Conditions: Systemic Lupus Erythematosus
Keywords: T regulatory cells (Tregs) Interleukin 2 Interleukin-2
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 291
Healthy volunteers: no

Brief summary:
The reason for this study is to see if the study drug LY3471851 (NKTR-358) is safe and effective in adults with systemic lupus erythematosus (SLE).

Detailed description:
LY3471851 is a potential first-in-class therapeutic that may address an underlying immune system imbalance in people with many autoimmune conditions. It targets the interleukin (IL-2) receptor complex in the body in order to stimulate proliferation of inhibitory immune cells known as regulatory T cells. By activating these cells, LY3471851 may act to bring the immune system back into balance.

Arms:
arm 1: LY3471851 administered subcutaneously (SC). arm 2: LY3471851 administered SC. arm 3: LY3471851 administered SC arm 4: Placebo administered SC.

Interventions: intervention 1: LY3471851 intervention 2: Placebo
Intervention descriptions: intervention 1: Administered SC intervention 2: Administered SC

Protocol document:
Prot_000.pdf: 
 
 
 
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) 
 
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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. 
 
 


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


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


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Protocol J1P-MC-KFAJ(a) 
 
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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.  
 
 
 
 
 
 
 
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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. 


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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. 
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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). 


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[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). 


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[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, 


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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). 


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[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 


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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. 
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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. 


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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 


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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: 


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●  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. 


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6.7. 
Intervention after the End of the Study 
LY3471851 will not be available to participants following completion of the study. 


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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 
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●  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 


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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. 


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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 


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●  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. 


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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. 


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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. 
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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) 


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●  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 
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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). 
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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). 


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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. 


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•  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. 
 
 


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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, 


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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. 


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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). 


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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 
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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 
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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. 


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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. 
 
 
 
 
 
 
 
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8.10. 
Medical Resource Utilization and Health Economics 
This section is not applicable. 
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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 
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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. 
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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 
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●  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 
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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. 
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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). 
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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 


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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 


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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. 
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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 
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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 
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●  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. 
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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 
  
 
 
 
 
 
 
 
 
 
 
 
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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. 
 


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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]) 
 
 
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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. 
 
 
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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 
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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 


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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. 
 
 


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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. 
 
 
 


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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). 
 
 


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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). 
 
 


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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 
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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. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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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 
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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 
 
 
 
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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 
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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.) 
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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. 
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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 
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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 

SAP_001.pdf: 
 
 
 
Statistical Analysis Plan Version 3 J1P-MC-KFAJ  
 
 
A Randomized, Double-Blind, Placebo-Controlled, 
Phase 2 Study of LY3471851 (NKTR-358) in Adults 
with Systemic Lupus Erythematosus 
 
NCT04433585 
 
Approval Date: 31 January 2023 


J1P-MC-KFAJ Statistical Analysis Plan Version 3 
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1. Statistical Analysis Plan: 
J1P-MC-KFAJ: A Randomized, Double-Blind, 
Placebo-Controlled, Phase 2 Study of 
LY3471851 (NKTR-358) in Adults with Systemic 
Lupus Erythematosus  
Confidential Information 
The information contained in this document is confidential and the information contained 
within it may not be reproduced or otherwise disseminated without the approval of 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. 
LY3471851 
Study J1P-MC-KFAJ is a randomized, double-blind, placebo-controlled, Phase 2 study of 
LY3471851 (NKTR-358), designed to investigate the efficacy and safety of LY3471851 
 in adult patients with Systemic Lupus Erythemotosus.  
Eli Lilly and Company 
Indianapolis, Indiana USA 46285 
Protocol J1P-MC-KFAJ 
Phase 2 
 
Document ID: VV-CLIN-074563 
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2. Table of Contents  
Section 
Page  
1. 
Statistical Analysis Plan: J1P-MC-KFAJ: A Randomized, 
Double-Blind, Placebo-Controlled, Phase 2 Study of LY3471851 
(NKTR-358) in Adults with Systemic Lupus Erythematosus .................................................1 
2. 
Table of Contents ....................................................................................................................2 
3. 
Revision History ....................................................................................................................11 
4. 
Study Objectives ....................................................................................................................14 
4.1. 
Primary Objective .............................................................................................................14 
4.2. 
Secondary Objectives .......................................................................................................14 
 
 
5. 
Study Design .........................................................................................................................16 
5.1. 
Summary of Study Design................................................................................................16 
5.2. 
Method of Assignment to Treatment ................................................................................17 
6. 
A Priori Statistical Methods ..................................................................................................18 
6.1. 
Determination of Sample Size ..........................................................................................18 
6.2. 
General Considerations ....................................................................................................18 
 
 
 
 
6.4. 
Definition of Baseline and Postbaseline Measures ..........................................................21 
6.5. 
Primary, Secondary, and Supportive Estimands ..............................................................22 
6.5.1. 
Primary Estimand .....................................................................................................22 
6.5.2. 
Secondary Estimands ...............................................................................................22 
6.5.3. 
Supportive Estimand for Primary and Secondary Objectives ..................................23 
6.6. 
Definition of Populations .................................................................................................24 
6.7. 
Participant Characteristics ................................................................................................24 
6.7.1. 
Demographics and Baseline Characteristics ............................................................24 
6.7.2. 
Historical Illness and Preexisting Conditions ..........................................................28 
6.8. 
Participant Disposition .....................................................................................................28 
6.9. 
Concomitant Therapy .......................................................................................................28 
6.9.1. 
Corticosteroids .........................................................................................................29 
6.10. Treatment Compliance .....................................................................................................30 
6.11. Handling of Dropouts or Missing Data ............................................................................30 
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7. 
Unblinding Plan .....................................................................................................................52 
8. 
References .............................................................................................................................53 
9. 
Appendices ............................................................................................................................54 
 
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Table of Contents 
Table KFAJ.5.1. Countries and Their Geographical Regions ......................................................17 
Table KFAJ.6.1. Categorical Criteria for Abnormal Treatment-Emergent Blood Pressure 
and Pulse Measurement, and Categorical Criteria for Weight Changes 
for Adults ...........................................................................................................47 
 
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Table of Contents 
Figure 
Page 
Figure 5.1. 
Schema of Study J1P-MC-KFAJ, a Phase 2 study to evaluate the 
efficacy and safety of LY3471851 in adults with systemic lupus 
erythematosus. ...................................................................................................16 
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Table of Contents 
Appendix 
Page 
Appendix 1. 
Description and Derivation of Efficacy Outcomes Measures and 
Endpoints ...........................................................................................................55 
Appendix 2. 
Description of Efficacy Analyses ......................................................................66 
Appendix 3. 
Corticosteroid ....................................................................................................79 
Appendix 4. 
List of MedDRA Preferred Terms for Potential Opportunistic Infections 
(POI) ..................................................................................................................81 
Appendix 5. 
List of MedDRA Preferred Terms for Elevated or Increased Lipids 
from the Dyslipidemia SMQ (SMQ 20000026) ................................................95 
Appendix 6. 
List of Planned Laboratory Analytes with Reference Range Sources ..............97 
Appendix 7. 
Common Terminology Criteria for Adverse Events (CTCAE) Related 
to Myelosuppressive Events ............................................................................100 
 
 
 
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List of Abbreviations and Definitions of Terms  
Term 
Definition 
AE 
adverse events 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANCOVA 
analysis of covariance 
Anti-HBc 
hepatitis B core antibody 
AST 
aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
BICLA 
BILAG-based Composite Lupus Assessment 
BILAG 
British Isles Lupus Assessment Group – 2004 
CD 
cluster of differentiation 
CI 
confidence interval 
CLASI 
Cutaneous Lupus Erythematosus Disease Area and Severity Index 
CSR 
clinical study report 
C-SSRS 
Columbia Suicide Severity Rating Scale 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTR 
Clinical Trial Registry 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
eDISH 
evaluation of Drug-Induced Serious Hepatotoxicity 
ETV 
early termination visit 
HbsAb 
hepatitis B surface antigen 
HbcAb 
hepatitis B core antibody 
HBV 
hepatitis B virus 
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Term 
Definition 
HDL 
high-density lipoprotein 
IAC 
internal assessment committee 
ICE 
intercurrent event 
ICH 
International Conference on Harmonisation 
Ig 
immunoglobulin 
IL 
interleukin 
IR 
incidence rate 
ISR 
injection site reaction 
IWRS 
interactive web-response system 
LCTPB 
Large Clinical Trial Population Based 
LDL 
low-density lipoprotein 
LLDAS 
Lupus Low Disease Activity State 
LS 
least squares 
LTT 
Lowest Level Term 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
modified intent-to-treat 
MMRM 
mixed models for repeated measures 
NRI 
nonresponder imputation 
 
  
NK 
natural killer 
NMSC 
nonmelanoma skin cancers 
 
 
PEG 
polyethylene glycolated 
PK 
pharmacokinetic 
POI 
potential opportunistic infections 
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Term 
Definition 
PRO 
patient-reported outcomes 
PT 
Preferred Term 
PY 
patient-year 
Q2W 
every 2 weeks 
QIDS-SR16 
Quick Inventory of Depressive Symptomatology Self-Rated 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SLE 
systemic lupus erythematosus 
SLEDAI-2K 
Systemic Lupus Erythematosus Disease Activity Index 2000 
SLEDAI-4 
a ≥4-point reduction in SLEDAI-2K score from baseline 
SMQ 
Standardised MedDRA Query 
SOC 
System Organ Class 
SRI-4 
Systemic Lupus Erythematosus Responder Index-4 
 
 
TEAE 
treatment-emergent adverse events 
ULN 
upper limit of normal 
 
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4. Study Objectives  
4.1. Primary Objective  
Objectives 
Endpoints/Estimands 
 
To determine whether treatment with LY3471851 
Q2W is superior to placebo in reducing the signs 
and symptoms of SLE as measured by SLEDAI-4 
 
The study will compare LY3471851 with placebo in 
participants with SLE. 
 
 
The primary comparison of interest is the difference 
in proportion of participants who achieve 
SLEDAI-4 response at Week 24. 
 
 
The primary comparison will be assessed using a 
composite estimand where the intercurrent events of 
premature discontinuation and use of prohibited 
medication are part of the response definition. 
Abbreviations: Q2W = every 2 weeks; SLE = systemic lupus erythematosus; SLEDAI-4 = a ≥4-point reduction in 
SLEDAI-2K score from baseline; SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index 2000. 
4.2. Secondary Objectives  
The secondary objectives of the study are the following:  
Objectives 
Endpoints/Estimands 
 
To determine whether treatment with LY3471851 
Q2W is superior to placebo in reducing other 
measures of signs and symptoms of SLE 
 
The study will compare LY3471851 with placebo in 
participants with SLE. 
 
 
Secondary comparisons of interest are the difference 
in proportion of participants who at Week 24 (V15) 
achieve: 
o 
BILAG-based Composite Lupus Assessment 
(BICLA) response 
o 
SRI-4 response 
o 
Lupus Low Disease Activity State (LLDAS) 
 
 
Secondary objectives will be assessed using a 
composite estimand. 
 
To characterize the pharmacokinetics of 
LY3471851 in participants with SLE 
 
LY3471851 plasma trough concentrations at Week 
24 (V15) 
Abbreviations: BILAG = British Isles Lupus Assessment Group – 2004; Q2W = every 2 weeks; SLE = systemic 
lupus erythematosus; SRI-4 = Systemic Lupus Erythematosus Responder Index-4; V = Visit. 
 
 
 
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Participants will be stratified at randomization according to disease activity at baseline, 
corticosteroid dose at baseline, and geographic region (Section 5.2). Study interventions will be 
administered via subcutaneous injection. 
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 protocol. 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 
protocol. 
Follow-up period: All participants will have a posttreatment follow-up visit (Visit 801) for 
safety assessments. Randomized participants who were positive for anti-HBc at screening will 
have one additional posttreatment follow-up visit (Visit 802). 
Early discontinuation: Participants who permanently discontinue the study drug early or 
withdraw from the study will undergo early termination procedures, including an ETV and the 
post-treatment follow-up visits specified in the protocol. 
5.2. Method of Assignment to Treatment  
Subjects who meet all criteria for enrollment will be randomized 1:1:1:1 to double-blind 
treatment at Visit 2. Participants will be stratified at randomization according to disease activity 
at baseline (SLEDAI-2K <10; SLEDAI-2K ≥10), corticosteroid dose at baseline (<10 mg/day or 
≥10 mg/day), and geographic region. Table KFAJ.5.1 describes how each region will be defined 
for the stratification at randomization as well as the statistical analyses and summaries. 
Assignment to treatment groups will be determined by a computer-generated random sequence 
using an IWRS. The IWRS will be used to assign vials containing double-blind investigational 
product to each patient. Site personnel will confirm that they have located the correct vials by 
entering a confirmation number found on the vials into the IWRS. The IWRS will be used to 
assign investigational product to each patient. Site personnel will confirm that they have located 
the correct packages by entering a confirmation number found on packages into the IWRS. 
Table KFAJ.5.1. 
Countries and Their Geographical Regions  
Geographical Region 
Country or Countries 
North America 
Canada, United States, Puerto Rico 
Latin America 
Argentina, Mexico 
Europe 
Belgium, Czech Republic, France, Germany, Hungary, 
Italy, Poland, Romania, Spain, United Kingdom 
Asia 
South Korea, Taiwan 
Japan 
Japan 
Rest of World 
Australia, India, Israel, Russia, Ukraine 
 
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6. A Priori Statistical Methods  
6.1. Determination of Sample Size  
 will be randomly assigned to study intervention. All randomized 
participants in the mITT population as defined in Section 6.6 will be considered evaluable. 
Pairwise 2-sided tests of proportions with alpha = 0.05 will be performed on each LY3471851 
dose versus placebo
, a placebo response of 0.40, and a 
LY3471851 response of 0.64 for the maximally efficacious LY3471851 dose, there is at least 
80% power to detect a statistically-significant difference in SLEDAI-4 response between 
LY3471851 and placebo at Week 24 (Visit 15). 
6.2. General Considerations  
Statistical analysis of this study will be the responsibility of the sponsor or its designee. For 
primary and key secondary objectives, statistical analyses will be performed
 
 
   
Not all displays described in this SAP will necessarily be included in the CSR. Not all displays 
will necessarily be created as a “static” display. Some may be incorporated into interactive 
display tools such as Spotfire instead of, or in addition to, a static display. Any display described 
in this SAP and not included in the CSR would be available upon request. 
All tests of treatment effects will be conducted at a 2-sided alpha level of 0.05, unless otherwise 
stated. The p-values will be rounded up to 3 decimal places. For example, any p-value strictly 
>0.049 and ≤0.05 will be displayed as 0.050. This guarantees that on any printed statistical 
output, the unrounded p-value will always be less than or equal to the displayed p-value. A 
displayed p-value of 0.001 will always be understood to mean ≤0.001. Likewise, any p-value 
displayed as 1.000 will be understood to mean >0.999 and ≤1. 
The primary analysis method for treatment comparisons of categorical efficacy and health 
outcome variables will be made using a logistic regression analysis with treatment group, 
baseline disease activity (SLEDAI-2K <10; SLEDAI-2K ≥10), corticosteroid dose at baseline 
(<10 mg/day or ≥10 mg/day), and geographic region (North America, Latin America, Europe, 
Asia, Japan, Rest of World) in the model. For each treatment comparison, an estimate of the 
treatment difference with corresponding Wald 95% CI, the odds ratio with corresponding Wald 
95% CI and p-value will be presented. Each treatment group will be compared to the placebo 
group. The p-value for all other explanatory variables will also be presented. When logistic 
regression sample size requirements are not met (<5 subjects in any category for any factor), 
treatment comparison will be performed using the Fisher’s exact test. 
The primary analyses for continuous efficacy and health outcome variables will be made using 
MMRM. When MMRM is used, the model will include treatment, baseline score, baseline 
disease activity (SLEDAI-2K <10; SLEDAI-2K ≥10), corticosteroid dose at baseline 
(<10 mg/day or ≥10 mg/day), geographic region (North America, Latin America, Europe, Asia, 
Japan, Rest of World), visit (as categorical variable), the interaction of treatment-by-visit, and 
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the interaction of baseline value-by-visit as fixed factors. An unstructured covariance matrix will 
be used to model the within-patient variance-covariance errors. If this analysis fails to converge, 
the following structures will be tested in this pre-specified order: 1) heterogeneous Toeplitz, 2) 
heterogeneous autoregressive, 3) heterogeneous compound symmetry, 4) Toeplitz, 5) 
autoregressive), and 6) compound symmetry. The first covariance structure that converges using 
this prespecified order will be used. The Kenward-Roger method will be used to estimate the 
degrees of freedom. Type III sums of squares for the LS means will be used for the statistical 
comparison. The LS mean for each treatment group along with the estimate of the difference 
between treatments (difference between each LY3471851 dose group and placebo), standard 
error, p-value, and the 95% CIs will be reported at each visit along with p-values. For variables 
that are not collected at each postbaseline visit, data may exist at visits where the variable was 
not scheduled to be collected, due to early discontinuation visits. In these situations, data from 
the early discontinuation visit that do not correspond to the planned collection schedule will be 
excluded from the MMRM analyses (Andersen and Millen 2013). However, the data will still be 
used in other analyses. 
When ANCOVA is used for efficacy/Health Outcomes measures, the model will include 
treatment, baseline score, baseline disease activity (SLEDAI-2K <10; SLEDAI-2K ≥10), 
corticosteroid dose at baseline (<10 mg/day or ≥10 mg/day), and geographic region as fixed 
factors. Type III sums of squares will be used. Differences in LS means between treatment 
groups will be displayed, with the p-value associated with the LS mean comparison to placebo 
(for each LY3471851 dose group) along with the 95% CI of the LS mean difference also 
provided. In addition to the LS means and tests, mean, SD, minimum, first quartile, median, third 
quartile, and maximum will be displayed. 
When Cox regression is used for time-to-event variables, the model will include treatment, 
baseline score, baseline disease activity (SLEDAI-2K <10; SLEDAI-2K ≥10), corticosteroid 
dose at baseline (<10 mg/day or ≥10 mg/day) and geographic region (North America, Latin 
America, Europe, Asia, Japan, Rest of World). Treatment comparisons will use the hazard ratios 
and corresponding p-values from the Cox regression. The Kaplan-Meier product limit method 
will be used to estimate the survival curves for time-to-event variables. Patients completing the 
treatment period without event will be censored at the date of completion. Patient without an 
event, a date of completion, or discontinuation for the treatment period will be censored at the 
latest nonmissing date out of the following dates: date of last dose and date of last attended visit 
in the treatment period. Under the hypothetical estimand strategy, patients without an event prior 
to the first violation of concomitant medication rules will be censored at the time of the first 
violation of concomitant medication rules. 
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Efficacy and PRO analysis models may contain the independent variables such as treatment 
group, baseline disease activity, and geographic region. 
Any change to the data analysis methods described in the SAP will require an amendment only if 
the change affects a principal feature of the SAP. Any other change to the data analysis methods 
described in the SAP, and the justification for making the change, will be described in the CSR. 
Additional exploratory analyses of the data will be conducted as deemed appropriate. 
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6.4. Definition of Baseline and Postbaseline Measures  
Baseline will be defined as the last available value before the first dose of study drug for both 
efficacy and safety analyses, unless otherwise specified. In most cases, this will be the measure 
recorded at Week 0 (Visit 2). The treatment period starts after the first study drug administration 
and ends on one of the following: 
 date of Visit 15 (Week 24) for patients who completed the treatment period 
 for patients who discontinued treatment early 
o date of ETV, if ETV occurs less than 42 days after treatment discontinuation 
o date of the last visit that occurs less than 42 days after treatment discontinuation, 
if ETV occurs after 42 days since treatment discontinuation.   
Change from baseline will be calculated as the visit value of interest minus the baseline value. 
Percent change from baseline will be calculated as 100 times change from baseline divided by 
baseline.   
Postbaseline measurements are collected after study drug administration through Visit 15 
(Week 24) or an early discontinuation visit. For electronic PROs related to efficacy assessments, 
unscheduled postbaseline visits that fall within the protocol-defined visit windows will be 
summarized in the by-visit analyses if there is no scheduled visit available. If more than 1 value 
is reported for the same scheduled visit, then the first value will be summarized in the by-visit 
analyses. 
The Follow-up Period includes all visits that are 42 days or more after treatment discontinuation 
for patients who discontinue the treatment period early. For patients who complete the treatment 
period, the Follow-up Period includes Visit 801 for safety assessment. Randomized participants 
who were positive for anti-HBc at screening will have one additional posttreatment follow-up 
visit (Visit 802). The baseline value for the safety analysis of the posttreatment follow-up period 
is defined as the last nonmissing assessment prior to entering the posttreatment Follow-up 
Period, that is Week 24 (Visit 15) for treatment completers or last visit that occurred less than 
42 days after treatment discontinuation for patients that discontinued treatment early. When the 
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Follow-up Period includes more than 1 visit, any safety analyses that are done for this period will 
only include the first visit of this period. 
6.5. Primary, Secondary, and Supportive Estimands  
Unless otherwise specified, a composite strategy will be used for categorical efficacy endpoints, 
as described in Section 6.5.1. A hypothetical strategy will be used for continuous efficacy 
endpoints, as described in Section 6.5.4. 
6.5.1. Primary Estimand  
The primary clinical question of interest is: What is the difference between LY3471851 and 
placebo in the target patient population, in achieving a successful response at Week 24 without 
violating concomitant medication rules? 
The violation of concomitant medication rules for this study includes (i) initiating or increasing 
in dose of corticosteroids, antimalarial, or immunosuppressant, or (ii) using prednisone >10 mg 
per day (or equivalent) after Week 12. 
The estimand for the primary objective is described by the following attributes: 
 population: modified intent-to-treat population  
 endpoint: SLEDAI-4 at Week 24 
 how to account for ICEs: A composite estimand strategy will be used. Participants with 
violation of concomitant medication rules will be considered as treatment failure, that is, 
a nonresponder, after the first occurrence of violation of concomitant medication rules.  
 population-level summary: difference in response rate of SLEDAI-4 at Week 24 between 
LY3471851 and placebo, and 
 rationale for estimand: the primary estimand strategy assumes that a participant, who 
violates concomitant medications, was not receiving sufficient benefits from study 
intervention. This estimand is free of confounding effects of increase in concomitant 
medication use. Under the primary estimand strategy, a participant is considered a 
SLEDAI-4 responder at Week 24 if both of the following are met: 
o ≥ 4 points reduction from baseline in SLEDAI-2K score at Week 24  
o no violation of concomitant medication rules prior to Week 24.  
If either or both of these criteria are not met, a participant is considered as a SLEDAI-4 
nonresponder at Week 24. Apart from the primary estimand strategy, missing data imputation is 
described separately in Section 6.11.  
6.5.2. Secondary Estimands  
The secondary estimands for the secondary objectives are described by the following attributes: 
 population: mITT population  
 endpoints: SRI-4 at Week 24, BICLA at Week 24 (in the subset of participants with ≥1 A 
or ≥2 B at baseline), LLDAS at Week 24 
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 ICE will be accounted using the same estimand strategy as for the primary estimand 
(Section 6.5.1). 
 population-level summary: difference in response rate of a secondary endpoint between 
LY3471851 and placebo 
 rationale for estimand is provided in Section 6.5.1.  
6.5.3. Supportive Estimand for Primary and Secondary Objectives  
A supportive estimand for the primary and secondary objectives will be considered to address a 
clinical question: What is the difference between LY3471851 and placebo in the target patient 
population, in achieving successful response at Week 24 without regards to violation of 
concomitant medication rules?  
For the supportive estimands, a treatment policy estimand strategy will be used to account for 
ICEs, and treatment effect will be assessed regardless of whether ICEs has occurred or not. That 
is, observed data after ICEs will be included as is in the analysis. Population, endpoints, and 
population-level summary are the same as described in Sections 6.5.1 and 6.5.2.  
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6.6. Definition of Populations  
The following populations are defined for this study: 
Population 
Description 
Entered population 
All participants who sign the informed consent form 
Modified Intent-to-Treat 
(mITT) population 
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. 
Per-Protocol (PP) population 
All randomized patients who do not commit an Important Protocol Deviation 
(IPD) that could potentially compromise efficacy results. IPDs are specified in 
the Trial Issue Management Plan.  
Safety population 
All participants randomly assigned to study intervention and who take at least 1 
dose of study intervention and did not discontinue the study for the reason “lost 
to follow-up” at the first postbaseline visit. Participants will be analyzed 
according to the intervention they actually received within each study period. 
Pharmacokinetic (PK) 
Analysis population 
All participants randomly assigned to study intervention and who take at least 1 
dose of study intervention they actually received and have PK data available. 
 
The mITT population will be used in analyses of efficacy and PRO, unless otherwise specified. 
6.7. Participant Characteristics  
6.7.1. Demographics and Baseline Characteristics  
Demographics and baseline characteristics will be summarized using the mITT population by 
treatment group. The summary will include descriptive statistics such as the number of patients 
(n), mean, SD, median, min, and max for continuous measures, and frequency counts and 
percentages for categorical measures. No formal statistical comparisons will be made among 
treatment groups, unless otherwise stated.   
The continuous demographic and baseline characteristic variables outlined in Table KFAJ.6.1 
will be summarized using descriptive statistics. 
 
 
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Table KFAJ.6.1. 
Continuous Demographic and Baseline Characteristic Variables  
Variable 
Quantitative 
Categorical Summary 
Subgroup Analysis 
Demographic Characteristics 
Age a 
Yes 
<65, 65 to <75, ≥75 
 
Height 
Yes 
 
 
Weight 
Yes 
 
 
BMI b 
Yes 
 
 
Sex 
No 
Female, Male 
Yes 
Race 
No 
American Indian/Alaska Native, Asian, 
Black/African American, Native 
Hawaiian or other Pacific Islander, 
White, or Multiple 
Yes 
Country 
 
Canada, United States, Puerto Rico, 
Argentina, Mexico, Belgium, Czech 
Republic, France, Germany, Hungary, 
Italy, Poland, Romania, Spain, United 
Kingdom, South Korea, Taiwan, Japan, 
Australia, India, Israel, Russia, Ukraine 
 
Region (Table KFAJ.5.1) 
 
North America, Latin America, 
Europe, Asia, Japan, Rest of World  
Yes 
Country GDP 
No 
Category 1 [Mexico, India, Ukraine] 
Category 2 [Argentina, Czech 
Republic, Hungary, Poland, Romania, 
Spain, Russia] 
Category 3 [Canada, United States, 
Puerto Rico, Belgium, France, 
Germany, Italy, United Kingdom, 
South Korea, Taiwan, Japan, Australia, 
Israel] 
Yes 
Ethnicity (only US sites) 
 
Hispanic/Latino, Non-Hispanic/Non-
Latino, Missing 
Yes 
Time since onset of lupus 
(years) c 
Yes 
 
 
Concomitant Medication Use at Baseline 
Daily dose of prednisone (or 
equivalent) in mg/day d 
Yes 
<7.5 mg/day, ≥7.5 mg/day 
<10 mg/day, ≥10 mg/day 
Yes 
Immunosuppressant use 
No  
Yes, No 
 
Mycophenolate mofetil use 
No 
 
 
Azathioprine use 
No 
 
 
Methotrexate use 
No 
 
 
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Variable 
Quantitative 
Categorical Summary 
Subgroup Analysis 
Antimalarial use (for each 
drug) 
No 
Yes, No 
 
NSAID use 
No 
 
 
Disease Severity at Baseline 
SLEDAI-2K 
Yes 
<10, ≥10 
Yes 
SLEDAI-2K organ system 
involvement at baseline 
No  
Yes, No 
 
British Isles Lupus 
Assessment Group 
(BILAG) organ system 
involvement at baseline 
(either A or B) 
No 
Yes, No  
 
BILAG A organ system 
involvement at baseline 
No  
Yes, No 
Yes 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes 
 
 
Physician’s Global 
Assessment of Disease 
Activity score 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Variable 
Quantitative 
Categorical Summary 
Subgroup Analysis 
SLE Risk Probability Index 
(SLEPRI) 
Yes 
≤7, 7 to ≤11, 11 to ≤14, >14 (lower 
bounds are strictly greater than) 
Yes 
Prior Benlysta (belimumab) 
use 
No 
Yes, No 
 
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Abbreviations: 
; GDP = 
gross domestic product; NRS = numeric rating scale; NSAID = nonsteroidal anti-inflammatory drug; SLE = 
Systemic Lupus Erythematosus; SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index 2000. 
a Age will be calculated using an imputed date of birth of July 1st in the year of birth collected in the electronic 
case report form (eCRF). It will be calculated as: Age (in years) = (date of first dose – imputed date of 
birth)/365.25 
b Body mass index (BMI) (kg/m2) at Visit 2. BMI (kg/m2) = Weight [kg] / Height [m]2 
c Time since onset of lupus will be calculated using the date of onset of lupus (as recorded on the SLE History 
eCRF page) as follows: Time since onset of lupus (years) = (date of first dose - date of onset of lupus + 1) / 
365.25. 
d Patients with a non-zero dose at Visit 2 will be included in this baseline summary, see Section 6.9.1 for details of 
prednisone (or equivalent) baseline dose. 
6.7.2. Historical Illness and Preexisting Conditions  
Historical illness/condition is defined as the condition/event recorded on the Pre-Existing 
Conditions and Medical History eCRF page or on the Prespecified Medical History eCRF page 
with an end date prior to the date of informed consent. Preexisting condition is defined as the 
condition/event recorded on the Pre-Existing Conditions and Medical History eCRF page or on 
the Prespecified Medical History eCRF page with a start date prior to the date of informed 
consent, and no end date (that is, the event is ongoing) or an end date on or after the date of 
informed consent. Notice if a preexisting condition worsens in severity on or after the date of 
informed consent, it will be recorded as an AE on Adverse Events eCRF page from the date of 
worsening onwards. Historical illnesses and preexisting conditions will be classified using the 
latest version of the MedDRA. The number and percentage of patients with historical illnesses 
and preexisting conditions will be provided by treatment group, overall and by SOC and PT 
using the mITT population. Note that conditions with a partial or missing start date will be 
assumed to be “not preexisting” unless there is evidence, through comparison of partial dates, to 
suggest otherwise. Patients will only be counted once if same PT is listed in 2 or more different 
SOC categories.   
6.8. 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, the number and 
percentage of participants who complete the study or discontinue, both overall and by reason for 
discontinuation, and the frequency and percentage of patients who discontinue study treatment. 
A summary of important protocol deviations will be provided. 
6.9. Concomitant Therapy  
Previous and concomitant medications will be summarized by treatment group and will be 
presented by ATC drug classes using the latest version of the World Health Organization drug 
dictionary. 
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Under the composite estimand strategy described in Section 6.5.1, a patient will be considered a 
nonresponder after the first occurrence of a violation of any of the following concomitant 
medication rules, regardless of the patient’s efficacy status or disposition status: 
 no initiation or increase in dose from baseline of  
o nonsteroidal anti-inflammatory drug intended for treatment of signs and 
symptoms of SLE 
o prednisone (or equivalent) 
o antimalarial. and 
o immunosuppressant 
 prednisone ≤10 mg/day (or equivalent) by Week 12  
Violations of concomitant medication rules will be first identified via programming and then 
reviewed by a blinded medical to confirm the violations align with the criteria specified in the 
protocol. The confirmed list provided by the blinded medical will be used for analyses.  
6.9.1. Corticosteroids  
To allow for assessments of changes in doses of various corticosteroids, it was necessary to 
standardize all corticosteroid doses to an equivalent prednisone dose. Table KFAJ.6.2 provides a 
summary of frequent corticosteroids and their prednisone-equivalent dose. The dose of the drug 
listed in Column 1 is multiplied by the conversion factor in Column 2 to provide the prednisone 
equivalent dose (in milligrams). This dose of corticosteroid will be referred to as “prednisone (or 
equivalent)” throughout this document.   
See Appendix 3 for a complete table showing conversion factors for each corticosteroid 
medication identified during the study, instructions for selecting corticosteroids, and the manual 
review process. References for this table can also be found in Appendix 3. 
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Baseline prednisone (or equivalent) dose will be the total daily dose of all corticosteroids being 
taken by a patient at Visit 2. This baseline dose will be used for baseline summaries and for 
comparisons to later visits. A daily dose of prednisone (or equivalent) will be calculated for each 
day between baseline and treatment discontinuation. The daily dose of prednisone (or equivalent) 
at each visit date will be used as the corticosteroid dose for that visit.   
6.10. Treatment Compliance  
Patient compliance with study medication will be assessed from the randomization visit 
(Week 0) to Visit 15 (Week 24) during the treatment period. Compliance will be summarized 
from randomization until end of treatment using the mITT population. A patient is considered 
noncompliant if 2 or more of the prescribed doses during the study are missed, not including 
doses withheld by the investigator. A patient who takes more than 12 of the prescribed doses 
during the treatment period is also considered noncompliant.   
Compliance to study drug in the period of interest will be calculated as follows:   
actual total # of doses
Expected total # of doses ∗100. 
If a patient has a dose temporarily interrupted by the investigator during the period, the total 
number of days that drug was withheld will be deducted from the total number of days in the 
calculation of the expected total number of doses used. 
The summary statistics of the percent of compliance and noncompliance rate will be summarized 
by treatment group. The percent of compliance for Week 0 (Visit 2) through Week 24 (Visit 15) 
will be presented, along with the associated noncompliance rates.   
6.11. Handling of Dropouts or Missing Data  
Missing data imputation is handled separately from the estimand strategy. After intercurrent 
events are accounted for according to an estimand strategy described in Section 6.5, any 
remaining missing data will be handled using missing data imputation methods described in this 
section. Reasons for such missing data include, but are not limited to,  
 intermittent missing visits, assessments, or some components of assessments 
 temporary treatment interruptions, and  
 early treatment discontinuation.  
When NRI is used, missing binary data will be imputed as non-response.  
When last observation carried forward is used, missing continuous data will be imputed with the 
last nonmissing postbaseline observation prior to the first occurrence of intercurrent events. For 
patients without at least one postbaseline observation, missing continuous data will not be 
imputed.  
When baseline observation carried forward is used, missing continuous data will be imputed with 
baseline observation (last nonmissing data before the first injection). For patients without 
baseline observation, missing continuous data at postbaseline visits will not be imputed.  
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The missing data imputation methods for planned analyses are specified in Sections 6.14, 6.15, 
and 6.16.  
6.12. 
Multicenter Studies  
This study will be conducted by multiple investigators at multiple sites internationally. The 
countries will be categorized into geographic regions, as described in Section 5.2. Geographic 
region will be included in a statistical model as a fixed effect, unless otherwise specified. 
6.13. Multiple Comparisons/Multiplicity  
No adjustments for multiplicity will be made for any analyses in this study. 
6.14. Primary Endpoint/Estimand Analyses  
The primary efficacy endpoint per composite estimand strategy (the primary estimand as 
described in Section 6.5.1) is 
 SLEDAI-4 at Week 24 after accounting for violation of concomitant medication 
rules: (i) initiating or increasing in dose of corticosteroids, antimalarial, or 
immunosuppressant, or (ii) using prednisone >10 mg per day (or equivalent) after 
Week 12 
Under the composite estimand strategy, participants will be considered nonresponders at all 
subsequent visits after the first violation of concomitant medication rules regardless of their 
discontinuation status. 
The primary analysis for treatment comparison of each LY3471851 dose with placebo will be 
analyzed using a logistic regression model with treatment group, baseline disease activity 
(SLEDAI-2K <10; SLEDAI-2K ≥10), corticosteroid dose at baseline (<10 mg/day or 
≥10 mg/day), and geographic region (North America, Latin America, Europe, Asia, Japan, Rest 
of World) in the model. The analysis will be based on the mITT population and missing data will 
be handled using NRI. P-values from the Fisher’s exact test will also be reported as a sensitivity 
analysis, when logistic regression sample size requirements are not met (<5 subjects in any 
category for any factor).  
As supplementary analyses,  
 to determine the impact of important protocol deviations, the primary analysis 
detailed above will also be conducted on the per-protocol population  
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6.15. Secondary Endpoints/Estimand Analyses  
The secondary endpoints per composite estimand strategy (the primary estimand as described in 
Section 6.5.2) without violation of concomitant medication rules: (i) initiating or increasing in 
dose of corticosteroids, antimalarial, or immunosuppressant, or (ii) using prednisone >10 mg per 
day (or equivalent) after Week 12 are 
 BICLA at Week 24 
 SRI-4 at Week 24, and 
 LLDAS at Week 24.  
Under the composite estimand strategy, participants will be considered nonresponders at all 
subsequent visits after the first violation of concomitant medication rules regardless of their 
discontinuation status. 
The analytical details specified in Section 6.14 will be followed. The supplementary analyses in 
Section 6.14 may also be considered for the secondary efficacy endpoints if deemed appropriate. 
Description and derivation of secondary endpoints are described in a separate document, and the 
handling of missing data due to, for example, a missed visit is detailed in Appendix 1.  
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6.19. Safety Analyses  
All safety data will be descriptively summarized by treatment groups and analyzed based on the 
safety population. The safety population is defined as those patients who received at least 1 dose 
of study drug and did not discontinue the study for the reason “lost to follow-up” at the first 
postbaseline visit. The safety analyses include AEs, safety in special groups and circumstances, 
including adverse events of special interest, laboratory analytes, QIDS-SR16, C-SSRS, ECGs, 
and vital signs. The duration of exposure will also be summarized. The categorical safety 
measures will be summarized using IRs and analyzed by Fisher’s exact test. The mean change in 
the continuous safety measures including vital signs, QIDS-SR16, physical characteristics, and 
laboratory values will be summarized by visits and analyzed by ANCOVA, with treatment and 
baseline values in the model. More details are provided in subsequent sections.   
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Not all displays described in this section will necessarily be included in the CSRs. Any display 
described and not provided in the CSR would be available upon request. Not all displays will 
necessarily be created as a “static” display. Some may be incorporated into interactive display 
tools instead of or in addition to a static display. Any display created interactively will be 
included in the CSR if deemed relevant to the discussion. 
6.19.1. Extent of Exposure  
Duration of exposure to study drug will be summarized for the safety population by treatment 
group. Exposure will be calculated as the date of last dose of study drug (or date of 
discontinuation) minus the date of first dose of study drug plus 1 day. Total PYs of exposure will 
be reported for each treatment group for overall duration of exposure. Descriptive statistics (n, 
mean, SD, minimum, first quartile, median, third quartile, and maximum) will be provided for 
patient-days of exposure and the frequency of patients falling into different exposure ranges will 
be summarized. Exposure ranges are as follows:   
 ≥4 weeks, ≥12 weeks, and ≥24 weeks 
 >0 to <4 weeks, ≥4 weeks to <12 weeks, ≥12 weeks to <24 weeks, and ≥24 weeks 
Overall exposure will be summarized in total PYs, which are calculated according to the 
following: 
Exposure in PYs = sum of duration of exposure in days (for all patients in 
treatment group) / 365.25 
No p-values will be reported in these tables as they are intended to describe the 
characteristics of the study sets. 
6.19.2. Adverse Events  
6.19.2.1. Adverse Events  
AEs are recorded in the eCRF. Each AE will be coded to SOC and PT, using the MedDRA 
version that is current at the time of database lock. Severity of AEs is recorded as mild, 
moderate, or severe.   
TEAEs are defined as events that either first occurred or worsened in severity after the first dose 
of study drug and the earliest of the visit study drug disposition date or the last visit date during 
the treatment period, whichever occurred first, and up to 30 days after study treatment 
discontinuation. The MedDRA LLT will be used in defining which events are treatment-
emergent. The maximum severity for each LLT during the baseline period until the first dose of 
the study medication will be used as baseline. If an event is preexisting during the baseline 
period, but it has missing severity, and the event persists during the treatment period or up to 
30 days after treatment discontinuation, then the baseline severity will be considered mild for 
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determining any postbaseline treatment-emergence (that is, the event is treatment-emergent 
unless the severity is coded mild at postbaseline). If an event occurring postbaseline has a 
missing severity rating, then the event is considered treatment-emergent. Should there be 
insufficient data for an AE start date to make this comparison (for example, the AE start year is 
the same as the treatment start year, but the AE start month and day are missing), the AE will be 
considered treatment-emergent. For events occurring on the day of the first dose of study 
treatment, the day and time of the onset of the event will both be used to distinguish between 
pretreatment and posttreatment in order to derive treatment-emergence. 
In general, summaries will include the number of patients in the safety population (N), frequency 
of patients experiencing the event (n), and relative frequency (that is, percentage; n/N*100).   
In an AE overview table, the number and percentage of patients in the safety analysis set who 
experienced death, an SAE, any TEAE, permanent discontinuation from study drug due to an 
AE, temporary interruption of study drug due to an AE or laboratory abnormality, or a severe 
TEAE will be summarized by treatment group.   
The number and percentage of patients with TEAEs will be summarized by treatment group in 
2 formats listed below. For events that are gender specific, the denominator and computation of 
the percentage will only include patients from the given gender. 
 by MedDRA PT nested within SOC with SOCs ordered alphabetically, and events 
ordered within each SOC by decreasing frequency in the LY3471851 
 treatment 
group. 
 by MedDRA PT with events ordered by decreasing frequency in the LY3471851
 
treatment group. 
AEs leading to permanent discontinuation of study drug and AEs leading to temporary 
interruption of study drug will also be summarized by treatment group using MedDRA PT nested 
within SOC. Events will be ordered by decreasing frequency within SOC in the LY3471851 
 treatment group. 
The number and percentage of patients with TEAEs will be summarized by maximum severity 
by treatment using MedDRA PT ordered by decreasing frequency for the common TEAEs. For 
each patient and TEAE, the maximum severity for the MedDRA level being displayed is the 
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maximum postbaseline severity observed from all associated LLTs mapping to that MedDRA 
PT.   
6.19.2.2. Serious Adverse Events  
An individual listing of all AEs including preexisting conditions will be provided. A separate 
listing will include AEs that led to permanent discontinuation from the study drug. In addition, a 
listing of AEs that occur more than 30 days after study treatment discontinuation will be 
provided. 
With the ICH E2A guideline, a SAE is any AE that results in 1 of the following outcomes: 
 death 
 initial or prolonged inpatient hospitalization 
 a life-threating experience (that is, immediate risk of dying) 
 persistent or significant disability/incapacity 
 congenital anomaly/birth defect, or 
 considered significant by the investigator for any other reason. 
The number and percentage of patients who experienced any ICH-defined SAE will be 
summarized by treatment group during the treatment and follow-up periods using MedDRA PT 
nested within SOC. Events will be ordered by decreasing frequency within SOC in the 
LY3471851
 treatment group. In addition, the SAEs will be summarized by treatment 
group using MedDRA PT without SOC. An individual listing of all SAEs will be provided. 
  
  
 
   
 
 
   
 
   
 
   
 
 
 
 
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A listing including all malignancy cases will be provided. An NMSC flag will be provided using 
the following MedDRA PTs (the list will be updated depending on the MedDRA version used 
for analysis):   
 Squamous cell carcinoma of skin (10041834)  
 Bowen’s disease (10006059) 
 Basal cell carcinoma (10004146) 
 Basosquamous carcinoma (10004178) 
 Basosquamous carcinoma of skin (10004179) 
 Squamous cell carcinoma (10041823) 
 Skin squamous cell carcinoma metastatic (10077314) 
 Skin cancer (10040808), and 
 Carcinoma in situ of skin (10007390). 
The number and percentage of patients with TEAE-associated malignancies excluding NMSC 
and NMSC will be summarized by treatment group. In addition, the IR (for detail, see 
Section 6.19) and 95% CI will be calculated for the overall observation time. All cases identified 
by Malignant tumors SMQ will be assessed after database lock by the medical team to determine 
(1) confirmed NMSC cases and (2) symptom and date that triggered the malignancy 
investigation or diagnosis. An additional listing based on medical review may also be provided if 
deemed necessary. All cases reported in the study database or by Lilly Safety System report, 
disregarding the length of gap between the last treatment dose date and the event date will be 
included.   
6.19.4. Injection Site Reaction  
At every visit following the first dose and prior to any blinded study activity, an independent ISR 
assessor who is not involved with other study procedures will evaluate each participant for the 
presence of ISRs between the visits.   
The number and percentage of patients who experienced an ISR will be summarized by 
treatment group and by visit. The number and percentage of patients with the following ISR 
records will be summarized by treatment group and by visit. Details about ISR records are 
referred to the case report form. 
 anatomical location of the injection site reaction 
 abdomen side 
 directionality of the anatomical location of the administration 
 arm side 
 thigh side 
 whether the subject have any injection site erythema (reddening) or not 
 severity of the injection site erythema 
 whether the subject have any injection site induration (hardening or thickening of tissue) 
or not 
 severity of the injection site induration 
 whether the subject have any injection site pain (including burning) or not 
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 severity of the injection site pain 
 whether the subject have any injection site pruritus 
 severity of the injection site pruritus 
 whether the subject have any injection site edema (swelling or accumulation of fluid in 
tissues at height above normal skin) or not 
 severity of the injection site edema, and 
 when did the injection related event occur, in relationship to the study treatment. 
 
The frequency of the maximum severity of ISRs will be summarized by treatment group.  
 
 
 
 
 
 It will not be considered a protocol violation 
if the planned sample size is not achieved due to an insufficient number of consenting and 
eligible participants. 
6.19.5. Clinical Laboratory Evaluation  
All laboratory tests will be presented using the Système International of units (SI) and 
conventional (CN) units. For topics of safety in special groups and circumstances, laboratory test 
units will be specified for each analysis. 
Lilly LCTPB reference limits will be used to define the low and high limits because it is 
generally desirable for limits used for analyses to have greater specificity (identify fewer false 
positive cases) than reference limits used for individual patient management. When Lilly LCTPB 
reference ranges are unavailable, then central laboratory (Covance) reference ranges will be 
used. For the 4 key hepatic laboratory assessments (ALT, AST, total bilirubin, and ALP), central 
laboratory reference ranges (Covance) will be used and all results pertaining to these assessments 
will be included as a separate analysis to address the risk of liver injury as a special safety topic 
(see Section 6.19.5.1). Central laboratory reference ranges (Covance) will also be used to 
evaluate immunoglobulins and lymphocyte cell subsets (see Sections 6.19.5.3 and 6.19.5.7). See 
Appendix 6 for details of the reference range by laboratory analytes.   
The LDL/HDL ratio will be derived as the ratio of LDL cholesterol to HDL cholesterol. There 
are no Lilly LCTPB reference ranges or central lab reference ranges for the LDL/HDL ratio.   
The following will be conducted for laboratory analyte measurements collected quantitatively: 
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 Box plots for observed values: Values at each visit (starting at randomization) 
and change from baseline to each visit and to last postbaseline measure will be 
displayed in box plots for patients who have a baseline and at least 
1 postbaseline visit. For visits included in the treatment period, patients will 
be included only if the visit occurs on or before the date of treatment 
discontinuation/completion. Follow-up visit will be the first visit that occurred 
during the Follow-up period. Individual measurements outside of reference 
limits will also be displayed using distinct symbols overlaying the box plot. 
Original-scale data will be used for the display but for some analytes (for 
example, immunoglobulins) a logarithmic scale will be used to aid in viewing 
the measures of central tendency and dispersion. Unplanned measurements 
will be excluded. Descriptive summary statistics will be included in a table 
below the box plot. These box plots will be used to evaluate trends over time 
and to assess a potential impact of outliers on central tendency summaries. A 
p-value for change from baseline to endpoint will be provided using an 
ANCOVA model with explanatory term for treatment and the baseline value 
as a covariate. Endpoint will be the last observation where patient is on 
treatment.   
 Treatment-emergent high/low analyses: the number and percentage of patients 
with treatment-emergent high and low laboratory results at any time will be 
summarized by treatment group. Planned and unplanned measurements will 
be included. A treatment-emergent high result is defined as a change from a 
value less than or equal to the high limit at all baseline visits to a value greater 
than the high limit at any time during the treatment period and up to 60 days 
after treatment discontinuation. A treatment-emergent low result is defined as 
a change from a value greater than or equal to the low limit at all baseline 
visits to a value less than the low limit at any time during the treatment period 
and up to 60 days after treatment discontinuation. The Fisher’s exact test will 
be used for the treatment comparisons. 
A listing of abnormal findings will be provided. The listing will include, but not be limited to, 
patient ID, treatment group, laboratory collection date, analyte name, and analyte finding. 
6.19.5.1. Abnormal Hepatic Tests  
Analyses for abnormal hepatic tests involve 4 laboratory analytes: ALT, AST, total bilirubin, and 
ALP. Analyses for the change from baseline to last visit that occurred on or before the date of 
treatment discontinuation and shift tables are described in Section 6.19.5. This section describes 
additional analyses for the topic. The central laboratory reference ranges (Covance) will be used 
for ALT, AST, total bilirubin, and ALP hepatic laboratory assessments. 
The number and percentage of patients with the following abnormal elevations in hepatic 
laboratory tests at any time up to 60 days after treatment discontinuation will be summarized by 
treatment group. LY3471851 groups will be compared to placebo using Fisher’s exact text: 
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 The percentages of patients with an ALT measurement ≥3×, 5×, and 10× the 
central laboratory ULN during the treatment and follow-up periods will be 
summarized for all patients with a postbaseline value and for subsets based on 
various levels of baseline. 
o The analysis of 3× ULN will contain 4 subsets: patients whose nonmissing 
maximum baseline value is ≤1× ULN; patients whose maximum baseline 
is >1× ULN, but <3× ULN; patients whose maximum baseline value is 
≥3× ULN; and patients whose baseline values are missing. 
o The analysis of 5× ULN will contain 5 subsets: patients whose nonmissing 
maximum baseline value is ≤1× ULN; patients whose maximum baseline 
is >1× ULN, but <3× ULN; patients whose maximum baseline is ≥3× 
ULN, but <5× ULN; patients whose maximum baseline value is ≥5× 
ULN; and patients whose baseline values are missing. 
o The analysis of 10× ULN will contain 6 subsets: patients whose 
nonmissing maximum baseline value is ≤1× ULN; patients whose 
maximum baseline is >1× ULN, but <3× ULN; patients whose maximum 
baseline is ≥3× ULN, but <5× ULN; patients whose maximum baseline is 
≥5× ULN, but <10× ULN; patients whose maximum baseline value is 
≥10× ULN; and patients whose baseline values are missing. 
 The percentages of patients with an AST measurement greater than or equal to 
3×, 5×, and 10× the central laboratory ULN during the treatment and follow-
up periods will be summarized for all patients with a postbaseline value and 
for subsets based on various levels of baseline. Analyses will be constructed 
as described above for ALT.   
 The percentages of patients with a total bilirubin measurement greater than or 
equal to 2 × the central laboratory ULN during the treatment period will be 
summarized for all patients with a postbaseline value and subset into 
4 subsets: patients whose nonmissing maximum baseline value is ≤1× ULN; 
patients whose maximum baseline is >1× ULN but < 2× ULN; patients whose 
maximum baseline value is ≥2× ULN; and patients whose baseline values are 
missing. 
 The percentages of patients with an ALP measurement ≥1.5× the central 
laboratory ULN during the treatment and follow-up periods will be 
summarized for all patients with a postbaseline value and subset into 
4 subsets: patients whose nonmissing maximum baseline value is ≤1× ULN; 
patients whose maximum baseline is >1× ULN but <1.5× ULN; patients 
whose maximum baseline value is ≥1.5× ULN; and patients whose baseline 
values are missing. 
Second, to further evaluate potential hepatotoxicity, an eDISH plot will be created for all patients 
whether treated with LY3471851 and/or other treatment using the whole study and follow-up 
periods. Each patient with at least 1 postbaseline ALT and total bilirubin will be included in the 
eDISH. The points correspond to maximum total bilirubin and maximum ALT, even if not 
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obtained from the same blood draw. A listing of patients potentially meeting Hy’s rule will be 
provided (defined as greater than or equal to 3× ULN for ALT or AST, and greater than or equal 
to 2× ULN for total bilirubin, not necessarily at the same time). 
Third, a listing will be provided to the medical safety team for internal review according to the 
following SMQs:   
 broad and narrow terms in the Liver-related investigations, signs and symptoms SMQ 
(SMQ 20000008) 
 broad and narrow terms in the Cholestasis and jaundice of hepatic origin SMQ 
(SMQ 20000009) 
 broad and narrow terms in the Hepatitis non-infectious SMQ (SMQ 20000010) 
 broad and narrow terms in the Hepatic failure, fibrosis and cirrhosis and other liver 
damage-related conditions SMQ (SMQ 20000013), and  
 narrow terms in the Liver-related coagulation and bleeding disturbances SMQ 
(SMQ 20000015) 
6.19.5.2. Hematologic Changes  
Hematologic changes will be defined based on clinical laboratory assessments. CLASI will be 
applied for laboratory tests potentially related to myelosuppressive events (refer to Appendix 7). 
Treatment-emergent laboratory abnormalities potentially related to myelosuppression occurring 
at any time during the treatment and follow-up periods and shift tables of baseline to maximum 
grade during the treatment and follow-up periods will be tabulated. Planned and unplanned 
measurements will be included. Treatment emergence will be characterized using the following 
5 criteria (as appropriate to the grading scheme): 
 any increase in postbaseline CTCAE grade from worst baseline grade 
 increase to Grade 1 or above at worst postbaseline 
 increase to Grade 2 or above at worst postbaseline 
 increase to Grade 3 or above at worst postbaseline, and 
 increase to Grade 4 at worst postbaseline. 
Shift tables will show the number and percentage of patients based on baseline to maximum 
during the treatment and follow-up periods, with baseline depicted by the most extreme grade 
during the baseline period. With each shift table, a shift table summary displaying the number 
and percentage of patients with maximum postbaseline results will be presented by treatment 
group for each treatment period within the following categories: 
 decreased; post-baseline category < baseline category 
 increased; post-baseline category > baseline category, and 
 same; postbaseline category = baseline category. 
A laboratory-based treatment-emergent outcome related to increased platelet count will be 
summarized in a similar fashion. Treatment-emergent thrombocytosis as a laboratory-based 
abnormality will be defined as an increase in platelet count from a maximum baseline value 
≤600 billion/L to any postbaseline value >600 billion/L. Planned and unplanned measurements 
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will be included. A listing of patients with treatment-emergent thrombocytosis will be provided 
for safety review. 
6.19.5.4. Lipids Effects  
Analyses for the change from baseline to last observation, and shift tables in total cholesterol, 
LDL cholesterol, HDL cholesterol, and triglycerides are described in Section 6.19.5.   
TEAEs potentially related to hyperlipidemia will also be analyzed, based on reported AEs. The 
target surveillance term “Hyperlipidemia” is a Lilly-defined MedDRA search criteria list that is a 
subset of the PTs in the MedDRA SMQ “Dyslipidemia” that are related to elevated or increased 
lipids. MedDRA PTs, each with a narrow scope from the SMQ, for the target surveillance term 
are shown in Appendix 5. Frequency and relative frequency for each PT will be provided, 
ordered by decreasing frequency in the LY3471851 
 treatment group.   
6.19.5.5. Renal Function Effects  
Effects on renal function will be assessed through analyses of creatinine, which are described in 
Section 6.19.5.   
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6.19.5.6. Elevations in Creatine Phosphokinase  
Analyses of creatine phosphokinase are described in Section 6.19.5.   
6.19.6. Vital Signs and Other Physical Findings  
Vital signs and physical characteristics include systolic blood pressure, diastolic blood pressure, 
pulse, weight, body mass index, and body temperature. Original-scale data will be analyzed. 
When these parameters are analyzed as continuous numerical variables, unplanned 
measurements will be excluded. When these parameters are analyzed as categorical outcomes, 
planned and unplanned measurements will be included.   
The planned analyses described for the laboratory analytes in Section 6.19.5 will be used to 
analyze the vital signs and physical characteristics. 
Table KFAJ.6.1 defines the low and high baseline values as well as the criteria used to define 
treatment-emergence based on postbaseline values. Postbaseline values include all values after 
baseline in the treatment and follow-up periods. The blood pressure and pulse rate criteria are 
consistent with the document Selected Reference Limits for Blood Pressure, Orthostasis, and 
ECG Numerical Parameters (Including Heart Rate) for Use in Phase II-IV Clinical Trials 
Version 1.1 approved on 8 March 2013 as recommended by the Lilly Cardiovascular Safety 
Advisory Committee. 
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Table KFAJ.6.1. 
Categorical Criteria for Abnormal Treatment-Emergent Blood 
Pressure and Pulse Measurement, and Categorical Criteria for 
Weight Changes for Adults  
Parameter 
(Units of Measure) 
Low 
High 
Systolic Blood Pressure 
(mm Hg) 
≤90 (low limit) and decrease from 
lowest value during baseline ≥20 if 
>90 at each baseline visit 
≥140 (high limit) and increase from highest 
value during baseline ≥20 if <140 at each 
baseline visit 
Diastolic Blood Pressure 
(mm Hg) 
≤50 (low limit) and decrease from 
lowest value during baseline ≥10 if 
>50 at each baseline visit 
≥90 (high limit) and increase from highest 
value during baseline ≥10 if <90 at each 
baseline visit 
Pulse  
(beats per minute)  
<50 (low limit) and decrease from 
lowest value during baseline ≥15 if 
≥50 at each baseline visit 
>100 (high limit) and increase from highest 
value during baseline ≥15 if ≤100 at each 
baseline visit 
Weight 
(kilograms) 
(Loss) decrease ≥7% from lowest 
value during baseline 
(Gain) increase ≥7% from highest value 
during baseline 
Abbreviation: mm Hg = millimeters of mercury. 
6.19.7. Additional Safety Sections  
6.19.7.1. Symptoms of Depression (QIDS-SR16)  
The QIDS-SR16 is a 16-item, self-report 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, 4th Edition (DSM-IV; APA 1994). Patients are asked to 
consider each statement as it relates to the way they have felt for the past 7 days. There is a 
unique 4-point ordinal scale for each item with scores ranging from 0 to 3 reflecting increasing 
depressive symptoms as the item score increases. Additional information and the QIDS-SR16 
questions may be found on the University of Pittsburgh Epidemiology Data Center website 
(http://www.ids-qids.org/index.html). A key reference for this instrument covers its 
psychometric properties for use in patients with chronic major depression (Rush et al. 2003). 
Quick Inventory of Depressive Symptomatology was developed at UT Southwestern. 
The QIDS-SR16 total score is derived as the sum of the scores across the 9 scale domains. For 
scale domains that contain more than 1 item, the domain score is the highest item rating given 
across the items within that domain: 
 sleep: the highest score on any 1 of the 4 sleep items (items 1 to 4) 
 depressed mood: Item 5 
 weight/appetite change: the highest score on any 1 of the 4 weight items (items 6 to 9) 
 psychomotor changes: the highest score on either of the 2 psychomotor items (items 15 
and 16) 
 concentration: item 10 
 worthlessness/Guilt: item 11 
 suicidal ideation: item 12 
 decreased interest: item 13, and 
 decreased energy: item 14. 
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In the presence of missing data, the following rules will be employed to derive the total score. 
Firstly, considering the 3 multi-item domains (sleep, weight/appetite change, psychomotor 
changes), the domain score should be based on the maximum value across the appropriate items, 
and it should be missing only if each item is missing. Further, considering the 9 domain scores, 
the total score should be derived as missing if there are 3 or more domains that are missing; if 1 
or 2 domain scores are missing, then the total score should be derived using a total score that is 
prorated to the full scale range (0 to 27) based on the available domain scores, retaining 1 
decimal place in the total score derived in the presence of missing data. 
The QIDS-SR16 total scores will also be categorized in the following severity classes as shown 
in Table KFAJ.6.3. 
Table KFAJ.6.3. 
QIDS-SR16 Severity of Depressive Symptoms Categories Based on 
the QIDS-SR16 Total Score  
QIDS-SR16 Severity of Depressive Symptoms 
Category 
QIDS-SR16 Total Score 
0 = None 
0-5 
1 = Mild 
6-10 
2 = Moderate 
11-15 
3 = Severe 
16-20 
4 = Very Severe 
21-27 
Abbreviation: QIDS-SR16 = Quick Inventory of Depressive Symptomatology Self-Rated. 
 
Treatment differences in mean change QIDS-SR16 total score will be analyzed using the 
MMRM model described in Section 6.2. Only visits that occur on or before the date the patient 
discontinued treatment will be included in this analysis.   
Using the QIDS-SR16 Severity of Depressive Symptoms Categories shown in Table KFAJ.6.3, 
shift tables will show the number and percentage of patients with total score in each category 
based on baseline to maximum category during the treatment period and up to 60 days after 
treatment discontinuation, with baseline depicted by the most extreme category during the 
baseline period, with further summarization of change from baseline in severity using categories 
of any improvement, no change, and any worsening, by treatment. Similarly, shift tables will be 
created for the QIDS-SR16 suicidal ideation item (Item 12) responses.   
Treatment-emergent changes in QIDS-SR16 total score severity categories will be characterized 
as follows: 
 Increase (from None) to Mild, Moderate, Severe, or Very Severe 
 Increase (from None or Mild) to Moderate, Severe, or Very Severe 
 Increase (from None, Mild, or Moderate) to Severe or Very Severe 
 Increase (from None, Mild, Moderate, or Severe) to Very Severe 
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Treatment-emergent changes in QIDS-SR16 suicidal ideation item (Item 12) responses will be 
characterized as follows: 
 Increase (from 0) to 1 to 3 
 Increase (from 0 to1) to 2 to 3, and 
 Increase (from 0 to 2) to 3. 
6.19.7.2. Columbia Suicide Severity Rating Scale  
Suicidal ideation, suicidal behavior, and self-injurious behavior without suicidal intent, based on 
the C-SSRS, will be listed by patient and visit. Only patients that show suicidal ideation/behavior 
or self-injurious behavior without suicidal intent will be displayed (that is, if a patient’s answers 
are all ‘no’ for the C-SSRS, then that patient will not be displayed). However, if a patient 
reported any suicidal ideation/ behavior or self-injurious behavior without suicidal intent at any 
time point then all their ideation and behavior will be displayed, even if not positive.  
6.20. Other Analyses  
6.20.1. Subgroup Analyses  
Subgroup analysis will be conducted on SLEDAI-4 and SRI-4 at Week 24 with the composite 
estimand strategy based on the mITT population. Subgroup analysis may be conducted on 
BICLA at Week 24 with the composite estimand strategy for mITT population with at least 1 
baseline BILAG A score or 2 baseline BILAG B scores. Missing data will be handled using NRI. 
Subgroups to be analyzed are listed in Section 6.7.1. Subgroup analyses on other efficacy 
endpoints may be performed as deemed appropriate.  
Descriptive statistics will be provided for each treatment and stratum of a subgroup as outlined, 
regardless of sample size. Each categorical variable will be analyzed individually with a logistic 
model that contains the treatment, the subgroup variable, and subgroup by treatment interaction. 
The treatment-by-subgroup interaction will be tested at the 10% significance level to determine 
whether treatment differences are the same for each subgroup category. For the categorical 
variables, the number of responders and response rate will be reported for each subgroup.   
6.20.3. Annual Report Analyses  
Annual report analyses will be stated in a separate document. 
6.20.4. Clinical Trial Registry Analyses  
Additional analyses will be performed for the purpose of fulfilling the CTR requirements.   
Analyses provided for the CTR requirements include the following: 
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Summary of AEs, provided as a dataset that will be converted to an XML file. Both SAEs and 
“other” AEs are summarized by treatment group, by MedDRA PT. 
 An AE is considered “serious,” whether or not it is a TEAE. 
 An AE is considered in the “other” category if it is both a TEAE and is not serious. 
For each SAE and “other” AE, for each term and treatment group, the following are 
provided: 
o the number of participants at risk of an event 
o the number of participants who experienced each event term, and 
o the number of events experienced 
 AE reporting is consistent with other document disclosures for example, the CSR, 
manuscripts, and so forth.   
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6.22. Data Monitoring Committee  
Not applicable. An IAC will be used to conduct the interim analysis. 
Details of the planned interim data analyses and the assessment committee data review process 
are included in an assessment committee charter. 
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7. Unblinding Plan  
A separate unblinding plan will be prepared.  
 
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8. References  
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th 
ed. Arlington (VA): American Psychiatric Association; 1994. 
Andersen, Scott W, Millen BA. On the practical application of mixed effects models for repeated 
measures to clinical trial data. Pharmaceutical statistics 12.1 (2013): 7-16. 
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 
[FDA] Food and Drug Administration. 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. 22 April 2015. Accessed December 09, 2022. 
https://www.fda.gov/media/99313/download 
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 
Rush AJ, Trivedi MH, Ibrahim HM, et al. The 16-Item Quick Inventory of Depressive 
Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): 
a psychometric evaluation in patients with chronic major depression. Biol Psychiatry. 
2003;54(5):573-583. 
Winthrop KL, Novosad SA, Calabrese L, et al. Opportunistic infections and biologic therapies in 
immune-mediated inflammatory disease: 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. 
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9. Appendices  
 
 
 
 
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Appendix 1. 
Description and Derivation of Efficacy 
Outcomes Measures and Endpoints  
 
 
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Abbreviations: ACR = American College of Rheumatology; BICLA = British Isles Lupus Assessment Group-based Composite Lupus Assessment; BILAG = 
British Isles Lupus Assessment Group - 2004; 
 CNS = central nervous system; 
; LLDAS = Lupus Low Disease Activity State; N = no; PGA = Physician 
Global Assessment; Q2W = every 2 weeks; SFI = Self-Report Family Instrument; SLE = systemic lupus erythematosus; SLEDAI-2K = Systemic Lupus 
Erythematosus Disease Activity Index 2000; SLEDAI-4 = a ≥4-point reduction in SLEDAI-2K score from baseline; 
 
; SRI-4 = Systemic Lupus Erythematosus Responder Index-4; VAS = Visual Analog Scale; Y = yes. 
 
 
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Appendix 2. 
Description of Efficacy Analyses  
The table below provides the detailed analyses including estimand strategy, analysis method, 
missing data imputation, analysis population, and analysis type.  
 
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Measure 
Endpoint 
Estimand 
Strategy 
Analysis 
Population 
Comparison/ 
Timepoint 
Analysis Method 
Analysis Type 
SLEDAI 
SLEDAI-4 
Composite  
mITT  
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
Logistic Regression with 
NRI; 
Fisher’s Exact Test with 
NRI 
Logistic Regression 
with NRI for 
Week 24 – Primary 
Other – Exploratory  
Composite  
Per-Protocol 
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
Logistic Regression with 
NRI; 
Fisher’s Exact Test with 
NRI 
Exploratory  
Treatment 
Policy 
mITT 
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
Logistic Regression with 
NRI 
Fisher’s Exact Test with 
NRI 
Exploratory  
No worsening from 
baseline in 
SLEDAI-2K 
Composite 
mITT 
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
Logistic Regression with 
NRI 
Fisher’s Exact Test with 
NRI 
Exploratory  
SLEDAI Change 
from Baseline 
Hypothetical  
mITT 
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
MMRM 
Exploratory 
Composite 
mITT 
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
MMRM with BOCF 
Exploratory 
Individual Organ 
Domain 
Improvement 
Defined by 
SLEDAI-2K 
Composite 
mITT – Patients 
with SLEDAI-2K 
score > 0 within the 
organ domain at 
baseline  
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
Logistic Regression with 
NRI 
Fisher’s Exact Test with 
NRI 
Exploratory  
Individual Organ 
Domain Worsening 
Defined by 
SLEDAI-2K 
Composite 
mITT – Patients 
with at least one 
baseline SLEDAI-
2K = 0 in the organ 
domain at baseline 
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
Logistic Regression with 
NRI 
Fisher’s Exact Test with 
NRI 
Exploratory  
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Measure 
Endpoint 
Estimand 
Strategy 
Analysis 
Population 
Comparison/ 
Timepoint 
Analysis Method 
Analysis Type 
 
Resolution of 
Arthritis and/or 
Rash by SLEDAI-
2K Components 
Composite  
mITT – Patients 
with SLEDAI-2K 
arthritis and/or rash 
‘Present’ at baseline 
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
Logistic Regression with 
NRI; 
Fisher’s Exact Test with 
NRI 
Logistic Regression 
with NRI for 
Week 24 – 
Secondary 
Other – Exploratory  
SRI-4 
SRI-4 
Composite  
mITT  
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
Logistic Regression with 
NRI; 
Fisher’s Exact Test with 
NRI 
Logistic Regression 
with NRI for 
Week 24 – 
Secondary 
Other – Exploratory  
Composite 
Per-Protocol 
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
Logistic Regression with 
NRI; 
Fisher’s Exact Test with 
NRI 
Exploratory 
BICLA 
BICLA 
Composite  
mITT – Patients 
with at least 
1 BILAG A or 
2 BILAG B scores 
at baseline 
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
Logistic Regression with 
NRI; 
Fisher’s Exact Test with 
NRI 
Logistic Regression 
with NRI for 
Week 24 – 
Secondary 
Other – Exploratory  
Composite 
Per-Protocol – 
Patients with at least 
1 BILAG A or 
2 BILAG B scores 
at baseline 
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
Logistic Regression with 
NRI; 
Fisher’s Exact Test with 
NRI 
Exploratory 
LLDAS 
LLDAS 
Composite  
mITT  
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
Logistic Regression with 
NRI; 
Fisher’s Exact Test with 
NRI 
Logistic Regression 
with NRI for 
Week 24 – 
Secondary 
Other – Exploratory  
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J1P-MC-KFAJ Statistical Analysis Plan Version 3 
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LY3471851 
 
 
 
Measure 
Endpoint 
Estimand 
Strategy 
Analysis 
Population 
Comparison/ 
Timepoint 
Analysis Method 
Analysis Type 
BILAG  
BILAG 
Improvement 
Composite 
mITT – Patients 
with at least 
1 BILAG A or 
2 BILAG B at 
baseline 
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
Logistic Regression with 
NRI 
Fisher’s Exact Test with 
NRI 
Exploratory  
BILAG No 
Worsening 
Composite 
mITT  
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
Logistic Regression with 
NRI 
Fisher’s Exact Test with 
NRI 
Exploratory  
Individual Organ 
Domain - 
Improvement 
Defined by BILAG 
Composite 
mITT – Patients 
with BILAG A or B 
within the organ 
domain at baseline  
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
Logistic Regression with 
NRI 
Fisher’s Exact Test with 
NRI 
Exploratory  
Individual Organ 
Domain - No 
Worsening Defined 
by BILAG 
Composite 
mITT – Patients 
with no BILAG A 
within the organ 
domain at baseline 
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
Logistic Regression with 
NRI 
Fisher’s Exact Test with 
NRI 
Exploratory  
PGA  
PGA Change from 
Baseline 
Hypothetical 
mITT 
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
MMRM 
Exploratory  
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J1P-MC-KFAJ Statistical Analysis Plan Version 3 
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LY3471851 
Measure 
Endpoint 
Estimand 
Strategy 
Analysis 
Population 
Comparison/ 
Timepoint 
Analysis Method 
Analysis Type 
 
 
Composite 
mITT 
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
MMRM with BOCF 
Exploratory 
No worsening in 
PGA 
Composite 
mITT  
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
Logistic Regression with 
NRI 
Fisher’s Exact Test with 
NRI 
Exploratory  
PGA ≤1 
Composite 
mITT – Patients 
with PGA > 1 at 
baseline 
LY3471851 vs Placebo 
at postbaseline visits in 
the treatment period 
Logistic Regression with 
NRI 
Fisher’s Exact Test with 
NRI 
Exploratory  
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CCI


J1P-MC-KFAJ Statistical Analysis Plan Version 3 
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CCI


J1P-MC-KFAJ Statistical Analysis Plan Version 3 
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CCI


J1P-MC-KFAJ Statistical Analysis Plan Version 3 
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CCI


J1P-MC-KFAJ Statistical Analysis Plan Version 3 
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J1P-MC-KFAJ Statistical Analysis Plan Version 3 
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LY3471851 
Abbreviations: Anti-dsDNA = anti-double stranded deoxyribonucleic acid; BICLA = British Isles Lupus Assessment Group-based Composite Lupus 
Assessment; BILAG = British Isles Lupus Assessment Group - 2004; BOCF = baseline observation carried forward;
 
 FACIT-Fatigue = Functional Assessment of Chronic Illness Therapy – Fatigue Scale; LLDAS = Lupus Low 
Disease Activity State; mITT = modified intent-to-treat; MMRM = mixed models for repeated measures; NRI = nonresponder imputation; PGA = Physician 
Global Assessment; 
 SF = Short Form;  
SF-36 = 36-Item Short Form Health Survey; 
 SLE = systemic lupus erythematosus; SLEDAI-2K = Systemic Lupus Erythematosus 
Disease Activity Index 2000; SLEDAI-4 = a ≥4-point reduction in SLEDAI-2K score from baseline; SLICC = Systemic Lupus Erythematosus International 
Collaborating Clinics; SRI-4 = Systemic Lupus Erythematosus Responder Index-4. 
 
 
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CCI
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LY3471851 
Appendix 3. 
Corticosteroid  
All corticosteroid doses need to be converted to prednisone equivalent doses (as detailed in 
Section 6.9). If additional conversion factors are required, these will be added to the table 
below in a statistical analysis plan amendment prior to database lock. 
The following table should be used for converting nonprednisone medications to prednisone 
equivalent: 
Multiply the dose of the corticosteroid taken by the patient (in 
milligrams) in Column 1 by the conversion factor in Column 2 to 
get the equivalent dose of prednisone (in milligrams). 
Example: Patient is taking 16 mg of methylprednisolone po daily. 
To convert to prednisone: 16 mg methylprednisolone × 1.25 = 20 
mg prednisone. 16 mg of methylprednisolone po daily is equivalent 
to 20 mg of prednisone po daily. 
 
 
 
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LY3471851 
Appendix 4. 
List of MedDRA Preferred Terms for Potential 
Opportunistic Infections (POI)  
Category 
Potential Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Mycobacterial/ 
Actino 
Nocardiosis (II) 
Nocardia sepsis  
10064952 
Narrow 
Nocardiosis 
10029444 
Nocardia test positive 
10070131 
Broad 
Mycobacterial/ 
Actino 
Nontuberculous 
mycobacterium disease 
(II) 
Atypical mycobacterial 
infection  
10061663 
Narrow 
Atypical mycobacterial 
lower respiratory tract 
infection  
10075026 
Atypical mycobacterial 
lymphadenitis  
10003755 
Atypical mycobacterium 
pericarditis 
10055036 
Atypical mycobacterial 
pneumonia  
10071075 
Borderline leprosy 
10006029 
Bovine tuberculosis 
10006049 
Indeterminate leprosy  
10021700 
Leprosy 
10024229 
Lepromatous leprosy 
10024227 
Mycobacterial infection  
10062207 
Mycobacterial 
peritonitis  
10073514 
Mycobacterium 
abscessus infection 
10064789 
Mycobacterium avium 
complex immune 
restoration disease  
10058449 
 
Mycobacterium avium 
complex infection  
10058806 
Mycobacterium 
chelonae infection 
10071401 
Mycobacterium 
fortuitum infection  
10049659 
Mycobacterium kansasii 
infection 
10028447 
Mycobacterium 
marinum infection  
10028452 
Mycobacterium ulcerans 
infection  
10066289 
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J1P-MC-KFAJ Statistical Analysis Plan Version 3 
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LY3471851 
Category 
Potential Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Superinfection 
mycobacterial 
10075381 
Tuberculoid leprosy 
10044729 
Type 1 lepra reaction 
10070516 
Type 2 lepra reaction 
10070517 
Atypical mycobacterium 
test positive  
10070326 
Broad 
Mycobacterial disease 
carrier 
10075025 
Mycobacterium leprae 
test positive 
10070324 
Mycobacterium test  
10070407 
Mycobacterium test 
positive 
10070323 
Ureaplasmal 
ulvovaginitis 
10081280 
Mycobacterial/ 
Actino 
Tuberculosis (I) 
Adrenal gland 
tuberculosis  
10001358 
Narrow 
Bone tuberculosis  
10056377 
Choroid tubercles 
10008779 
Congenital tuberculosis 
10010657 
Conjunctivitis 
tuberculous 
10010754 
Cutaneous tuberculosis  
10011684 
Disseminated Bacillus  
Calmette-Guerin 
infection  
10076666 
Disseminated 
tuberculosis 
10013453 
Ear tuberculosis  
10014027 
Epididymitis 
tuberculous  
10015004 
Extrapulmonary 
tuberculosis  
10064445 
Female genital tract 
tuberculosis  
10061150 
Immune reconstitution 
inflammatory syndrome 
associated tuberculosis 
10072797 
 
Intestinal tuberculosis  
10075268 
Joint tuberculosis  
10056367 
Lupus vulgaris  
10025143 
Lymph node 
tuberculosis  
10025183 
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J1P-MC-KFAJ Statistical Analysis Plan Version 3 
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LY3471851 
Category 
Potential Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Male genital tract 
tuberculosis  
10061234 
Meningitis tuberculous  
10027259 
Oesophageal 
tuberculosis  
10030200 
Oral tuberculosis  
10076879 
Pericarditis tuberculous  
10055069 
Peritoneal tuberculosis  
10053583 
Prostatitis tuberculous  
10064743 
Pulmonary tuberculoma  
10066927 
Pulmonary tuberculosis  
10037440 
Renal tuberculosis  
10038534 
Salpingitis tuberculous  
10039463 
Silicotuberculosis  
10068876 
Spleen tuberculosis  
10041640 
Thyroid tuberculosis  
10043774 
Tuberculoma of central 
nervous system 
10052883 
Tuberculosis 
10044755 
Tuberculosis bladder  
10044758 
Tuberculosis 
gastrointestinal  
10061390 
Tuberculosis liver  
10058120 
Tuberculosis of central 
nervous system  
10061391 
Tuberculosis of eye  
10044819 
Tuberculosis of 
genitourinary system  
10044828 
Tuberculosis of 
intrathoracic lymph 
nodes  
10044846 
Tuberculosis of 
peripheral lymph nodes  
10044965 
Tuberculosis ureter  
10045026 
Tuberculous abscess 
central nervous system  
10052884 
Tuberculous 
endometritis  
10071559 
Tuberculous laryngitis  
10045072 
Tuberculous pleurisy  
10045104 
Tuberculous 
tenosynovitis 
10059161 
Interferon gamma 
release assay 
10073542 
Broad 
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J1P-MC-KFAJ Statistical Analysis Plan Version 3 
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LY3471851 
Category 
Potential Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Interferon gamma 
release assay positive 
10072866 
Mycobacterium 
tuberculosis complex 
test 
10070472 
Mycobacterium 
tuberculosis complex 
test positive 
10070325 
Tuberculid  
10044725 
Tuberculin test  
10044726 
Tuberculin test false 
negative  
10074840 
Tuberculin test positive 
10044728 
Bacteria 
 
Bartonellosis 
(disseminated disease 
only) (V) 
Bacillary angiomatosis 
10003971 
Narrow 
Trench fever 
10044582 
Bartonella test  
10075209 
Broad 
Bartonella test positive  
10070157 
Bartonellosis 
10004145 
Cat scratch disease 
10007729 
Peliosis hepatis  
10034229 
Splenic peliosis 
10068851 
Campylobacteriosis 
(invasive disease only) 
(V) 
Campylobacter sepsis  
10070681 
Narrow 
Campylobacter colitis 
10076769 
Broad 
Campylobacter 
gastroenteritis  
10007048 
Campylobacter infection 
10051226 
Campylobacter test 
positive 
10070025 
Legionellosis (II) 
Legionella infection 
10061266 
Narrow 
Pneumonia legionella  
10035718 
Pontiac fever 
10054161 
Legionella test  
10070410 
Broad 
Legionella test positive 
10070092 
Bacteria 
 
Listeria monocytogenes 
(invasive disease only) 
(II) 
Listeria encephalitis  
10054116 
Narrow 
Listeria sepsis  
10063085 
Meningitis listeria 
10027248 
Listeria test  
10075707 
Broad 
Listeria test positive 
10070094 
Listeriosis 
10024641 
Salmonellosis (invasive 
disease only) (II) 
Aortitis salmonella  
10074937 
Narrow 
Arthritis salmonella 
10003271 
Meningitis salmonella 
10027254 
Osteomyelitis 
salmonella 
10031262 
Paratyphoid fever 
10033971 
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J1P-MC-KFAJ Statistical Analysis Plan Version 3 
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LY3471851 
Category 
Potential Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Pneumonia salmonella 
10035733 
Salmonella bacteraemia 
10058924 
Salmonella sepsis 
10058878 
Typhoid fever 
10045275 
Salmonella test positive  
10070127 
Broad 
 
Salmonellosis 
10039447 
Salmonella test 
10079854 
Bacteria 
Shigellosis (invasive 
disease only) (V) 
Shigella sepsis  
10074481 
Narrow 
Shigella infection  
10054178 
Broad 
Shigella test positive 
10070129 
Vibriosis (invasive 
disease due to V. 
vulnificus) (V) 
Gastroenteritis vibrio  
10017917 
Broad 
Vibrio test positive 
10070161 
None 
 
Narrow 
Infective Pneumonia 
SMQ 
 
Pneumonia 
acinetobacter 
10079866 
 
 
Narrow 
Pneumonia proteus 
10079867 
Pneumonia serratia 
10079868 
Fungal 
Aspergillosis (invasive 
disease only) (II) 
Aspergillosis oral  
10003489 
 
Cerebral aspergillosis  
10051597 
Meningitis aspergillus  
10073245 
Oro-pharyngeal 
aspergillosis 
10053029 
Aspergillus infection  
10074171 
 
Aspergillus test  
10070450 
Aspergillus test positive 
10070448 
Bronchopulmonary 
aspergillosis 
10006473 
Sinusitis aspergillus 
10051016 
Blastomycosis (IV) 
 
Blastomycosis  
10005098 
Narrow 
Epididymitis 
blastomyces  
10015001 
Osteomyelitis 
blastomyces  
10031255 
Pneumonia blastomyces 
10035671 
None 
 
Broad 
Candidiasis (invasive 
disease, or oral not 
limited to the tongue) (II) 
Candida 
endophthalmitis 
10059449 
Narrow 
Candida osteomyelitis 
10064699 
Candida pneumonia  
10053158 
Candida retinitis  
10068612 
Candida sepsis  
10053166 
Candida urethritis 
10081262 
Candidiasis of trachea  
10064459 
Cerebral candidiasis  
10078126 
Endocarditis candida 
10014669 
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J1P-MC-KFAJ Statistical Analysis Plan Version 3 
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LY3471851 
Category 
Potential Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Gastrointestinal 
candidiasis  
10017938 
Hepatic candidiasis 
10049653 
Hepatosplenic 
candidiasis 
10051590 
Meningitis candida  
10027205 
Oesophageal candidiasis  10030154 
Oral candidiasis  
10030963 
Oropharyngeal 
candidiasis  
10050346 
Peritoneal candidiasis 
10056562 
Splenic candidiasis  
10051725 
Systemic candida 
10042938 
Bladder candidiasis  
10058523 
Broad 
Candida infection  
10074170 
Candida test  
10070453 
Candida test positive  
10070451 
Mucocutaneous 
candidiasis1  
10028080 
Respiratory moniliasis 
10038705 
Coccidioidomycosis (II) 
Coccidioides 
encephalitis  
10054214 
Narrow 
Coccidioidomycosis  
10009825 
Cutaneous 
coccidioidomycosis  
10068747 
Meningitis coccidioides 
10027207 
None 
 
Broad 
Cryptococcosis (II) 
Cryptococcal cutaneous 
infection  
10054216 
Narrow 
Cryptococcal fungaemia  10067112 
Cryptococcosis  
10011490 
Disseminated 
cryptococcosis  
10013439 
Gastroenteritis 
cryptococcal  
10011485 
Meningitis cryptococcal  
10027209 
Neurocryptococcosis  
10068368 
Pneumonia cryptococcal 
10067565 
Cryptococcus test  
10070456 
Broad 
 
Cryptococcus test 
positive 
10070455 
Histoplasmosis (II) 
Acute pulmonary 
histoplasmosis  
10001027 
Narrow 
Chronic pulmonary 
histoplasmosis  
10009115 
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J1P-MC-KFAJ Statistical Analysis Plan Version 3 
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LY3471851 
Category 
Potential Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Endocarditis 
histoplasma  
10014676 
Histoplasmosis 
10020141 
Histoplasmosis 
cutaneous  
10049142 
Histoplasmosis 
disseminated 
10020144 
Meningitis histoplasma 
10027243 
Pericarditis histoplasma 
10034489 
Retinitis histoplasma 
10038912 
Presumed ocular 
histoplasmosis 
syndrome 
10063664 
Broad 
Microsporidiosis (IV) 
Microsporidia infection  
10053982 
Narrow 
None 
 
Broad 
Other invasive fungi:  
Mucormycosis 
(=zygomycosis) 
[Rhizopus, Mucor, and 
Lichtheimia], 
Scedosporum/ 
Pseudallescheria boydii, 
Fusarium (II) 
Allescheriosis  
10001754 
Narrow 
Fusarium infection  
10051919 
Mucormycosis  
10028098 
Scedosporium infection  
10059045 
Pseudallescheria 
infection  
10061919 
Pseudallescheria sepsis 
10058973 
See “Non-specific 
terms” below  
 
Broad 
Paracoccidioides 
infections (V) 
Paracoccidioides 
infection  
10061906 
Narrow 
None 
 
Broad 
Penicillium marneffei 
(V) 
Penicillium infection 
10078580 
Narrow 
None 
 
Broad 
Pneumocystis jirovecii 
(II) 
 
Pneumocystis jirovecii 
infection 
10073756 
Narrow 
 
Pneumocystis jirovecii 
pneumonia 
10073755 
Blood beta-D-glucan  
10068725 
Broad 
Blood beta-D-glucan 
abnormal  
10051795 
Blood beta-D-glucan 
increased 
10051793 
Gomori methenamine 
silver stain  
10075549 
Carbon monoxide 
diffusing capacity 
decreased  
10065906 
Carbon monoxide 
diffusing capacity 
10071738 
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Category 
Potential Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Pneumocystis test 
positive 
10070454 
Sporothrix schenckii (V) 
Cutaneous 
sporotrichosis  
10011676 
Narrow 
Sporotrichosis 
10041736 
None 
 
Broad 
Viral 
Cytomegalovirus disease 
(V) 
Cytomegalovirus 
chorioretinitis  
10048843 
Narrow 
Cytomegalovirus colitis  
10048983 
Cytomegalovirus 
duodenitis 
10049014 
Cytomegalovirus 
enteritis  
10049074 
Cytomegalovirus 
enterocolitis  
10049015 
Cytomegalovirus 
gastritis  
10049016 
Cytomegalovirus 
gastroenteritis  
10051349 
Cytomegalovirus 
gastrointestinal infection 
10052817 
Cytomegalovirus 
gastrointestinal ulcer 
10075619 
Cytomegalovirus 
hepatitis  
10011830 
Cytomegalovirus 
infection  
10011831 
Cytomegalovirus 
mononucleosis  
10011834 
Cytomegalovirus 
mucocutaneous ulcer  
10065036 
Cytomegalovirus 
myelomeningoradiculitis  
10065621 
Cytomegalovirus 
myocarditis 
10056261 
Cytomegalovirus 
nephritis 
10079095 
Cytomegalovirus 
oesophagitis 
10049018 
Cytomegalovirus 
pancreatitis  
10049566 
Cytomegalovirus 
pericarditis  
10056721 
Cytomegalovirus 
syndrome 
10056262 
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Category 
Potential Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Cytomegalovirus 
urinary tract infection  
10051350 
Cytomegalovirus 
viraemia  
10058854 
Disseminated 
cytomegaloviral 
infection 
10049075 
Encephalitis 
cytomegalovirus  
10014586 
Pneumonia 
cytomegaloviral 
10035676 
Cytomegalovirus test  
10061806 
Broad 
Cytomegalovirus test 
positive 
10051620 
HBV reactivation (IV) 
None 
 
Narrow 
Asymptomatic viral 
hepatitis  
10063838 
Broad 
Chronic hepatitis B  
10008910 
HBV-DNA polymerase 
increased 
10058937 
Hepatitis B 
10019731 
Hepatitis B antigen 
10063414 
Hepatitis B antigen 
positive  
10063411 
Hepatitis B core antigen  
10051160 
Hepatitis B core antigen 
positive 
10052328 
Hepatitis B DNA assay  
10060027 
Hepatitis B DNA assay 
positive  
10060047 
Hepatitis B DNA 
increased 
10068379 
Hepatitis B e antigen  
10050914 
Hepatitis B e antigen 
positive  
10052329 
Hepatitis B reactivation 
10058827 
Hepatitis B surface 
antigen  
10050529 
Hepatitis B surface 
antigen positive 
10019742 
Hepatitis B virus test  
10068415 
Hepatitis B virus test 
positive  
10070217 
Hepatitis A 
10019780 
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Category 
Potential Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Hepatitis post 
transfusion 
10019791 
Hepatitis viral  
10019799 
Withdrawal hepatitis 
10071220 
Viral 
HCV progression (V) 
None 
 
Narrow 
Chronic hepatitis C  
10008912 
Broad 
Hepatitis C 
10019744 
Hepatitis C RNA  
10019748 
Hepatitis C RNA 
fluctuation  
10068727 
Hepatitis C RNA 
increased  
10068377 
Hepatitis C RNA 
positive  
10019750 
Hepatitis C virus test  
10068416 
Hepatitis C virus test 
positive 
10070218 
Herpes simplex (IV) 
 
 
 
 
Colitis herpes  
10051782 
Narrow 
 
 
 
Eczema herpeticum  
10014197 
Gastritis herpes  
10051784 
Herpes oesophagitis  
10052330 
Herpes sepsis 
10058876 
Herpes simplex colitis  
10074239 
Herpes simplex 
encephalitis 
10019953 
Herpes simplex gastritis  
10074240 
Herpes simplex hepatitis  10067389 
Herpes simplex 
meningitis  
10019956 
Herpes simplex 
meningoencephalitis  
10074247 
Herpes simplex 
meningomyelitis  
10074250 
Herpes simplex 
necrotising retinopathy 
10074252 
Herpes simplex 
oesophagitis  
10074242 
Herpes simplex 
pneumonia 
10065046 
Herpes simplex sepsis   
10074246 
Herpes simplex visceral 
10019963 
Meningitis herpes  
10027242 
Meningoencephalitis 
herpetic 
10027285 
Meningomyelitis herpes  
10074249 
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Category 
Potential Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Pneumonia herpes viral 
10035703 
Genital herpes simplex 
10073931 
Herpes dermatitis  
10062639 
Herpes pharyngitis  
10066888 
Herpes simplex otitis 
externa  
10019959 
Herpes simplex 
pharyngitis  
10074244 
Ophthalmic herpes 
simplex  
10073938 
Proctitis herpes 
10036780 
Kaposi's varicelliform 
eruption 
10051891 
Herpes simplex test 
positive 
10077969 
Broad 
 
 
 
 
Herpes simplex 
10019948 
Herpes virus infection  
10019973 
Nasal herpes  
10074936 
Oral herpes  
10067152 
Genital herpes  
10018150 
Herpes zoster (any form) 
(II) 
 
Disseminated varicella 
zoster vaccine virus 
infection  
10076667 
 
Narrow 
Encephalitis post 
varicella  
10014603 
Genital herpes zoster  
10072210 
Herpes zoster 
10019974 
Herpes zoster cutaneous 
disseminated  
10074297 
Herpes zoster 
disseminated 
10065038 
Herpes zoster infection 
neurological  
10061208 
Herpes zoster meningitis 
10074259 
Herpes zoster 
meningoencephalitis 
10074248 
Herpes zoster 
meningomyelitis  
10074251 
Herpes zoster 
meningoradiculitis 
10079327 
Herpes zosternecrotising 
retinopathy  
10074253 
Herpes zoster oticus 
10063491 
Herpes zoster 
pharyngitis  
10074245 
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LY3471851 
Category 
Potential Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Necrotising herpetic 
retinopathy 
10065119 
Ophthalmic herpes 
zoster 
10030865 
Varicella 
10046980 
Varicella keratitis  
10077496 
Varicella post vaccine  
10063522 
Varicella zoster gastritis 
10074241 
Varicella zoster 
oesophagitis  
10074243 
Varicella zoster 
pneumonia 
10074254 
Varicella zoster virus 
infection 
10075611 
Herpes ophthalmic  
10062004 
Varicella virus test  
10070444 
Broad 
Varicella virus test 
positive 
10070214 
Human Polyomavirus 
infection including BK 
virus disease and PVAN 
(V), and Progressive 
Multifocal 
Leukoencephalopathy 
(IV) 
BK virus infection 
10055181 
Narrow 
 
Human polyomavirus 
infection  
10057366 
JC virus granule cell 
neuronopathy  
10074361 
JC virus infection 
10023163 
Polyomavirus-associated 
nephropathy  
10065381 
Progressive multifocal 
leukoencephalopathy 
10036807 
JC virus test  
10068794 
Broad 
 
Polyomavirus test  
10075038 
Polyomavirus test 
positive 
10070342 
Post-transplant 
lymphoproliferative 
disorder (EBV) (V) 
Epstein-Barr virus 
associated 
lymphoproliferative 
disorder  
10068349 
Narrow 
Post-transplant 
lymphoproliferative 
disorder 
10051358 
Epstein-Barr viraemia 
10065110 
Broad 
Epstein-Barr virus 
associated lymphoma 
10071441 
Epstein-Barr virus 
infection 
10015108 
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J1P-MC-KFAJ Statistical Analysis Plan Version 3 
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LY3471851 
Category 
Potential Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Lymphoproliferative 
disorder 
10061232 
Lymphoproliferative 
disorder in remission  
10061233 
Oral hairy leukoplakia 
10030979 
Parasites 
 
Trypanosoma cruzi 
infection (Chagas’ 
Disease) (disseminated 
disease only) (V) 
None 
 
Narrow 
American 
trypanosomiasis  
10001935 
Broad 
Trypanosomiasis 
10044707 
Meningitis 
trypanosomal 
10027258 
Cryptosporidium species 
(chronic disease only) 
(IV) 
Biliary tract infection 
cryptosporidial  
10067319 
Narrow 
Cryptosporidiosis 
infection  
10011502 
Broad 
Gastroenteritis 
cryptosporidial 
10017899 
Leishmaniasis (Visceral 
only) (IV) 
Visceral leishmaniasis  
10047505 
Narrow 
Leishmaniasis 
10024198 
Broad 
Stronglyoides 
(hyperinfection 
syndrome and 
disseminated forms only) 
(IV) 
None  
 
Narrow 
Strongyloidiasis 
10042254 
Broad 
Toxoplasmosis (IV) 
Cerebral toxoplasmosis 
10057854 
Narrow 
Eye infection 
toxoplasmal  
10015939 
Hepatitis toxoplasmal  
10019798 
Meningitis toxoplasmal  
10048848 
Myocarditis toxoplasmal  10028617 
Pneumonia toxoplasmal 
10067566 
Toxoplasma serology  
10050941 
Broad 
Toxoplasmosis 
10044272 
Non-specific 
terms 
 
Non-specific terms  
 
 
None 
 
Narrow 
 
 
Delftia acidovorans 
infection 
10081339 
Sphingomonas 
paucimobilis 
bacteraemia 
10081563 
Central nervous system 
immune reconstitution 
inflammatory response 
10080100 
Broad 
Abscess fungal  
10000269 
Alternaria infection  
10054207 
Arthritis fungal  
10060966 
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Category 
Potential Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Biliary tract infection 
fungal  
10065203 
Central nervous system 
fungal infection 
10072805 
Cerebral fungal 
infection  
10049657 
Encephalitis fungal  
10065170 
Erythema induratum  
10015213 
Eye infection fungal  
10015933 
Fungaemia 
10017523 
Fungal abscess central 
nervous system  
10017524 
Fungal endocarditis  
10017529 
Fungal labyrinthitis  
10065174 
Fungal oesophagitis  
10049656 
Fungal peritonitis  
10061138 
Fungal pharyngitis  
10076516 
Fungal retinitis  
10068613 
Fungal sepsis 
10058872 
Fungal urethritis 
10081163 
Hepatic infection fungal  
10065217 
Meningitis fungal  
10027236 
Mycotic 
endophthalmitis  
10063202 
Myocarditis mycotic  
10059026 
Oral fungal infection  
10061324 
Oropharyngitis fungal  
10061891 
Osteomyelitis fungal  
10065239 
Otitis media fungal  
10065175 
Pancreatitis fungal  
10065190 
Pericarditis fungal  
10065220 
Phaehyphomycosis 
10034799 
Pneumonia fungal  
10061354 
Pulmonary mycosis  
10037422 
Pulmonary 
trichosporonosis  
10068184 
Sinusitis fungal  
10058678 
Splenic infection fungal 
10065194 
Systemic mycosis 
10052366 
Pneumonia 
Infective Pneumonia 
SMQ 
All PTs (exclude 
COVID-19 and 
influenza PTs) 
20000231 
Narrow 
Abbreviations: DNA = deoxyribonucleic acid; EBV= Epstein-Barr virus; HBV = hepatitis B virus;  
MedDRA = Medical Dictionary for Regulatory Activities; PT = Preferred Term; PVAN = Polyomavirus-
associated nephropathy; SMQ = Standardized MedDRA Query. 
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Appendix 5. 
List of MedDRA Preferred Terms for Elevated 
or Increased Lipids from the Dyslipidemia SMQ 
(SMQ 20000026)  
Preferred Term (MedDRA Version 20.0) 
Preferred Term Code 
Apolipoprotein B/Apolipoprotein A-1 ratio increased 
10065516 
Autoimmune hyperlipidaemia 
10071577 
Blood cholesterol abnormal 
10005423 
Blood cholesterol increased 
10005425 
Blood triglycerides abnormal 
10005837 
Blood triglycerides increased 
10005839 
Diabetic dyslipidaemia 
10070901 
Dyslipidaemia 
10058108 
Familial hypertriglyceridaemia 
10059183 
Fat overload syndrome 
10074028 
High density lipoprotein abnormal 
10020051 
High density lipoprotein decreased 
10020060 
High density lipoprotein increased 
10020061 
Hypercholesterolaemia 
10020603 
Hyperlipidaemia 
10062060 
Hypertriglyceridaemia 
10020869 
Hypo HDL cholesterolaemia 
10068961 
Intermediate density lipoprotein increased 
10064236 
LDL/HDL ratio increased 
10049030 
Lipid metabolism disorder 
10061227 
Lipids abnormal 
10024588 
Lipids increased 
10024592 
Lipoprotein (a) abnormal 
10054023 
Lipoprotein (a) increased 
10054009 
Low density lipoprotein abnormal 
10024901 
Low density lipoprotein increased 
10024910 
Non-high-density lipoprotein cholesterol increased 
10063967 
Remnant hyperlipidaemia 
10038316 
Total cholesterol/HDL ratio abnormal 
10058633 
Total cholesterol/HDL ratio increased 
10058630 
 
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LY3471851 
Preferred Term (MedDRA Version 20.0) 
Preferred Term Code 
Type I hyperlipidaemia 
10060749 
Type II hyperlipidaemia 
10045254 
Type IIa hyperlipidaemia 
10045261 
Type IIb hyperlipidaemia 
10045263 
Type III hyperlipidaemia 
10060751 
Type IV hyperlipidaemia 
10060753 
Type V hyperlipidaemia 
10060755 
Very low density lipoprotein abnormal 
10047352 
Very low density lipoprotein increased 
10047361 
Abbreviation: MedDRA = Medical Dictionary for Regulatory Activities. 
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J1P-MC-KFAJ Statistical Analysis Plan Version 3 
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Appendix 6. List of Planned Laboratory Analytes with 
Reference Range Sources  
Laboratory  
Laboratory Analyte 
Reference  
Analysis Type 
Group/Order 
 
Range Name 
Central 
Tendency 
Outlier/Shift 
Analysis 
Hematology 
 
 
1 
Hemoglobin 
LCTPB 
Yes 
Yes 
2 
Hematocrit 
LCTPB 
Yes 
Yes 
3 
Erythrocyte Count  
LCTPB 
Yes 
Yes 
4 
Mean Cell Volume 
LCTPB 
Yes 
Yes 
5 
Mean Cell Hemoglobin 
LCTPB 
Yes 
Yes 
6 
MCHC 
LCTPB 
Yes 
Yes 
7 
Platelets 
LCTPB 
Yes 
Yes 
8 
Leukocyte Count  
LCTPB 
Yes 
Yes 
9 
Bands   
LCTPB 
Yes 
Yes 
10 
Neutrophils 
LCTPB 
Yes 
Yes 
11 
Lymphocytes 
LCTPB 
Yes 
Yes 
12 
Monocytes 
LCTPB 
Yes 
Yes 
13 
Eosinophils 
LCTPB 
Yes 
Yes 
14 
Basophils 
LCTPB 
Yes 
Yes 
Chemistry 
 
 
1 
ALT/SGPT 
Covance 
Yes 
Yes 
2 
AST/SGOT 
Covance 
Yes 
Yes 
3 
Alkaline Phosphatase 
Covance 
Yes 
Yes 
4 
Total Bilirubin 
Covance 
Yes 
Yes 
5 
Direct Bilirubin 
Covance 
Yes 
Yes 
6 
Albumin 
LCTPB 
Yes 
Yes 
7 
Creatine Phosphokinase 
LCTPB 
Yes 
Yes 
8 
Creatinine 
Covance 
Yes 
Yes 
9 
Urea Nitrogen 
LCTPB 
Yes 
Yes 
11 
estimated GFR  
Covance 
Yes 
Yes 
12 
Creatinine Clearance 
Covance 
Yes 
Yes 
13 
Sodium 
LCTPB 
Yes 
Yes 
14 
Potassium 
LCTPB 
Yes 
Yes 
15 
Calcium 
LCTPB 
Yes 
Yes 
16 
Total Protein 
LCTPB 
Yes 
Yes 
17 
Fasting Glucose 
LCTPB 
Yes 
Yes 
18 
Glucose, Non-Fasting or Random 
LCTPB 
Yes 
Yes 
19 
Uric Acid 
LCTPB 
Yes 
Yes 
20 
Cholesterol 
LCTPB 
Yes 
Yes 
21 
Triglycerides 
LCTPB 
Yes 
Yes 
22 
LDL Cholesterol – Direct 
Covance 
Yes 
Yes 
23 
HDL Cholesterol – Direct 
Covance 
Yes 
Yes 
24 
LDL/HDL Ratio – Calculated 
None 
Yes 
No 
 
 
 
 
 
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J1P-MC-KFAJ Statistical Analysis Plan Version 3 
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LY3471851 
Laboratory  
Laboratory Analyte 
Reference  
Analysis Type 
Group/Order 
 
Range Name 
Central 
Tendency 
Outlier/Shift 
Analysis 
Immunoglobulins 
 
 
1 
Immunoglobulin A 
Covance 
Yes 
Yes 
2 
Immunoglobulin G 
Covance 
Yes 
Yes 
3 
Immunoglobulin M 
Covance 
Yes 
Yes 
Urinalysis 
 
 
1 
Specific Gravity 
LCTPB 
Yes 
Yes 
2 
pH 
LCTPB 
Yes 
Yes 
3 
UA-color 
None 
No 
Yes 
4 
UA-glucose 
None 
No 
Yes 
5 
UA-protein 
None 
No 
Yes 
6 
UA-bilirubin 
None 
No 
Yes 
7 
UA-urobilinogen 
None 
No 
Yes 
8 
UA-nitrites 
None 
No 
Yes 
9 
UA-leukoesterase 
None 
No 
Yes 
10 
UA-ketones 
None 
No 
Yes 
11 
UA-occult blood 
None 
No 
Yes 
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J1P-MC-KFAJ Statistical Analysis Plan Version 3 
Page 99 
LY3471851 
Laboratory  
Laboratory Analyte 
Reference  
Analysis Type 
Group/Order 
 
Range Name 
Central 
Tendency 
Outlier/Shift 
Analysis 
Abbreviations: ALT/SGPT = alanine aminotransferase/serum glutamic pyruvic transaminase;  
AST/SGOT = aspartate aminotransferase/serum glutamic oxaloacetic transaminase; CD = cluster of 
differentiation; HDL = high-density lipoprotein; Ig = immunoglobulin; LCTPB = Lilly Large Clinical Trial 
Population Based; LDL = low-density lipoprotein; MCHC = mean corpuscular hemoglobin concentration; 
 UA = urinalysis. 
 
Approved on 31 Jan 2023 GMT
CCI
CCI


J1P-MC-KFAJ Statistical Analysis Plan Version 3 
Page 100 
LY3471851 
Appendix 7. Common Terminology Criteria for Adverse 
Events (CTCAE) Related to Myelosuppressive Events  
 
Approved on 31 Jan 2023 GMT


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Abbreviation: CTCAE = Common Terminology Criteria for Adverse Events; Fe = iron. 
a CTCAE grading was adjusted by replacing lower limit of normal (LLN) with a single value. 
Event 
Laboratory 
Test 
Grade 
Criteria in Système International (SI) Units 
Criteria in Conventional (CN) Units 
Anemiaa 
Hemoglobin 
 
 
0 (normal) 
 
1 
 
2 
3 
4 
≥7.27 mmol (Fe)/L for females and ≥8.18 mmol 
(Fe)/L for males 
<7.27 mmol (Fe)/L for females and 8.18 mmol 
(Fe)/L for males and ≥6.2 mmol (Fe)/L 
<6.2 mmol (Fe)/L and ≥4.9 mmol (Fe)/L  
<4.9 mmol (Fe)/L and ≥4.0 mmol (Fe)/L 
<4.0 mmol (Fe)/L 
≥12 g/dL for females and ≥13.5 g/dL for males 
 
<12 g/dL for females and 13.5 g/dL for males and 
≥10 g/dL 
<10 g/dL and ≥8.0 g/dL  
<8.0 g/dL and ≥6.5 g/dL 
<6.5 g/dL 
Leukopeniaa 
White blood 
cell (WBC) 
count 
0 (normal) 
1 
2 
3 
4 
≥4.0 billion cells/L 
<4.0 billion cells/L and ≥3.0 billion cells/L 
<3.0 billion cells/L and ≥2.0 billion cells/L 
<2.0 billion cells/L and ≥1.0 billion cells/L 
<1.0 billion cells/L 
≥4.0 thousand cells/uL 
<4.0 thousand cells/uL and ≥3.0 thousand cells/uL 
<3.0 thousand cells/uL and ≥2.0 thousand cells/uL 
<2.0 thousand cells/uL and ≥1.0 thousand cells/uL 
<1.0 thousand cells/uL 
Neutropeniaa 
Absolute 
neutrophil 
count (ANC) 
0 (normal) 
1 
2 
3 
4 
≥2 billion cells/L 
<2 billion cells/L and ≥1.5 billion cells/L 
<1.5 billion cells/L and ≥1.0 billion cells/L 
<1.0 billion cells/L and ≥0.5 billion cells/L 
<0.5 billion cells/L  
≥2 thousand cells/uL 
<2 thousand cells/uL and ≥1.5 thousand cells/uL 
<1.5 thousand cells/uL and ≥1.0 thousand cells/uL 
<1.0 thousand cells/uL and ≥0.5 thousand cells/uL 
<0.5 thousand cells/uL 
Lymphopeniaa 
Lymphocyte 
count 
0 (normal) 
1 
2 
3 
4 
≥1.1 billion cells/L 
<1.1 billion cells/L and ≥0.8 billion cells/L 
<0.8 billion cells/L and ≥0.5 billion cells/L 
<0.5 billion cells/L and ≥0.2 billion cells/L 
<0.2 billion cells/L 
≥1.1 thousand cells/uL 
<1.1 thousand cells/uL and ≥0.8 thousand cells/uL 
<0.8 thousand cells/uL and ≥0.5 thousand cells/uL 
<0.5 thousand cells/uL and ≥0.2 thousand cells/uL 
<0.2 thousand cells/uL 
Thrombocytopeniaa 
Platelet count 
0 (normal) 
1 
2 
3 
4 
≥150 billions/L 
<150 billions/L and ≥75 billions/L 
<75 billions/L and ≥50 billions/L 
<50 billions/L and ≥25 billions/L 
<25 billions/L 
≥150 thousands/uL 
<150 thousands/uL and ≥75 thousands/uL 
<75 thousands/uL and ≥50 thousands/uL 
<50 thousands/uL and ≥25 thousands/uL 
<25 thousands/uL 
Approved on 31 Jan 2023 GMT


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