A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of LY3972406 in Adults With Moderate-to-Severe Plaque Psoriasis
Phase: PHASE2
Conditions: Plaque Psoriasis
Sponsor: Eli Lilly and Company

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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 LY3972406, 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. 
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Amendment Number: E 
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Brief Title: $6WXG\RI/<LQ$GXOWVZLWK0RGHUDWHWR6HYHUH3ODTXH3VRULDVLV
Study Phase: 
Sponsor Name: (OL/LOO\DQG&RPSDQ\ 
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Regulatory Agency Identifier Number: 
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Approval Date: 3URWRFRO$PHQGPHQWE(OHFWURQLFDOO\6LJQHGDQG$SSURYHGE\/LOO\RQGDWH
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Date 
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31-Oct-2023 
Original Protocol  
28-Mar-2023 
 
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Table of Contents  
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1. 
Protocol Summary ........................................................................................................10 
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2. 
Introduction ...................................................................................................................28 
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3. 
Objectives, Endpoints, and Estimands .......................................................................32 
4. 
Study Design ..................................................................................................................35 
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Study Population ...........................................................................................................37 
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Study Intervention(s) and Concomitant Therapy .....................................................43 
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7. 
Discontinuation of Study Intervention and Participant 
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8. 
Study Assessments and Procedures.............................................................................51 
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9. 
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References ....................................................................................................................120 
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1. 
Protocol Summary  
1.1. 
Synopsis  
Protocol Title: $3KDVH5DQGRPL]HG'RXEOHEOLQG3ODFHER&RQWUROOHG6WXG\WR,QYHVWLJDWH
WKH(IILFDF\DQG6DIHW\RI/<LQ$GXOWVZLWK0RGHUDWHWR6HYHUH3ODTXH3VRULDVLV 
Brief Title:$6WXG\RI/<LQ$GXOWVZLWK0RGHUDWHWR6HYHUH3ODTXH3VRULDVLV
Regulatory Agency Identifier Number:
,1'
Rationale: 
7KLVVWXG\ZLOOHYDOXDWHWKHHIILFDF\DQGVDIHW\RI/<LQDGXOWVZLWKPRGHUDWHWRVHYHUH
SODTXHSVRULDVLV7KLVLVWKHILUVW3KDVHVWXG\IRUWKLVFRPSRXQGDQGGDWDIURPWKLVVWXG\ZLOO
LQIRUPGHFLVLRQVIRUWKHFOLQLFDOGHYHORSPHQWRI/<
Objectives, Endpoints, and Estimands: 
2EMHFWLYHV
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SODTXHSVRULDVLV
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LQFOLQLFDOVLJQVDQG
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366,VFRUHRIDDW:HHN
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Estimands 
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:KDWLVWKHGLIIHUHQFHEHWZHHQHDFKGRVLQJUHJLPHQRI/<DQGSODFHERLQWKH
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Overall Design 
7KLVLVD3KDVHUDQGRPL]HGGRXEOHEOLQGSODFHERFRQWUROOHGVWXG\WRHYDOXDWHWKHHIILFDF\
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Brief Summary:
7KHSXUSRVHRIWKLVVWXG\LVWRPHDVXUHKRZ/<FRPSDUHVZLWKSODFHERLQLPSURYLQJ
WKHVLJQVDQGV\PSWRPVRISODTXHSVRULDVLV
6WXG\GHWDLOVLQFOXGH
Ɣ 7KHVWXG\GXUDWLRQZLOOEHXSWRZHHNV
Ɣ 7KHWUHDWPHQWGXUDWLRQZLOOEHXSWRZHHNV
Ɣ 7KHWUHDWPHQWSHULRGZLOOEHGRXEOHEOLQGZKLFKPHDQVQHLWKHUWKHSDUWLFLSDQWV
QRUWKHUHVHDUFKHUVZLOONQRZZKLFKVWXG\LQWHUYHQWLRQSDUWLFLSDQWVDUHUHFHLYLQJ
XQWLOWKHVWXG\LVRYHU
Ɣ 'XULQJWKHWUHDWPHQWSHULRGWKHYLVLWIUHTXHQF\ZLOOEHHYHU\ZHHNVVWDUWLQJDW
:HHN'XULQJWKHSRVWWUHDWPHQWIROORZXSWKHYLVLWIUHTXHQF\ZLOOEHHYHU\
ZHHNVIRUWKHILUVWYLVLWVDQGWKHQHYHU\ZHHNVIRUWKHODVWYLVLWV
ż 7KHODVWYLVLWVZLOOQRWEHSHUIRUPHGIRUSDUWLFLSDQWVZLWKD3$6,VFRUHDWRU
DIWHU:HHNWKDWLVJUHDWHUWKDQRUHTXDOWRWKHEDVHOLQH3$6,VFRUH
Study Population: 
$GXOWVZLWKPRGHUDWHWRVHYHUHSODTXHSVRULDVLVZKRDUHFDQGLGDWHVIRUV\VWHPLFWKHUDS\
Number of Participants: 
$SSUR[LPDWHO\
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Intervention Groups and Duration: 
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2. 
Introduction  
2.1. 
Study Rationale  
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2.2. 
Background  
Disease state and treatment goals 
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LY3972406 and the role of 
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Nonclinical and clinical data for LY3972406  
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2.3. 
Benefit/Risk Assessment  
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2.3.1. 
Risk Assessment  
Study intervention 
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4. 
Study Design  
4.1. 
Overall Design  
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4.2. 
Scientific Rationale for Study Design  
Primary endpoint definition 
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Choice of control and number of treatment groups 
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Patient Input into Design  
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Justification for Dose  
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4.4. 
End of Study Definition  
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Study Population  
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5.1. 
Inclusion Criteria  
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Study procedures 
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Exclusion Criteria  
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Other medical conditions 
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Vaccines 
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Prior/concomitant therapy 
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Prior/concurrent clinical study experience 
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5.3. 
Lifestyle Considerations  
Blood donation
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Sperm donation and contraception 
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Prohibited medications and procedures 
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5.4. 
Screen Failures  
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5.5. 
Criteria for Temporarily Delaying Enrollment of a Participant  
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6. 
Study Intervention(s) and Concomitant Therapy  
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6.1. 
Study Intervention(s) Administered  
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Intervention Name
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Dose Level(s) 
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Frequency of Administration 
Route of Administration 
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Packaging and labeling 
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6.2. 
Preparation, Handling, Storage, and Accountability  
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6.3. 
Assignment to Study Intervention  
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6.4. 
Blinding  
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GHVFULEHGLQWKHVHSDUDWH%OLQGLQJDQG8QEOLQGLQJ3ODQ 
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Emergency unblinding 
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PDNLQJVXFKDGHWHUPLQDWLRQ,IDSDUWLFLSDQW¶VLQWHUYHQWLRQDVVLJQPHQWLVXQEOLQGHGWKHVSRQVRU
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Discontinuation from the study in case of unblinding 
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IURPWKHVSRQVRU¶VPHGLFDOPRQLWRUIRUWKHSDUWLFLSDQWWRFRQWLQXHLQWKHVWXG\
6.5. 
Study Intervention Compliance  
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DVSUHVFULEHGDVDSSURSULDWH
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6.6. 
Dose Modification  
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6.7. 
Continued Access to Study Intervention after the End of the Study  
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6.8. 
Treatment of Overdose  
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Ɣ &RQWDFWWKHPHGLFDOPRQLWRULPPHGLDWHO\
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6.9. 
Prior and Concomitant Therapy  
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7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal  
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7.1. 
Discontinuation of Study Intervention  
7.1.1. 
Liver Chemistry Stopping Criteria  
Interrupting study LQWHUYHQWLRQ based on liver test elevations in participants with normal or 
near-normal baseline liver tests 
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Interrupting study LQWHUYHQWLRQ based on elevated liver tests in participants with abnormal 
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Elevation 
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7.1.3. 
Permanent Discontinuation of Study Intervention  
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Participant decision 
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Pregnancy 
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Infections 
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Suicidal ideation or behavior 
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Malignancy 
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Hepatic event or liver test abnormality6HFWLRQ
Concomitant medications  
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Hematologic test abnormality:
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7.1.4. 
Temporary Discontinuation of Study Intervention  
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Criteria for temporary discontinuation of study 
intervention 
Next steps 
Infection criteria 
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Hematology laboratory criteria
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Hold study intervention if the following laboratory test 
results occur: 
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(or its designee) if the following laboratory results 
occur: 
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7.2. 
Participant Discontinuation/Withdrawal from the Study  
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7.3. 
Lost to Follow-up  
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8. 
Study Assessments and Procedures  
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8.1. 
Efficacy Assessments  
8.1.1. 
Primary Efficacy Assessment: Psoriasis Area and Severity Index 75 (PASI 75)  
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8.1.2. 
Secondary Efficacy Assessments  
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8.1.2.1. 
Patient-Reported Outcome Instruments  
Psoriasis Symptoms Scale (PSS) 
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Dermatology Life Quality Index (DLQI) 
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8.1.2.2. 
Clinician-Administered Assessments  
Body Surface Area (BSA) 
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PASI 90 and PASI 100 
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Psoriasis Scalp Severity Index (PSSI) 
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Noninvasive skin sampling 
 and skin punch biopsy 
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8.2. 
Safety Assessments  
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8.2.1. 
Vital Signs  
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8.2.2. 
Physical Examinations  
Physical examination at screening 
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Symptom-directed physical examination after screening 
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8.2.3. 
Skin Assessment with Fitzpatrick Scale of Skin Phototypes  
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8.2.4. 
Electrocardiograms  
ECG collection 
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ECG interpretation 
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Participant assessment after ECGs 
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8.2.5. 
Chest Imaging  
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Conditions for using a previous chest x-ray at screening 
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8.2.6. 
Clinical Safety Laboratory Tests  
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Tuberculosis Testing and Monitoring  
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Hepatitis B Testing and Monitoring  
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Additional Hepatic Data Collection (Hepatic Safety CRF) in Study Participants 
Who Have Abnormal Liver Tests During the Study
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Suicidal Ideation and Behavior Risk Monitoring  
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Timing and Mechanism for Collecting Events  
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8.3.2. 
Pregnancy  
Collection of pregnancy information 
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Female participants who become pregnant 
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8.4. 
Pharmacokinetics  
Pharmacokinetic sample visits and times 
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Collection, handling, and analysis of pharmacokinetic samples 
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Blinding pharmacokinetic data 
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Pharmacodynamics  
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Genetics  
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Genetic sample use 
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8.7. 
Biomarkers  
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Sample confidentiality 
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Sample retention 
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8.8. 
Immunogenicity Assessments  
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8.9. 
Health Economics  
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9. 
Statistical Considerations  
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9.1. 
Statistical Hypothesis  
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9.1.1. 
Multiplicity Adjustment  
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9.2. 
Analyses Sets  
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Population 
Description 
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9.3. 
Statistical Analyses  
9.3.1. General Considerations  
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Changes to the data analysis methods
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Continuous and categorical data analyses 
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Baseline definitions 
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EDVHOLQHSHULRGLVGHILQHGDVWKHWLPHIURP9LVLWWRWKHGDWHWLPHRIWKHILUVWGRVLQJ
Data analysis methods 
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Handling of missing, unused, and spurious data
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9.3.1.1. 
Missing Data Imputation  
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9.3.2. 
Primary Endpoint/Estimand Analysis  
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9.3.3. 
Secondary Endpoints/Estimands Analysis  
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9.3.4. 
Exploratory Endpoints/Estimands Analysis  
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9.3.5. 
Safety Analyses  
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Adverse events analyses 
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Laboratory analytes and vital signs 
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9.3.6. 
Pharmacokinetic Analyses  
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9.3.7. 
Other Analyses  
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9.4. 
Interim Analyses  
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9.5. 
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10. 
Supporting Documentation and Operational Considerations  
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations  
10.1.1. 
Regulatory and Ethical Considerations  
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10.1.2. 
Financial Disclosure  
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10.1.3. 
Informed Consent Process  
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10.1.4. 
Data Protection  
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10.1.5. 
Committees Structure  
Internal Assessment Committee (IAC) 
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10.1.6. 
Dissemination of Clinical Study Data  
Reports
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Records retention and audits 
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Data capture system 
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Electronic data capture system 
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Clinical outcome assessments 
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Data storage and access 
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10.1.8. 
Source Documents  
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10.1.9. 
Study and Site Start and Closure  
First act of recruitment 
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Study or site termination 
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For study termination: 
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For site termination: 
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10.1.10. 
Publication Policy  
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10.1.11. 
Investigator Information  
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10.1.12. 
Sample Retention  
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Maximum Retention Period After Last  
Participant Visit 
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10.2. 
Appendix 2: Clinical Laboratory Tests  
Use of central or local laboratories 
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Laboratory tests for inclusion/exclusion of potential study participants 
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Allowance for additional laboratory testing 
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Investigator responsibilities 
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Provision of laboratory test results 
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Clinical chemistry 
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TB, HIV, and Hepatitis Serology 
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Chemistry 
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Other 
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Genetics sample 
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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 
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DQGZKLFKGRHVQRWQHFHVVDULO\KDYHDFDXVDOUHODWLRQVKLSZLWKWKHVWXG\LQWHUYHQWLRQ$Q$(FDQ
WKHUHIRUHEHDQ\XQIDYRUDEOHDQGXQLQWHQGHGVLJQLQFOXGLQJDQDEQRUPDOODERUDWRU\ILQGLQJ
V\PSWRPRUGLVHDVHQHZRUH[DFHUEDWHGWHPSRUDOO\DVVRFLDWHGZLWKWKHXVHRIDPHGLFLQDO
LQYHVWLJDWLRQDOSURGXFWZKHWKHURUQRWUHODWHGWRWKHPHGLFLQDOLQYHVWLJDWLRQDOSURGXFW
Events meeting the AE definition 
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RWKHUVDIHW\DVVHVVPHQWVIRUH[DPSOH(&*UDGLRORJLFDOVFDQVYLWDOVLJQV
PHDVXUHPHQWVLQFOXGLQJWKRVHWKDWZRUVHQIURPEDVHOLQHFRQVLGHUHGFOLQLFDOO\
VLJQLILFDQWLQWKHPHGLFDODQGVFLHQWLILFMXGJPHQWRIWKHLQYHVWLJDWRUWKDWLVQRWUHODWHG
WRSURJUHVVLRQRIXQGHUO\LQJGLVHDVH
 ([DFHUEDWLRQRIDFKURQLFRULQWHUPLWWHQWSUHH[LVWLQJFRQGLWLRQLQFOXGLQJHLWKHUDQ
LQFUHDVHLQIUHTXHQF\DQGRULQWHQVLW\RIWKHFRQGLWLRQ
 1HZFRQGLWLRQGHWHFWHGRUGLDJQRVHGDIWHUVWXG\LQWHUYHQWLRQDGPLQLVWUDWLRQHYHQWKRXJK
LWPD\KDYHEHHQSUHVHQWEHIRUHWKHVWDUWRIWKHVWXG\
 6LJQVV\PSWRPVRUWKHFOLQLFDOVHTXHODHRIDVXVSHFWHGGUXJGUXJLQWHUDFWLRQ
 0HGLFDWLRQHUURUPLVXVHRUDEXVHRI,03LQFOXGLQJVLJQVV\PSWRPVRUFOLQLFDO
VHTXHODH
 /DFNRIHIILFDF\RUIDLOXUHRIH[SHFWHGSKDUPDFRORJLFDODFWLRQSHUVHZLOOQRWEHUHSRUWHG
DVDQ$(RU6$(6XFKLQVWDQFHVZLOOEHFDSWXUHGLQWKHHIILFDF\DVVHVVPHQWV+RZHYHU
WKHVLJQVV\PSWRPVDQGRUFOLQLFDOVHTXHODHUHVXOWLQJIURPODFNRIHIILFDF\ZLOOEH
UHSRUWHGDV$(RU6$(LIWKH\IXOILOOWKHGHILQLWLRQRIDQ$(RU6$(
Events NOT meeting the AE definition 
 $Q\FOLQLFDOO\VLJQLILFDQWDEQRUPDOODERUDWRU\ILQGLQJVRURWKHUDEQRUPDOVDIHW\
DVVHVVPHQWVWKDWDUHDVVRFLDWHGZLWKWKHXQGHUO\LQJGLVHDVHXQOHVVMXGJHGE\WKH
LQYHVWLJDWRUWREHPRUHVHYHUHWKDQH[SHFWHGIRUWKHSDUWLFLSDQW¶VFRQGLWLRQ
 7KHGLVHDVHGLVRUGHUEHLQJVWXGLHGRUH[SHFWHGSURJUHVVLRQVLJQVRUV\PSWRPVRIWKH
GLVHDVHGLVRUGHUEHLQJVWXGLHGXQOHVVPRUHVHYHUHWKDQH[SHFWHGIRUWKHSDUWLFLSDQW¶V
FRQGLWLRQ
 0HGLFDORUVXUJLFDOSURFHGXUHIRUH[DPSOHHQGRVFRS\DSSHQGHFWRP\WKHFRQGLWLRQ
WKDWOHDGVWRWKHSURFHGXUHLVWKH$(
 6LWXDWLRQVLQZKLFKDQXQWRZDUGPHGLFDORFFXUUHQFHGLGQRWRFFXUVRFLDODQGRU
FRQYHQLHQFHDGPLVVLRQWRDKRVSLWDO
 $QWLFLSDWHGGD\WRGD\IOXFWXDWLRQVRISUHH[LVWLQJGLVHDVHVRUFRQGLWLRQVSUHVHQWRU
GHWHFWHGDWWKHVWDUWRIWKHVWXG\WKDWGRQRWZRUVHQ
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10.3.2. 
Definition of SAE  
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or 
more of the criteria listed: 
 5HVXOWVLQGHDWK
 ,VOLIHWKUHDWHQLQJ
o 7KHWHUPlife-threateningLQWKHGHILQLWLRQRIseriousUHIHUVWRDQHYHQWLQZKLFK
WKHSDUWLFLSDQWZDVDWULVNRIGHDWKDWWKHWLPHRIWKHHYHQW,WGRHVQRWUHIHUWRDQ
HYHQWZKLFKK\SRWKHWLFDOO\PLJKWKDYHFDXVHGGHDWKLILWZHUHPRUHVHYHUH
 5HTXLUHVLQSDWLHQWKRVSLWDOL]DWLRQRUSURORQJDWLRQRIH[LVWLQJKRVSLWDOL]DWLRQ
o ,QJHQHUDOKRVSLWDOL]DWLRQVLJQLILHVWKDWWKHSDUWLFLSDQWKDVEHHQDGPLWWHGWR
KRVSLWDORUHPHUJHQF\ZDUGXVXDOO\LQYROYLQJDWOHDVWDQRYHUQLJKWVWD\IRU
REVHUYDWLRQDQGRUWUHDWPHQWWKDWZRXOGQRWKDYHEHHQDSSURSULDWHLQWKH
SK\VLFLDQ¶VRIILFHRURXWSDWLHQWVHWWLQJ&RPSOLFDWLRQVWKDWRFFXUGXULQJ
KRVSLWDOL]DWLRQDUH$(V,IDFRPSOLFDWLRQSURORQJVKRVSLWDOL]DWLRQRUIXOILOOVDQ\
RWKHUVHULRXVFULWHULDWKHHYHQWLVVHULRXV:KHQLQGRXEWDVWRZKHWKHU
KRVSLWDOL]DWLRQRFFXUUHGRUZDVQHFHVVDU\WKH$(VKRXOGEHFRQVLGHUHGVHULRXV
o +RVSLWDOL]DWLRQIRUHOHFWLYHWUHDWPHQWRIDSUHH[LVWLQJFRQGLWLRQWKDWGLGQRW
ZRUVHQIURPEDVHOLQHLVQRWFRQVLGHUHGDQ$(
 5HVXOWVLQSHUVLVWHQWGLVDELOLW\LQFDSDFLW\
o 7KHWHUPGLVDELOLW\PHDQVDVXEVWDQWLDOGLVUXSWLRQRIDSHUVRQ¶VDELOLW\WRFRQGXFW
QRUPDOOLIHIXQFWLRQV
o 7KLVGHILQLWLRQLVQRWLQWHQGHGWRLQFOXGHH[SHULHQFHVRIUHODWLYHO\PLQRUPHGLFDO
VLJQLILFDQFHVXFKDVXQFRPSOLFDWHGKHDGDFKHQDXVHDYRPLWLQJGLDUUKHD
LQIOXHQ]DDQGDFFLGHQWDOWUDXPDIRUH[DPSOHVSUDLQHGDQNOHZKLFKPD\
LQWHUIHUHZLWKRUSUHYHQWHYHU\GD\OLIHIXQFWLRQVEXWGRQRWFRQVWLWXWHDVXEVWDQWLDO
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o $EQRUPDOSUHJQDQF\RXWFRPHVIRUH[DPSOHVSRQWDQHRXVDERUWLRQIHWDOGHDWK
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 2WKHUVLWXDWLRQV
o 0HGLFDORUVFLHQWLILFMXGJPHQWVKRXOGEHH[HUFLVHGE\WKHLQYHVWLJDWRULQGHFLGLQJ
ZKHWKHU6$(UHSRUWLQJLVDSSURSULDWHLQRWKHUVLWXDWLRQVVXFKDVLPSRUWDQW
PHGLFDOHYHQWVWKDWPD\QRWEHLPPHGLDWHO\OLIHWKUHDWHQLQJRUUHVXOWLQGHDWKRU
KRVSLWDOL]DWLRQEXWPD\MHRSDUGL]HWKHSDUWLFLSDQWRUPD\UHTXLUHPHGLFDORU
VXUJLFDOLQWHUYHQWLRQWRSUHYHQWRQHRIWKHRWKHURXWFRPHVOLVWHGLQWKHDERYH
GHILQLWLRQ7KHVHHYHQWVVKRXOGXVXDOO\EHFRQVLGHUHGVHULRXV
o ([DPSOHVRIVXFKHYHQWVLQFOXGHLQYDVLYHRUPDOLJQDQWFDQFHUVLQWHQVLYH
WUHDWPHQWLQDQHPHUJHQF\URRPRUDWKRPHIRUDOOHUJLFEURQFKRVSDVPEORRG
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10.3.3. 
Definition of Product Complaints  
Product complaint 
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WKHLGHQWLW\TXDOLW\GXUDELOLW\UHOLDELOLW\VDIHW\HIIHFWLYHQHVVRUSHUIRUPDQFHRIDVWXG\
LQWHUYHQWLRQ:KHQWKHDELOLW\WRXVHWKHVWXG\LQWHUYHQWLRQVDIHO\LVLPSDFWHGWKH
IROORZLQJDUHDOVR3&V
o GHILFLHQFLHVLQODEHOLQJLQIRUPDWLRQDQG
o XVHHUURUVIRUGHYLFHRUGUXJGHYLFHFRPELQDWLRQSURGXFWVGXHWRHUJRQRPLF
GHVLJQHOHPHQWVRIWKHSURGXFW
 3&VUHODWHGWRVWXG\LQWHUYHQWLRQVXVHGLQFOLQLFDOWULDOVDUHFROOHFWHGWRHQVXUHWKHVDIHW\
RISDUWLFLSDQWVPRQLWRUTXDOLW\DQGWRIDFLOLWDWHSURFHVVDQGSURGXFWLPSURYHPHQWV
 ,QYHVWLJDWRUVZLOOLQVWUXFWSDUWLFLSDQWVWRFRQWDFWWKHVLWHDVVRRQDVSRVVLEOHLIKHRUVKH
KDVD3&RUSUREOHPZLWKWKHVWXG\LQWHUYHQWLRQVRWKDWWKHVLWXDWLRQFDQEHDVVHVVHG
 $QHYHQWPD\PHHWWKHGHILQLWLRQRIERWKD3&DQGDQ$(6$(,QVXFKFDVHVLWVKRXOG
EHUHSRUWHGDVERWKD3&DQGDVDQ$(6$(
10.3.4. 
Recording and Follow-Up of AE and/or SAE and Product Complaints  
AE, SAE, and PC recording
 :KHQDQ$(6$(3&RFFXUVLWLVWKHUHVSRQVLELOLW\RIWKHLQYHVWLJDWRUWRUHYLHZDOO
GRFXPHQWDWLRQIRUH[DPSOHKRVSLWDOSURJUHVVQRWHVODERUDWRU\UHSRUWVDQGGLDJQRVWLFV
UHSRUWVUHODWHGWRWKHHYHQW
 7KHLQYHVWLJDWRUZLOOWKHQUHFRUGDOOUHOHYDQW$(6$(3&LQIRUPDWLRQLQWKHSDUWLFLSDQW¶V
PHGLFDOUHFRUGVLQDFFRUGDQFHZLWKWKHLQYHVWLJDWRU¶VQRUPDOFOLQLFDOSUDFWLFH$(6$(
LQIRUPDWLRQLVUHSRUWHGRQWKHDSSURSULDWH&5)SDJHDQG3&LQIRUPDWLRQLVUHSRUWHGRQ
WKH3URGXFW&RPSODLQW)RUP
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VKRXOGEHUHSRUWHGDVERWKD3&DQGDVDQ$(6$(
 ,WLVnotDFFHSWDEOHIRUWKHLQYHVWLJDWRUWRVHQGSKRWRFRSLHVRIWKHSDUWLFLSDQW¶VPHGLFDO
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VSRQVRURUGHVLJQHH,QWKLVFDVHDOOSDUWLFLSDQWLGHQWLILHUVZLWKWKHH[FHSWLRQRIWKH
SDUWLFLSDQWQXPEHUZLOOEHUHGDFWHGRQWKHFRSLHVRIWKHPHGLFDOUHFRUGVEHIRUH
VXEPLVVLRQWRVSRQVRURUGHVLJQHH
 7KHLQYHVWLJDWRUZLOODWWHPSWWRHVWDEOLVKDGLDJQRVLVRIWKHHYHQWEDVHGRQVLJQV
V\PSWRPVDQGRURWKHUFOLQLFDOLQIRUPDWLRQ:KHQHYHUSRVVLEOHWKHGLDJQRVLVQRWWKH
LQGLYLGXDOVLJQVV\PSWRPVZLOOEHGRFXPHQWHGDVWKH$(6$(
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Assessment of intensity 
7KHLQYHVWLJDWRUZLOOPDNHDQDVVHVVPHQWRILQWHQVLW\IRUHDFK$(DQG6$(UHSRUWHGGXULQJWKH
VWXG\DQGDVVLJQLWWRRQHRIWKHIROORZLQJFDWHJRULHV
 0LOG$W\SHRI$(WKDWLVXVXDOO\WUDQVLHQWDQGPD\UHTXLUHRQO\PLQLPDOWUHDWPHQWRU
WKHUDSHXWLFLQWHUYHQWLRQ7KHHYHQWGRHVQRWJHQHUDOO\LQWHUIHUHZLWKXVXDODFWLYLWLHVRI
GDLO\OLYLQJ
 0RGHUDWH$W\SHRI$(WKDWLVXVXDOO\DOOHYLDWHGZLWKDGGLWLRQDOVSHFLILFWKHUDSHXWLF
LQWHUYHQWLRQ7KHHYHQWLQWHUIHUHVZLWKXVXDODFWLYLWLHVRIGDLO\OLYLQJFDXVLQJGLVFRPIRUW
EXWSRVHVQRVLJQLILFDQWRUSHUPDQHQWULVNRIKDUPWRWKHUHVHDUFKSDUWLFLSDQW
 6HYHUH$W\SHRI$(WKDWLQWHUUXSWVXVXDODFWLYLWLHVRIGDLO\OLYLQJRUVLJQLILFDQWO\
DIIHFWVFOLQLFDOVWDWXVRUPD\UHTXLUHLQWHQVLYHWKHUDSHXWLFLQWHUYHQWLRQ$Q$(WKDWLV
DVVHVVHGDVVHYHUHVKRXOGQRWEHFRQIXVHGZLWKD6$(6HYHUHLVDFDWHJRU\XWLOL]HGIRU
UDWLQJWKHLQWHQVLW\RIDQHYHQWDQGERWK$(VDQG6$(VFDQEHDVVHVVHGDVVHYHUH
$QHYHQWLVGHILQHGDV³VHULRXV´ZKHQLWPHHWVDWOHDVWRQHRIWKHSUHGHILQHGRXWFRPHVDV
GHVFULEHGLQWKHGHILQLWLRQRIDQ6$(127ZKHQLWLVUDWHGDVVHYHUH
Assessment of causality
 7KHLQYHVWLJDWRULVREOLJDWHGWRDVVHVVWKHUHODWLRQVKLSEHWZHHQVWXG\LQWHUYHQWLRQDQG
HDFKRFFXUUHQFHRIHDFK$(6$(7KHLQYHVWLJDWRUZLOOXVHFOLQLFDOMXGJPHQWWR
GHWHUPLQHWKHUHODWLRQVKLS
 $³UHDVRQDEOHSRVVLELOLW\´RIDUHODWLRQVKLSFRQYH\VWKDWWKHUHDUHIDFWVHYLGHQFHDQGRU
DUJXPHQWVWRVXJJHVWDFDXVDOUHODWLRQVKLSUDWKHUWKDQDUHODWLRQVKLSFDQQRWEHUXOHGRXW
 $OWHUQDWLYHFDXVHVVXFKDVXQGHUO\LQJGLVHDVHVFRQFRPLWDQWWKHUDS\DQGRWKHUULVN
IDFWRUVDVZHOODVWKHWHPSRUDOUHODWLRQVKLSRIWKHHYHQWWRVWXG\LQWHUYHQWLRQ
DGPLQLVWUDWLRQZLOOEHFRQVLGHUHGDQGLQYHVWLJDWHG
 7KHLQYHVWLJDWRUZLOODOVRFRQVXOWWKH,%LQWKHLUDVVHVVPHQW
 )RUHDFK$(6$(WKHLQYHVWLJDWRUmustGRFXPHQWLQWKHPHGLFDOQRWHVWKDWKHVKHKDV
UHYLHZHGWKH$(6$(DQGKDVSURYLGHGDQDVVHVVPHQWRIFDXVDOLW\
 7KHUHPD\EHVLWXDWLRQVLQZKLFKDQ6$(KDVRFFXUUHGDQGWKHLQYHVWLJDWRUKDVPLQLPDO
LQIRUPDWLRQWRLQFOXGHLQWKHLQLWLDOUHSRUWWRVSRQVRURUGHVLJQHH+RZHYHULWLVYHU\
LPSRUWDQWWKDWWKHLQYHVWLJDWRUDOZD\VPDNHDQDVVHVVPHQWRIFDXVDOLW\IRUHYHU\HYHQW
EHIRUHWKHLQLWLDOWUDQVPLVVLRQRIWKH6$(GDWDWRVSRQVRURUGHVLJQHH
 7KHLQYHVWLJDWRUPD\FKDQJHWKHLURSLQLRQRIFDXVDOLW\LQOLJKWRIIROORZXSLQIRUPDWLRQ
DQGVHQGD6$(IROORZXSUHSRUWZLWKWKHXSGDWHGFDXVDOLW\DVVHVVPHQW
 7KHFDXVDOLW\DVVHVVPHQWLVRQHRIWKHFULWHULDXVHGZKHQGHWHUPLQLQJUHJXODWRU\
UHSRUWLQJUHTXLUHPHQWV
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Follow-up of AEs and SAEs 
 7KHLQYHVWLJDWRULVREOLJDWHGWRSHUIRUPRUDUUDQJHIRUWKHFRQGXFWRIVXSSOHPHQWDO
PHDVXUHPHQWVDQGRUHYDOXDWLRQVDVPHGLFDOO\LQGLFDWHGRUDVUHTXHVWHGE\VSRQVRURU
GHVLJQHHWRHOXFLGDWHWKHQDWXUHDQGRUFDXVDOLW\RIWKH$(RU6$(DVIXOO\DVSRVVLEOH
7KLVPD\LQFOXGHDGGLWLRQDOODERUDWRU\WHVWVRULQYHVWLJDWLRQVKLVWRSDWKRORJLFDO
H[DPLQDWLRQVRUFRQVXOWDWLRQZLWKRWKHUKHDOWKFDUHSURIHVVLRQDOV
 ,IDSDUWLFLSDQWGLHVGXULQJSDUWLFLSDWLRQLQWKHVWXG\RUGXULQJDUHFRJQL]HGIROORZXS
SHULRGWKHLQYHVWLJDWRUZLOOSURYLGHVSRQVRURUGHVLJQHHZLWKDFRS\RIDQ\SRVWPRUWHP
ILQGLQJVLQFOXGLQJKLVWRSDWKRORJ\
10.3.5. 
Reporting of SAEs  
SAE reporting via an electronic data collection tool 
 7KHSULPDU\PHFKDQLVPIRUUHSRUWLQJDQ6$(ZLOOEHWKHHOHFWURQLFGDWDFROOHFWLRQWRRO
 ,IWKHHOHFWURQLFV\VWHPLVXQDYDLODEOHWKHQWKHVLWHZLOOXVHWKH6$(SDSHUIRUPVHHQH[W
VHFWLRQWRUHSRUWWKHHYHQWZLWKLQKRXUV
 7KHVLWHZLOOHQWHUWKH6$(GDWDLQWRWKHHOHFWURQLFV\VWHPDVVRRQDVLWEHFRPHV
DYDLODEOH
 $IWHUWKHVWXG\LVFRPSOHWHGDWDJLYHQVLWHWKHHOHFWURQLFGDWDFROOHFWLRQWRROZLOOEH
WDNHQRIIOLQHWRSUHYHQWWKHHQWU\RIQHZGDWDRUFKDQJHVWRH[LVWLQJGDWD
 ,IDVLWHUHFHLYHVDUHSRUWRIDQHZ6$(IURPDVWXG\SDUWLFLSDQWRUUHFHLYHVXSGDWHGGDWD
RQDSUHYLRXVO\UHSRUWHG6$(DIWHUWKHHOHFWURQLFGDWDFROOHFWLRQWRROKDVEHHQWDNHQRII
OLQHWKHQWKHVLWHFDQUHSRUWWKLVLQIRUPDWLRQRQD6$(SDSHUIRUPVHHQH[WVHFWLRQRUWR
WKHVSRQVRURUGHVLJQHHE\WHOHSKRQH
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SAE reporting via paper form 
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10.3.6. 
Regulatory Reporting Requirements  
SAE regulatory reporting 
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10.4. 
Appendix 4: Contraceptive and Barrier Guidance  
10.4.1. 
Definitions  
Word/Phrase 
Definition 
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SRWHQWLDO:2&%3
$GXOWIHPDOHVDUHFRQVLGHUHG:2&%3XQOHVVWKH\DUH:12&%3
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FKLOGEHDULQJSRWHQWLDO
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LQFRQILUPHGLQIHUWLOLW\
 
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DUHPHQRSDXVDO
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VDOSLQJRRRSKRUHFWRP\ELODWHUDOVDOSLQJHFWRP\RUELODWHUDO
RRSKRUHFWRP\
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7KHPHQRSDXVDOVWDWHLVGHILQHGDVDZRPDQ
 
DWDQ\DJHDWOHDVWZHHNVSRVWVXUJLFDOELODWHUDORRSKRUHFWRP\
ZLWKRUZLWKRXWK\VWHUHFWRP\FRQILUPHGE\RSHUDWLYHQRWHRU
 
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RQKRUPRQHWKHUDS\DZKRKDVKDGFHVVDWLRQRIPHQVHVIRUDWOHDVW
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VWDUWLQJKRUPRQHUHSODFHPHQWWKHUDS\
D:RPHQVKRXOGQRWEHWDNLQJPHGLFDWLRQVGXULQJDPHQRUUKHDVXFKDV
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UHOHDVLQJKRUPRQHDQWLHVWURJHQVVHOHFWLYHHVWURJHQUHFHSWRUPRGXODWRUV
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10.4.2. 
Contraception Guidance  
Contraception guidance for Females 
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WKLVWDEOH
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DSUHJQDQF\GXULQJWKHVWXG\
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o RYXODWLRQ 
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:2&%3ZKRDUH127FRPSOHWHO\DEVWLQHQWDVWKHLUSUHIHUUHGDQGXVXDOOLIHVW\OHRUZKRGR
127H[FOXVLYHO\HQJDJHLQVDPHVH[UHODWLRQVKLSDVWKHLUSUHIHUUHGDQGXVXDOOLIHVW\OHPXVW
IROORZWKHUXOHVLQWKLVWDEOH
Must.. 
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7KHVHPHWKRGVRIFRQWUDFHSWLRQPXVWEHXVHGIRUWKHGXUDWLRQRIWKHVWXG\
Contraception guidance for all male participants 
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Examples of different methods of contraception 
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Methods 
Examples 
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10.6. 
Appendix 6: Liver Safety: Suggested Actions and Follow-up 
Assessments  
Hepatic evaluation testing 
6HH6HFWLRQIRUJXLGDQFHRQDSSURSULDWHWHVWVHOHFWLRQ
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Tests assayed by Lilly-designated central laboratory 
Hepatic Hematology Panel 
Hepatitis A virus (HAV) testing: 
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Hepatitis B virus (HBV) testing:
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Hepatic Clinical Chemistry Panel 
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Anti-nuclear antibody (ANA) 
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Anti-smooth muscle antibody (ASMA)D 
Hepatic Coagulation Panel 
Anti-actin antibodyc 
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Immunoglobulin IgA (quantitative) 
Urine Chemistry 
Immunoglobulin IgG (quantitative) 
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Haptoglobin 
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Acetaminophen 
Cytomegalovirus (CMV) testing: 
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Alkaline phosphatase isoenzymes 
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Ceruloplasmin 
Herpes simplex virus (HSV) testing: 
Copper 
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Ethyl alcohol (EtOH) 
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Microbiology Culture: 
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10.7. 
Appendix 7: Tuberculosis Testing  
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10.8. 
Appendix 8: Examples of Infections That May Be Considered 
Opportunistic  
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10.10. 
Appendix 10: Noninvasive Skin Sampling and Skin Punch Biopsy  
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Skin punch biopsy (optional) 
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10.11. 
Appendix 11: Permitted and Prohibited Concomitant Medications  
10.11.1. 
Permitted Concomitant Medications   
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Permitted Concomitant Medications (Study FVAA) 
 
Drug Class
Comments 
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Prohibited Concomitant Medications and Procedures  
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Prohibited Concomitant Medications and Procedures (Study FVAA) 
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10.12. 
Appendix 12: Country-specific Requirements  
For sites in EU Member States 
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10.13. 
Appendix 13: Provisions for Changes in Study Conduct During 
Exceptional Circumstances  
Implementation of this appendix 
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Exceptional circumstances 
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Implementing changes under exceptional circumstances 
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Considerations for making a change 
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Informed consent 
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Changes in study conduct during exceptional circumstances 
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Remote visits 
Types of remote visits
Telemedicine: 7HOHSKRQHRUWHFKQRORJ\DVVLVWHGYLUWXDOYLVLWVRUERWKDUHDFFHSWDEOHWR
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Other alternative locations:$ORFDOODERUDWRU\PD\EHXVHGIRUODERUDWRU\GUDZV
Data capture 
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Safety reporting 
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Return to on-site visits 
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Local laboratory testing option 
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Study intervention and ancillary supplies 
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Screening period guidance  
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Adjustments to visit windows 
:KHQHYHUSRVVLEOHDQGVDIHWRGRVRDVGHWHUPLQHGE\WKHLQYHVWLJDWRU¶VGLVFUHWLRQSDUWLFLSDQWV
VKRXOGFRPSOHWHWKHXVXDO6R$7RPD[LPL]HWKHSRVVLELOLW\WKDWWKHVHYLVLWVFDQEHFRQGXFWHGDV
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EHSURYLGHGWRDYRLGLQWHUUXSWLRQDQGPDLQWDLQRYHUDOOLQWHJULW\RIWKHVWXG\
Documentation 
Changes to study conduct will be documented 
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UHFRUGV
Source documents at alternate locations 
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10.14. 
Appendix 14: Abbreviations and Definitions  
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Term 
Definition 
Abuse 
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ALP 
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ALT 
DODQLQHDPLQRWUDQVIHUDVH
AST 
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anti-HCV 
KHSDWLWLV&YLUXVDQWLERG\ 
AUC 
DUHDXQGHUWKHFXUYH
blinding/masking 
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DZDUHRIWKHWUHDWPHQWEXWWKHSDUWLFLSDQWLVQRWRUYLFHYHUVDRUZKHQWKHVSRQVRULV
DZDUHRIWKHWUHDWPHQWEXWWKHLQYHVWLJDWRUDQGWKHLQYHVWLJDWRU¶VVWDIIDQGWKH
SDUWLFLSDQWDUHQRW
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DUHDZDUHRIWKHWUHDWPHQWUHFHLYHG
BMI 
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Cmin,ss 
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Complaint 
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Term 
Definition 
Compliance 
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CONSORT 
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CRF 
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CSR 
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DMC 
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ECG 
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eGFR 
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Enroll 
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Enter 
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GCP 
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GGT 
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HBsAg 
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HBV 
KHSDWLWLV%YLUXV
HCV 
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HIV 
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Term 
Definition 
IAC 
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IB 
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IC50 
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Appendix 15: Protocol Amendment History  
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Amendment [a]: 31-Oct-2023 
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Signature Page for VV-CLIN-075822 v3.0
Signature Page for VV-CLIN-075822 v3.0
Approval
Medical Director
19-Jul-2024 17:04:04 GMT+0000
Approval
Statistician
19-Jul-2024 19:32:17 GMT+0000
Approved on 19 Jul 2024 GMT
PPD
PPD