 24 hours before the study drug is administered. 
Urine pregnancy testing may be performed at additional time points during the study treatment 
period and/or follow-up period, at the discretion of the investigator or if this is required by local 
regulations. 
If a urine pregnancy test is not available, a local serum pregnancy test is an acceptable 
alternative. 
Optional follicle-stimulating hormone (FSH) testing 
The participant’s FSH level can be obtained during screening at the discretion of the investigator 
to assist in determining whether a woman meets the definition of “postmenopausal.” The FSH 
level can also be optionally obtained during the study to determine the participant’s 
postmenopausal status (see Section 1.3 and Appendix 10.4, Section 10.4.1). 
8.2.6. 
Tuberculosis Testing and Monitoring 
Tuberculosis testing 
During screening, all participants are to be assessed for risk factors, symptoms, and signs of TB 
with all of the following: 
●  Thorough history to determine the lifetime risk factors for TB infection, for TB 
progression, and for symptoms and/or signs of active TB, and 
●  Signs of previous or active TB by means of 
−  Thorough physical examination for signs of active TB, including measurement of 
body temperature (Section 8.2.1) and assessment of peripheral lymph nodes 
(Section 8.2.2), and 
−  PA CXR interpreted and reported by radiologist or pulmonologist (Section 8.2.4). 
All participants with no history of LTBI or active TB, and no history of positive Mantoux 
tuberculin skin test (TST) using purified protein derivative (PPD) or positive Mycobacterium 
tuberculosis interferon gamma release assay (IGRA) must have one of the following. 
●  PPD TST 
−  The TST is performed by injecting 0.1 mL of tuberculin PPD into the inner surface of 
the forearm. The injection should be made with a tuberculin syringe, with the needle 
bevel facing upward. The TST is an intradermal injection. When placed correctly, the 
injection should produce a pale elevation of the skin (a wheal) 6 to 10 mm in diameter. 
Measure induration at site of intradermal injection 48 to 72 hours after intradermal 
injection. The test must be read during this window of time. The reaction should be 
measured in millimeters of induration (palpable, raised, hardened area or swelling). 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
58 
The reader should not measure erythema (redness). The diameter of the indurated area 
should be measured across the forearm (perpendicular to the long axis). 
−  An induration of 5 or more millimeters is considered positive. Two-step testing (repeat 
TST from 1 to 3 weeks after the first TST) is recommended for certain participant 
groups, based on investigator judgment, including:  
¤  persons receiving immunosuppressant treatment 
¤  persons with a history of temporally remote increased risk of TB infection  
¤  persons for whom the first test is negative, as per local public health and/or 
professional medical society recommendations. 
•  IGRA for M tuberculosis. Ensure that specimen handling, transport, timing, and laboratory 
procedures meet all requirements per package insert. 
Retesting 
One retest is allowed for participants with an “indeterminate” QuantiFERON-TB Gold assay or 
“borderline” T-SPOT.TB assay. Participants with 2 indeterminate QuantiFERON-TB Gold 
assays or 2 borderline T-SPOT.TB assays will be excluded. 
Diagnosed LTBI 
Participants diagnosed with LTBI are excluded (Section 5.2) unless they are candidates for LTBI 
treatment, are treated for LTBI, and the following criteria are met: 
•  After receiving at least 4 weeks of appropriate LTBI therapy (as per World Health 
Organization and/or the United States Centers for Disease Control guidelines), there is no 
evidence of hepatotoxicity (ALT/AST must remain ≤2 times ULN) or other treatment 
intolerance. The participant may be rescreened and is not excluded due to LTBI. 
•  The participant must continue and complete appropriate LTBI therapy in order to remain 
eligible to continue to receive study intervention. 
Monitoring during the study 
For all participants, monitoring for TB is to be continuous throughout the study. At a minimum, 
each participant is to have the following documented at least every 3 months: 
•  Thorough history to determine any risk factors for TB infection and for TB progression, 
symptoms or signs of active TB, and 
•  Physical examination that includes assessment for signs of active TB, including 
measurement of body temperature and assessment of peripheral lymph nodes (Section 
8.2.2). 
8.2.7. 
Hepatitis B Testing and Monitoring 
Initial testing for hepatitis B virus (HBV) infection includes hepatitis B surface antigen (HBsAg) 
and antibody to hepatitis B core antigen (anti-HBc). 
•  If HBsAg is positive, the participant is excluded. 
•  If HBsAg is negative and anti-HBc is negative, the participant is not excluded. 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
59 
•  If HBsAg is negative and anti-HBc is positive, further testing for HBV DNA is required. 
−  If the screening HBV DNA is positive, the participant is excluded. 
−  If the screening HBV DNA is negative, the participant is not excluded. Repeat testing 
for HBV DNA is required at least every 3 months during the study (Section 1.3), with 
temporary withholding or permanent discontinuation of study intervention if HBV 
DNA is positive, as described in Section 7.1.2 and Section 7.1.1, respectively. 
Management of enrolled participants with detectable HBV DNA during the study 
If HBV DNA is detected during the study, the study drug will be temporarily withheld or 
discontinued and participants should receive appropriate follow-up medical care as described in 
Section 7.1.1 and Section 7.1.2. 
8.2.8. 
Hepatitis C Testing and Monitoring 
Initial testing for HCV infection includes testing for antibodies to HCV. 
• If anti-HCV is positive, a serum test for circulating HCV RNA is required. 
• If HCV RNA test is negative, the participant is not excluded. 
• If HCV RNA test is positive, the participant is excluded (see Section 5.2). 
Participants who have had HCV infection and been successfully treated, defined as a sustained 
virologic response (HCV RNA by PCR negative for at least 24 weeks following treatment 
completion) are not excluded on the basis of HCV as long as HCV RNA test is negative at 
screening. 
If HCV RNA is detected during the study, the study drug will be discontinued (Section 7.1.1), 
and the participant should receive appropriate follow-up medical care. 
 
 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
60 
8.2.9. 
Hepatic Safety Monitoring 
Close hepatic monitoring 
The laboratory tests listed in Appendix 10.5, including ALT, AST, ALP, TBL, direct bilirubin, 
gamma-glutamyl transferase (GGT), and creatine kinase (CK), should be repeated within 48 to 
72 hours, to confirm the abnormality and to determine whether it is increasing or decreasing, if 
these conditions occur: 
If a participant with baseline...  
has the following elevations: 
ALT or AST <1.5 times ULN 
ALT or AST ≥3 times ULN 
ALP <1.5 times ULN 
ALP ≥2 times ULN 
TBL <1.5 times ULN 
TBL ≥2 times ULN 
ALT or AST ≥1.5 times ULN 
ALT or AST ≥2 times baseline 
ALP ≥1.5 times ULN 
ALP ≥2 times baseline 
If the abnormality persists or worsens, clinical and laboratory monitoring, and evaluation for the 
possible causes of the abnormal liver tests should be initiated by the investigator in consultation 
with the sponsor’s designated medical monitor. At a minimum, this evaluation should include a 
physical examination and a thorough medical history, including symptoms, recent illnesses (for 
example, heart failure, systemic infection, hypotension, or seizures), recent travel, history of 
concomitant medications (including over-the-counter), herbal and dietary supplements, history of 
alcohol drinking, and other substance abuse. 
Initially, monitoring of symptoms and hepatic biochemical tests should be done at a frequency of 
1 to 3 times weekly, based on the participant’s clinical condition and hepatic biochemical tests. 
Subsequently, the frequency of monitoring may be lowered to once every 1 to 2 weeks, if the 
participant’s clinical condition and lab results stabilize. Monitoring of ALT, AST, ALP and TBL 
should continue until levels normalize or return to approximate baseline levels. 
Comprehensive hepatic evaluation 
A comprehensive evaluation should be performed to search for possible causes of liver injury if 
these conditions occur: 
If a participant with baseline... 
has the following elevations: 
ALT or AST  <1.5 times ULN 
ALT or AST ≥3 times ULN with hepatic signs/symptoms*, or  
ALT or AST ≥5 times ULN 
ALP <1.5 times ULN 
ALP ≥3 times ULN 
TBL <1.5 times ULN 
TBL ≥2 times ULN 
ALT or AST ≥1.5 times ULN 
ALT or AST ≥2 times baseline with hepatic signs/symptoms*, or 
ALT or AST ≥3 times baseline 
ALP ≥1.5 times ULN 
ALP ≥2 times baseline 
* Hepatic signs/symptoms are severe fatigue, nausea, vomiting, right upper quadrant abdominal pain, 
fever, rash, and/or eosinophilia >5%. 
At a minimum, this evaluation should include a physical examination and a thorough medical 
history, as outlined above, as well as tests for prothrombin time (PT-INR); viral hepatitis A, B, 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
61 
C, and E; tests for autoimmune hepatitis, and an abdominal imaging study (for example, 
ultrasound or CT scan). 
Based on the participant’s history and initial results, further testing should be considered in 
consultation with the sponsor’s designated medical monitor, including tests for hepatitis D virus 
(HDV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), acetaminophen levels, 
acetaminophen protein adducts, urine toxicology screen, Wilson’s disease, blood alcohol levels, 
urinary ethyl glucuronide, and serum phosphatidylethanol. 
Based on the circumstances and the investigator’s assessment of the participant’s clinical 
condition, the investigator should consider referring the participant for a hepatologist/ 
gastroenterologist consultation, magnetic resonance cholangiopancreatography (MRCP), 
endoscopic retrograde cholangiopancreatography (ERCP), cardiac echocardiogram, or a liver 
biopsy. 
8.2.9.1. 
Additional Hepatic Data Collection in Participants Who Have Abnormal Liver 
Tests During the Study 
Additional hepatic safety data collection (hepatic safety eCRF) should be performed for 
participants who meet one or more of the following conditions: 
●  Elevation of serum ALT to ≥5 times ULN on two or more consecutive blood tests (if 
baseline ALT <1.5 times ULN) 
○  In participants with baseline ALT ≥1.5 times ULN, the threshold is ALT ≥3 times 
baseline on 2 or more consecutive tests. 
●  Elevated TBL to ≥ 2 times ULN (if baseline TBL <1.5 times ULN) (except for cases of 
known Gilbert’s syndrome) 
○  In participants with baseline TBL ≥1.5 times ULN, the threshold should be 
TBL ≥2 times baseline. 
●  Elevation of serum ALP to ≥2 times ULN on two or more consecutive blood tests (if 
baseline ALP <1.5 times ULN) 
○  In participants with baseline ALP≥1.5 times ULN, the threshold is ALP ≥2 times 
baseline on two or more consecutive blood tests. 
●  Hepatic event considered to be a SAE. 
●  Discontinuation of study drug due to a hepatic event (Section 7.1.1). 
Note that the interval between the two consecutive blood tests should be at least 2 days. 
8.2.10. 
Suicidal Ideation and Behavior Risk Monitoring 
Participants should be monitored appropriately and observed closely for suicidal ideation and 
behavior or any other unusual changes in behavior, especially at the beginning and end of the 
course of intervention. Participants who have signs of suicidal ideation or behavior should be 
considered for discontinuation of study drug, following a risk assessment (see Section 7.1.1). See 
Section 8.3.1.1 for timing of adverse event collection relative to collection of the C-SSRS. 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
62 
8.2.10.1. Columbia Suicide Self-Reported Scale (C-SSRS) 
The Columbia Suicide-Severity Rating Scale (C-SSRS) is a scale that captures the occurrence, 
severity, and frequency of suicidal ideation and behavior during the assessment period via a 
questionnaire. The scale was developed by the National Institute of Mental Health (NIMH) trial 
group (TASA) for the purpose of being counterpart to the Columbia Classification Algorithm of 
Suicide Assessment (C-CASA) categorization of suicidal events. 
For this study, the C-SSRS is adapted for the assessment of the ideation and behavior categories 
only. The Intensity of Ideation and Lethality of Behavior sections are removed. 
8.2.10.2. Depression Assessment with 16-Item Quick Inventory of Depressive 
Symptomatology–Self Report (QIDS-SR16) QIDS-SR16 
The 16-Item Quick Inventory of Depressive Symptomatology–Self Report (QIDS-SR16) is a 
self-administered, 16-item instrument intended to assess the existence and severity of symptoms 
of depression as listed in the American Psychiatric Association’s Diagnostic and Statistical 
Manual of Mental Disorders, 5th Edition (DSM-V) (APA 2013). A participant is asked to 
consider each statement as it relates to the way he or she has felt for the past 7 days. There is a 
4-point scale for each item ranging from 0 to 3. The 16 items corresponding to 9 depression 
domains are summed to give a single score ranging from 0 to 27, with higher scores denoting 
greater symptom severity. The domains assessed by the instrument include 1) sad mood, 2) 
concentration, 3) self-criticism, 4) suicidal ideation, 5) interest, 6) energy/fatigue, 7) sleep 
disturbance (initial, middle, and late insomnia or hypersomnia), 8) decrease/increase in 
appetite/weight, and 9) psychomotor agitation/retardation. 
8.2.11. 
Injection Site Assessment 
Symptoms of a local injection site reaction may include erythema, induration, pain, pruritus, and 
edema. See Section 6.3 for activities relating to assessment of injection site reactions. 
Solicited Events 
Solicited data from injection site assessments will not be routinely classified as an adverse event. 
Unsolicited Events 
If a participant reports symptoms (that is, an unsolicited event, volunteered by participant) or if 
the investigator determines that a clinically relevant injection site reaction has occurred, the 
event will be captured as an adverse event. In such a case, a specific adverse event of Injection 
site reaction will be reported and the event followed up to completion, in addition to completing 
the injection site assessment questionnaire in the eCRF. 
8.3. 
Adverse Events and Serious Adverse Events 
Adverse events (AEs) will be reported by the participant or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative. 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study intervention or study procedures, or that 
caused the participant to discontinue the study intervention or the study (see Section 7). 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
63 
Pregnancy after maternal or paternal exposure to IP does not meet the definition of an AE. 
However, to fulfill regulatory requirements, any pregnancy should be reported using the SAE 
process described in Appendix 10.3, Section 10.3.4, to collect data on the outcome for both 
mother and fetus. See also Section 8.3.5. 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs will be collected from the time of the participant’s signing of the main Study KFAJ ICF 
until the participant’s last post-treatment follow-up visit. 
Likewise, all SAEs will be collected from the signing the Study KFAJ ICF until the last 
post-treatment follow-up visit. 
Adverse events that begin before the start of study intervention but after signing of the ICF will 
be recorded on the Adverse Event eCRF. 
Although all AEs after signing the ICF are recorded by the site in the eCRF/electronic data entry 
tool, SAE reporting to the sponsor begins after the participant has signed the ICF and has 
received study drug. However, if an SAE occurs after signing the ICF but prior to receiving 
study drug, the SAE needs to be reported ONLY if the SAE is considered reasonably possibly 
related to study procedures. 
All SAEs will be recorded and reported to the sponsor or the sponsor’s designee immediately, 
and under no circumstance should this exceed 24 hours, as indicated in Appendix 10.3. The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it being 
available. 
Investigators are not obligated to actively seek AE or SAEs after the conclusion of study 
participation, that is, once the participants have discontinued and/or completed the study (the 
Participant Study Disposition eCRF has been completed). However, if the investigator learns of 
any SAE, including a death, at any time after a participant has been discharged from the study, 
and the investigator considers the event to be reasonably related to the study intervention or 
study participation, the investigator must promptly notify the sponsor. 
8.3.1.1. 
Adverse Event Monitoring with a Systematic Questionnaire 
Nonleading (spontaneous) AE collection should occur before the collection of the C-SSRS. 
If a suicide-related event is discovered during the C-SSRS collection but was not captured during 
the nonleading AE collection, sites should not change the adverse event form. However, if an 
adverse event is serious or leads to discontinuation, the adverse event should be included on the 
adverse event form. Also, the process for reporting SAEs should be followed. 
8.3.2. 
Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 10.3. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
64 
8.3.3. 
Follow-up of AEs and SAEs 
After the initial AE or SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs 
 
 will be followed until resolution, stabilization, the event is 
otherwise explained, or the participant is lost to follow-up (Section 7.3). Further information on 
follow-up procedures is provided in Appendix 10.3.3. 
8.3.4. 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
intervention under clinical investigation are met. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, Institutional Review Boards (IRB)/Independent Ethics Committees 
(IEC), and investigators. 
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information (for example, summary or listing of SAEs) from the sponsor will review and 
then file it along with the IB and will notify the IRB/IEC, if appropriate according to local 
requirements. 
8.3.5. 
Pregnancy 
For female participants and female partners of male participants, details will be collected for 
pregnancies occurring from after the start of study intervention and until 12 weeks after the last 
dose. 
If a pregnancy is reported, the investigator should inform the sponsor within 24 hours of learning 
of the pregnancy and should follow the reporting procedures outlined in Appendix 10.4, Section 
10.4.3. 
Abnormal pregnancy outcomes (for example, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs. 
 
 
 
 
 
 
 
8.3.6.1. 
Systemic Hypersensitivity Reactions 
Many drugs, but particularly biologic agents, carry the risk of systemic hypersensitivity 
reactions. If such a reaction occurs, additional data describing each symptom should be provided 
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
65 
to the sponsor in the eCRF. It is recommended that participants who experience a systemic 
hypersensitivity reaction be treated per the local standard of care. 
Sites should have appropriately trained medical staff and appropriate medical equipment 
available when the study participants are receiving study drug. 
Blood sample collection for systemic allergic/hypersensitivity events, including CRS. 
In the case of generalized urticaria or anaphylaxis, additional blood samples as described in 
Appendix 10.2 should be collected. Laboratory results are provided to the sponsor via the central 
laboratory. 
8.3.6.2. 
Serious Infections and Opportunistic Infections 
Completion of the Infection eCRF page is required for each infection reported as an AE or SAE. 
The sponsor will identify infections considered to be opportunistic based on the article by 
Winthrop et al. (2015) (Appendix 10.6). 
8.3.7. 
Complaint Handling 
A product complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, durability, reliability, safety, effectiveness or performance of a 
trial intervention. The sponsor collects product complaints on investigational products and drug 
delivery systems used in clinical studies in order to ensure the safety of study participants, 
monitor quality, and to facilitate process and product improvements. 
Participants will be instructed to contact the investigator as soon as possible if they have a 
complaint or problem with the investigational product so that the situation can be assessed. 
Note: Any AEs/SAEs that are associated with a product complaint will follow the processes 
outlined in Section 8.3.3 and Appendix 10.3.  
Time period for detecting product complaints 
Product complaints that result in an AE will be detected, documented, and reported to the 
sponsor during all periods of the study in which the drug/device is used. If the investigator learns 
of any product complaint at any time after a participant has been discharged from the study, and 
such incident is considered reasonably related to a drug/device provided for the study, the 
investigator will promptly notify the sponsor. 
Prompt reporting of product complaints to the sponsor 
Product complaints will be reported to the sponsor within 24 hours after the investigator becomes 
aware of the complaint. The Product Complaint Form will be sent to the sponsor by a method 
designated by the sponsor. 
Follow-up of product complaints 
Follow-up applies to all participants, including those who discontinue study intervention. The 
investigator is responsible for ensuring that follow-up includes any supplemental investigations 
as indicated to elucidate the nature and/or causality of the product complaint. New or updated 
information will be recorded on the originally completed form with all changes signed and dated 
by the investigator and submitted to the sponsor. 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
66 
8.4. 
Treatment of Overdose 
For this study, an overdose of LY3471851 is considered any dose greater than the highest dose 
planned to be used in this study. The treatment for suspected overdose is supportive care. 
In the event of an overdose, the investigator should: 
1.  Contact the sponsor’s medical monitor immediately. 
2.  Closely monitor the participant for any AE or SAE and laboratory abnormalities until the 
study intervention can no longer be detected systemically (at least 12 weeks). 
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the sponsor’s medical monitor based on clinical evaluation of the participant. 
8.5. 
Pharmacokinetics 
Visits and times 
At the visits and times specified in the SoA (Section 1.3), venous blood samples will be collected 
to determine the plasma concentrations of LY3471851. The actual date and time (24-hour clock 
time) of dosing and sample collection must be recorded accurately on the appropriate forms. 
Collection, handling, and analysis of samples 
Instructions for the collection and handling of blood samples will be provided by the sponsor. 
Samples will be analyzed at a laboratory approved by the sponsor. Concentrations of LY3471851 
will be assayed using a validated PK assay. Analyses of samples collected from participants who 
received placebo are not planned. 
Additional and unused samples 
 
 
 
 
 
In the case of systemic allergic/hypersensitivity reactions, additional blood samples will be 
obtained for PK analyses (Section 8.3.6.1). 
Blinding 
Drug concentration information that may unblind the study will not be reported to investigative 
sites or to personnel who are blinded to study data. 
 
 
 
 
 
 
 
CCI
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
67 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CCI
CCI
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
68 
 
 
 
 
8.10. 
Medical Resource Utilization and Health Economics 
This section is not applicable. 
CCI
CCI
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
69 
9. 
Statistical Considerations 
9.1. 
Statistical Hypotheses 
The null hypothesis for the primary endpoint is that there is no difference between LY3471851 
and placebo in reducing the signs and symptoms of SLE as measured by the proportion of 
participants who achieve a SLEDAI-4 response at Week 24. 
9.2. 
Sample Size Determination 
will be randomly assigned to study intervention. All randomized 
participants in the modified intent-to-treat (mITT) population will be considered evaluable. 
Pairwise 2-sided tests of proportions with alpha = 0.05 will be performed on each LY3471851 
dose versus placebo. With 70 participants per group, Study KFAJ has at least 80% power to 
detect a statistically-significant difference of 24% improvement over placebo in SLEDAI-4 
response between LY3471851 and placebo at Week 24.  
9.3. 
Populations for Analyses 
The mITT population, which includes all randomized participants receiving at least 1 dose of 
study intervention, will be used in analyses of efficacy and patient-reported outcomes (PRO), 
unless otherwise noted in the SAP). 
The following populations are defined for this study: 
Population 
Description 
Entered 
All participants who sign the informed consent form 
Modified Intent-to-Treat (mITT) 
All participants randomly assigned to study intervention and who take at least 
1 dose of study intervention. Participants will be analyzed according to the 
intervention to which they were assigned. 
Safety 
All participants randomly assigned to study intervention and who take at least 
1 dose of study intervention. Participants will be analyzed according to the 
intervention they actually received within each study period. 
Pharmacokinetic (PK) Analysis 
All participants randomly assigned to study intervention and who take at least 
1 dose of study intervention and have PK data available. 
 
9.4. 
Statistical Analyses 
9.4.1. General Considerations 
 Unless 
other indicated in the SAP, the analyses will be conducted as follows: 
●  Primary and secondary endpoint analyses will be tested at a 2-sided  level of 0.05 for 
frequentist analyses. 
●  The primary estimand that will be used to analyze primary and secondary endpoints is a 
composite response estimand where comparisons will not include data collected after 
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
70 
intercurrent events of changes to background therapies or discontinuation. Participants 
who discontinue treatment prior to 24 weeks or who are noncompliant with concomitant 
medication rules are defined as nonresponders. Endpoint definition effectively gives 
complete data which will be analyzed as described in Section 9.4.2 and Section 9.4.3. 
●  No adjustments for multiplicity will be performed. 
●  Efficacy and PRO analysis models may contain the independent variables such as 
treatment group, baseline disease activity, and geographic region. 
●  Missing data for dichotomous responder endpoints will be imputed using the 
nonresponder imputation (NRI) method. 
●  Participants will be considered nonresponders for the NRI analysis if 
○  they do not meet all the clinical response criteria 
○  they are noncompliant with concomitant medication rules (Section 6.5) 
○  they permanently discontinue study intervention at any time before the end of the 
treatment period for any reason, or 
○  they are randomized and do not have at least 1 postbaseline observation. 
●  Mixed-effects model for repeated measures (MMRM) is the main method for analyzing 
continuous efficacy endpoints.  
●  Additional imputation methods may be considered for all endpoint types. 
Baseline will be defined as the last available value before the first dose of study intervention for 
both efficacy and safety analyses. In most cases, this value will be what is recorded at the 
randomization visit (Visit 2). Change from baseline will be calculated as the visit value of 
interest minus the baseline value. For the post-treatment Follow-up Period, the baseline is 
defined as the last nonmissing assessment on or prior to entering the post-treatment Follow-up 
Period, that is, on or prior to the Week 24 visit, or the early termination visit (including ETV). 
Any change to the data analysis methods described in the protocol will require an amendment 
only if the change affects a principal feature of the protocol. Any other change to the data 
analysis methods described in the protocol, and the justification for making the change, will be 
described in the SAP and the clinical study report. 
 
 
The SAP will be finalized prior to unblinding. It will include a more technical and detailed 
description of the statistical analyses described in this section. This section is a summary of the 
planned statistical analyses of the primary and secondary endpoints. 
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
71 
9.4.1.1. 
Participant Disposition 
A detailed description of participant disposition will be provided, including a summary of the 
number and percentage of participants entered into the study and randomized, and number and 
percentage of participants who complete the study or discontinue, both overall and by reason for 
discontinuation. A summary of important protocol deviations will be provided. 
9.4.1.2. 
Participant Characteristics 
Demographic data are collected and responded to demonstrate that the study population 
represents the target patient population. A summary of baseline participant characteristics, 
historical diagnoses, preexisting conditions, and prior therapies will be reported by treatment 
group using descriptive statistics. Other participant characteristics will be summarized by 
treatment group as deemed appropriate. 
9.4.1.3. 
Concomitant Therapy 
Previous and concomitant medications will be summarized by treatment group and will be 
presented by Anatomical Therapeutic Chemical (ATC) drug classes using the latest version of 
the World Health Organization (WHO) drug dictionary. 
Participants who require initiation or increase in dosage of corticosteroids, antimalarials, or 
immunosuppressants after randomization will be analyzed as nonresponders from the day of 
initiation or increase in medication (see Section 6.5). 
9.4.1.4. 
Treatment Compliance 
No analyses are planned to assess treatment compliance, given that participants will receive 
study intervention directly from the investigator or designee at the study site, under medical 
supervision (Section 6.4). 
9.4.2. 
Primary Endpoints 
The primary endpoint is the SLEDAI-4 response rate at Week 24 for the LY3471851 treatment 
group compared to placebo. Participants who fail to complete the 24-week treatment period or 
violate the concomitant medication rules will be imputed to nonresponse for the purpose of the 
primary endpoint analysis. The objective of the primary endpoint is to determine whether 
LY3471851 is superior to placebo. 
The primary endpoint will be analyzed using a logistic regression model with baseline disease 
activity, corticosteroid dose at baseline, and geographic region as model covariates. 
Treatment difference and 95% CIs will be reported. 
9.4.3. 
Secondary Efficacy Endpoints 
Secondary efficacy endpoints include the following at Week 24: 
●  the proportion of participants who achieve a BILAG-based Composite Lupus Assessment 
(BICLA) response 
●  the proportion of participants who achieve SRI-4 response, and 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
72 
●  the proportion of participants who achieve LLDAS. 
Dichotomous secondary endpoints will be analyzed using the model specified for the primary 
analysis. 
9.4.3.1. 
Pharmacokinetic Analysis 
Plasma concentrations of LY3471851 will be listed by time point using descriptive statistics. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9.4.5. 
Safety Analyses 
Safety analyses will include AEs, SAEs, 
C-SSRS, QIDS-SR16, vital signs, ECGs, and 
laboratory analytes, using the Safety Population data descriptively summarized by treatment 
group. Categorical safety measures will be summarized with incidence rates. Continuous safety 
CCI
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
73 
measures will be summarized as mean change by visit. Exposure to study intervention will be 
calculated for each participant and summarized by treatment group. 
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA) and summarized by system organ class, preferred term, severity, and relationship to 
the study intervention. A treatment-emergent adverse event (TEAE) is defined as an event that 
first occurred or worsened in severity after baseline, with baseline defined as all pre-existing 
conditions recorded at Visit 1 and any AEs recorded before the first dose of study intervention 
(that is, during the interval between Visits 1 and 2 and recorded with the time of onset before the 
first dose of study intervention). The treatment period will be used as the postbaseline period for 
the analysis. For events that are gender specific, the denominator and computation of the 
percentage will include only participants from the given gender. 
The number and percentage of participants who experienced TEAEs, TEAEs by maximum 
severity, deaths, SAEs, TEAEs related to study intervention, discontinuations from the treatment 
due to an AE, 
 will be summarized. Treatment-emergent adverse events (all, by 
maximum severity), SAEs including deaths, and AEs that lead to treatment discontinuation will 
be summarized and analyzed by MedDRA system organ class (SOC) and preferred term. 
Treatment-related TEAEs (TEAEs related to study intervention) are defined as events that are 
indicated by the investigator on the eCRF to be related to treatment. 
 
 
Suicide-related thoughts and behaviors occurring during treatment will be summarized based on 
responses to the C-SSRS consistent with the C-SSRS Scoring and Data Analysis Guide 
(Columbia Lighthouse Project WWW). 
Follow-up emergent AEs, SAEs including deaths, and AEs that lead to study discontinuation will 
be summarized. All AEs, including pre-existing conditions, will be listed by participant, visit, 
preferred term, treatment group, severity, and relationship to the treatment. 
9.4.6. 
Other Analyses  
9.4.6.1. 
Subgroup Analyses 
Subgroup analyses may be conducted for the primary endpoint SLEDAI-4 at Week 24 using the 
mITT population. Subgroups that may be evaluated include interferon gene signature status, 
gender, race, geographic region, 
 
 previous therapies, and disease duration, 
9.4.6.2. 
Supplemental Analyses 
Supplemental analyses will be performed on the primary endpoint using a treatment policy 
estimand where comparisons will be made while on treatment, but without regard to changes to 
background therapies or premature discontinuation. When using a treatment policy estimand, 
data will be analyzed using a logistic random effects model with treatment, baseline, visit, and 
visit-by-treatment interaction. Additional analyses of secondary endpoints may be performed 
using the same treatment policy estimand. Analysis details are in the statistical analysis plan. 
CCI
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
74 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9.6. 
Data Monitoring Committee (DMC) 
Not applicable. An IAC will be used to conduct the interim analysis (see Section 9.5 and 
Appendix 10.1, Section Appendix 10.1.5). 
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
75 
10. 
Supporting Documentation and Operational Considerations 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
●  Consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines 
●  Applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP) 
Guidelines, and 
●  Applicable laws and regulations. 
The protocol, protocol amendments and addenda, ICF, IB, and other relevant documents (for 
example, advertisements) must be submitted to an IRB/IEC by the investigator and reviewed and 
approved by the IRB/IEC before the study is initiated. 
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants. 
The investigator will be responsible for the following: 
●  Substantial amendments to the protocol require European Competent Authority approval 
before implementation. 
●  Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC 
●  Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures, and 
●  Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 United States Code of Federal Regulations (CFR), ICH guidelines, the IRB/IEC, 
European regulation 536/2014 for clinical studies (if applicable), and all other applicable 
local regulations. 
●  After reading the protocol, each principal investigator will sign the separate protocol 
signature page and send a copy of the signed page to a Lilly representative. 
Investigator sites are compensated for participation in the study as detailed in the clinical trial 
agreement. 
10.1.2. 
Financial Disclosure 
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
76 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
one year after completion of the study. 
10.1.3. 
Informed Consent Process 
The investigator or his or her representative will explain the nature of the study, including the 
risks and benefits, to the participant or his or her legally authorized representative and answer all 
questions regarding the study. 
Participants must be informed that their participation is voluntary. 
Participants or their legally authorized representatives will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, ICH guidelines, 
Health Insurance Portability and Accountability Act (HIPAA) requirements, where applicable, 
and the IRB/IEC or study center. The sponsor or its representatives must approve the ICFs, 
including any changes made by the ERB/IECs, before the ICFs are used at the investigative sites. 
The medical record must include a statement that written informed consent was obtained before 
the participant was entered in the study. The statement must include the date on which the 
written consent was obtained. The authorized person obtaining the informed consent must also 
sign the ICFs. 
Participants who are rescreened are required to sign a new ICF (see Section 5.4). 
Participants must be re-consented to the most current version of the ICF during their 
participation in the study. 
A copy of the ICFs must be provided to the participant or the participant’s legally authorized 
representative and must be kept on file. 
10.1.4. 
Data Protection 
Participants will be assigned a unique identifier by the sponsor. Any participant records, datasets 
or tissue samples that are transferred to the sponsor will contain the identifier only; participant 
names or any information which would make the participant identifiable will not be transferred. 
The participant must be informed that his or her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant who will be required to give consent for his or her data to be used as 
described in the informed consent. 
The participant must be informed that his or her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
10.1.5. 
Committees Structure 
Eligibility Review Committee 
An eligibility review committee, also called adjudication panel, will review study entry data to 
ensure that prospective study participants meet the study entry criteria, particularly SLE disease 
activity criteria, prior to randomization. In addition, the committee will help ensure that high 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
77 
quality data are entered into the electronic lupus assessment system. The committee may include 
members of a third-party organization, members of the study team, and external SLE consultants 
as needed. Membership, responsibilities, operations, and measures to maintain confidentiality 
will be described in a committee charter. 
Internal Assessment Committee (IAC) 
In addition to the safety reviews routinely performed by the blinded study team, an IAC will 
review the safety data in an unblinded fashion periodically or on an ad hoc basis during the study 
and will determine whether any changes (for example, dose reductions or other protocol 
modifications) should be made (see also Section 10.1.9). 
The IAC reviewing the safety data will be fully independent from the study team and will 
include, at a minimum, a Lilly medical physician, a statistician, and a representative from the 
Lilly Global Patient Safety organization. Details about IAC membership, purpose, 
responsibilities, and operation will be described in an IAC charter, which will be approved prior 
to the first unblinding. 
 
 
10.1.6. 
Dissemination of Clinical Study Data 
Reports 
The sponsor will disclose a summary of study information, including tabular study results, on 
publicly available websites where required by local law or regulation. 
 
 
 
 
 
  
 
 
 
  
 
 
10.1.7. 
Data Quality Assurance 
Investigator responsibilities 
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (for example, laboratory data). 
The investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the CRF. 
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
78 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. This documentation might include laboratory and diagnostic 
test reports, medical records, and clinical notes. 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
Data monitoring and management 
Monitoring details describing strategy (for example, risk-based initiatives in operations and 
quality, such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities and requirements, including handling of noncompliance issues and 
monitoring techniques are provided in the Monitoring Plan. 
The sponsor or designee is responsible for the data management of this study, including quality 
checking of the data. The sponsor assumes accountability for actions delegated to other 
individuals (for example, contract research organizations). 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
Records retention and audits 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the sponsor. No records may be transferred to 
another location or party without written notification to the sponsor. 
In addition, the sponsor or its representatives will periodically check a sample of the participant 
data recorded against source documents at the study site. The study may be audited by the 
sponsor or its representatives, and/or regulatory agencies at any time. Investigators will be given 
notice before an audit occurs. 
Data Capture System 
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported to the sponsor. 
An electronic data capture system (EDC) will be used in this study for the collection of eCRF 
data. The investigator maintains a separate source for the data entered by the investigator or 
designee into the sponsor-provided EDC system. The investigator is responsible for the 
identification of any data to be considered source and for the confirmation that data reported are 
accurate and complete by signing the eCRF. 
Additionally, some of the clinician-administered questionnaires data will be collected by the 
investigative site personnel, via a paper source document and will be transcribed by the 
investigative site personnel into the EDC system. See the SoA (Section 1.3) for scales 
administered via paper. 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
79 
Additionally, electronic clinical outcome assessment (eCOA) data (patient-reported outcome and 
clinician-administered questionnaires) will be directly recorded by the participant and 
investigative site personnel, into an instrument (for example, tablet). The eCOA data will serve 
as the source documentation and the investigator does not maintain a separate, written or 
electronic record of these data. See the SoA (Section 1.3) for scales administered electronically. 
Data collected via the sponsor-provided data capture systems will be stored at third parties. The 
investigator will have continuous access to the data during the study and until decommissioning 
of the data capture systems. Prior to decommissioning, the investigator will receive an archival 
copy of pertinent data for retention. 
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system and reports will be provided to the investigator for review 
and retention. Data will subsequently be transferred from the central vendor to the sponsor’s data 
warehouse. 
Data from complaint forms submitted to the sponsor will be encoded and stored in the global 
product complaint management system. 
10.1.8. 
Source Documents 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site. 
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents, or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on the 
study. Also, current medical records must be available. 
The definition of what constitutes source data can be found in Section 10.1.7. 
10.1.9. 
Study and Site Start and Closure 
The study start date is the date on which the clinical study is open for recruitment of participants. 
The sponsor or designee reserves the right to close the study site or to terminate the study at any 
time for any reason at the sole discretion of the sponsor. 
Closure of study sites 
Study sites will be closed upon study completion. A study site is considered closed when all 
required documents and study supplies have been collected and a study-site closure visit has 
been performed. 
The investigator may initiate study-site closure at any time, provided a reasonable cause exists 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include, but are 
not limited to, these: 
●  Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the sponsor's procedures, or GCP guidelines 
●  Inadequate recruitment of participants by the investigator, and 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
80 
●  Discontinuation of further study intervention development. 
 
Study stopping rules 
The IAC will convene to evaluate unblinded safety data if  
●  5 or more participants experience TEAEs in the same SOC or 3 or more participants 
experience a TEAE of CRS, and 
●  these TEAEs are judged as either serious or severe, and  
●  these TEAEs are related to blinded study treatment. 
Study enrollment and/or further dosing may be stopped, pending the decision of the IAC 
 Section 10.1.5). If the study is not stopped, the IAC will meet periodically; 
details are provided in the IAC charter. 
 
 
 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organizations 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator shall promptly inform the participant and assure 
appropriate participant therapy and/or follow-up. 
10.1.10. 
Publication Policy 
In accordance with the sponsor’s publication policy, the results of this study will be submitted 
for publication by a peer-reviewed journal. 
10.1.11. 
Investigator Information 
Physicians with a specialty in rheumatology will participate as investigators in this clinical trial. 
Physicians and other qualified healthcare professionals with other specialties and experience in 
treatment of patients with SLE may also participate as investigators. 
10.1.12. 
Long-Term Sample Retention 
Sample retention enables use of new technologies, response to regulatory questions, and 
investigation of variable responses that may not be observed until later in the development of  
LY3471851 or after LY3471851 becomes commercially available. 
The following table lists the maximum retention period for sample types. The retention period 
begins after the last participant visit for the study. 
The maximum retention times may be shorter, if specified in local regulations and/or if 
ERBs/IRBs impose shorter time limits. 
Any samples remaining after the specified retention period will be destroyed. 
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
81 
The sample retention facility will be selected by the sponsor or its designee. 
Sample Type 
Custodian 
Retention Period after Last Participant Visit 
Pharmacokinetics 
Sponsor or designee 
2 years 
  
 
 
 
 
 
 
 
 
 
 
 
CCI
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
82 
10.2. 
Appendix 2: Clinical Laboratory Tests 
The clinical laboratory tests listed in the table below will be performed by a central laboratory or 
by a local laboratory as specified in the table. 
Additional tests may be performed at any time during the study as determined necessary by the 
investigator or as required by local regulations. 
Protocol-specific requirements for the inclusion or exclusion of participants are specified in 
Section 5 of the protocol. 
Pregnancy testing is described in the SoA (Section 1.3), in Section 8.2.5.1, and in the table 
below. 
Investigators must document their review of each laboratory safety report. 
Laboratory test results that could unblind the study will not be reported to investigative sites or 
other blinded personnel. 
If tests are done to obtain laboratory results with an intent to resume the study drug after a 
temporary withholding, the samples must be assayed centrally. 
 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
83 
Clinical Laboratory Tests 
Hematology a 
Clinical Chemistry a 
Hemoglobin 
Sodium 
Hematocrit 
Potassium 
Erythrocyte count (RBCs) 
Chloride 
Mean cell volume 
Bicarbonate 
Mean cell hemoglobin 
Total bilirubin (TBL) 
Mean cell hemoglobin concentration 
Direct bilirubin 
Leukocytes (WBCs) 
Alkaline phosphatase (ALP) 
Absolute count of 
Alanine aminotransferase (ALT) 
   Neutrophils, segmented 
Aspartate aminotransferase (AST) 
   Neutrophils, juvenile (bands) 
Gamma-glutamyl transferase (GGT) 
   Lymphocytes 
Blood urea nitrogen (BUN) 
   Monocytes 
Creatinine 
   Eosinophils 
Creatine kinase (CK) 
   Basophils 
Uric acid 
Platelets 
Total protein 
Cell morphology (RBC and WBC) 
Albumin 
 
Calcium 
Urinalysis a 
Phosphorus 
Specific gravity 
Glucose 
pH 
Amylase 
Protein 
Lipase 
Glucose 
Cholesterol (total) 
Ketones 
Triglycerides 
Bilirubin 
 
Urobilinogen 
 
Blood 
Lipid Panel a 
Nitrite 
High-density lipoprotein (HDL) 
Urine leukocyte esterase 
Low-density lipoprotein (LDL) 
Microscopic examination of sediment 
 
 
 
Urine Chemistry a 
Hormones (female) 
Total protein 
Pregnancy test (serum a and urine b) 
Creatinine 
Follicle-stimulating hormone (FSH) a, c 
 
 
Calculation a 
 
Urine protein/urine creatinine ratio 
 
Estimated glomerular filtration rate (eGFR; 
calculated using the Modification of Diet in 
Renal Disease [MDRD]) 
 
 
table continues 
 
 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
85 
Selected tests may be obtained in the event of anaphylaxis or systemic allergic/hypersensitivity 
reactions. The samples should be collected as close as possible to the onset of the event. 
Hypersensitivity Tests a 
LY concentration (PK) 
N-methylhistamine 
 
Complements 
 
Cytokine panel 
Abbreviation: PK = pharmacokinetic. 
a Assayed by Lilly-designated laboratory. 
 
 
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
91 
10.4. 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information 
10.4.1. 
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below). If fertility is unclear (for example, amenorrhea in 
adolescents or athletes) and a menstrual cycle cannot be confirmed before first dose of study 
intervention, consider additional evaluation. 
Woman NOT of Childbearing Potential (not-WOCBP) 
Women in the following categories are not considered WOCBP: 
●  Premenarchal 
●  Premenopausal female with 1 of the following: 
○  Documented hysterectomy 
○  Documented bilateral salpingectomy 
○  Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other than the 
above (for example, mullerian agenesis, androgen insensitivity), apply investigator 
discretion to determining study entry. Determination can come from the site personnel’s 
review of the participant’s medical records, medical examination, or medical history 
interview. 
●  Postmenopausal female, defined as women meeting one of the following criteria: 
○  At least 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy, 
confirmed by operative note 
○  Spontaneous amenorrhea for at least 12 months, not induced by a medical condition 
such as anorexia nervosa and not taking medications during the amenorrhea (for 
example, oral contraceptives, hormones, gonadotropin-releasing hormone, 
anti-estrogens, selective estrogen receptor modulators [SERMs], or chemotherapy 
that induced the amenorrhea); additionally, if less than or equal to 50 years of age, 
has a FSH of ≥40 mIU/mL 
○  At least 40 years of age with an intact uterus, not on hormone therapy, with 
cessation of menses for at least 1 year, and without an alternative medical cause, 
AND a FSH of ≥40 mIU/mL 
○  At least 55 years of age, not on hormone therapy, having at least 12 months of 
spontaneous amenorrhea 
○  At least 55 years of age with a diagnosis of menopause prior to starting hormone 
replacement therapy. 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
92 
10.4.2. 
Contraception 
Females 
Women of childbearing potential 
Women of childbearing potential who are abstinent (if this is complete abstinence, as their 
preferred and usual lifestyle) or in a same sex relationship (as part of their preferred and usual 
lifestyle) must agree to either remain abstinent or stay in a same sex relationship without sexual 
relationships with males. Periodic abstinence (for example, calendar, ovulation, symptothermal, 
post-ovulation methods), declaration of abstinence just for the duration of a trial, and withdrawal 
are not acceptable methods of contraception. 
Otherwise, women of childbearing potential participating must agree to use 2 forms of effective 
contraception, where at least one form is highly effective (less than 1% failure rate), for the 
entirety of the study. Contraception must continue following completion of study drug 
administration for 12 weeks. 
●  Women of child-bearing potential participating must test negative for pregnancy prior to 
initiation of treatment as indicated by a negative serum pregnancy test at the screening 
visit followed by a negative urine pregnancy test within 24 hours prior to exposure. 
●  Two forms of effective contraception, where at least one form is highly effective (such as 
combination oral contraceptives, implanted contraceptives or intrauterine devices), will be 
used. Effective contraception (such as male or female condoms with spermicide, 
diaphragms with spermicide or cervical sponges) may be used as the second therapy. 
Barrier protection methods without concomitant use of a spermicide are not a reliable or 
acceptable method. Thus, each barrier method must include use of a spermicide (that is, 
condom with spermicide, diaphragm with spermicide, female condom with spermicide). It 
should be noted that the use of male and female condoms as a double-barrier method is 
not considered acceptable due to the high failure rate when these methods are combined. 
Women not of child-bearing potential (not-WOCBP) 
Women who are not-WOCBP may participate in the study if they meet all study entry criteria. 
For such women, there are no conception requirements. 
Males 
No male contraception is required except in compliance with specific local government study 
requirements. 
10.4.3. 
Collection of Pregnancy Information 
Male participants with partners who become pregnant 
The investigator will attempt to collect pregnancy information on any male participant’s female 
partner who becomes pregnant while the male participant is in this study. This applies only to 
male participants who receive study intervention. 
After obtaining the necessary signed informed consent from the pregnant female partner directly, 
the investigator will record pregnancy information on the appropriate form and submit it to the 
sponsor within 24 hours of learning of the partner’s pregnancy. The female partner will be 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
93 
followed to determine the outcome of the pregnancy. Information on the status of the mother and 
child will be forwarded to the sponsor. Generally, the follow-up will be no longer than 6 to 
8 weeks following the estimated delivery date. Any termination of the pregnancy will be 
reported regardless of fetal status (presence or absence of anomalies) or indication for the 
procedure.  
Female participants who become pregnant 
The investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. The initial information will be recorded on the 
appropriate form and submitted to the sponsor within 24 hours of learning of a participant's 
pregnancy. 
The participant will be followed to determine the outcome of the pregnancy. The investigator 
will collect follow-up information on the participant and the neonate, and the information will be 
forwarded to the sponsor. Generally, follow-up will not be required for longer than 6 to 8 weeks 
beyond the estimated delivery date. Any termination of pregnancy will be reported, regardless of 
fetal status (presence or absence of anomalies) or indication for the procedure. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. 
A spontaneous abortion (occurring at <22 weeks gestational age) or still birth (occurring at 
>22 weeks gestational age) is always considered to be an SAE and will be reported as such. 
Any post-study pregnancy-related SAE considered reasonably related to the study intervention 
by the investigator will be reported to the sponsor as described in Section 8.3.4. While the 
investigator is not obligated to actively seek this information in former study participants, he or 
she may learn of an SAE through spontaneous reporting. 
Any female participant who becomes pregnant while participating in the study will discontinue 
study intervention and be withdrawn from the study. 
 
 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
94 
10.5. 
Appendix 5: Liver Safety: Hepatic Monitoring Tests 
Samples for selected tests may be obtained in the event of a treatment-emergent hepatic 
abnormality and may be required during follow-up with participants in consultation with the 
clinical research physician of the sponsor or sponsor’s designee. 
Hepatic Monitoring Tests 
Hepatic Hematologya 
Haptoglobina 
Hemoglobin 
 
Hematocrit 
Hepatic Coagulationa 
RBC 
Prothrombin Time 
WBC 
Prothrombin Time, INR 
Neutrophils, segmented 
 
Lymphocytes 
Hepatic Serologiesa,b 
Monocytes 
Hepatitis A antibody, total 
Eosinophils 
Hepatitis A antibody, IgM 
Basophils 
Hepatitis B surface antigen 
Platelets 
Hepatitis B surface antibody 
 
Hepatitis B core antibody 
Hepatic Chemistrya 
Hepatitis C antibody 
Total bilirubin 
Hepatitis E antibody, IgG 
Direct bilirubin 
Hepatitis E antibody, IgM 
Alkaline phosphatase 
 
ALT 
Antinuclear antibodya 
AST 
 
GGT 
Alkaline Phosphatase Isoenzymesa 
CPK 
 
 
 
Anti-smooth muscle antibody (or anti-actin antibody)a 
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; CPK = creatinine 
phosphokinase; GGT = gamma-glutamyl transferase; Ig = immunoglobulin; INR = international normalised 
ratio; RBC = red blood cells; WBC = white blood cells. 
a Assayed by Sponsor-designated or local laboratory. 
b Reflex/confirmation dependent on regulatory requirements and/or testing availability. 
 
 
 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
95 
10.6. 
Appendix 6: Examples of Infections That May Be Considered 
Opportunistic in the Setting of Biologic Therapy 
The following table lists examples of infections that may be considered opportunistic in the 
setting of biologic therapy (adapted from Winthrop et al. [2015]). This table is provided to aid 
the investigator in recognizing such infections. This list is not exhaustive. Infections will be 
categorized by Lilly as opportunistic according to Opportunistic Infections and Biologic 
Therapies in Immune-Mediated Inflammatory Diseases: Consensus Recommendations for 
Infection Reporting during Clinical Trials and Postmarketing Surveillance by 
Winthrop et al. (2015). 
 
 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
96 
Examples of Infections That May Be Considered Opportunistic in the Setting of Biologic 
Therapy 
Bacterial 
 
Bartonellosis (disseminated disease only) 
 
Campylobacteriosis (invasive disease only) 
 
Legionellosis 
 
Listeriosis (invasive disease only) 
 
Nocardiosis 
 
Tuberculosis 
 
Non-tuberculous mycobacterial disease 
 
Salmonellosis (invasive disease only) 
 
Shigellosis (invasive disease only) 
 
Vibriosis (invasive disease due to Vibrio vulnificus) 
Viral 
 
BK virus disease including polyomavirus-associated nephropathy 
 
Cytomegalovirus disease 
 
Hepatitis B virus reactivation 
 
Hepatitis C virus progression 
 
Herpes simplex (invasive disease only) 
 
Herpes zoster (any form) 
 
Post-transplant lymphoproliferative disorder (Epstein-Barr virus) 
 
Progressive multifocal leukoencephalopathy (PML), John Cunningham (JC) virus 
Fungal 
 
Aspergillosis (invasive disease only) 
 
Blastomycosis 
 
Candidiasis (invasive disease or oropharyngeal, esophageal. Not isolated lingual.) 
 
Coccidioidomycosis 
 
Cryptococcosis 
 
Histoplasmosis 
 
Paracoccidioides infections 
 
Penicilliosis 
 
Pneumocystosis 
 
Sporotrichosis 
 
Other invasive molds: Mucormycosis (zygomycosis) (Rhizopus, Mucor, and Lichtheimia), 
Scedosporium/Pseudallescheria boydii, Fusarium 
Parasitic 
 
Leishmaniasis (visceral only) 
 
Strongyloidosis (hyperinfection syndrome or disseminated disease) 
 
Microsporidiosis 
 
Toxoplasmosis 
 
Trypanosoma cruzi infection (Chagas’ disease progression) (disseminated disease only) 
 
Cryptosporidiosis (chronic disease only) 
Source: Adapted from Winthrop et al. (2015). 
 
 

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
97 
10.7. 
Appendix 7: Efficacy and Patient-Reported Outcomes Assessments 
 the 
outcome measures used in this study are standard, widely used, and generally recognized as 
reliable, accurate, and relevant. 
10.7.1. 
British Isles Lupus Assessment Group 2004 (BILAG-2004) 
The BILAG 2004 index is a validated global disease activity index designed on the basis of the 
physician’s intent-to-treat, focusing on changes in disease manifestations (not present, improving, 
same, worse, or new) occurring in the last 4 weeks compared with the previous 4 weeks. The 
instrument assesses 97 clinical signs, symptoms, and laboratory parameters across 9 organ 
system domains: constitutional, mucocutaneous, neuropsychiatric, musculoskeletal, 
cardiorespiratory, gastrointestinal, ophthalmic, renal, and hematology. 
●  The BILAG A disease activity score is severe disease activity requiring high-dosage oral 
or intravenous corticosteroids, immunomodulators, or high-dosage anticoagulation along 
with high-dosage corticosteroids or immunomodulators. 
●  The BILAG B disease activity score is moderate disease activity requiring low-dosage oral 
corticosteroids, intramuscular or intra-articular corticosteroid injections, topical 
corticosteroids or immunomodulators, antimalarials, or symptomatic therapy. 
●  The BILAG C corresponds to stable, mild disease. 
●  The BILAG D is inactive disease that was active previously. 
●  The BILAG E indicates the system was never involved. 
 
 
 
 
 
 
 
10.7.3. 
Physician’s Global Assessment (PGA) of Disease Activity – Visual Analog Scale 
The PGA of Disease Activity is the physician’s assessment of the participant’s overall disease 
activity because of SLE, as compared with all possible subjects with SLE. The PGA of Disease 
Activity is scored using a 100-mm visual analog scale, where 0 mm (measured from the left 
starting point of the line) indicates no disease activity, and 100 mm (measured from the left 
starting point of the line) indicates severe disease activity. The PGA of Disease Activity score is 
indicated by making a vertical tick mark on the line between 0 and 100 mm. There are 
benchmarks of 0 (0 mm), 1 (33 mm), 2 (67 mm), and 3 (100 mm) on the line corresponding to no, 
mild, moderate, and severe SLE disease activity, respectively. 
10.7.4. 
Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) 
The SLEDAI-2K is a validated global disease activity instrument that focuses on disease 
manifestations across 9 organ systems. It includes 24 clinical and laboratory variables with 
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
98 
manifestations graded by the affected organ system as follows: Central nervous system (CNS) 
(seizure, psychosis, organic brain syndrome, visual disturbance, cranial nerve disorder, lupus 
headache, cerebral vascular accident); Vascular (vasculitis); Musculoskeletal (arthritis, myositis); 
Renal (urinary casts, hematuria, proteinuria, pyuria); Mucocutaneous (rash, alopecia, mucosal 
ulcers); Cardiovascular and Respiratory (pleurisy, pericarditis); Immunologic (low complement, 
increased DNA binding); Constitutional (fever); and Hematologic (thrombocytopenia, 
leukopenia). 
10.7.5. 
Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index 
The SLEDAI Flare Index uses the SLEDAI-2K score, disease activity scenarios, treatment 
changes, and Physician’s Global Assessment (PGA) of Disease Activity to define mild/moderate 
and severe flares. The index takes into account the absolute change in total scores, new or 
worsening symptoms, and increases in medication use or hospitalization because of the disease 
activity. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
99 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CCI
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
100 
 
 
 
 
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
101 
10.8. 
Appendix 8: Abbreviations 
 
Term 
Definition 
 
 
AE 
adverse event 
 
 
ALC 
absolute lymphocyte count 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANA 
antinuclear antibody 
ANC 
absolute neutrophil count 
anti-HBc 
antibody to hepatitis B core antigen 
AST 
aspartate aminotransferase 
AUC 
area under the concentration versus time curve 
BICLA 
BILAG-based Composite Lupus Assessment 
BILAG 
British Isles Lupus Assessment Group 
blinding 
A double-blind study is one in which neither the participant nor any of the investigator 
or sponsor staff who are involved in the treatment or clinical evaluation of the subjects 
are aware of the treatment received. 
CBD 
cannabidiol 
CFR 
United States Code of Federal Regulations 
CK 
creatine kinase 
complaint 
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system. 
compliance 
Adherence to all study-related, good clinical practice (GCP), and applicable regulatory 
requirements. 
CPK 
creatinine phosphokinase 
clinical research 
physician 
Individual responsible for the medical conduct of the study. Responsibilities of the 
clinical research physician may be performed by a physician, clinical research scientist, 
global safety physician or other medical officer. 
COA 
clinical outcome assessment 
CRF 
case report form 
CRS 
cytokine release syndrome 
C-SSRS 
Columbia–Suicide Severity Rating Scale 
CT 
computed tomography 
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
102 
CXR 
chest x-ray 
DMC 
data monitoring committee 
DNA 
deoxyribonucleic acid 
ECG 
electrocardiogram 
eCOA 
electronic clinical outcome assessment 
eCRF 
electronic case report form 
EDC 
electronic data capture system 
enroll 
The act of assigning a participant to a treatment. Participants who are enrolled in the 
study are those who have been assigned to a treatment. 
enrollment 
The act or time point of randomization, or the condition of have been assigned to a 
treatment (randomized). 
enter 
Participants entered into a study are those who sign the informed consent form directly 
or through their legally acceptable representatives. 
ERB 
Ethical Review Board (see IRB) 
ETV 
early termination visit 
FSH 
follicle-stimulating hormone 
GCP 
good clinical practice 
GGT 
gamma-glutamyl transferase 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
IAC 
internal assessment committee 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee (see IRB) 
IGRA 
interferon gamma release assay 
Informed consent 
A process by which a participant voluntarily confirms his or her willingness to 
participate in a particular study, after having been informed of all aspects of the study 
that are relevant to the participant’s decision to participate. Informed consent is 
documented by means of a written, signed and dated informed consent form. 
INR 
international normalized ratio 
 
 
 
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
103 
investigational 
product (IP) 
A pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical trial, including products already on the market when used or 
assembled (formulated or packaged) in a way different from the authorized form, or 
marketed products used for an unauthorized indication, or marketed products used to 
gain further information about the authorized form. 
IRB 
Institutional Review Board (IRB), also called Independent Ethics Committee (IEC) or 
Ethical Review Board (ERB) 
ISR 
injection site reaction 
IWRS 
interactive web-response system 
LLDAS 
Lupus Low Disease Activity State 
LTBI 
latent tuberculosis infection 
MAD 
multiple-ascending dose 
MDRD 
Modification of Diet in Renal Disease 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
mixed-effects model of repeated measures 
NK 
natural killer  
NONMEM 
nonlinear mixed effects modeling 
NRI 
nonresponder imputation 
NSAID 
nonsteroidal anti-inflammatory drug 
PA 
posterior–anterior 
participant 
Equivalent to Clinical Data Interchange Standards Consortium (CDISC) term “subject,” 
meaning an individual who participates in a clinical trial, either as recipient of an 
investigational medicinal product or as a control. 
In this protocol, the term “participant” is used to indicate an individual who participates 
in a clinical trial, either as a recipient of an investigational medicinal product or as a 
control. This usage reflects preferences indicated by patient advocates to more 
accurately reflect the role of people who take part in clinical trials. 
PEG 
polyethylene glycol 
PGA 
Physician’s Global Assessment 
PK/PD 
pharmacokinetics/pharmacodynamics 
 
 
PK 
pharmacokinetic 
PPD 
purified protein derivative 
PRO/ePRO 
patient-reported outcomes/electronic patient-reported outcomes 
Q2W 
every 2 weeks 
QIDS-SR16 
16-Item Quick Inventory of Depressive Symptomatology–Self Report 
QTc 
corrected QT interval 
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
104 
 
 
 
RNA 
ribonucleic acid 
SAD 
single-ascending dose 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SC 
subcutaneous 
screen 
The act of determining if an individual meets minimum requirements to become part of 
a pool of potential candidates for participation in a clinical study.  
SELENA-SLEDAI 
Safety of Estrogens in Lupus National Assessment – Systemic Lupus Erythematosus 
Disease Activity Index 
SLE 
systemic lupus erythematosus 
SLEDAI 
Systemic Lupus Erythematosus Disease Activity Index 
SoA 
Schedule of Activities 
SOC 
system organ class 
SRI-4 
Systemic Lupus Erythematosus Responder Index-4 
SRI-5 
Systemic Lupus Erythematosus Responder Index-5 
study drug 
See “study intervention” 
study intervention 
Any investigational intervention, marketed product, placebo, or medical device 
intended to be administered to a study participant according to the study protocol 
TB 
tuberculosis 
TBL 
total bilirubin level 
TEAE 
Treatment-emergent adverse event: An untoward medical occurrence that emerges 
during a defined treatment period, having been absent pretreatment, or worsens relative 
to the pretreatment state, and does not necessarily have to have a causal relationship 
with this treatment. 
TST 
tuberculin skin test 
ULN 
upper limit of normal 
WBC 
white blood cell  
WOCBP 
women of childbearing potential (see Appendix 10.4.1.) 
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
105 
11. 
References 
Ad Hoc Committee on Systemic Lupus Erythematosus Response Criteria for Fatigue. 
Measurement of fatigue in systemic lupus erythematosus: a systematic review. Arthritis 
Rheum. 2007;57(8):1348–1357. https://doi.org/ 10.1002/art.23113 
[APA] American Psychiatric Association. Diagnostic and Statistical Manual of Mental 
Disorders. 5
th ed. Arlington, VA: American Psychiatric Publishing.; 2013. 
 
 
 
Bretz F, Pinheiro JC, Branson M. Combining multiple comparisons and modeling techniques in 
dose-response studies. Biometrics. 2005;61(3):738-748. https://doi.org/ 10.1111/j.1541-
0420.2005.00344.x 
 
 
 
 
 
 
 
 
  
[Columbia Lighthouse Project.] The Columbia Protocol for Research. Columbia-Suicide 
Severity Rating Scale Scoring and Data Analysis Guide. Version 2.0. Available at: http:// 
cssrs.columbia.edu/wp-content/uploads/ScoringandDataAnalysisGuide-for-Clinical-Trials-
1.pdf. Accessed 30 January 2019 
Cooper GS, Treadwell EL, St Clair EW, et al. Sociodemographic associations with early disease 
damage in patients with systemic lupus erythematosus. Arthritis Rheum. 2007;57(6):993–999. 
https://doi.org/ 10.1002/art.22894 
 
 
 
[FDA] Office of Clinical Pharmacology Division of Pharmacometrics. “Request for 
Qualification of MCP-Mod as an efficient statistical methodology for model-based design and 
analysis of Phase II dose finding studies under model uncertainty.” FDA (2015). Available at: 
https: //www.fda.gov /media/99313/download. Accessed January 27, 2020. 
[FDA] Food and Drug Administration. Guidance for industry: pharmacokinetics in patients with 
impaired renal function – study design, data analysis, and impact on dosing and labeling; 2010. 
Available at: https://www.fda.gov/media/78573/download. Accessed January 27, 2020. 
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
106 
Franklyn K, Lau CS, Navarra SV, et al. Definition and initial validation of a Lupus Low Disease 
Activity State (LLDAS). Ann Rheum Dis. 2016;75:1615–1621. https://doi.org/  
10.1136/annrheumdis-2015-207726 
Furie R, Khamashta M, Merrill JT, et al. Anifrolumab, an anti–interferon-α receptor monoclonal 
antibody, in moderate-to-severe systemic lupus erythematosus. Arthritis Rheumatol. 
2017;69(2):376–386. https://doi.org/10.1002/art.39962 
Furie R, Petri M, Zamani O, et al. A phase III, randomized, placebo-controlled study of 
belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with 
systemic lupus erythematosus. Arthritis Rheum. 2011;63(12):3918–3930. https://doi.org/ 
10.1002/art.30613 
Gladman DD, Urowitz MB, Kagal A, Hallett D. Accurately describing changes in disease 
activity in Systemic Lupus Erythematosus. J Rheumatol. 2000;27(2):377-379.  
Gould AL. BMA-Mod: A Bayesian model averaging strategy for determining dose-response 
relationships in the presence of model uncertainty. Biom J. 2019;61(5):1141-1159. 
https://doi.org/ 10.1002/bimj.201700211 
He J, Zhang R, Shao M, et al. Efficacy and safety of low-dose IL-2 in the treatment of systemic 
lupus erythematosus: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 
2020;79(1):141-149. https://doi.org/ 10.1136/annrheumdis-2019-215396 
He J, Zhang X, Wei Y, et al. Low-dose interleukin-2 treatment selectively modulates CD4(+) T 
cell subsets in patients with systemic lupus erythematosus. Nat Med. 2016;22(9):991–993. 
https://doi.org/ 10.1038/nm.4148 
 
 
 
Hochberg MC. Updating the American College of Rheumatology revised criteria for the 
classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725. 
https://doi.org/ 10.1002/art.1780400928 
Isenberg DA, Petri M, Kalunian K, et al. Efficacy and safety of subcutaneous tabalumab in 
patients with systemic lupus erythematosus: results from ILLUMINATE-1, a 52-week, phase 
III, multicentre, randomised, double-blind, placebo-controlled study. Ann Rheum Dis. 
2016;75(2):323–331. https://doi.org/ 10.1136/annrheumdis-2015-207653 
Kalunian K, Urowitz M, Isenberg D, et al. Clinical trial parameters that influence outcomes in 
lupus trials that use the systemic lupus erythematosus responder index. Rheumatology 
(Oxford). 2018;57(1):125–133. https://doi.org/ 10.1093/rheumatology/kex368 
Merrill JT, van Vollenhoven RF, Buyon JP, et al. Efficacy and safety of subcutaneous 
tabalumab, a monoclonal antibody to B-cell activating factor, in patients with systemic lupus 
erythematosus: results from ILLUMINATE-2, a 52-week, phase III, multicentre, randomised, 
double-blind, placebo-controlled study. Ann Rheum Dis. 2016;75(2):332–340. https://doi.org/ 
10.1136/annrheumdis-2015-207654 
CCI

CONFIDENTIAL 
Protocol J1P-MC-KFAJ(a) 
 
107 
Navarra SV, Guzmán RM, Gallacher AE, et al. Efficacy and safety of belimumab in patients 
with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. 
Lancet. 2011;377(9767):721–731. https://doi.org/ 10.1016/S0140-6736(10)61354-2 
Ohl K, Tenbrock K. Regulatory T cells in systemic lupus erythematosus. Eur J Immunol. 
2015;45(2):344-355. https://doi.org/ 10.1002/eji.201344280 
Özel F, Argon G. The effects of fatigue and pain on daily life activities in systemic lupus 
erythematosus. Agri. 2015;27(4):181–189. https://doi.org/ 10.5505/agri.2015.38278 
Rosenzwajg M, Lorenzon R, Cacoub P, et al. Immunological and clinical effects of low-dose 
interleukin-2 across 11 autoimmune diseases in a single, open clinical trial. Ann Rheum Dis. 
2019;78(2):209–217. https://doi.org/ 10.1136/annrheumdis-2018-214229 
Sampson HA, Muñoz-Furlong A, Campbell RL, et al. Second symposium on the definition and 
management of anaphylaxis: summary report–Second National Institute of Allergy and 
Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin 
Immunol. 2006;117(2):391–397. https://doi.org/ 10.1016/j.jaci.2005.12.1303 
Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic 
lupus erythematosus. Arthritis Rheum. 1982;25(11):1271–1277.  
van Vollenhoven RF, Hahn BH, Tsokos GC, et al. Efficacy and safety of ustekinumab, an IL-12 
and IL-23 inhibitor, in patients with active systemic lupus erythematosus: results of a 
multicentre, double-blind, phase 2, randomised, controlled study. Lancet. 
2018;392(10155):1330–1339. https://doi.org/ 10.1016/S0140-6736(18)32167-6 
von Spee-Mayer C, Siegert E, Abdirama D, et al. Low-dose interleukin-2 selectively corrects 
regulatory T cell defects in patients with systemic lupus erythematosus. Ann Rheum Dis. 
2016;75(7):1407–1415. https://doi.org/ 10.1136/annrheumdis-2015-207776 
Wallace DJ, Furie RA, Tanaka Y, et al. Baricitinib for systemic lupus erythematosus: a 
double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. 2018;392(10143):222–
231. https://doi.org/ 10.1016/S0140-6736(18)31363-1 
Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36): I. Conceptual 
framework and item selection. Med Care. 1992;30(6):473-483.  
Winthrop KL, Novosad SA, Baddley JW, et al. Opportunistic infections and biologic therapies in 
immune-mediated inflammatory diseases: consensus recommendations for infection reporting 
during clinical trials and postmarketing surveillance. Ann Rheum Dis. 2015;74(12):2107-2116. 
https://doi.org/ 10.1136/annrheumdis-2015-207841 
Yurkovich M, Vostretsova K, Chen W, Aviña-Zubieta JA. Overall and cause-specific mortality 
in patients with systemic lupus erythematosus: a meta-analysis of observational studies. 
Arthritis Care Res (Hoboken). 2014;66(4):608–616. https://doi.org/ 10.1002/acr.22173