A Phase 2b, Double-Blind, Placebo-Controlled Study to Evaluate Peresolimab in Adult Participants With Moderately-to-Severely Active Rheumatoid Arthritis
Phase: PHASE2
Conditions: Rheumatoid Arthritis, Arthritis, Joint Diseases, Musculoskeletal Diseases, Rheumatic Diseases, Connective Tissue Diseases, Autoimmune Diseases, Immune System Diseases
Sponsor: Eli Lilly and Company

Protocol A
 
-MC-
 ( ) 
NCT0
Approval Date: 
-Ma -20

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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 peresolimab (LY3462817), 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 Phase 2b, Double-Blind, Placebo-Controlled Study to Evaluate Peresolimab in 
Adult Participants with Moderately-to-Severely Active Rheumatoid Arthritis 
Protocol Number: J1A-MC-KDAF 
Amendment Number: e  
Compound: Peresolimab (LY3462817) 
Brief Title: A Phase 2b Study to Evaluate Peresolimab in Adult Participants with Moderately-to-
Severely Active Rheumatoid Arthritis 
Study Phase: 2b 
Acronym: RESOLUTION-1 
Sponsor Name: Eli Lilly and Company 
Legal Registered Address: Indianapolis, Indiana, USA 46285 
Regulatory Agency Identifier Number: 
IND: 150710 
EU trial number: 2022-501425-20-00 
Document ID: VV-CLIN-116958 
Approval Date: Protocol Amendment (e) Electronically Signed and Approved by Lilly on date 
provided below.  

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Medical monitor name and contact information will be provided separately.  
 
 
 

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Protocol Amendment Summary of Changes Table  
 
DOCUMENT HISTORY
Document 
Date
Amendment d
07 March 2023
Amendment c
31 January 2023
Amendment b
07 October 2022
Amendment a
11 August 2022
Original Protocol
19 July 2022
Amendment [e]  
This amendment is considered to be nonsubstantial. 
Overall Rationale for the Amendment: 
The primary rationale for this amendment is to address regulatory feedback. Changes and 
rationale are summarized in this table. Editorial or formatting changes to maintain document 
consistency are not shown in this table. 
 

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Table of Contents  
1. 
Protocol Summary ..........................................................................................................8 
1.1. 
Synopsis ............................................................................................................................8 
1.2. 
Schema ............................................................................................................................15 
1.3. 
Schedule of Activities (SoA) ..........................................................................................16 
1.3.1. 
Period I Screening, Period II Double-blind, Placebo-controlled 
Treatment, and Period III Double-blind Treatment Visits ..............................................17 
1.3.2. 
Early Discontinuation and Post-treatment Follow-up Visits 801 
and 802 ............................................................................................................................26 
2. 
Introduction ...................................................................................................................29 
2.1. 
Study Rationale ...............................................................................................................29 
2.2. 
Background .....................................................................................................................30 
2.3. 
Benefit/Risk Assessment ................................................................................................32 
2.3.1. 
Risk Assessment .............................................................................................................32 
2.3.2. 
Benefit Assessment .........................................................................................................32 
2.3.3. 
Overall Benefit Risk Conclusion ....................................................................................32 
3. 
Objectives, Endpoints, and Estimands .......................................................................33 
4. 
Study Design ..................................................................................................................38 
4.1. 
Overall Design ................................................................................................................38 
4.2. 
Scientific Rationale for Study Design ............................................................................39 
4.3. 
Justification for Dose ......................................................................................................40 
4.4. 
End of Study Definition ..................................................................................................41 
5. 
Study Population ...........................................................................................................42 
5.1. 
Inclusion Criteria ............................................................................................................42 
5.2. 
Exclusion Criteria ...........................................................................................................44 
5.3. 
Lifestyle Considerations .................................................................................................48 
5.4. 
Screen Failures ................................................................................................................48 
5.5. 
Criteria for Temporarily Delaying Enrollment of a Participant .....................................48 
6. 
Study Intervention(s) and Concomitant Therapy .....................................................49 
6.1. 
Study Intervention(s) Administered................................................................................49 
6.1.1. 
Rescue Medicine .............................................................................................................50 
6.2. 
Preparation, Handling, Storage, and Accountability ......................................................51 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ............................................52 
6.4. 
Study Intervention Compliance ......................................................................................53 
6.5. 
Dose Modification ..........................................................................................................53 
6.6. 
Continued Access to Study Intervention after the End of the 
Study ...............................................................................................................................53 
6.7. 
Treatment of Overdose ...................................................................................................53 
6.8. 
Concomitant Therapy .....................................................................................................53 
7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal........................................................................................55 
7.1. 
Discontinuation of Study Intervention ............................................................................55 
7.1.1. 
Liver Chemistry Stopping Criteria ..................................................................................56 

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7.1.2. 
QTc Stopping Criteria .....................................................................................................57 
7.1.3. 
Temporary Discontinuation of Study Intervention .........................................................57 
7.2. 
Participant Discontinuation/Withdrawal from the Study ................................................58 
7.3. 
Lost to Follow up ............................................................................................................58 
8. 
Study Assessments and Procedures.............................................................................59 
8.1. 
Efficacy Assessments .....................................................................................................60 
8.1.1. 
 ...................................................................61 
8.1.2. 
Health Assessment Questionnaire - Disability Index .....................................................61 
8.1.3. 
..................................................62 
8.1.6.
Morning Joint Stiffness Severity NRS............................................................................63
8.1.7. 
Functional Assessment of Chronic Illness Therapy-Fatigue 
(FACIT-F) .......................................................................................................................63 
8.1.8. 
Clinician Administered Tender or Swollen Joint Count (TSJC) 
(68/66) .............................................................................................................................63 
8.1.9. 
 .............................................64 
8.1.10. American College of Rheumatology (ACR) Criteria ACR20, 
ACR50, and ACR70 .......................................................................................................65 
8.1.11. Disease Activity Score High-Sensitivity C-Reactive Protein 
(DAS28-hsCRP) .............................................................................................................65 
8.1.12. Disease Activity Score Erythrocyte Sedimentation Rate 
(DAS28-ESR) .................................................................................................................66 
8.1.13. Simplified Disease Activity Index (SDAI) .....................................................................66 
8.1.14. Clinical Disease Activity Index (CDAI) .........................................................................66 
8.1.15. MRI Imaging and Synovitis Score ..................................................................................67 
8.2. 
Safety Assessments .........................................................................................................67 
8.2.1. 
Physical Examinations ....................................................................................................67 
8.2.2. 
Vital Signs .......................................................................................................................67 
8.2.3. 
Electrocardiograms .........................................................................................................67 
8.2.4. 
Clinical Safety Laboratory Tests ....................................................................................68 
8.2.5. 
Pregnancy Testing ...........................................................................................................68 
8.2.6. 
Suicidal Ideation and Behavior Risk Monitoring ...........................................................68 
8.2.7. 
Hepatic Monitoring .........................................................................................................69 
8.2.8. 
Tuberculosis Testing and Monitoring .............................................................................71 
8.2.9. 
Hepatitis B Testing and Monitoring ...............................................................................73 
8.2.10. Hepatitis C Testing and Monitoring ...............................................................................73 
8.3. 
Adverse Events, Serious Adverse Events, and Product 
Complaints ......................................................................................................................74 
8.3.1. 
Timing and Mechanism for Collecting Events ...............................................................74 
8.3.2. 
Pregnancy ........................................................................................................................76 
8.3.3. 
Adverse Events of Special Interest .................................................................................77 
8.4. 
Pharmacokinetics ............................................................................................................78 
8.5. 
Pharmacodynamics .........................................................................................................78 
8.6. 
Genetics ..........................................................................................................................78 
8.7. 
Biomarkers ......................................................................................................................78 

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8.8. 
Immunogenicity Assessments.........................................................................................78 
8.9. 
Health Economics ...........................................................................................................79 
9. 
Statistical Considerations .............................................................................................80 
9.1. 
Statistical Hypotheses .....................................................................................................80 
9.1.1. 
Multiplicity Adjustment ..................................................................................................80 
9.2. 
Analyses Sets ..................................................................................................................80 
9.3. 
Statistical Analyses .........................................................................................................80 
9.3.1. 
General Considerations ...................................................................................................80 
9.3.2. 
Primary Endpoint/Estimand Analysis .............................................................................82 
9.3.3. 
Secondary Endpoints Analysis .......................................................................................82 
9.3.4. 
Exploratory Analysis ......................................................................................................82 
9.3.5. 
Safety Analyses ...............................................................................................................83 
9.3.6. 
Pharmacokinetic Analyses ..............................................................................................83 
9.3.7. 
Evaluation of Immunogenicity .......................................................................................84 
9.3.8. 
Other Analyses ................................................................................................................84 
9.4. 
Interim Analysis ..............................................................................................................85 
9.5. 
Sample Size Determination ............................................................................................86 
10. 
Supporting Documentation and Operational Considerations ..................................87 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ................................................................................................................87 
10.1.1. Regulatory and Ethical Considerations ...........................................................................87 
10.1.2. Financial Disclosure........................................................................................................87 
10.1.3. Informed Consent Process ..............................................................................................88 
10.1.4. Data Protection................................................................................................................88 
10.1.5. Committees Structure......................................................................................................88 
10.1.6. Dissemination of Clinical Study Data.............................................................................89 
10.1.7. Data Quality Assurance ..................................................................................................89 
10.1.8. Source Documents ..........................................................................................................91 
10.1.9. Study and Site Start and Closure ....................................................................................91 
10.1.10. Publication Policy ...........................................................................................................92 
10.1.11. Investigator Information .................................................................................................92 
10.1.12. Sample Retention ............................................................................................................92 
10.2. 
Appendix 2: Clinical Laboratory Tests ...........................................................................93 
10.2.1. Laboratory Samples to be Obtained at the Time of a Systemic 
Hypersensitivity Event ....................................................................................................97 
10.3. 
Appendix 3: Adverse Events and Serious Adverse Events: 
Definitions and Procedures for Recording, Evaluating, Follow-
up, and Reporting ............................................................................................................98 
10.3.1. Definition of AE .............................................................................................................98 
10.3.2. Definition of SAE ...........................................................................................................99 
10.3.3. Definition of Product Complaints .................................................................................100 
10.3.4. Recording and Follow-Up of AE and/or SAE and Product 
Complaints ....................................................................................................................100 
10.3.5. Reporting of SAEs ........................................................................................................102 
10.3.6. Regulatory Reporting Requirements .............................................................................103 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ........................................................104 

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10.4.1. Definitions.....................................................................................................................104 
10.4.2. Contraception Guidance................................................................................................105 
10.5. 
Appendix 5: Genetics....................................................................................................108 
10.6. 
Appendix 6: Liver Safety: Suggested Actions and Follow-up 
Assessments ..................................................................................................................109 
10.7. 
Appendix 7: Examples of Infections Considered Possibly 
Opportunistic ................................................................................................................111 
10.8. 
Appendix 8: Provisions for Changes in Study Conduct During 
Exceptional Circumstances ...........................................................................................112 
10.9. 
Appendix 9: Country-Specific Requirements ...............................................................116 
10.9.1. EU Member States ........................................................................................................116 
10.10. 
Appendix 10: Abbreviations and Definitions ...............................................................117 
10.11. 
Appendix 11: Protocol Amendment History ................................................................122 
11. 
References ....................................................................................................................126 
 

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1. 
Protocol Summary  
1.1. 
Synopsis  
Protocol Title:  
A Phase 2b, Double-Blind, Placebo-Controlled Study to Evaluate Peresolimab in Adult 
Participants with Moderately-to-Severely Active Rheumatoid Arthritis  
Brief Title:  
A Phase 2b Study to Evaluate Peresolimab in Adult Participants with Moderately-to-Severely 
Active Rheumatoid Arthritis  
Regulatory Agency Identifier Number:  
IND: 150710 
EU trial number: 2022-501425-20-00 
Rationale: 
This study aims to find the appropriately 
for 
peresolimab in adults with moderately-to-severely active rheumatoid arthritis (RA) for further 
clinical development.  
Objectives, Endpoints, and Estimands: 
Objectives 
Endpoints 
Primary 
 
To evaluate the efficacy of peresolimab 
compared to placebo in achieving ACR20 
 Proportion of participants achieving 
ACR20 at Week 12 
Secondary 
 
To evaluate the effect of peresolimab 
compared to placebo for measures of disease 
activity  
 
 Proportion of participants achieving 
ACR50 or ACR70 at Week 12 
 Proportion of participants achieving LDA 
or remission at Week 12 for  
o
DAS28-hsCRP
 Change from baseline at Week 12 for 
mean  
o
DAS28-hsCRP

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To evaluate the effect of peresolimab 
compared to placebo for patient-reported 
outcome measures 
o
Arthritis Pain (VAS), and 
o 
physical function using 
HAQ-DI.  
To evaluate the effect of peresolimab for 
measures of disease activity 

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To characterize the pharmacokinetics of 
peresolimab 
Primary estimand 
The primary clinical question of interest is  
What is the difference between peresolimab and placebo in the target patient population, 
in achieving a successful response at 
 
 
The estimand is described by the following attributes: 
 Population: Participants with moderately-to-severely active RA. 
 Endpoint: 
 
 Intercurrent events (ICEs) related to study intervention include the use of rescue or 
prohibited medication and early discontinuation from the study or study intervention. A 
composite strategy will be used for ICEs. Specifically, participants with an ICE will be 
considered as a nonresponder after the first occurrence of the ICE.   
 Population-level summary: Difference in proportion of participants achieving response at 
 between intervention conditions. 
 Rationale for estimand: The data collected after the treatment discontinuation or post-rescue 
medication will be considered as treatment failures and categorized as nonresponder since it 
is assumed the participant was not receiving benefit from the intervention.   
Overall Design: 
Study J1A-MC-KDAF is a Phase 2b, randomized, double-blind, placebo-controlled study to 
determine the appropriate dose and dosing frequency of peresolimab in adult participants with 
moderately-to-severely active RA. 
This study includes a  
 screening period
 
 

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 post-treatment follow-up.
Treatment period design 
Study Population: 
In general, an individual may take part in this study if they 
 Are 18 years of age or older at the time of signing the informed consent. 

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 Were diagnosed with RA as an adult, at least 3 months prior to screening, as defined by 
the 2010 American College of Rheumatology (ACR)/European League Against 
Rheumatism (EULAR) classification criteria. 
 Currently have moderately-to-severely active RA.  
 Have positive test results for rheumatoid factor or anti-cyclic citrullinated peptide 
antibodies at screening OR previous radiographs that show images of the hands or feet 
consistent with RA. 
 Have C-reactive protein (CRP) >1.2 times upper limit of normal (ULN).  
 
  
 Have up to date vaccinations per regional and national guidelines, specifically influenza, 
pneumonia, and zoster.  
In general, an individual may not take part in this study if they 
 Have 1 or more of these medical conditions   
 poorly controlled diabetes or hypertension  
 chronic kidney disease stage IIIb, IV, or V  
 symptomatic heart failure according to New York Heart Association Class II, III, 
or IV 
 heart attack, poor blood flow to the heart, stroke or temporary symptoms of a 
stroke, within the past 12 months before randomization  
 severe chronic lung disease  
 major chronic inflammatory disease or connective tissue disease other than RA, or 
 multiple sclerosis.  
 Have had any of these types of infections within 3 months of screening or develop any of 
these infections before the randomization visit 
 Serious - requires hospitalization or IV or equivalent oral antibiotic treatment  
 Opportunistic  infections caused by bacteria, viruses, fungus, or parasites that occur 
more often or are more severe in people with weakened immune systems  
 Chronic  duration of symptoms, signs, or treatment of 6 weeks or longer  
 Recurring  including, but not limited to, herpes simplex, herpes zoster, recurring 
bacterial skin infections (cellulitis), or chronic bone infections  

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o Herpes zoster is considered active and ongoing until all vesicles are dry and 
crusted over 
o Exception: If the investigator determines that a participant with recurrent 
nonserious infections such as cellulitis and uncomplicated orolabial or 
genital herpes, is not at an increased risk of complications.  
 Have any of these infections 
 human immunodeficiency virus (HIV) infection 
 current infection with hepatitis B virus (HBV), for example, positive for hepatitis B 
surface antigen or polymerase chain reaction (PCR) positive for HBV DNA  
 current infection with hepatitis C virus (HCV), for example, positive for HCV RNA, 
or  
 active tuberculosis (TB). 
 Have a current or recent acute active infection, or fever of 100.5°F (38°C) or above, at 
screening or baseline. For at least 30 days prior to screening, participants must have no 
symptoms or signs of confirmed or suspected infection and must have completed any 
appropriate treatment for the infection. 
Approximately 70% of the participants randomly assigned to study intervention will have a 
history of inadequate response to bDMARDs or tsDMARDs, while approximately 30% of 
participants will have a history of inadequate response to only conventional synthetic DMARDs.  
Number of Participants: 
Approximately 420 participants will be randomly assigned to study intervention.  
Intervention Groups and Duration: 

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Ethical Considerations of Benefit/Risk: 
The safety data available to date suggest that there is no increased risk to participant safety with 
peresolimab compared to other approved humanized monoclonal antibody or 
immunomodulatory therapy.  
Considering the measures taken to minimize risk to participants in this study, the potential 
benefit risk balance for this study is acceptable for testing in Phase 2 and justified by the 
potential benefits for participants with moderately-to-severely active RA.  
Data Monitoring Committee: No 
An internal assessment committee will review the interim efficacy and safety data in an 
unblinded fashion. 
 

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1.2. 
Schema  

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1.3. 
Schedule of Activities (SoA)  
Two tables describe the SoA. 
Table 1 (Section 1.3.1) describes Period I Screening, Period II Double-blind, Placebo-controlled Treatment, and Period III Double-
blind Treatment visits. 
Table 2 (Section 1.3.2) describes the ED Visit and Period IV Post-treatment Follow-up Visits 801 and 802. 
Period I  Screening 
Visit 1 procedures may be conducted over more than 1 day if all activities are completed within the allowable visit tolerance.  
Periods II and III  Double-blind Treatment periods 
If an ED occurs before the last visit in the Period III treatment period, see the activities listed for the ED visit in Table 2.    
 
 
 

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2. 
Introduction  
Rheumatoid arthritis 
RA is a common, systemic autoimmune inflammatory disease, characterized by synovial 
inflammation leading to pain, swelling, stiffness, and progressive destruction and deformity of 
small and large joints. Patients experience impaired physical function, social participation, and 
health-related quality of life. Patients also have increased risk of significant comorbidities that 
are not musculoskeletal (Picerno et al. 2015; Simon et al. 2015; Ogdie et al. 2018).  
Current treatment of rheumatoid arthritis 
Current treatment of RA includes timely initiation and modification of DMARD therapy to bring 
patients to a target of sustained LDA or remission (Smolen et al. 2020). Achievement of these 
targets improves short- and long-term patient health outcomes, including prevention of 
progressive, irreversible structural joint damage (Smolen et al. 2020).  
The treatment target can be met in most patients with the therapeutic options currently available, 
which include csDMARDs, bDMARDs, and tsDMARDs. However, 20% to 30% of the patients 
with RA fail to respond to current therapies. For these patients, new treatment options are needed 
(Smolen et al. 2020).  
Peresolimab (otherwise known as LY3462817) 
Peresolimab is a
 
Peresolimab binding to 
 is expected to trigger the physiological 
immune inhibitory pathway to restore immune regulation, which is a novel treatment approach 
for patients with autoimmune or auto-inflammatory diseases.  
 target and autoimmune disease 
The 
 and its ligands, 
, are important elements of the 
 
pathway involved in immune homeostasis. There is evidence of the PD-1 pathway having a 
significant pathophysiologic role in autoimmune diseases such as psoriasis (Gulati et al. 2015), 
psoriatic arthritis (Bommarito et al. 2017), giant cell vasculitis (Zhang et al. 2017), multiple 
sclerosis (Trabattoni et al. 2009), systemic sclerosis (Fukasawa et al. 2017) and RA (Canavan et 
al. 2021).    
In RA patients, reported biomarker changes that reflect disruption of the PD-1 pathway included 
significant increases in PD-1 expression and decreases in PD-L1 expression (Guo et al. 2018).  
Additionally, auto-antibodies to PD-L1 (Dong et al. 2003) and increases in soluble PD-1 in the 
synovium, which can bind PD-L1 (Bommarito et al. 2017), were reported in RA patients, that 
may reflect disrupted signaling through the PD-1 receptor and defects in immune inactivation 
pathways. 
2.1. 
Study Rationale  
This study aims to find the appropriately 
for 
peresolimab in adults with moderately-to-severely active RA for further clinical development. 

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2.2. 
Background  
Peresolimab  
Information on the safety, tolerability, PK, and PD of peresolimab comes from completed study 
J1A-MC-KDAB (KDAB) and from the ongoing studies J1A-MC-KDAC (KDAC) and J1A-MC-
KDAD (KDAD). This table summarizes the clinical studies for peresolimab as of June 2022.  
Study 
Study design 
Population 
Number of
Participants 
Randomly 
Assigned to 
Intervention
Study Interventions
Study
Status 
KDAB 
Phase 1, single 
ascending dose, first 
in human study 
Healthy 
participants 
64 
 
Completed 
KDAC 
Phase 1b, 
randomized, 
placebo-controlled, 
multiple ascending 
dose study
Participants 
with psoriasis 
(BSA 2) 
27
 
Ongoing 
KDAD 
Phase 2, 
proof-of-concept, 
placebo-controlled, 
double-blind, 
randomized study 
 
Participants 
with 
moderately-to-
severely active 
RA with 
98
 
Ongoing 

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Overview of clinical data 
Safety  
Phase 1 Studies KDAB and KDAC  
In Studies KDAB and KDAC, there were no reports of  
 deaths or SAEs  
 discontinuations because of an AE  
 infusion reactions 
 injection site reactions  
 malignancy  
 serious infection  
 reactivation of latent infection, or  
 opportunistic infections. 
The most frequently reported TEAEs related to treatment overall were in the Nervous System 
Disorders system organ class. The most frequently reported TEAE following dosing with 
peresolimab was headache.  
Phase 2 Study KDAD   
Efficacy 
Pharmacokinetics  

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Pharmacodynamics  
2.3. 
Benefit/Risk Assessment  
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of peresolimab may be found in the IB.  
2.3.1. 
Risk Assessment  
Potential risks for this study  
The risks associated with peresolimab are similar to risks generally expected with approved 
humanized monoclonal antibodies or immunomodulatory therapies, such as  
 hypersensitivity and cytokine release reaction 
 injection site reactions, for example, injection site rash, erythema, or pruritus or 
lipohypertrophy 
 risk of developing infection or of an infection becoming more serious 
 immunogenicity, and  
 malignancy. 
In participants who received peresolimab, there are no apparent trends in any AE.  
All AEs from the 3 clinical studies were mild or moderate in severity with only 1 SAE observed 
during the treatment in Study KDAD. See Section 2.2 and the IB for clinical safety results.  
Management of risks 
Sections 5.1, 5.2, 7.1, and 8.2 address known potential risks associated with peresolimab.  
2.3.2. Benefit Assessment  
Study KDAD established the efficacy of peresolimab (Section 2.2).    
Participants may also benefit by receiving personal health information from the physical 
examinations and from other routine safety assessments performed in this study.  
2.3.3. Overall Benefit Risk Conclusion  

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3. 
Objectives, Endpoints, and Estimands  
Objectives 
Endpoints 
Primary 
 
To evaluate the efficacy of peresolimab 
compared to placebo in achieving ACR20 
 Proportion of participants achieving 
ACR20 at Week 12 
Secondary 
 
To evaluate the effect of peresolimab 
compared to placebo for measures of disease 
activity  
 
 Proportion of participants achieving 
ACR50 or ACR70 at Week 12 
 Proportion of participants achieving LDA 
or remission at Week 12 for  
o
DAS28-hsCRP
 Change from baseline at Week 12 for 
mean  
o
DAS28-hsCRP
To evaluate the effect of peresolimab 
compared to placebo for patient-reported 
outcome measures 
o
p
physical function using 
HAQ-DI.

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To evaluate the effect of peresolimab for 
measures of disease activity 
To characterize the pharmacokinetics of 
peresolimab 
Exploratory 
 

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Primary estimand  
The primary clinical question of interest is:  
What is the difference between peresolimab and placebo in the target patient population, 
in achieving a successful response at 
 without use of rescue medication or 
discontinuing the study intervention?  
The estimand is described by the following attributes: 
 Population: Participants with moderately-to-severely active RA (see Section 5). 
 Endpoint: 
 
 ICEs related to study intervention include the use of rescue or prohibited medication and ED 
from the study or study intervention. A composite strategy will be used for ICEs. 
Specifically, participants with an ICE will be considered as a nonresponder after the first 
occurrence of the ICE.   
 Population-level summary: Difference in proportion of participants achieving response at 
 
 Rationale for estimand: The data collected after the treatment discontinuation or post-rescue 
medication will be considered as treatment failures and categorized as nonresponder since it 
is assumed the participant was not receiving benefit from the intervention.   
Secondary estimands for categorical endpoints 
For secondary objectives that have categorical endpoints analyzed up to 
 the clinical 
question of interest is:  
What is the difference between peresolimab and placebo in the target patient population, 
in achieving a successful response at 
 without use of rescue medication or 
discontinuing the study intervention? 
The estimand is described by the following attributes: 
 Population: Participants with moderately-to-severely active RA (see Section 5).
 
 ICE will be accounted using the same estimand strategy as for the primary estimand.

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 Population-level summary:  
Difference in proportion of participants achieving response at 
 between 
intervention conditions. 
 Rationale for estimand is described above for the primary estimand.   
Secondary estimands for continuous endpoints 
For secondary objectives that have continuous endpoints analyzed up to 
 the clinical 
question of interest is:  
What is the difference between peresolimab and placebo in the target patient population, 
in average at 
 without use of rescue medication or discontinuing the study 
intervention?   
The estimand is described by the following attributes: 
 Population: Participants with moderately-to-severely active RA (see Section 5). 
Endpoint: change from baseline for
 How to account for ICEs: A hypothetical estimand strategy will be used. That is, data 
collected after the first occurrence of ICE will be excluded from an analysis and what the 
treatment effect would have been if rescued medication was not used.  
 Population-level summary:  
Difference in mean change from baseline to 
 between intervention 
conditions.   
Supportive estimands 
Additional details on supportive estimands for primary and secondary objectives will be 
provided in the SAP.  

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4. 
Study Design  
4.1. 
Overall Design  
Study J1A-MC-KDAF (KDAF) is a Phase 2b, randomized, double-blind, placebo-controlled 
study to determine the appropriate dose and dosing frequency of peresolimab in adult 
participants with moderately-to-severely active RA. 
This study includes a  
 screening period 
 
 double-blind, placebo-controlled treatment period 
 
double-blind treatment period, and 
 post-treatment follow-up. 
See the SoA for visit schedule, procedural and assessment details (Section 1.3). 
Participant population 
of the participants randomly assigned to study intervention will have a 
history of 
 of 
participants will have a history of 
 
Treatment period design 

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Follow-up period 
Two follow-up visits occur at 
 after the final treatment period visit. 
Participation in an open-label extension study 
If an open-label extension study is enrolling at the time the participant completes 
 
 they will be given the opportunity to enroll in that study.  
4.2. 
Scientific Rationale for Study Design  
Primary endpoint 
Clinical 
 in disease activity is the main target for participants with RA. 
The 
 are an accepted measure of reduction in RA disease activity per 
FDA, guidance (FDA 2013).  
Independent Joint and Safety Assessors 
To prevent potential bias from 
approach will be used to evaluate efficacy and safety (see Section 8).  
Overall design  
Follow-up period duration
The 
 follow-up duration is considered acceptable to evaluate safety and to explore the 
durability of biomarker and clinical disease activity changes achieved during the treatment 
period.  
Collection of race and ethnicity data  
In this study, collection of demographic information includes race and ethnicity as allowed per 
local regulations. The scientific rationale is based on the need to assess variable response in 
safety and/or efficacy based on race or ethnicity. This question can be answered only if all the 
relevant data are collected.  
 
 

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4.3. 
Justification for Dose  

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4.4. 
End of Study Definition  
The end of the study is defined as the date of the last visit of the last participant in the study. 
A participant is considered to have completed the study if the participant has completed all 
periods of the study including the last scheduled procedure shown in the SoA.  

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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. 
5.1. 
Inclusion Criteria  
Participants are eligible to be included in the study only if all of the following criteria apply: 
Age 
1. 
18 years of age at the time of signing the informed consent. 
Type of participant and disease characteristics 
2. Have a diagnosis of adult onset RA for at least 3 months prior to screening, as defined by 
the 2010 ACR/European League Against Rheumatism (EULAR) classification criteria 
(Aletaha et al. 2010). 
3. Have moderately-to-severely active RA, at screening and baseline, defined by the 
presence of 
 
, and  
 
 
Notes:  
The distal interphalangeal joints should be evaluated but not included in the total 
count to determine eligibility.  
If a participant has received corticosteroid treatment per Criterion 27, the treated joint 
should be excluded from the joint count. 
4. Have positive test results for rheumatoid factor or anti-cyclic citrullinated peptide 
antibodies at screening OR previous radiographs documenting bony erosions in hands or 
feet consistent with RA. 
5. Have C-reactive protein (CRP) >1.2 times ULN per the central laboratory at screening. 
7. Have up to date vaccinations per regional and national guidelines, specifically influenza, 
pneumonia, and zoster.  
 Live vaccines should be administered >3 months before randomization.  
 All vaccinations 
 days before randomization.   
8. Have clinical laboratory test results within normal reference range or results with 
acceptable deviations that are judged as not clinically significant by the investigator at 
screening. This table outlines laboratory test results with required ranges for inclusion in 
this study. 

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Test 
Result
Hematology
Absolute neutrophil count  
x 109
x 103
Platelet count
100 x 109/L ( 100 x 103
00 GI/L)
Hemoglobin level
 
Lymphocyte count
>500 cells/µL (>0.50 x 103/µL or >0.50 GI/L) 
Total leukocyte count
9
x 103
 
Clinical Chemistry
Serum creatinine, ALT, and AST
x upper limit of normal (ULN)
TBL and ALP
<1.5 x ULN. P
bilirubin <1.5 mg/dL
See Section 6.8 for allowed treatments during the study if the 
 weeks 
 
Note to sites in EU Member States: See Section 10.9.1 for country-specific 
modifications to Criterion 9. 
Sex and contraceptive/barrier requirements 
10.  Male or female 
Women of childbearing potential (WOCBP) and women not of childbearing potential 
(WNOCBP) may participate in this study.  
Males who agree to use highly effective methods of contraception may participate in this 
study. 
See Section 10.4 for definitions and additional requirements related to contraception. 
Contraceptive use by participants 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 Section 10.4. 
Informed consent 
11. Are capable of giving signed informed consent as described in Section 10.1.3, which 
includes compliance with the requirements and restrictions listed in the ICF and in this 
protocol.  

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5.2. 
Exclusion Criteria  

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20. Have had any surgical procedure, within 12 weeks prior to screening, or any planned 
surgical procedure scheduled to occur during the study, with the exception of minor 
surgery requiring local or no anesthesia and without any complications or sequelae. 
21. Have had any of the following types of infections within 3 months of screening or 
develops any of these infections before the randomization visit 
 Serious - requires hospitalization or IV or equivalent oral antibiotic treatment  
 Opportunistic - as defined in Section 10.7  
 Chronic - duration of symptoms, signs, or treatment of 6 weeks or longer  
 Recurring - including, but not limited to, herpes simplex, herpes zoster, recurring 
cellulitis, or chronic osteomyelitis  
o Note: Herpes zoster is considered active and ongoing until all vesicles are dry 
and crusted over 
o Exception: If the investigator determines that a participant with recurrent 
nonserious infections such as cellulitis and uncomplicated orolabial or 
genital herpes, is not at an increased risk of complications.  
22. Have any of these infections 
 HIV infection 
 current infection with HBV, for example, positive for hepatitis B surface antigen 
(HBsAg) or polymerase chain reaction (PCR) positive for HBV DNA  
 current infection with HCV, for example, positive for HCV RNA, or  
 active TB. 
23. Have or had LTBI that has not been treated with a complete course of appropriate therapy 
as defined by the WHO or the United States CDC, unless such treatment is underway, as 
per Section 8.2.8. 
24. Have a current or recent acute active infection, or fever of 100.5°F (38°C) or above, at 
screening or baseline. For at least 30 days prior to screening, participants must have no 
symptoms or signs of confirmed or suspected infection and must have completed any 
appropriate anti-infective treatment. 
25. Are women who are currently pregnant or breastfeeding, or who intend to become 
pregnant or to breastfeed at any time during the study or within 20 weeks after receiving 
the last dose of study intervention. 

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Prior/concomitant therapy 
26. Have failed more than 
 
27. Are currently receiving or have received any of these therapies within 28 days 
 
  
Therapy
Notes
28. Have received these treatments 
 or plan on receiving any of these 
biologic immunosuppressive treatments during the study  
 

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30. Have received a Bacillus Calmette-Guérin (BCG) vaccination or BCG treatment within 
12 months of screening.   
Prior/concurrent clinical study experience 
31. Were previously enrolled in a clinical study investigating peresolimab (LY3462817) or 
any other molecule targeting PD-1 for the treatment of auto-immune or auto-
inflammatory conditions.  
32. Are currently enrolled in any other clinical study involving a study intervention or any 
other type of medical research judged not to be scientifically or medically compatible 
with this study. 
33. Have participated, within the last 30 days, in a clinical study involving study intervention. 
If the previous study intervention has a long half-life, 3 months or 
 whichever 
is longer, should have passed prior to screening. 
34. Have previously completed or withdrawn from this study. 
Diagnostic assessments 
Other exclusions 
36. Have donated more than a single unit of blood within 4 weeks before randomization or 
plan on donating blood during the study. 
37. Are investigator 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. 
38. Are Lilly employees or employees of third-party organizations involved with the study 
that require exclusion of their employees. 
39. Are not willing to receive 
 

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40. Are unsuitable for inclusion in the study, in the opinion of the investigator or sponsor, for 
. 
41. Have experienced allergic/hypersensitivity reaction to any component of peresolimab 
(LY3462817), including excipients. 
5.3. 
Lifestyle Considerations  
All study participants should not donate blood or blood products during the study or for 
 
after the last dose of the study intervention. 
Reproductive and contraceptive guidance is provided in Section 10.4. 
5.4. 
Screen Failures  
A screen failure occurs when a participant who consents to participate in the clinical study is not 
subsequently enrolled in the study. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials (CONSORT) publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, eligibility criteria, 
and any SAE. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened 1 time.  
A possible reason for rescreening may be a status change such that the eligibility criterion that 
caused the participant to screen fail would not cause the participant to screen fail again. 
If an individual is rescreened, a new participant number is assigned, and the individual must sign 
a new ICF. 
5.5. 
Criteria for Temporarily Delaying Enrollment of a Participant  
This section is not applicable for this study. All entry criteria must be met within the specified 
visit intervals in the SoA. 

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6. 
Study Intervention(s) and Concomitant Therapy  
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to/used by a study participant 
according to the study protocol. 
6.1. 
Study Intervention(s) Administered  
Study intervention will be administered at the study sites, at visits summarized in the SoA. 
This table provides information for the interventions used in this clinical study. 
 
Study intervention dosing information 
Each dose of study intervention is planned to be 
 The sponsor will 
provide detailed instructions for study intervention administration in a separate document.  
After dosing, the investigator should monitor all participants for 1 hour or longer according to 
investigator practice or local standard of care.  
Packaging and labeling 
Study interventions will be supplied by the sponsor or its designee in accordance with current 
Good Manufacturing Practice. Study interventions will be labeled as appropriate for country 
requirements. 
 
 

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6.1.1. 
Rescue Medicine  
Guidance for starting rescue therapy 

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6.2. 
Preparation, Handling, Storage, and Accountability  
The investigator or designee must confirm appropriate storage conditions have been maintained 
during transit for all study intervention received and any discrepancies are reported and resolved 
before use of the study intervention. 
Only participants enrolled in the study may receive study intervention. Only authorized study 
personnel may supply, prepare, 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 study personnel. 
The investigator or authorized study personnel are 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.  
 
 

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6.3. 
Measures to Minimize Bias: Randomization and Blinding  
Randomization 
Blinding  
This is a double-blind study. Blinding will be maintained throughout the conduct of the study, as 
described in the separate Blinding and Unblinding Plan.  
within each 
dose group, throughout the course of the study.  
Emergency unblinding 
The IWRS will be programmed with blind-breaking instructions. In case of an emergency, the 
intervention assignment is warranted. Participant safety must always be the first consideration in 
making such a determination.  

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intervention assignment is unblinded, the sponsor must be notified immediately 
within 24 hours of this occurrence. The date and reason that the blind was broken must be 
recorded. 
Discontinuation from the study in case of unblinding 
If an investigator, site personnel performing assessments, or participant is unblinded, the 
participant must be discontinued from the study. In cases where there are ethical reasons to have 
the participant remain in the study, the investigator must obtain specific approval from the 
sponsor for the participant to continue in the study. 
6.4. 
Study Intervention Compliance  
6.5. 
Dose Modification  
This protocol does not allow dose adjustments. 
6.6. 
Continued Access to Study Intervention after the End of the Study  
Study intervention will not be available to participants after completion of the study.  
If an open-label extension study is enrolling at the time the participant completes Visit 18 (Week 
60), they will be given the opportunity to enroll in that study.  
6.7. 
Treatment of Overdose  
The sponsor does not recommend specific treatment for an overdose. 
In the event of an overdose, the investigator should 
 contact the medical monitor immediately 
 evaluate the participant to determine, in consultation with the medical 
monitor, whether study intervention should be interrupted  
 closely monitor the participant for any AE/SAE and laboratory abnormalities 
6.8. 
Concomitant Therapy  
General considerations 

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Concomitant therapy data collection 
For therapy that the participant is receiving at the time of enrollment or receives during the 
study, whether prescription or over-the-counter, authorized study personnel should collect 
 the name of medication, vaccine or therapy 
 the reason for use 
 route of administration, and  
 dates of administration, including start and end dates.  
For RA background therapy and rescue therapy, study personnel should collect additional dosing 
information, including dose and frequency. 
The medical monitor should be contacted if there are any questions regarding concomitant or 
prior therapy.  

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7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal  
This section outlines  
 Permanent discontinuation of study intervention 
 Temporary interruption of study intervention 
 Discontinuation from the study, and 
 Participants lost to follow-up. 
Discontinuation of specific sites or of the study as a whole are handled as part of Section 10.1, 
Appendix 1. 
7.1. 
Discontinuation of Study Intervention  
Permanent discontinuation of study intervention 
When necessary, a participant may be permanently discontinued from study intervention. If so, 
the participant will be encouraged to remain in the study and follow procedures for all remaining 
study visits, as shown in the SoA.  
A participant should be permanently discontinued from study intervention if the participant 
 requests to discontinue the study intervention 
 becomes pregnant during the study 
 is diagnosed with an active or untreated malignancy, except for successfully treated 
basal or squamous cell carcinoma 
 is diagnosed with HIV infection 
 is diagnosed with active TB  
 is diagnosed with LTBI and are not a candidate for treatment as described in 
Section 8.2.8  
 tests positive for HBV DNA or HCV RNA (see Sections 8.2.9 and 8.2.10 for details) 
 answered "yes" to Question 4 or Question 5 on the "Suicidal Ideation" portion of the 
C-SSRS 
 answered "yes" to any of the suicide-related behaviors on the Suicidal Behavior 
portion of the C-SSRS 
A psychiatrist or appropriately trained professional may assist in the decision to 
discontinue the participant. 
 has a systemic hypersensitivity reaction related to study intervention administration, 
or 
 in the opinion of the investigator, the participant should permanently discontinue the 
study intervention for safety reasons. 
 
 

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Additional guidance 
Escape criteria  
A participant not achieving
 
or example, if a participant meets rescue criteria at Week 16 and does 
not achieve a 20% improvement from baseline in both TJC and SJC at Weeks 20 and 24, then 
they should be permanently discontinued from study intervention. Participants may continue in 
  
Systemic hypersensitivity reactions 
If the investigator determines that a systemic hypersensitivity reaction has occurred related to 
study intervention administration, the s
 
If the investigator is uncertain about whether a systemic hypersensitivity reaction has occurred 
and whether discontinuation of study intervention is warranted, the investigator may consult the 
sponsor. 
HBV DNA  
Prior to discontinuation of any immunomodulatory or immunosuppressive therapy, including 
study intervention, the participant should be referred to, evaluated, and managed by a physician 
with expertise in evaluation and management of viral hepatitis.  
The timing of discontinuation from study intervention relative to the initiation of any antiviral 
treatment for hepatitis should be based on the recommendation of the consulting physician with 
expertise in hepatology, in conjunction with the investigator, and aligned with medical guidelines 
and standard of care. 
7.1.1. 
Liver Chemistry Stopping Criteria  
Interrupting study intervention based on elevated liver tests 
The study intervention should be interrupted and close hepatic monitoring initiated (see Section 
8.2.7), if 1 or more of the conditions in this table occur.  
Elevation
Exception
ALT or AST >8x ULN
ALT or AST >5x ULN for more than 2 weeks
ALT or AST >3x ULN and either TBL >2x ULN or INR >1.5 
If baseline direct bilirubin is >0.5 mg/dL, 
then doubling of direct bilirubin should be 
used for drug interruption decisions rather 
than TBL>2x ULN.
ALT or AST >3x ULN with the appearance of fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, fever, rash, 
and/or eosinophilia (>5%)
ALP >3x ULN, when the source of increased ALP is the liver
ALP >2.5x ULN and TBL > 2x ULN  
If baseline direct bilirubin is >0.5 mg/dL 
then doubling of direct bilirubin should be 
used for drug interruption decisions rather 
than TBL>2x ULN.

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ALP >2.5x ULN with the appearance of fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, fever, rash, 
and/or eosinophilia (>5%)
Source: FDA 2009 and other consensus guidelines, with minor modifications.
 
Resuming study intervention after elevated liver tests 
Resumption of the study intervention can be considered only in consultation with the 
Lilly-designated medical monitor and only if the liver test results return to baseline and if a 
self-limited, non-drug etiology is identified. Otherwise, the study intervention should be 
permanently discontinued.  
7.1.2. 
QTc Stopping Criteria  
If a clinically significant finding is identified, including, but not limited to changes from baseline 
after enrollment, the investigator or qualified designee will determine if the participant can 
continue in the study and if any change in participant management is needed. This review of the 
ECG printed at the time of collection must be documented. Any new clinically relevant finding 
should be reported as an AE. 
7.1.3. 
Temporary Discontinuation of Study Intervention  
Infection-related criteria for temporary discontinuation of study intervention 
This table describes the required criteria for temporarily discontinuing study intervention and the 
next steps the site staff should follow. 
Then follow th
serious or opportunistic infections, as defined in the 
exclusion criteria (Section 5.2) 
Withhold study intervention until resolution of all 
acute clinical signs and symptoms, and completion of 
all appropriate anti-infective treatment. 
The investigator should consult with the sponsor-
designated medical monitor to determine when it is 
appropriate to restart study intervention.
any acute infection or illness 
At the discretion of the investigator and sponsor or its 
designee, withhold intervention until resolution of all 
acute clinical signs and symptoms, and completion of 
all appropriate anti-infective treatment.
positive HBV DNA results 
or  
results detecting HBV DNA, but the HBV DNA is 
below the level of quantification 
 
Contact the sponsor-designated medical monitor.  
 
Repeat HBV DNA testing as soon as possible.  
 
If HBV DNA is confirmed as positive, then 
permanently discontinue intervention.
LTBI and the participant is a candidate for LTBI 
treatment 
 
Withhold study intervention for at least the first 4 
weeks of LTBI treatment. 
 
If there is no evidence of hepatotoxicity 
treatment intolerance after receiving at least 4 
weeks of appropriate LTBI therapy, per WHO or 
CDC guidelines, then restart study intervention.  
 
The participant must complete appropriate LTBI 
therapy before restarting study intervention. 

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7.2. 
Participant Discontinuation/Withdrawal from the Study  
Discontinuation is expected to be uncommon. 
A participant may withdraw from the study: 
 at any time at 
 own request 
 at the request of 
 designee  
 at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons 
 if enrolled in any other clinical study involving an investigational product, or 
enrolled 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 a therapeutic agent 
that is prohibited by the protocol and 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. 
At the time of discontinuing from the study, if possible, the participant will complete procedures 
for an ED visit as shown in the SoA. If the participant has not already discontinued the study 
intervention, the participant will be permanently discontinued from the study intervention at the 
time of the decision to discontinue the study. 
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, the participant may request destruction of any samples taken and not 
tested, and the investigator must document this in the site study records. 
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 or designee 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.  
Immediate safety concerns should be discussed with the sponsor immediately upon occurrence or 
awareness to determine if the participant should continue or discontinue study intervention. 
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria. 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.  
Joint and safety assessors 
To prevent potential bias from 
approach will be used to evaluate efficacy and safety.  
The same assessor should perform the joint assessments of a participant, whenever possible, 
throughout the study to minimize interobserver variation.   
A back-up independent joint assessor should be identified.  
The independent joint assessors should be a 
 
Any other joint assessor must be trained and competent in 
performing such assessments.
 

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8.1. 
Efficacy Assessments  
Order of assessments 
The patient-reported and clinician-reported efficacy assessments should be completed in the 
following order 
Additional calculations and assessments 
Efficacy measurements also include calculations and assessments by 

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8.1.8. 
Clinician Administered Tender or Swollen Joint Count (TSJC) (68/66)  
The clinician administered TSJC (68/66) will be performed at visits according to the SoA.  
Data will be captured on an electronic tablet collected at site visits.  
The same assessor should perform the joint assessments of a participant, whenever possible, 
throughout the study to minimize interobserver variation. 
Tender Joint Counts  
The number of tender joints will be determined by examination of 68 joints, 34 joints on each 
side of the participant
 

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The 68 joints to be assessed and classified as tender or not tender include  
 2 temporomandibular joints
2 sternoclavicular joints
 2 acromioclavicular joints 
2 shoulder joints
 2 elbow joints 
2 wrist joints
 2 hip joints 
2 knee joints
 2 ankle joints
2 tarsal joints, and
 hands 
o 10 metacarpophalangeal joints  
o 2 interphalangeal joints of the 
thumb  
o 8 proximal interphalangeal 
joints, and  
o 8 distal interphalangeal joints.
feet 
o 10 metatarsophalangeal joints  
o 2 first proximal interphalangeal 
joints, and  
o 8 proximal interphalangeal 
joints. 
The investigator will identify any joints to be excluded from evaluation at each visit. Replaced, 
synovectomized, ankylosed, or arthrodesed joints should be excluded from evaluation.  
Any joint that has had an intra-articular corticosteroid injection within 4 weeks prior to baseline 
should be excluded from evaluation during the study. The locations or a listing of these previous 
procedures should be documented in the participant
 or CRF. 
The joint count will be assessed by scoring aspects of tenderness on pressure and passive 
movement of the particular joint. The participant will be asked for pain sensations on these 
manipulations and watched for spontaneous pain reactions. Any positive response on pressure, 
movement or both will be translated into a single tender-versus nontender dichotomy.  

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The 28 joints examined and assessed as tender or not tender for TJC and as swollen or not 
swollen for SJC include 14 joints on each side 
 al. 1995):  
 2 shoulders 
 2 elbows 
 2 wrists 
 10 metacarpophalangeal joints 
 2 interphalangeal joints of the thumb 
 8 proximal interphalangeal joints, and 
 2 knees. 

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8.2. 
Safety Assessments  
Planned time points for all safety assessments are provided in the SoA. 
8.2.1. 
Physical Examinations  
A complete physical examination will include, at a minimum, assessments of these system 
 cardiovascular 
 respiratory 
 gastrointestinal, and 
 neurological. 
The physical examination will determine if there are symptoms of active TB, including 
measurement of body temperature and assessment of peripheral lymph nodes. 
A complete physical examination may be repeated 
participant presents with physical complaints. 
Investigators should pay special attention to clinical signs related to previous serious illnesses. 
Symptom-directed physical assessments after screening 
These assessments are performed based on participant status and standard of care.  
8.2.2. 
Vital Signs  
For each participant, conduct vital signs measurements according to the SoA (Section 1.3).  
Measure vital signs after the participant has been sitting at least 5 minutes, and before obtaining 
an ECG tracing, or collection of blood samples for laboratory testing. 
8.2.3. 
Electrocardiograms  
For each participant, a single 12-lead digital ECG will be collected according to the SoA. The 
ECG should be recorded before collecting any blood. Participants must be supine for 
approximately 5 to 10 minutes before ECG collection and remain supine but awake during ECG 
collection. 
ECGs 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. 

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ECGs 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 after enrollment, the investigator in conjunction 
with the sponsor will determine if the participant can continue in the study and if any change in 
participant management is needed.  
8.2.4. 
Clinical Safety Laboratory Tests  
See Section 10.2, Appendix 2 for the list of clinical laboratory tests to be performed and the SoA 
for the timing and frequency. 
The investigator must review the laboratory results, document this review, and report any 
clinically relevant changes occurring during the study as an AE. The laboratory results must be 
retained with source documents unless a Source Document Agreement or comparable document 
cites an electronic location that accommodates the expected retention duration.  
 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study or within approximately 50 days 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 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. 
 All protocol-required laboratory assessments, as defined in Section 10.2, Appendix 2, 
must be conducted in accordance with the SoA, standard collection requirements, and 
laboratory manual. 
If laboratory values from non-protocol specified laboratory assessments performed at an 
investigator-designated local laboratory require a change in participant management or are 
considered clinically significant by the investigator, for example, SAE or AE or dose 
modification, then report the information as an AE.  
8.2.5. 
Pregnancy Testing  
Pregnancy testing will occur as outlined in the SoA. 
Details of all pregnancies in female participants and, if indicated, female partners of male 
participants will be collected as outlined in Sections 8.3.1 and 8.3.2. 
8.2.6. 
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. Participants who experience signs of suicidal 
ideation and behavior should undergo a risk assessment. All factors contributing to suicidal 

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ideation and behavior should be evaluated and consideration should be given to discontinuation 
of the study intervention.
Baseline assessment of suicidal ideation and behavior and intervention emergent suicidal 
ideation and behavior will be monitored during the study using the C-SSRS.
C-SSRS 
The 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 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.
Nonleading AE collection should occur prior to the collection of the C-SSRS.
If a suicide-related event is discovered during the C-SSRS but was not captured during the 
nonleading AE collection, sites should not change the AE form, except if a serious AE occurs or 
an AE leading to discontinuation occurs.
If a serious AE occurs, then capture the AE on the AE form and follow the process for reporting 
SAEs.
If an AE leads to discontinuation, then capture the AE on the AE form and record the reason for 
discontinuation.
8.2.7.
Hepatic Monitoring
Close hepatic monitoring
Initiating laboratory and clinical monitoring for abnormal liver laboratory test results
Laboratory tests, including ALT, AST, ALP, TBL, direct bilirubin, gamma-glutamyl transferase,
and creatine kinase, should be repeated within 48 to 72 hours to confirm the abnormality and to 
determine if it is increasing or decreasing, if 1 or more of the conditions in this table occur.
If a participant with baseline results of... 
Develops the following elevations
ALT or AST <1.5x ULN
ALP <1.5x ULN
TBL <1.5x ULN
participants
participants
syndrome)
If the abnormality persists or worsens, the investigator, in consultation with the Lilly-designated 
medical monitor, should initiate clinical and laboratory monitoring, and evaluation for possible 

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causes of abnormal liver tests. At a minimum, this evaluation should include 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, and 
history of alcohol drinking and other substance abuse. 
Frequency of monitoring
Initially, monitoring of symptoms and hepatic biochemical tests should be done 1 to 3 times 
Subsequently, the frequency of monitoring may be lowered to once every 1 to 2 weeks, if the 
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 
1 or more of the conditions in this table occur.
If a participant with baseline results of... 
Develops the following elevations
ALT or AST <1.5x ULN
a, or 
ALP <1.5x ULN
TBL <1.5x ULN
participants
baseline with hepatic signs/symptomsa, or
participants
a Hepatic signs or symptoms are severe fatigue, nausea, vomiting, right upper quadrant abdominal pain, fever, rash, 
and/or eosinophilia >5%.
At a minimum, this evaluation should include 
physical examination and a thorough medical history, as outlined above
tests for 
o
PT-INR 
o
viral hepatitis A, B, C, or E 
o
autoimmune hepatitis, and 
an abdominal imaging study, for example, ultrasound or CT scan. 

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Based on the 
history and initial results, further testing should be considered in 
consultation with the Lilly-designated medical monitor, including tests for  
 hepatitis D virus  
 cytomegalovirus  
 Epstein-Barr virus  
 acetaminophen levels  
 acetaminophen protein adducts  
 urine toxicology screen  
 
 
 blood alcohol levels  
 urinary ethyl glucuronide, and  
 blood phosphatidylethanol.  
condition, the investigator should consider referring the participant for a hepatologist or 
gastroenterologist consultation, magnetic resonance cholangiopancreatography, endoscopic 
retrograde cholangiopancreatography, cardiac echocardiogram, or a liver biopsy.   
Additional hepatic data collection (hepatic safety CRF) in study participants who have 
abnormal liver tests during the study 
Collect additional hepatic safety data in hepatic safety CRFs if a study participant develops a 
hepatic event considered to be an SAE or discontinues study intervention due to a hepatic event 
or meets 1 of the conditions described in this table.  
If a participant with baseline results 
of...  
D
 
ALT <1.5x ULN 
tests
TBL <1.5x ULN 
 
ALP <1.5x ULN 
ALP 
Note: the interval between the 2 consecutive blood tests should be at least 2 days. 
8.2.8. 
Tuberculosis Testing and Monitoring  
Tuberculosis testing at screening Visit 1 
Medical history will determine the lifetime risk factors for TB infection, for TB progression, and 
for symptoms or signs of active TB. 
A physical examination will determine symptoms of active TB, including measurement of 
body temperature and assessment of peripheral lymph nodes. 
A chest x-ray will be interpreted and reported by a radiologist or pulmonologist, as specified in 
the SoA (Section 1.3). Participants do not need to have a chest x-ray at screening if results from a 
chest x-ray within 3 months prior to the study are available. 

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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 either a PPD, TST or IGRA for 
M. tuberculosis. 
PPD TST 
An induration of 5 or more millimeters is considered positive in persons  
 with HIV-infection 
 with a recent contact with a person with TB disease 
 with fibrotic changes on chest radiograph consistent with prior TB 
 with organ transplants, or 
 who are immunosuppressed for other reasons, for example, taking the equivalent of 
>15 mg/day of prednisone for 1 month or longer, or taking tumor necrosis factor -
antagonists. 
An induration of 10 or more millimeters is considered positive in all other potential study 
participants. 
Two-step testing, repeating TST from 1 to 3 weeks after the first TST, is recommended for 
certain participant groups, including persons  
 receiving immunosuppressant treatment 
 with a history of temporally remote increased risk of TB infection, or 
 for whom the first test is negative, as per local public health or professional medical 
society recommendations. 
IGRA for M. tuberculosis 
Ensure that specimen handling, transport, timing, and laboratory procedures meet all 
requirements per package insert. 
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 LTBI therapy, per the WHO or the United States CDC 
guidelines, there is no evidence of hepatotoxicity, defined as 
 times ULN, or 
other treatment intolerance. 
 The participant completes appropriate LTBI therapy. 
Monitoring during the study 
At a minimum, each participant will 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 
 thorough physical examination that includes assessment for signs of active TB, 
including measurement of body temperature and assessment of peripheral lymph 
nodes. 

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8.2.9. 
Hepatitis B Testing and Monitoring  
The following actions should be taken in response to HBV DNA test results during the study. 
I
the test should be repeated within approximately 
2 weeks
 
monitoring may resume according to the study 
schedule 
the participant has 2 or more test results with a value 
 
HBV DNA testing should be performed approximately 
once per month for the remainder of the study and 
referral to a hepatologist is recommended
a result is ob
 
the participant will be permanently discontinued from 
the study intervention (see Section 7.1) and should be 
referred to a hepatologist immediately.
Management of enrolled participants with detectable HBV DNA during the study 
If HBV DNA is detected, study intervention will be temporarily withheld or permanently 
discontinued, as described in Sections 7.1 and 7.1.3, and the participant should receive 
appropriate follow-up medical care.  
8.2.10. 
Hepatitis C Testing and Monitoring  
Initial testing for HCV infection includes testing for antibodies to HCV.  
anti-HCV is positive
HCV RNA testing is required.  
HCV RNA test is negative
the participant is not excluded.
HCV RNA test is positive
the participant is excluded.
Participants who have had HCV infection and have been successfully treated must also have a 
negative HCV RNA test at screening to remain eligible for the study. Successful treatment is 
defined as a sustained virologic response of HCV RNA by PCR negative for at least 24 weeks 
following treatment completion. 
If HCV RNA is detected during the study, the study intervention will be permanently 
discontinued (Section 7.1), and the participant should receive appropriate follow-up medical 
care. 
 
 

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8.3. 
Adverse Events, Serious Adverse Events, and Product Complaints  
The definitions of the following events can be found in Section 10.3, Appendix 3: 
 AEs 
 SAEs, and 
 PCs. 
These events 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 these definitions and remain responsible for following up events 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). 
Care will be taken not to introduce bias when detecting events. Open-ended and non-leading 
verbal questioning of the participant is the preferred method to inquire about event occurrences. 
After the initial report, the investigator is required to proactively follow each participant at 
subsequent visits or contacts. All SAEs and AEs of special interest will be followed until 
resolution, stabilization, the event is otherwise explained, or the participant is lost to follow-up 
(as defined in Section 7.3). For PCs, the investigator is responsible for ensuring that follow-up 
includes any supplemental investigations as indicated to elucidate the nature or causality. Further 
information on follow-up procedures is provided in Section 10.3. 
8.3.1. 
Timing and Mechanism for Collecting Events  
This table describes the timing, deadlines, and mechanism for collecting events. 
Event 
Collection 
Start 
Collection 
Stop 
Timing for Reporting 
to Sponsor or 
Designee 
Mechanism for 
Reporting 
Back-up 
Method of 
Reporting 
Adverse Event 
AE 
Signing of 
the ICF  
Participation 
in study has 
ended 
As soon as possible 
upon site awareness 
AE CRF 
N/A 
Serious Adverse Event 
SAE and SAE 
updates  prior 
to start of study 
intervention and 
deemed 
reasonably 
possibly related 
to study 
procedures 
Signing of 
the ICF 
Start of 
intervention 
Within 24 hours of 
awareness 
SAE CRF  
SAE paper 
form 

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Event 
Collection 
Start 
Collection 
Stop 
Timing for Reporting 
to Sponsor or 
Designee 
Mechanism for 
Reporting 
Back-up 
Method of 
Reporting 
SAE and SAE 
updates  after 
start of study 
intervention 
Start of 
intervention 
Participation 
in study has 
ended 
Within 24 hours of 
awareness 
SAE CRF  
SAE paper 
form 
SAEa  after 
study 
participation has 
ended and the 
investigator 
becomes aware 
After 
study 
participation 
has ended 
N/A 
Promptly 
SAE paper form 
N/A 
Pregnancy 
Pregnancy in 
female 
participants and 
female partners 
of male 
participants 
After the 
start of study 
intervention 
at least 5 
terminal half-
lives after the 
last dose  
Within 24 hours  
(see Section 8.3.2) 
Pregnancy paper 
form 
Pregnancy 
paper form 
Product Complaints 
PC associated 
with an SAE or 
might have led 
to an SAE 
Start of study 
intervention 
End of study 
intervention 
Within 24 hours of 
awareness 
PC form 
N/A 
PC not 
associated with 
an SAE 
Start of study 
intervention 
End of study 
intervention 
Within 1 business day 
of awareness 
PC form 
N/A 
Updated PC 
information 
 
 
As soon as possible 
upon site awareness 
Originally 
completed PC form 
with all changes 
signed and dated by 
the investigator 
N/A 
PC (if 
investigator 
becomes aware) 
Participation 
in study has 
ended 
N/A 
Promptly 
PC form 
 

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Abbreviations: AE = adverse event; CRF = case report form; ICF = informed consent form; N/A = not applicable; 
PC = product complaint; SAE = serious adverse event 
a SAEs should not be reported unless the investigator deems them to be possibly related to study 
treatment or study participation. 
8.3.2. 
Pregnancy  
Collection of pregnancy information 
Male participants with partners who become pregnant 
partner who becomes pregnant while the male participant is in this study. This applies only to 
male participants who receive study intervention. 
After learning of a pregnancy in the female partner of a study participant, the investigator will 
 obtain a consent to release information from the pregnant female partner directly, 
and 
 within 24 hours after obtaining this consent will record pregnancy information on 
the appropriate form and submit it to the sponsor.  
The female partner will also be 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 12 weeks following the estimated delivery date. Any termination of the 
pregnancy will be reported regardless of gestational age, 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 12 weeks 
beyond the estimated delivery date. Any termination of pregnancy will be reported, regardless of 
gestational age, 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 <20 weeks gestational age) or still birth (occurring at 
 
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 8.3.1. While the 
investigator is not obligated to actively seek this information in former study participants, they 
may learn of an SAE through spontaneous reporting. 

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Any female participant who becomes pregnant while participating in the study will discontinue 
study intervention. If the participant is discontinued from the study, follow the standard 
discontinuation process and continue directly to the follow-up phase. The follow-up on the 
pregnancy outcome should continue independent of intervention or study discontinuation.   

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8.4. 
Pharmacokinetics  
8.5. 
Pharmacodynamics  

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Immunogenicity will be assessed by a validated assay designed to detect and characterize ADA 
in the presence of peresolimab at a laboratory approved by the sponsor. 
Antidrug antibodies may be further characterized for their ability to neutralize the activity of 
peresolimab. 
Instructions for the collection and handling of blood samples will be provided by the sponsor. 
Treatment-emergent ADAs are defined in Section 9.3.7. 
Sample retention is described in Section 10.1.12. 
8.9. 
Health Economics  
Health economics or medical resource utilization and health economics parameters are not 
evaluated in this study. 

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9. 
Statistical Considerations  
The SAP will be finalized prior to unblinding, and 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 most important endpoints, including primary and key 
secondary endpoints. 
9.1. 
Statistical Hypotheses  
9.1.1. 
Multiplicity Adjustment  
Adjustment for multiple comparisons will not be employed in the analysis for this study. 
9.2. 
Analyses Sets  
9.3. 
Statistical Analyses  
9.3.1. General Considerations  
Statistical analysis of this study will be the responsibility of sponsor or its designee. A detailed 
SAP describing the statistical methodologies will be developed by the sponsor or its designee. 
Handling of missing, unused, and spurious data are addressed prospectively in the overall 
statistical methods described in the protocol and in the SAP, where appropriate. Adjustments to 
the planned analyses are described in the final CSR. 

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Efficacy analyses will be conducted on the mITT population, unless otherwise specified. Safety 
analyses will be conducted on the safety population. Placebo participants will be pooled for 
  
This study includes  
 Period I - screening period 
 Period II - 
 double-blind, placebo-controlled treatment period 
 Period III -
 double-blind treatment period, and 
 Period IV - post-treatment follow-up. 
Efficacy and safety data will be analyzed and summarized by these treatment periods if 
appropriate 
 Period II - double-blind, placebo-controlled treatment period 
 
 Period III  double-blind treatment period. 
 
  
o 
 
o 
Baseline for the Treatment Period is defined as the last non-missing assessment on or prior to the 
date of the 
 of study treatment. Any assessment collected after the 
 is 
defined as post-baseline for the Treatment Period. Change from baseline will be calculated as the 
visit value of interest minus the baseline value. If a baseline value or the value at the visit is 
missing for a particular variable, then the change from baseline is defined as missing. 
Summary statistics for continuous variables may include mean, standard deviation, median, and 
minimum and maximum values.  
Categorical variables will be presented as counts and percentages. Variables will be analyzed in 
the original scale on which they are measured, unless otherwise specified.  
The parametric approach will be employed by default for statistical analysis except when 
nonparametric analysis, such as by a rank-based method, is more fitting.  
Additional exploratory analyses of the data will be conducted as deemed appropriate.  
Dichotomous responder endpoints including the primary endpoint will be analyzed using a 
The odd ratio and p-value based on odd ratio will be reported. 
 
of mean difference will also be reported without being adjusted by covariates. Missing data will 
be imputed using the nonresponder imputation method.  
Treatment comparisons of continuous efficacy endpoints with multiple postbaseline timepoints 
will be analyzed using 
will include  
 treatment  
 stratification factors  
 baseline value  
 visit, and treatment-by-visit interaction in the model as fixed factors, and  
 participant as a random factor.  

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The covariance structure to model the within-participant errors will be unstructured. If the 
unstructured covariance matrix results in a lack of convergence, the heterogeneous Toeplitz 
covariance structure, followed by the 
 will be 
used.  
The
 will be used to estimate the denominator degrees of freedom. Type 
III sums of squares for the LS means will be used for the statistical comparison. The 95% CI will 
also be reported. Missing data will be handled with the missing at random assumption. No 
additional imputation methods will be applied to the 
 
Where appropriate, treatment comparisons of continuous efficacy endpoints will be analyzed 
using 
 modeled with treatment group, stratification factors, and baseline value as 
covariates. Type III sums of squares for the LS means will be used for statistical comparison 
between treatment groups. The LS mean difference, standard error, p-value, and
 unless 
otherwise specified, will also be reported. Missing data imputation method for the 
 
model will the last observation carried forward.  
Dose response modeling will be performed on the primary objective to assist in dose selection 
decisions. More details will be provided in the SAP. 
Any change to the data analysis methods or imputation methods described in the protocol will 
require an amendment only if it changes 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. Additional exploratory analyses of the 
data may be conducted as deemed appropriate.  
9.3.2. 
Primary Endpoint/Estimand Analysis  
9.3.3. 
Secondary Endpoints Analysis  
The secondary efficacy and health outcome endpoints at 
 will use the statistical analysis 
methods described in Section 9.3.1. 
For the secondary efficacy endpoints at 
 summary statistics will be provided as 
described in Section 9.3.1.  
Additional details will be provided in the SAP. 
9.3.4. 
Exploratory Analysis  
Exploratory analyses will be further described in the SAP that is finalized before database lock. 

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9.3.5. 
Safety Analyses  
Safety analyses will be assessed by evaluating exposure, AEs, laboratory analytes, vital signs, 
and adverse events of special interests.   
Duration of exposure to therapy during the treatment periods will be calculated for each 
participant and summarized by treatment group. 
The AEs will be coded according to the MedDRA and summarized by system organ class, 
preferred term, severity, and relationship to the study intervention. All AEs, including pre-
existing conditions, will be listed by participant, visit, preferred term, treatment group, severity, 
and relationship to the treatment. 
A 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 reported TEAEs, TEAEs by maximum severity, 
deaths, SAEs, TEAEs related to study intervention, discontinuations from the treatment due to an 
AE, and adverse events of special interests will be summarized. TEAEs (all, by maximum 
severity), SAEs including deaths, and AEs that lead to treatment discontinuation will be 
summarized and analyzed by MedDRA system organ class and preferred term.  
Treatment-related TEAEs (TEAEs related to study intervention) are defined as events that are 
indicated by the investigator on the CRF to be related to treatment. 
Adverse events of special interest or special safety topics will be identified by a standardized 
MedDRA query or a Lilly-defined MedDRA preferred term listing. 
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.  
9.3.6. 
Pharmacokinetic Analyses  
Peresolimab concentrations will be illustrated graphically and summarized descriptively.  
A model-based approach using nonlinear mixed effects modeling or other appropriate software 
may be conducted. If appropriate, data from this study may be combined with data from other 
studies in model-based analyses. The impact of extrinsic and intrinsic patient factors, such as 
age, weight, and sex, on PK may be examined as needed. Estimates of PK model parameters and 
covariate effects will be reported. If ADA titers are detected from immunogenicity testing, then 
the impact of immunogenicity titers on peresolimab PK parameters may also be examined.  
If data warrant, analyses of exposure-response relationships may be conducted using both 
exploratory graphical approaches and model-based approaches.  
Exploratory graphical analysis approaches for categorical clinical endpoints may consist of 
graphs showing the percentage of participants that achieve the clinical endpoint at different 

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percentiles, for example, quartiles, of exposure of peresolimab at 
 Measures of 
exposure may include population PK estimated average concentrations at steady state (Cavg, ss) or 
observed trough concentrations at the time of the clinical endpoint.  
Model-based analyses of the categorical clinical endpoints may use population exposure-
response logistic regression models, where maximum effect (Emax) or other model structures may 
be used to relate exposure to the probability of achieving the endpoint. These models may be 
used to evaluate participant factors that may impact the relationship between exposure and the 
probability of achieving the endpoint. Longitudinal exposure-response models for ACR scores or 
response rates may be developed, which relate the time course and magnitude of peresolimab 
exposure to the time course and magnitude of ACR response. 
Exploratory PK/PD analyses may be conducted to evaluate the relationship between peresolimab 
exposure and select measures of response, such as, receptor occupancy. Additional analyses may 
be conducted if they are deemed appropriate.  
Further details on PK/PD analyses will be provided in the PK/PD analysis plan. 
9.3.7. 
Evaluation of Immunogenicity  
The frequency and percentage of patients with preexisting ADA and with treatment-emergent 
ADA to peresolimab may be tabulated. 
Treatment-emergent ADAs are defined as participants 
For the treatment-emergent ADA + patients, the distribution of maximum titers will be described 
by peresolimab dose. The frequency of neutralizing antibodies to peresolimab may be tabulated 
in treatment-emergent ADA-positive patients. 
The relationship between the presence of antibodies and the PK parameters and PD response 
including safety and efficacy to peresolimab may be assessed. Additional details may be 
provided in the SAP. 
9.3.8. 
Other Analyses  
9.3.8.1. 
Subgroup Analyses  
Summary of subgroups will be provided. Subgroup analyses may be conducted for the primary 
endpoint ACR20 at 
 using the mITT population. 
Subgroups that may be evaluated include previous RA therapy population, gender, race, 
geographic region, and disease duration.  
Detailed description of the summaries and/or statistical analyses are provided in the SAP. 
9.3.8.2. 
Supplemental Analyses  
Supplemental analyses may be performed as deemed necessary. 

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9.4. 
Interim Analysis   
Analyses for the primary database lock will be conducted as described in Section 9.3, when all 
participants have completed the 
 visit or have discontinued study intervention.  
Potential prespecified interim analyses  
Any of the predefined interim analyses may be not conducted at the discretion of the sponsor.   
 
An interim analysis prior to the analysis of the primary database lock may be conducted when 
approximately 
of participants have completed 
 or have discontinued 
intervention, for the purpose of supporting planning activities associated with the peresolimab 
clinical development program. The analysis may assess safety, PK, or efficacy measures.  No 
adjustments to study conduct and no adjustment of type I error will be performed. 
An interim analysis prior to the analysis of the primary database lock may be conducted to 
review the safety and efficacy data when approximately 
 of participants have 
completed 
 or have discontinued intervention, for the purpose of supporting planning 
activities associated the peresolimab clinical development program. The analysis may assess 
safety, PK, and/or efficacy measures.  No adjustments to study conduct and no adjustment of 
type I error will be performed. 
 
An interim analysis after the primary database lock may be conducted to review the safety and 
efficacy data when all participants have completed 
 or have discontinued intervention, 
for the purpose of supporting planning activities associated the peresolimab clinical development 
program. The analysis may assess safety, PK, and/or efficacy measures.  No adjustments to study 
conduct and no adjustment of type I error will be performed. 
 
An interim analysis after the primary database lock may be conducted to review the safety and 
efficacy data when 
 of participants have completed 
 or have discontinued 
intervention, for the purpose of supporting planning activities associated the peresolimab clinical 
development program. The analysis may assess safety, PK, and/or efficacy measures.  No 
adjustments to study conduct and no adjustment of type I error will be performed. 
Assessment of unblinded interim data  
Assessment of unblinded interim data will be conducted by an IAC with a limited number of 
prespecified team members who do not have direct site contact or data entry or validation 
responsibilities (see Section 10.1.5). Only the IAC will be authorized to evaluate unblinded 
interim efficacy and safety analyses.   
Prior to the interim or final database lock, a limited number of preidentified individuals may gain 
access to the unblinded data to initiate the final population PK/PD model development processes 
for interim or final analyses.  
To minimize bias, the SAP and PK/PD analysis plan will be finalized and approved before any 
unblinding.  

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Unblinding details will be specified in a separate unblinding document. Information that may 
unblind the study during the analyses will not be reported to study sites or to the blinded study 
team until the prespecified milestone for unblinding of study results. Study sites will receive 
information about interim results only if they need to know for the safety of their participants.  
9.5. 
Sample Size Determination  

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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 
International Ethical Guidelines 
 Applicable ICH GCP Guidelines, and 
 Applicable laws and regulations. 
The protocol, protocol amendments, 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. 
Protocols and any substantial amendments to the protocol will require health authority approval 
prior to initiation except for changes necessary to eliminate an immediate hazard to study 
participants. 
The investigator will be responsible for the following: 
 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 
 Providing oversight of study conduct for participants under their 
responsibility and adherence to requirements of 21 Code of Federal 
Regulations, ICH guidelines, the IRB/IEC, European regulation 536/2014 
for clinical studies (if applicable), and all other applicable local 
regulations, and 
 Reporting to the sponsor or designee significant issues related to 
participant safety, participant rights, or data integrity. 
Investigator sites are compensated for participation in the study as detailed in the clinical trial 
agreement. 
10.1.2. 
Financial Disclosure  
Investigators and sub-investigators 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 study and for 1 year after 
completion of the study. 
10.1.3. 
Informed Consent Process  
The investigator or 
 representative will explain the nature of the study, 
including the risks and benefits, to the participant and answer all questions regarding the study. 
Participants must be informed that their participation is voluntary. Participants will be required to 
sign a statement of informed consent that meets the requirements of 21 Code of Federal 
Regulations 50, local regulations, ICH guidelines, privacy and data protection requirements, 
where applicable, and the IRB/IEC or study center. 
The medical record must include a statement that written informed consent was obtained before 
the participant was entered in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
Participants must be reconsented to the most current version of the ICF(s) during their 
participation in the study. 
A copy of the ICF(s) must be provided to the participant and is kept on file. 
Participants who are rescreened are required to sign a new ICF. 
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 
 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 their data to be used as 
described in the informed consent.  
The participant must be informed that their 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. 
The sponsor has processes in place to ensure data protection, information security and data 
integrity. These processes include appropriate contingency plan(s) for appropriate and timely 
response in the event of a data security breach. 
10.1.5. 
Committees Structure  
10.1.5.1. Adjudication Committee  
An independent committee with membership external to the sponsor will be responsible for 
adjudication of 
in a blinded fashion. 

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10.1.5.2. Internal Assessment Committee  
An IAC will review the interim efficacy and safety data in an unblinded fashion.  
The IAC will consist of a limited number of prespecified members not part of the blinded study 
team who do not have direct site contact or data entry or validation responsibilities. Details about 
IAC membership, purpose, responsibilities, and operation will be described in an IAC charter, 
which will be approved prior to the first unblinding. 
Participant safety will be continuously monitored by the 
 safety review 
team, which includes safety signal detection at any time during the study. 
All safety data collected will be summarized and reviewed by 
review committee for agreement of next steps. 
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. 
The summary of results will be posted within the time frame specified by local law or regulation. 
If the study remains ongoing in some countries and a statistical analysis of an incomplete dataset 
would result in analyses lacking scientific rigor, for example, underpowered, or compromise the 
integrity of the overall analyses, for example, study not yet unblinded, the summary of results 
will be submitted within 1 year after the end of the study globally or as soon as available, 
whichever is earlier. 
Data 
The sponsor provides access to all individual participant data collected during the study, after 
anonymization, with the exception of PK or genetic data. 
Data are available to request 6 months after the indication studied has been approved in the US 
and EU and after primary publication acceptance, whichever is later. No expiration date of data 
requests is currently set once data are made available. 
Access is provided after a proposal has been approved by an independent review committee 
identified for this purpose and after receipt of a signed data sharing agreement. 
Data and documents, including the study protocol, SAP, CSR, and blank or annotated CRFs, will 
be provided in a secure data sharing environment for up to 2 years per proposal. 
For details on submitting a request, see the instructions provided at www.vivli.org. 
10.1.7. 
Data Quality Assurance  
All participant data relating to the study will be recorded on printed or electronic CRFs 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. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 

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The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
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 transcribed 
into the CRF 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 and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for the time period outlined in the clinical trial agreement 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, 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 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 will be used in this study for the collection of CRF data. The 
investigator maintains a separate source for the data entered by the investigator or designee into 
the sponsor-provided electronic data capture 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 CRF. 
Additionally, electronic Clinical Outcome Assessment data (participant-focused outcome 
instrument) will be directly recorded by the participant and investigator site personnel, into an 
instrument, for example a tablet. The electronic Clinical Outcome Assessment data will serve as 
the source documentation and the investigator does not maintain a separate written or electronic 
record of these data. 
Data collected via the sponsor-provided data capture system(s) 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 system(s). Prior to decommissioning, the investigator will receive or access 
an archival copy of pertinent data for retention. 

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Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
reports will be provided to the investigator for review 
and retention. Data will subsequently be transferred from the central vendor to the sponsor data 
warehouse. 
Data from complaint forms submitted to the sponsor will be encoded and stored in the global PC 
management system. 
10.1.8. 
Source Documents  
Source documents provide evidence for the existence of the participant and substantiate the 
 
Data reported on or entered in the CRF and 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. 
Definition of what constitutes source data can be found in Section 10.1.7. 
10.1.9. 
Study and Site Start and Closure  
First act of recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the first site open. 
Study or site termination 
The sponsor 
designee reserves the right to close the study site or terminate the study 
at any time for any reason at the sole discretion of the sponsor. 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 there is reasonable cause 
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 
For study termination: 
 Discontinuation of further study intervention development. 
For site termination: 
 Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
 Inadequate recruitment (evaluated after a reasonable amount of time) of 
participants by the investigator 
 Total number of participants included earlier than expected. 

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If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IRB/IEC, the regulatory authorities, and any contract research organization(s) 
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 should assure 
appropriate participant therapy and/or follow-up. 
10.1.10. 
Publication Policy  
, the results of this study will be submitted 
for publication by a peer-reviewed journal. 
10.1.11. 
Investigator Information  
Researchers with appropriate education, training, and experience, as determined by the sponsor, 
will participate as investigators in this clinical study. 
10.1.12. 
Sample Retention  
Sample retention enables use of new technologies, response to regulatory questions, and 
investigation of variable response that may not be observed until later in the development of 
peresolimab or after peresolimab become(s) commercially available for rheumatoid arthritis.  
 
 

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10.2. 
Appendix 2: Clinical Laboratory Tests  
The tests detailed in the table below will be performed by the Lilly-designated laboratory or by 
the local laboratory as specified in the table below. 
Local laboratory results are only required if the central laboratory results are not available in 
time for either study intervention administration and/or response evaluation. If a local sample is 
required, it is important that the sample for central analysis is obtained at the same time. 
Additionally, if the local laboratory results are used to make either a study intervention decision 
or response evaluation, the results must be recorded. 
In circumstances where the sponsor approves local laboratory testing in lieu of central laboratory 
testing, the local laboratory must be qualified in accordance with applicable local regulations. 
Protocol-specific requirements for inclusion or exclusion of participants are detailed in Section 5 
of the protocol. 
Additional tests may be performed at any time during the study as determined necessary by the 
investigator or required by local regulations. 
Investigators must document their review of the laboratory safety results.  
Laboratory results that could unblind the study will not be reported to investigative sites or other 
blinded personnel until the study has been unblinded. 
 
 

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10.3. 
Appendix 3: Adverse Events and Serious Adverse Events: Definitions 
and Procedures for Recording, Evaluating, Follow-up, and 
Reporting  
10.3.1. 
Definition of AE  
AE Definition 
 An AE is any untoward medical occurrence in a participant administered a 
pharmaceutical product and which does not necessarily have a causal relationship with 
the study intervention. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a medicinal (investigational) product, whether or 
not related to the medicinal (investigational) product.  
 
Events Meeting the AE Definition 
 Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (for example, ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (that is, not related 
to progression of underlying disease). 
 Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
 New condition detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study. 
 Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
 Medication error, misuse, or abuse of IMP, including signs, symptoms, or clinical 
sequelae.  
 Lack of efficacy or failure of expected pharmacological action per se will not be 
reported as an AE or SAE. Such instances will be captured in the efficacy assessments. 
However, the signs, symptoms, and/or clinical sequelae resulting from lack of efficacy 
will be reported as AE or SAE if they fulfill the definition of an AE or SAE.  
 
Events NOT Meeting the AE Definition 
 Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
 
 The disease or disorder being studied or expected progression, signs, or symptoms of 
the disease or disorder being studied, unless more severe than expected for the 
 

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 Medical or surgical procedure (for example, endoscopy, appendectomy): the condition 
that leads to the procedure is the AE. 
 Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
 Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.   
10.3.2. 
Definition of SAE  
 
An SAE is defined as any untoward medical occurrence that, at any dose, meets 1 or 
more of the criteria listed: 
a. Results in death 
b. Is life-threatening 
The term life-threatening in the definition of serious refers to an event in which the participant 
was at risk of death at the time of the event. It does not refer to an event, which hypothetically 
might have caused death, if it were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
 In general, hospitalization signifies that the participant has been admitted to hospital or 
emergency ward (usually involving at least an overnight stay) for observation and/or 
treatment that would not have 
setting. Complications that occur during hospitalization are AEs. If a complication 
prolongs hospitalization or fulfills any other serious criteria, the event is serious. When 
in doubt as to whether hospitalization occurred or was necessary, the AE should be 
considered serious. 
 Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE. 
d. Results in persistent disability or incapacity 
 Th
normal life functions. 
 This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (for example, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
e. 
Is a congenital anomaly or birth defect 
 Abnormal pregnancy outcomes (for example, spontaneous abortion, fetal death, 
stillbirth, congenital anomalies, ectopic pregnancy) are considered SAEs. 

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f. 
Other situations 
 Medical or scientific judgment should be exercised by the investigator in deciding 
whether SAE reporting is appropriate in other situations such as important medical 
events that may not be immediately life-threatening or result in death or hospitalization 
but may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events should 
usually be considered serious. 
 
Examples of such events include invasive or malignant cancers, intensive treatment in 
an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency or 
drug abuse.  
 
10.3.3. 
Definition of Product Complaints  
Product Complaint 
 A PC is any written, electronic, or oral communication that alleges deficiencies related 
to the identity, quality, durability, reliability, safety, effectiveness or performance of a 
study intervention. When the ability to use the study intervention safely is impacted, 
the following are also PCs: 
o Deficiencies in labeling information, and 
o Use errors for device or drug-device combination products due to ergonomic 
design elements of the product. 
 PCs related to study interventions used in clinical studies are collected in order to 
ensure the safety of participants, monitor quality, and to facilitate process and product 
improvements. 
 Investigators will instruct participants to contact the site as soon as possible if he or she 
has a PC or problem with the study intervention so that the situation can be assessed. 
 An event may meet the definition of both a PC and an AE/SAE. In such cases, it 
should be reported as both a PC and as an AE/SAE. 
 
10.3.4. 
Recording and Follow-Up of AE and/or SAE and Product Complaints  
AE, SAE, and PC Recording 
 When an AE/SAE/PC occurs, it is the responsibility of the investigator to review all 
documentation (for example, hospital progress notes, laboratory reports, and 
diagnostics reports) related to the event. 
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practice. AE/SAE information is reported on the appropriate CRF page and PC 
information is reported on the Product Complaint Form. 
Note: An event may meet the definition of both a PC and an AE/SAE. In such cases, it 
should be reported as both a PC and as an AE/SAE. 
 It is not 
records to sponsor or designee in lieu of completion of the CRF page for AE/SAE and 
the Product Complaint Form for PCs. 
 There may be instances when copies of medical records for certain cases are requested 
by sponsor or designee. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to sponsor or designee. 
 The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs or symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported during 
the study and assign it to one of the following categories: 
 Mild: A type of AE that is usually transient and may require only minimal treatment or 
therapeutic intervention. The event does not generally interfere with usual activities of 
daily living. 
 Moderate: A type of AE that is usually alleviated with additional specific therapeutic 
intervention. The event interferes with usual activities of daily living, causing 
discomfort but poses no significant or permanent risk of harm to the research 
participant. 
 Severe: A type of AE that interrupts usual activities of daily living, or significantly 
affects clinical status, or may require intensive therapeutic intervention. An AE that is 
assessed as severe should not be confused with a SAE. Severe is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as severe. 
An event is defined as serious  when it meets at least one of the predefined outcomes 
as described in the definition of an SAE, NOT when it is rated as severe.  
 
Assessment of Causality 
 The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. The investigator will use clinical judgment to 
determine the relationship. 
 A reasonable possibility  of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out. 

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 Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
 The investigator will also consult the IB for peresolimab in their assessment. 
 For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
 There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to sponsor or designee. However, it 
is very important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to sponsor or designee. 
 The investigator may change their opinion of causality in light of follow-up 
information and send a SAE follow-up report with the updated causality assessment. 
 The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of AEs and SAEs 
 The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by sponsor or 
designee to elucidate the nature and/or causality of the AE or SAE as fully as possible. 
This may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals. 
 If a participant dies during participation in the study or during a recognized follow-up 
period, the investigator will provide sponsor or designee with a copy of any 
post-mortem findings including histopathology. 
10.3.5. 
Reporting of SAEs  
SAE Reporting via an Electronic Data Collection Tool 
 The primary mechanism for reporting an SAE will be the electronic data collection 
tool. 
 If the electronic system is unavailable, then the site will use the SAE paper form (see 
next section) in order to report the event within 24 hours. 
 The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
 After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data. 
 If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a SAE paper form (see next 
section) or to the sponsor by telephone. 
 Contacts for SAE reporting can be found on the SAE paper form. 

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SAE Reporting via Paper Form 
 Facsimile transmission of the SAE paper form is the preferred method to transmit this 
information to the sponsor. 
 Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time frames. 
 Contacts for SAE reporting can be found on the SAE paper form. 
10.3.6. 
Regulatory Reporting Requirements  
SAE Regulatory Reporting 
Prompt notification by the investigator to the sponsor of a SAE is essential so 
that legal obligations and ethical responsibilities toward 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, 
IRB/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. 
 Consistent with the EU Clinical Trial Regulation (536/2014), the sponsor has 
procedures that will be followed for the identification, recording, and expedited 
reporting of SUSARs. 
will evaluate the data, including confirmation of relatedness and assessment of 
expectedness. The sponsor will submit any qualifying reports to the 
EudraVigilance database within the required time frame. Investigator safety 
reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and will be forwarded to investigators as 
necessary. 
 
 

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10.4. 
Appendix 4: Contraceptive and Barrier Guidance  
10.4.1. 
Definitions  
Word/Phrase 
Definition 
Women of 
childbearing 
potential 
(WOCBP) 
Adult females are considered WOCBP unless they meet the definition of 
WNOCBP.  
Women not of 
childbearing 
potential 
(WNOCBP) 
Females are considered WNOCBP if they 
 have a congenital anomaly such as Müllerian agenesis  
 are infertile due to surgical sterilization, or  
 are postmenopausal. 
Examples of surgical sterilization include total hysterectomy, bilateral 
salpingo-oophorectomy, bilateral salpingectomy, or bilateral oophorectomy.
Postmenopausal 
state 
The postmenopausal state is defined as a woman: 
 at any age at least 6 weeks post-surgical bilateral oophorectomy 
with or without hysterectomy, confirmed by operative note; or  
 aged at least 40 years and up to 55 years with an intact uterus, not 
on hormone therapya, who has had cessation of menses for at least 
12 consecutive months without an alternative medical cause, AND 
with a follicle-stimulating hormone >40 mIU/mL; or  
 55 years or older not on hormone therapy, who has had at least 12 
months of spontaneous amenorrhea, or 
 aged at least 55 years with a diagnosis of menopause prior to 
starting hormone replacement therapy. 
a Women should not be taking medications during amenorrhea such as oral 
contraceptives, hormones, gonadotropin-releasing hormone, anti-estrogens, 
selective estrogen receptor modulators, or chemotherapy that could induce 
transient amenorrhea. 
 
 
 

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10.4.2. 
Contraception Guidance  
Women 
WOCBP who are completely abstinent as their preferred and usual lifestyle, or in a same-sex 
relationship as their preferred and usual lifestyle need to adhere to the rules in this table. 
 
 
agree to either 
remain abstinent or 
stay in a same-sex 
relationship without 
sexual relationships 
with males 
 use periodic abstinence methods 
o calendar  
o ovulation  
o symptothermal, or 
o post-ovulation  
 declare abstinence just for the duration of the study, or 
 use the withdrawal method. 
 
WOCBP who are NOT completely abstinent as their preferred and usual lifestyle, or NOT in a 
same-sex relationship as their preferred and usual lifestyle, must adhere to the rules in this table. 
Topic 
Condition 
Pregnancy testing 
Have a negative serum test result at screening followed by a negative 
urine result within 24 hours prior to first dose of study intervention. See 
the SoA for subsequent pregnancy testing requirements. 
Contraception 
Agree to use 2 highly effective method of contraception, where at least 1 
form must be highly effective. 
These forms of contraception must be used during the study and after the 
study for at least 
 after the last dose of the study intervention. 
 
 
 

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Men 
The table below describes contraception guidance for all men. 
Topic 
Guidance 
All men  
should refrain from sperm donation for the 
duration of the study and for 
 after 
the last dose of study intervention.
Contraception for men with partners of 
childbearing potential  
either remain abstinent, if this is their 
preferred and usual lifestyle, or 
 must use condoms and one additional 
highly effective method of 
contraception during intercourse for 
the duration of the study, and  
 for 
 after the last dose of 
study intervention.
Contraception for men in exclusively same 
sex relationships, as their preferred and usual 
lifestyle 
Are not required to use contraception. 
 
 
 

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Examples of different forms of contraception: 
Methods 
Examples 
Highly effective 
contraception (less than 
1% failure rate) 
female sterilization
 combination oral contraceptive pill 
 progestin-only contraceptive pill (mini-pill) 
 implanted contraceptives 
 injectable contraceptives 
 contraceptive patch (only women <198 pounds or 90 kg) 
 total abstinence 
 vasectomy (if only sexual partner) 
 fallopian tube implants (if confirmed by hysterosalpingogram) 
 combined contraceptive vaginal ring, or  
intrauterine devices
Effective contraception 
male or female condoms with spermicide 
 diaphragms with spermicide or cervical sponges 
 barrier method with use of a spermicide 
o condom with spermicide 
o diaphragm with spermicide, or 
o female condom with spermicide 
Note: The barrier method must include use of a spermicide (that is, 
condom with spermicide, diaphragm with spermicide, or female 
condom with spermicide) to be considered effective. 
Ineffective forms of 
contraception whether 
used alone or in any 
combination 
spermicide alone 
 periodic abstinence 
 fertility awareness (calendar method, temperature method, 
cervical mucus, or symptothermal) 
 withdrawal 
 postcoital douche, or 
lactational amenorrhea
 
 
 

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10.5. 
Appendix 5: Genetics  
Use/Analysis of DNA 
Genetic 
severity and progression of disease. Variable response to study intervention may be due to 
genetic determinants that impact drug absorption, distribution, metabolism, and excretion; 
mechanism of action of the drug; disease etiology; and/or molecular subtype of the disease being 
treated. Therefore, where local regulations and IRB/IEC allow, a blood sample will be collected 
for DNA analysis from consenting participants. 
DNA samples will be used for research related to peresolimab or RA and related diseases. They 
may also be used to develop tests or assays including diagnostic tests related to peresolimab and 
RA. Genetic research may consist of the analysis of one or more candidate genes or the analysis 
of genetic markers throughout the genome, as appropriate. 
DNA samples will be analyzed for genetic variants thought to play a role in RA. Additional 
analyses may be conducted if it is hypothesized that this may help further understand the clinical 
data. 
The samples may be analyzed as part of a multi-study assessment of genetic factors involved in 
the response to peresolimab or study interventions of this class to understand study disease or 
related conditions. 
The results of genetic analyses may be reported in the CSR or in a separate study summary. 
The sponsor will store the DNA samples in a secure storage space with adequate measures to 
protect confidentiality. 
The samples will be retained while research on peresolimab or study interventions of this class, 
or RA continues but no longer than 15 years or other period as per local requirements. 
 
 

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10.6. 
Appendix 6: Liver Safety: Suggested Actions and Follow-up 
Assessments  
Hepatic Evaluation Testing 
See Section 8.2.7 for guidance on appropriate test selection. 
The Lilly-designated central laboratory should complete the analysis of all selected testing 
except for testing listed in the investigator-designated local laboratory table. The central 
laboratory will report results if a validated test or calculation is available. 
In circumstances where required in accordance with local regulations, local laboratory testing 
may be performed in lieu of Lilly-designated central laboratory testing (in the table below). 
Local testing may be performed in addition to central testing when necessary for immediate 
participant management.  
The local laboratory must be qualified in accordance with applicable local regulations. 
Tests assayed by Lilly-designated central laboratory 
Hepatic Hematology Panel 
Hepatitis A virus (HAV) testing:
  Hemoglobin 
   HAV total antibody
  Hematocrit 
   HAV IgM antibody 
  Erythrocytes (RBCs - red blood cells)
Hepatitis B virus (HBV) testing:
  Leukocytes (WBCs - white blood cells)
   Hepatitis B surface antigen (HBsAg)
  Differential:
   Hepatitis B surface antibody (HBsAb)
      Neutrophils, segmented
   Hepatitis B core total antibody (HBcAb)
      Lymphocytes
   Hepatitis B core IgM antibody
      Monocytes
   HBV DNA a
      Basophils
Hepatitis C virus (HCV) testing:
      Eosinophils 
   HCV antibody
  Platelets
   HCV RNA a
  Cell morphology (RBC and WBC)
Hepatitis D virus (HDV) testing:
Hepatic Clinical Chemistry Panel
   HDV antibody
  Total bilirubin
Hepatitis E virus (HEV) testing:
  Direct bilirubin 
   HEV IgG antibody
  Alkaline phosphatase (ALP)
   HEV IgM antibody
  Alanine aminotransferase (ALT)
   HEV RNA a
  Aspartate aminotransferase (AST)
Anti-nuclear antibody (ANA)
  Gamma-glutamyl transferase (GGT)
Anti-smooth muscle antibody (ASMA) b
  Creatine kinase (CK)
Anti-actin antibody c
Hepatic Coagulation Panel
Immunoglobulin IgA (quantitative)
  Prothrombin time, INR (PT-INR)
Immunoglobulin IgG (quantitative)
Urine Chemistry
Immunoglobulin IgM (quantitative)
  Drug screen
Epstein-Barr virus (EBV) testing:
Haptoglobin
   EBV antibody
a 
Reflex/confirmation dependent on regulatory requirements, testing availability, or both. 
b 
Not required if anti-actin antibody is tested. 
c 
Not required if anti-smooth muscle antibody (ASMA) is tested. 
 

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Tests assayed ONLY by investigator-designated local laboratory 
Acetaminophen
Cytomegalovirus (CMV) testing:
Acetaminophen protein adducts 
   CMV antibody
Alkaline phosphatase isoenzymes
   CMV DNA a
Ceruloplasmin
Herpes simplex virus (HSV) testing:
Copper
   HSV (Type 1 and 2) antibody
Ethyl alcohol (EtOH) 
   HSV (Type 1 and 2) DNA a
Phosphatidylethanol (PEth) 
Liver kidney microsomal type 1 (LKM-1) antibody
Urine Chemistry
Microbiology 
   Ethyl glucuronide (EtG)
Culture:
Epstein-Barr virus (EBV) testing: 
   Blood
   EBV DNA a
   Urine
a 
Reflex/confirmation dependent on regulatory requirements, testing availability, or both. 
 
 

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10.7. 
Appendix 7: Examples of Infections Considered Possibly 
Opportunistic  
This table is provided to aid the investigator in recognizing infections that may be considered 
opportunistic. This list is not exhaustive. 
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, and 
 Fusarium 
Parasitic 
Leishmaniasis (visceral only)
Strongyloidiasis (hyperinfection syndrome or disseminated disease)
Microsporidiosis 
Toxoplasmosis
Trypanosoma cruzi infection (Chaga s disease progression) (disseminated disease only)
Cryptosporidiosis (chronic disease only)
Source: Adapted from Winthrop et al. (2015).   
 

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10.8. 
Appendix 8: Provisions for Changes in Study Conduct During 
Exceptional Circumstances  
Implementation of this appendix 
The changes to procedures described in this appendix are temporary measures intended to be 
used only during specific time periods as directed by the sponsor in partnership with the 
investigator. 
Exceptional circumstances 
Exceptional circumstances are rare events that may cause disruptions to the conduct of the study. 
Examples include pandemics or natural disasters. These disruptions may limit the ability of the 
investigators, participants, or both to attend on-site visits or to conduct planned study procedures. 
Implementing changes under exceptional circumstances 
implement changes if permitted by local regulations.  
After approval by local Ethical Review Boards, regulatory bodies and any other relevant local 
authorities, implementation of these exceptional circumstance changes will not typically require 
additional notification to these groups, unless they have specific requirements in which 
notification is required, for example, upon implementation and suspension of changes. All 
approvals and notifications must be retained in the study records. 
If the sponsor grants written approval for changes in study conduct, the sponsor will also provide 
additional written guidance, if needed. 
Considerations for making a change 
The prevailing consideration for making a change is ensuring the safety of study participants. 
Additional important considerations for making a change are compliance with GCP, enabling 
participants to continue safely in the study and maintaining the integrity of the study.  
Informed consent 
Additional consent from the participant will be obtained, if required, for 
 participation in remote visits, as defined in Remote Visits  below 
 a change in the method of study intervention administration, or 
 provision of their personal or medical information required prior to implementation of 
these activities.  
 
 

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Changes in study conduct during exceptional circumstances 
Changes in study conduct not described in this appendix, or not consistent with applicable local 
regulations, are not allowed. 
The following changes in study conduct will not be considered protocol deviations. 
Remote visits 
Types of remote visits 
Telemedicine: Telephone or technology-assisted virtual visits, or both, are acceptable to 
complete appropriate assessments. Assessments to be completed in this manner may include, but 
are not limited to, AE collection, concomitant medication review, or administration of PROs if 
validated for these types of visits.  
 
Mobile healthcare: Healthcare visits may be performed by a mobile healthcare provider at 
locations other than the study site when participants cannot travel to the site due to an 
exceptional circumstance if written approval is provided by the sponsor.  Procedures performed 
at such visits may include, but are not limited to, AE collection, concomitant medication review, 
blood sample collection, physical assessments, study intervention administration, or 
administration of PROs if validated for these types of visits.  
 
Other alternative locations: Local laboratories may be used to collect laboratory samples only for 
safety assessments. 
Data capture 
In source documents and the CRF, the study site should capture the visit method, with a specific 
explanation for any data missing because of missed in-person site visits. 
Safety reporting 
Regardless of the type of remote visits implemented, the protocol requirements regarding the 
reporting of AEs, SAEs, and PCs remain unchanged.  
Return to on-site visits 
Every effort should be made to enable participants to return to on-site visits as soon as 
reasonably possible, while ensuring the safety of both the participants and the site staff. 
Local laboratory testing option 
Local laboratory testing may be conducted in lieu of central laboratory testing. However, central 
laboratory testing must be retained for hsCRP. The local laboratory must be qualified in 
accordance with applicable local regulations. 
 
 

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Study intervention and ancillary supplies including participant diaries 
When a participant is unable to go to the site to receive study supplies during normal on-site 
visits, the site should work with the sponsor to determine appropriate actions.  These actions may 
include   
 asking the participant to go to the site and receive study supplies from site staff 
without completion of a full study visit  
 asking the participant
designee to go to the site and receive study supplies on a 
 
 arranging delivery of study supplies, and 
 working with the sponsor to determine how study intervention that is typically 
administered on site will be administered to the participant; for example, during a 
mobile healthcare visit or at an alternate location such as an infusion center. 
These requirements must be met before action is taken: 
 Alternate delivery of study intervention should be performed in a manner that does 
not compromise treatment blinding and ensures product integrity. The existing 
protocol requirements for product accountability remain unchanged, including 
 
 When delivering supplies to a location other than the study site, for example, to the 
, the investigator, sponsor, or both should ensure oversight of the 
shipping process to ensure accountability and product quality, that is, storage 
conditions maintained and intact packaging upon receipt. 
 Instructions may be provided to the participant or designee on the final disposition of 
any unused or completed study supplies. 
If study intervention will be administered to the participant during a mobile healthcare visit or at 
an alternate location, only authorized study personnel may supply, prepare or administer study 
intervention. 
Screening period guidance  
To ensure safety of study participants, laboratory values and other eligibility assessments taken 
at the screening visit are valid for a maximum of 42 days.  
If screening is interrupted for more than 42 days from randomization visit: The participant must 
be discontinued because of screening interruption due to an exceptional circumstance.  This is 
documented as a screen failure in the CRF.  The participant can reconsent and be rescreened as a 
new participant. The screening procedures per the usual SoA should be followed, starting at the 
screening visit to ensure participant eligibility by the randomization visit. 
Adjustments to visit windows  
Whenever possible and safe to do so, as determined by the inves
, participants 
should complete the usual SoA. To maximize the possibility that these visits can be conducted as 
on-site visits, the windows for visits may be adjusted, upon further guidance from the sponsor. 
This minimizes missing data and preserves the intended conduct of the study. 

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For Visit 3 through Visit 18, the allowed tolerance is ±7 days. 
Documentation 
Changes to study conduct will be documented 
Sites will identify and document the details of how participants, visit types, and conducted 
activities were affected by exceptional circumstances. Dispensing/shipment records of study 
intervention and relevant communications, including delegation, should be filed with site study 
records. 
Source documents at alternate locations 
Source documents generated at a location other than the study site should be part of the 
 source documentation and should be transferred to the site in a secure and timely 
manner.  
 
 

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10.9. 
Appendix 9: Country-Specific Requirements  
10.9.1. 
EU Member States  
For sites in EU Member States, inclusion criterion 9 is revised as shown here. 
 
 
 

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10.10. 
Appendix 10: Abbreviations and Definitions  
 
Term 
Definition 
Abuse 
Use of a study intervention for recreational purposes or to maintain an addiction or 
dependence 
ACR 
American College of Rheumatology 
ACR20  20% improvement in the ACR core set values 
ACR50  50% improvement in the ACR core set values 
ACR70  70% improvement in the ACR core set values 
ADA 
anti-drug antibody 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
authorized IMP 
Applicable to the EU only: a medicinal product authorized in accordance with 
Regulation (EC) No 726/2004 or in any Member State concerned in accordance with 
Directive 2001/83/EC, irrespective of changes to the labelling of the medicinal product, 
which is used as an investigational medicinal product 
authorized AxMP 
Applicable to the EU only: a medicinal product authorized in accordance with 
Regulation (EC) No 726/2004, or in any Member State concerned in accordance with 
Directive 2001/83/EC, irrespective of changes to the labelling of the medicinal product, 
which is used as an auxiliary medicinal product 
AxMP 
auxiliary medicinal product. See also NIMP. 
A medicinal product used for the needs of a clinical study as described in the protocol, 
but not as an investigational medicinal product. Examples include rescue medication, 
challenge agents, agents to assess endpoints in the clinical study, or background 
treatment. AxMP does not include investigational medicinal product (IMP) or 
concomitant medications. Concomitant medications are medications unrelated to the 
clinical study and not relevant for the design of the clinical study 
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. 
CDC 
Centers for Disease Control and Prevention 
Companion diagnostic 
An in vitro diagnostic device (assay or test) that provides information that is essential 
for the safe and effective use of a corresponding therapeutic product 

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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. 
CRF 
case report form; a printed, optical, or electronic document designed to record all of the 
protocol-required information to be reported to the sponsor for each study participant. 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
DMARDs 
Disease-modifying antirheumatic drugs 
bDMARDs 
Biologic DMARDs include, but are not limited to, tumor necrosis factor (TNF) 
inhibitors, T-cell inhibitors, B-cell inhibitors, or interleukin-6 inhibitors. 
csDMARDs 
Conventional synthetic DMARDs include, but are not limited to methotrexate, 
sulfasalazine, hydroxychloroquine, or gold salts. 
tsDMARDs 
Targeted synthetic DMARDs include, but are not limited to, Janus kinas (JAK) 
inhibitors, tofacitinib and baricitinib. 
ECG 
Electrocardiogram 
ED 
early discontinuation 
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. 
Enter 
Participants entered into a study are those who sign the informed consent form directly 
or through their legally acceptable representatives. 
EU 
European Union 
EULAR 
European League Against Rheumatism 
GCP 
good clinical practice 
HAQ-DI 
Health Assessment Questionnaire-Disability Index 
HBV 
hepatitis B virus 
HBcAb 
hepatitis B core antibody 
HBsAg 
hepatitis B surface antigen 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 

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IAC 
internal assessment committee 
IB 
 
ICEs 
intercurrent events 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IGRA 
Interferon gamma release assay 
IMP 
Investigational Medicinal 
investigational product  
A medicinal product which is being tested or used as a reference, including as a 
placebo, in a clinical study. 
informed consent 
A process by which a participant voluntarily confirms their willingness to participate in 
a particular study, after having been informed of all aspects of the study that are 
relevant to the 
 decision to participate. Informed consent is documented by 
means of a written, signed and dated informed consent form. 
interim analysis 
An interim analysis is an analysis of clinical study data, separated into treatment groups, 
that is conducted before the final reporting database is created/locked. 
investigational 
product 
A pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical study, 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. 
 
ITT 
intention to treat:  The principle that asserts that the effect of a treatment policy can be 
best assessed by evaluating on the basis of the intention to treat a participant (that is, the 
planned treatment regimen) rather than the actual treatment given. It has the 
consequence that participant allocated to a treatment group should be followed up, 
assessed, and analyzed as members of that group irrespective of their compliance to the 
planned course of treatment. 
IWRS 
interactive web-response system 
LDA 
Low disease activity 
LTBI 
latent TB infection  

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medication error 
Errors in the prescribing, dispensing, or administration of a study intervention, 
regardless of whether or not the medication is administered to the participant or the 
error leads to an AE. Medication error generally involve a failure to uphold one or more 
he right 
dose, right route, at the right time. 
In addition to the core five rights, the following may also represent medication errors:  
 
 
ion past the recommended in-use date 
 
medication's labeling (for example, Summary of Product Characteristics, IB, local 
label, protocol), or 
 
MedDRA 
Medical Dictionary for Regulatory Activities 
Misuse 
Use of a study intervention for self-treatment that either is inconsistent with the 
prescribed dosing regimen, indication, or both, or is obtained without a prescription 
MMRM 
mixed-effect model for repeated measures 
NIMP 
Non-investigational Medicinal Product See AxMP. 
A medicinal product used for the needs of a clinical study as described in the protocol, 
but not as an investigational medicinal product. Examples include rescue medication, 
challenge agents, agents to assess endpoints in the clinical study, or background 
treatment. 
NRS 
Numeric rating scale 
NSAIDs 
nonsteroidal anti-inflammatory drugs 
Participant 
study, 
either as recipient of an investigational medicinal product or as a control 
PaGADA 
 
PhGADA 
 
PC 
product complaint 
PD-1 
programmed cell death protein 1 
PK/PD 
pharmacokinetics/pharmacodynamics 
PPD 
Purified protein derivative 

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PRO/ePRO 
patient-reported outcomes/electronic patient-reported outcomes 
PT-INR 
prothrombin time/international normalized ratio 
RA 
Rheumatoid arthritis 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
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.  
SDAI 
Simplified Disease Activity Index 
SF-36 
Short Form-36 version 2 health survey acute form 
SJC 
Swollen Joint Counts 
SUSAR 
suspected unexpected serious adverse reaction 
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. 
TJC 
Tender Joint Counts 
TSJC 
Tender Joint Counts and Swollen Joint Counts 
TST 
Tuberculin skin test 
ULN 
upper limit of normal 
VAS 
Visual analog scale 
WHO 
World Health Organization 
WOCBP 
Women of childbearing potential 
 
 

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10.11. 
Appendix 11: Protocol Amendment History  
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents (TOC). 
Amendment [d]: 7 March 2023 
This amendment is considered to be substantial. 
The amendment is considered to be substantial because it may have an impact on the robustness 
of the data generated in the clinical study. 
Overall Rationale for the Amendment: 
The primary rationale for this amendment is to address regulatory feedback. Changes and 
rationale are summarized in this table. Editorial or formatting changes to maintain document 
consistency are not shown in this table. 
 

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Amendment [c]: 31 January 2023 
This amendment is considered to be nonsubstantial. 
Overall Rationale for the Amendment: 
The primary rationale for this amendment is to address regulatory feedback. Changes and 
rationale are summarized in the table below.  
 

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Amendment [b]: 07 October 2022  
Overall Rationale for the Amendment: 
This amendment addresses changes requested by the Food and Drug Administration (FDA). 
 
 
 

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Amendment [a]: 11 August 2022 
This amendment is considered to be nonsubstantial. 
 
Overall Rationale for the Amendment 
Added a clarification that if a participant randomly assigned to 400 mg or 1000 mg peresolimab 
receives rescue medication prior to Week 24, they will not be eligible for the Q12W dosing 
schedule. 
 
 

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